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ORAL MANIFESTATION OF

SYSTEMIC DISEASES

ORAL MEDICINE, DIAGNOSIS AND RADIOLOGY

By
Dr. Puneeta Vohra

CONTENT
SR.NO
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TOPIC
Introduction
Gastrointestinal Disorders
Hematological Disorders
Endocrine Disorders
Immunological disorders
Nutritional Disorders
Renal Disorders
Infectious Disease
Sexually Transmitted Diseases
Bibliography

Obstacles are those frightful things you see,


When you take your eyes off your goal.
Introduction

PAGE NO.
3-8
9-22
23-82
83-125
126-169
170-189
190-196
197-245
246-290
291-302

It is often said that mouth is the mirror of ones own health. The
manifestations, which occur in oral cavity for any systemic disease, are due
to its embryonic origin1. Dentistry is one of several areas of medicine
concerned with oral mucosal lesions which are many times indicator for
underlying systemic illness to make a suspected diagnosis. A number of
these may develop because of complication of or as partial manifestation of
underlying systemic disease. These may also occur due to patients
concurrent drug therapy for underlying systemic conditions.
It is now widely recognized that certain systemic disease such as diabetes
mellitus any many immune disorders may increase risk for periodontal
diseases. The hypothesis that oral conditions such as periodontal infections
may be risk factors or indicators for important medical outcomes represents
a paradigm shift in thinking about causality and the directionality of oral and
systemic association. This paradigm shift is encapsulated by new term the
periodontal medicine which refers to perspective that periodontal disease is
interrelated with systemic health in important ways.
The concept that oral infections such as periodontitis, caries and candidiasis
can adversely affect systemic health is not new. At the end of last century a
theory of focal infection developed, that local foci of infection were
responsible for initiation and progression of various inflammatory systemic
conditions like arthritis, sub acute bacterial endocarditis, peptic ulcers etc. a
significant recent advances in health care has been the movement towards a
evidence based practice. The important aspect of this is risk assement
involving classification of individual probability o acquiring disease.
The oral cavity might be thought to be the window to the body. Oral lesions
and symptoms are usually the result of local disease, but can be earliest
indication of, or in some instances may be the primary features in, patients
3

with systemic disease. Oral manifestations can some times lead to diagnosis
alternatively; systemic disease may require oral health care to be modified
for patients or operators safety. Oral cavity reflects the state of systemic
health more frequently than other parts of body. Even in ancient times
examination of mouth and tongue was given great importance. The oral
tissues are in direct physical continuity with rest of body and they are also
related via blood, lymphatics, and nerve pathway. Dentist has an important
role in preventive medicine as many systemic diseases have primary oral
manifestations.
Individuals in oral medicine participate in interdisciplinary medical care in
the areas of oral manifestations of systemic disease, oral oncology, pain,
histopathology which are frequently hospital-based services.
These oral manifestations must be properly recognized if the patient is to
receive appropriate diagnosis and referral for treatment. The lesions of the
oral mucosa, tongue, gingiva, dentition, periodontium, salivary glands, facial
skeleton, extra oral skin and other related structures are caused by some of
the more common systemic diseases.
Most of these manifestations are nonspecific but should alert the dentist to
the possibility of concurrent systemic disease or latent systemic disease that
may develop subsequently.
ORAL MEDICINE is the specialty of dentistry that is concerned with the
oral health care of medically compromised patients and with the diagnosis
and non surgical management of medically related disorders or conditions
affecting the oral and maxillofacial region. Oral medicine specialists are
concerned with the non surgical medical aspects of dentistry. These
4

specialists are involved in the primary diagnosis and treatment of oral


diseases that do not respond to conventional dental oromaxillofacial surgical
procedures, recognition of the interaction of oral and systematic health
integration

of

medical

and

oral

health

care,

management

of

pharmacotherapeutics necessary for treatment of oral and systemic diseases


and investigation of the etiology and treatment of oral diseases through basic
science and clinical research
A disease is an abnormal condition of an organism that impairs bodily
functions. In human beings, "disease" is often used more broadly to refer to
any condition that causes discomfort, dysfunction, distress, social problems,
and/or death to the person afflicted, or similar problems for those in contact
with the person. In this broader sense, it sometimes includes injuries,
disabilities, disorders, syndromes, infections, isolated symptoms, deviant
behaviors, and atypical variations of structure and function, while in other
contexts and for other purposes these may be considered distinguishable
categories
A systemic disease is one that affects a number of organs and tissues, or
affects the body as a whole although most medical conditions will eventually
involve multiple organs in advanced stage
Oral lesions and symptoms are usually the result of local disease, but can be
the indication of, or in some instances may be main features in, patients with
systemic disease .Oral manifestation can some time lead to diagnosis.
Alternatively, systemic diseases may require oral health care to be modified
for patients or operators safety, many systemic diseases can produce oral
manifestations furthermore, drugs used in treatment of systemic disease can
5

some times have effects on mouth or salivary glands or dictate modification


of oral health care .However in practical terms problem is not often serious
because routine restorative and orthodontic care under local anaesthesia can
be carried out on most patients without any significant hazard .Major
problems are with patients suffering from bleeding disorders , allergies, on
corticosteroids, or cardiac problem .Not only systemic disease affect mouth
but, conversely , systemic disease can originate from mouth ,usually as
consequence of infection example infective endocarditis
Educational goals and objectives of performing oral manifestation of
systemic diseases for dentist/oral physician:
1. The Dentist/oral physician will properly interview and examine the
patients and accurately identify the oral diseases and risk factors .Objectives
will be to perform an appropriate dietary history focusing on factors that
increase the risk of oral diseases such as tobacco and alcohol use and the
frequency of sugar intake perform an appropriate oral examination that
effectively visualizes all intra-oral hard and soft tissue, and identifies normal
landmarks. Correctly identify common oral abnormalities including dental
caries, periodontal disease, oral infections, and common benign and
malignant oral lesions. Generate an appropriate differential diagnosis for
common abnormal oral findings and appropriately document oral findings
and diagnoses.
2. Dentist/oral physician will understand the importance of preventive care
in the maintenance of oral health and will be able to counsel patients and
families appropriately regarding appropriate diet for all age group

appropriate intervals for dental care and selection of an appropriate dental


professional. It will be a link between oral and systemic disease.
3. Dentist/oral physician will understand normal anatomy and function of
the oral cavity. He will correctly identify normal anatomy and describe the
function of the muscles, salivary glands, teeth, and temporomandibular joint,
describe common developmental abnormalities of the oral cavity and their
impact on function.
4. Dentist/oral physician will learn the epidemiology and pathophysiology of
oral diseases, and how oral problems affect patients ability to live with other
chronic illnesses, he will be able to describe the relationships between oral
diseases and systemic diseases, including the oral manifestations of tobacco
use (either smoked or chewed), systemic medications, alcohol use,
autoimmune disease, and immune deficiency, and associations with
cardiovascular disease, pregnancy, and diabetes mellitus.
5. Dentist/oral physician will understand common points of intersection
between medical and dental care, and the physicians role in those situations.
Understand the risks and indications for temporary cessation of
anticoagulation therapy in preparation for dental surgery. He will understand
how screening for oral disease in primary care can identify patients in need
of treatment and preventive interventions and how this can yield to
improved outcomes identify screening methods that can be used by a
primary care physician to detect oral problems, describe how screening can
yield improved outcomes and create and sustain effective therapeutic
relationships.

Last but not the least effectively communicate the importance of oral health
in the context of total health.

GASTROINTESTINAL DISORDERS
DISEASES OF THE UPPER DIGESTIVE TRACT
Gastro esophageal Reflux Disease
Hiatal Hernia

DISEASES OF THE LOWER DIGESTIVE TRACT


Disorders of the Stomach
Disorders of the Intestines

DISEASES OF THE HEPATOBILIARY SYSTEM


Jaundice
Alcoholic Hepatitis
Drug-Induced Hepatotoxicity
Liver Cirrhosis

GASTROINTESTINAL SYNDROMES
Eating Disorders: Anorexia and Bulimia
Gardners Syndrome
Plummer-Vinson Syndrome
Peutz-Jeghers Syndrome
Cowdens Syndrome

INTRODUCTION
To provide safe and appropriate dental care, dentists are typically concerned
with the proper diagnosis of oral manifestations of gastrointestinal disorders,
homeostasis, risk of infection, drug actions and interactions, the patients
ability to withstand the stress and trauma of dental procedures, and proper
medical referral (when necessary).
The digestive system is composed of the esophagus, stomach, small
intestine, and large intestine. Each of these components performs specific
functions as ingested substances move through the different anatomic areas.
Additionally, the exocrine functions of the pancreas, liver, and gall bladder
combine to complete the assimilation of dietary calories and nutrients.
Both dentists and gastroenterologists have their primary focus within the
alimentary canal. The common embryogenesis of the oral cavity and
gastrointestinal tract is occasionally reinforced for the clinician when he or
she finds heterotopic gastric mucosal cysts in the oral mucous membranes or
on the tongue2,3. However, in addition to these relatively rare anomalies, the
9

paths of gastroenterologists and dentists cross quite frequently in clinical


practice.
The oral cavity is the portal of entry to the GI tract. Lined by stratified
squamous epithelium, the tissues of the mouth are often involved when
individuals have conditions affecting the GI system. These may be immunemediated or chemically mediated processes. There is hypersensitivity to
gluten, a constituent of wheat and other cereals not uncommon in some
ethnic groups such as celtic descendants, though not always recognized if
not severe.
GASTRTOESOPHAGAL REFLUX DISEASE6
Gastroesophageal reflux disease (GERD) is one of the most commonly
occurring diseases affecting the upper gastrointestinal tract. The incidence of
GERD is increasing in the developed population experience heartburn daily.
Symptoms can range from mild to severe. There is no difference between the
percentage of men and the percentage of women that are affected by GERD.
GERD is a disease which has a significant effect on ones activities of daily
living as well as an economic effect on individuals and society. During
gastroesophageal reflux, gastric contents (chyme) passively move up from
the stomach into the esophagus.While this can occur normally, it may be
attributed to GERD if it is associated with symptoms. GERD is often
considered a syndrome because it can present with a wide variety of
symptoms. Patients may experience mild symptoms with an esophagus that
appears to be clinically normal or they may have severe symptoms with
surface abnormalities that can be detected with an endoscope. A presumptive
diagnosis of GERD may be made for any symptomatic condition that is the
10

result of gastric contents moving into the esophagus. Functional bowel


disease is a syndrome with similar symptoms and may mimic GERD; it is
often misdiagnosed as GERD. Heartburn is the cardinal symptom of GERD
and is defined as a sensation of burning or heat that spreads upward from the
epigastrium to the neck.4 Although symptoms of GERD can be quite varied,
they are primarily symptoms that are associated with the sequelae of
mucosal injury. These resultant injuries include esophagitis, esophageal
ulceration, stricture, and dysplasia. Chest pain is another important symptom
that is related to disorders of the esophagus. Chest pain can mimic the
symptoms of an acute cardiovascular disorder and is often the impetus for
patients seeking medical care. Dysphagia is also a common presenting
complaint that may serve to prompt the dentist to refer the patient to the
patients physician. Several studies have shown that a number of airway
problems that were previously thought to be idiopathic, such as laryngitis,
chronic cough, hoarseness, and asthma, are in fact the result of
microaspiration of refluxate into the airway.3,5
Barretts esophagus7 is a variant of GERD in which normal squamous
epithelium is replaced by columnar epithelium. 4Patients with this
phenomenon show an increased incidence of adenocarcinoma. This
condition may increase the incidence of carcinoma by as much as 10%. A
protective effect for adenocarcinoma may result if Helicobacter pylori is
present.
The relaxation of the lower esophageal sphincter for the purpose of relieving
pressure in the stomach (from gas and the ingestion of food) is called the
burp mechanism. This phenomenon is a normal process and occurs only
11

when a person is in an erect posture; gastric contents are thereby prevented


from flowing into the esophagus and possibly being aspirated. The
gastroesophageal junction, which prevents the regurgitation (retrograde or
upward flow) of gastric contents, is composed of an internal lower
esophageal sphincter. External pressure on the junction by the diaphragm
also assists in this function. When this barrier fails, gastric contents may
make their way into the esophagus and cause symptoms. The cause of loweresophageal sphincter incompetence is unknown; however, it does not appear
to be mechanical. Hiatal hernia was historically recognized as a cause of
GERD, but there is no correlation between sphincter pressure and the
presence of a hiatal hernia, which leads to the widely accepted position that
GERD is not caused by hiatal hernia. Surgery, scleroderma, and drugs such
as anticholinergics, cardiac vasoconstrictors, and nicotine can also cause an
incompetent sphincter.

Oral health consideration


Regurgitation of gastric contents (pH 1-2) reduces the pH of the oral cavity
below 5.5; this acidic pH begins to dissolve enamel. It is most commonly
seen on the palatal surfaces. Erosion of the enamel exposes the underlying
dentin, which is a softer, opaque material. The extent of erosion depends on
the frequency and the quantity of exposure along with the duration of
disease. Newly exposed dentin is smooth and shiny, while dentin from
previous exposures may be stained.
Erosion differs from dental caries in that it is a hard, dished-out area where
enamel has dissolved and the underlying dentin is exposed. On the other

12

hand, caries reveals soft, discolored dentin and results from the bacterial
breakdown of sugars on the surface of the teeth (Schroeder, 1995). The
prevalence of caries is not increased in persons with GERD, possibly
because the acidic environment interferes with the formation of the dental
biofilm. Good dental care and control of acid helps decrease the prevalence
of erosion. However, once the erosion occurs, it is irreversible and can only
be treated with surgical restorative procedures. Therefore, early recognition
and patient education is the most effective treatment.
Smoking cessation will increase the production of saliva and therefore
counteract the symptoms of GERD. Fatty meals slow down gastric emptying
and produce distention and reflux. An increase in the fat content of meals
may be an important factor in explaining Patients who have a diagnosis of
GERD may need to be treated in a semisupine position and premedicated
with H2 receptor antagonists or antacids.Any medications that may cause
nausea (such as narcotic analgesics) should be prescribed judiciously
because of the increased likelihood of regurgitation and possible
aspiration.Mild baking soda mouth rinses (one-half teaspoon of sodium
bicarbonate in 8 ounces of water) may be rinsed and expectorated to
minimize dysgeusia due to acid reflux. Topical fluoride applications via a
custom-made occlusive tray will ensure optimal dental minealization.
Treatment
Estrogen/progesterone combinations used in contraceptives and during
pregnancy also have been shown to decrease sphincter pressures. Proton
pump inhibitors (PPIs) such as omeprazole and (more recently) lansoprazole
have been found to heal erosive esophagitis more efficaciously than do H2

13

receptor antagonists. PPIs provide not only symptomatic relief but also
resolution of signs, including those that involve significant ulcers and/or
esophageal damage.8 Studies have shown that PPI therapy can provide
complete endoscopic mucosal healing of esophagitis at 6 to 8 weeks in 75 to
100% of cases. Daily PPI treatment provides the best long-term reduction of
symptoms for patients with moderate to severe esophagitis. Remission for as
long as 5 years has been seen. Promotility drugs are effective in the
treatment of mild to moderately symptomatic GERD. These drugs increase
loweresophageal sphincter pressure (which helps decrease acid reflux) and
improve the movement of food from the stomach.

DISEASES OF LOWER GASTROINTESTINAL


TRACT
CROHN DISEASE
Crohn disease is an idiopathic disorder that can involve the entire GI tract
with transmural inflammation, noncaseating granulomas, and fissures. This
14

disease is most common in Western countries and is slightly more prevalent


among white males. The peak incidence is in the second and third decades of
life, with a second peak occurring in the sixth and seventh decades.
Symptoms of Crohn disease include intermittent attacks of diarrhea,
constipation, abdominal pain, and fever. Patients may develop malabsorption
and subsequent malnutrition. Fissures or fistulas may occur in persons with
chronic disease.
Crohns disease is a chronic inflammatory bowel disease of unknown
aetiology, affecting mainly the ileum.
Clinical features
It presents typically with abdominal pain, persistent diarrhoea with passage
of blood and mucus, anaemia, and weight loss. However any part of
gastrointestinal tract can be involved including the mouth.
An oral biopsy may conform the presence of lymphoedema and
granulomas ,blood tests and intestinal radiology, endoscopy, and biopsy may
be required to exclude gastrointestinal lesions .
Secondary deficiencies should be corrected, intralesional corticosteroids
may help control oral lesions such as swelling, but occasionally systemic
sulphasalazine or other agents are required.
Intraoral involvement in Crohn disease occurs in 8-9% of patients and may
precede intestinal involvement. With oral involvement, the likelihood of
extraintestinal manifestations is greater. Extraintestinal features are also
common in persons with Crohn disease, and these may manifest

15

systemically as arthritis, clubbing of the fingers, sacroilitis, and erythema


nodosum.
Oral manifestations
Orofacial symptoms of Crohn disease include (1) Diffuse labial, gingival, or
mucosal swelling; (2)Cobble stoning of the buccal mucosa and gingiva; (3)
aphthous ulcers; (4) Mucosal tags; and (5) Angular cheilitis.6) Noncaseating
granulomas are characteristic of Orofacial Crohn disease. Oral granulomas
may occur without characteristic alimentary involvement (orofacial
granulomatoses). However, the term orofacial granulomatoses encompasses
a variety of other disorders, including sarcoidosis, Melkersson-Rosenthal
syndrome, and, rarely, tuberculosis. Whether patients with orofacial
granulomatoses will subsequently develop intestinal manifestations of Crohn
disease is uncertain, but histologic similarities between the oral lesions and
the intestinal lesions are obvious.
Labial swelling is most often a cosmetic complaint, but it can be a painful
manifestation of the disease. Gingival and mucosal involvement may cause
difficulty while eating. The pattern of swelling, inflammation, ulcers, and
fissures is similar to that of the lesions occurring in the intestinal tract. Acute
and chronic inflammation, with lymphocytic and giant cell perivascular
infiltrates, and lymphoid follicles are the most common histologic findings
in oral and GI Crohn disease. Noncaseating granulomas are present in
biopsy samples in a number of cases. Increased dental caries and nutritional
deficiencies may be related to decreased saliva production and
malabsorption in the intestinal tract.

16

Oral findings as described above warrant a full systemic evaluation for


intestinal Crohn disease, including referral for colonoscopy and biopsy with
histopathologic correlation. Oral involvement may precede systemic
manifestations and symptoms. Negative findings on GI evaluations should
be repeated in patients with oral symptoms. The severity of oral lesions may
coincide with the severity of the systemic disease, and it may be used as a
marker for intestinal impairment (Halme, 1993).
ULCERATIVE COLITIS
Ulcerative colitis is an inflammatory condition with some similarities to
Crohn disease. However, it is restricted to the colon and is limited to the
mucosa and submucosa, sparing the muscularis. Lesions in the colon consist
of areas of hemorrhage and ulcerations along with abscesses. Similar lesions
may manifest in the oral cavity as aphthous ulcerations or superficial
hemorrhagic ulcers. Ulcerative colitis is characterized by periods of
exacerbation and remission, and, generally, oral lesions coincide with
exacerbations of the colonic disease. Similar ulcerations may arise on the
buttocks, abdomen, thighs, and face (Handlers, 1999). Aphthous ulcers or
angular stomatitis occurs in as many as 5-10% of patients.
DISEASE OF HEPATOBILLARY SYSTEM
Chronic liver disease impacts many systems of the body. The coagulation
pathway is one such system. The liver synthesizes many of the clotting
factors necessary to stop bleeding. In addition, vitamin K, a fat-soluble
vitamin, requires proper liver function to be adequately absorbed from the
intestines. In patients with liver disease, the resultant impaired hemostasis

17

can be manifested in the mouth as petechiae or excessive gingival bleeding


with minor trauma. This is especially suggestive if it occurs in the absence
of inflammation. Therefore, special care must be taken during any type of
surgery, oral or otherwise; severe hemorrhage can ensue as a result of the
paucity of clotting factors.
Oral manifestation
The only manifestation of advanced liver disease visible in the oral mucosa
is jaundice, which is the yellow pigmentation that results from the deposition
of bilirubin in the submucosa. Jaundice may occur following disorders in
bilirubin metabolism, production, or secretion. Hepatocellular damage
affects secretion, the rate-limiting step in bilirubin metabolism, allowing
conjugated bilirubin to leak out of the cells and into the blood stream. This
water-soluble substance is loosely albumin bound, and it is deposited in the
mucus membranes throughout the body. When jaundice is due to chronic
liver disease, the yellow color reflects a direct relation to liver function.
Jaundice manifests at serum levels of bilirubin greater than 2.5-3 mg/dL or
2-3 times baseline. Because they are thinner, the mucosae on the soft palate
and in the sublingual region are often first to reveal a yellow hue. With time,
the yellow changes can be visible at any mucosal site.
Because of its high rate of progression to chronic hepatitis (50%) and
cirrhosis, hepatitis C is the leading infectious cause of chronic liver disease
worldwide. The association between hepatitis C and oral lichen planus is
controversial. The link between the two conditions is tenuous and not
sufficient to warrant screening for hepatitis C infection in all patients with
lichen planus
18

GARDNERS SYNDROME
This genetic syndrome is chracterised by osteomas, fibromas, epidermoid
cysts includes polyposis. Gardners syndrome consists of intestinal polyposis
(which

represents

premalignant

lesions)

and

multiple

impacted

supernumerary (extra) teeth. This disorder is inherited as an autosomal


dominant trait, and few patients afflicted with this syndrome reach the age of
50 years without surgical intervention.15 In a young patient with a family
history of Gardners syndrome, dental radiography (such as pantomography)
can provide the earliest indication of the presence of this disease process.10
PLUMMER-VINSON SYNDROME
Plummer-Vinson syndrome, originally described as hysterical dysphagia,
is noted primarily in women in the fourth and fifth decades of life. The
hallmark of this disorder is dysphagia resulting from esophageal stricture,
causing many patients to have a fear of choking.56 Patients may present
with a lemontinted pallor and with dryness of the skin, spoon-shaped
fingernails, koilonychia, and splenomegaly. The oral manifestations are the
result of an iron deficiency anemia. Oral findings include atrophic glossitis
with erythema or fissuring, angular cheilitis, thinning of the vermilion
borders of the lips, and leukoplakia of the tongue. Inspection of the oral
mucous membranes will disclose atrophy and hyperkeratinization.These oral
changes are similar to those encountered in the pharynx and esophagus.
Carcinoma of the upper alimentary tract has been reported in 10 to 30% of
patients.11Thorough oral, pharyngeal, and esophageal examinations are
mandatory to ensure that carcinoma is not present. Artificial saliva may
reduce the sensation (and thereby, the fear) of choking.

19

PEUTZ-JEGHERS SYNDROME
Peutz-Jeghers syndrome is characterized by multiple intestinal polyps
throughout the gastrointestinal tract but primarily in the small intestine.
Malignancies in the gastrointestinal tract and elsewhere in the body have
been reported in approximately 10% of patients with this syndrome.
Pigmentation (present from birth) of the face, lips, and oral cavity is a
hallmark of this syndrome.12 Interestingly, the facial pigmentation fades later
in life although the intraoral mucosal pigmentation persists. No specific oral
treatment is necessary.
COWDENS SYNDROME
Cowdens syndrome (multiple hamartoma and neoplasia syndrome) is an
autosomal dominant disease characterized chiefly by facial trichilemmomas,
gastrointestinal

polyps,

breast

and

thyroid

neoplasms,

and

oral

abnormalities. Cowdens syndrome is considered to be a cutaneous markerof


internal malignancies.13 Pebbly papilloma-like lesions and multiple fibromas
may be found widely distributed throughout the oral cavity.14

PYOSTOMATITIS VEGETANS
Oral lesions in mouth, related to inflammatory bowel disease, are termed
pyostomatitis vegetans, include deep fissures, pustules, ulcers, and papillary
projections. The course of these lesions tends to follow that of bowel
disease. Most patients with these lesions have ulcerative colitis or Crohns
disease. Some have liver disease Oral lesional biopsy and gastrointestinal

20

investigation are required. Management is with sulphasalazine or systemic


coricosteroids

Pyostomatitis Vegetans
ulcerations on labial mucosa

COLOR PLATE-I

21

CROHNS DISEASE cobble stoning


of buccal mucosa and ulcerations

PEUTZ-JEGHERS SYNDROME
Pigmentation present on face and lip since birth

HAEMATOLOGICAL DISORDERS
22

RED BLOOD CELL DISORDERS


Polycythemia
Anemia

WHITE BLOOD CELL DISORDERS


Quantitative Disorders
Qualitative Leukocyte Disorders
Leukemia

LYMPHOMA
Hodgkins Disease
Non-Hodgkins Lymphoma
Burkitts Lymphoma
Oral and Dental Considerations

MULTIPLE MYELOMA
Treatment
Oral Manifestations
Dental Management

The process of haematopoiesis is the formation of cellular components of


the blood from a small population of pluripotential stem cells, which are
formed in embryonic life and persists there after through self regeneration.
When stimulated by haemopoietic growth factors such as cytokines, these
precursors give rise to progenitor cells committed to development along
specific pathways.

RED BLOOD CELL DISORDERS


23

POLYCYTHEMIA
Polycythemia may be defined as an abnormal increase in the erythrocyte
count in the peripheral blood, usually accompanied by an increase in
hemoglobin and hematocrit. Polycythemia is divided into absolute
erythrocytosis (a true increase in red-cell mass) and relative erythrocytosis
(the red cell mass is normal, but the plasma volume is reduced). Relative
polycythemia is caused by the loss of tissue and intravascular fluid, which
may be the result of such diverse conditions as diabetic ketoacidosis,
postsurgical dehydration, prolonged vomiting or diarrhea, or rapid diuresis
secondary to treatment for congestive heart failure. In relative polycythemia,
the hemoglobin rarely rises more than 25gm%, and there are no appreciable
oral changes.
Three main groups of polycythemia are recognized: primary proliferative
polycythemia (polycythemia rubra vera), secondary polycythemia resulting
from changes in erythropoietin concentration, and apparent polycythemia.
The latter condition lacks a true increase in red-cell mass.
POLYCYTHEMIA VERA
Polycythemia vera (PV) is a myeloproliferative disorder characterized
by excessive proliferation of erythroid elements along with granulocytic and
megakaryocytic cells; it usually begins after 50 years of age. The etiology of
PV is unknown; however,it is likely a result of acquired genetic changes in
the stem cell leading to disturbances of normal cellular growth.
Oral Manifestations
A purplish red discoloration of the oral mucosa is visible on the tongue,
cheeks, and lips. The gingivae are red and may bleed spontaneously.
Petechiae and ecchymoses are observed in patients with platelet
abnormalities. Varicosities seen on the ventral surface of tongue, a frequent
24

normal finding, are exaggerated in cases of polycythemia. Taken in patients


with definite cardiovascular risks16.
SECONDARY POLYCYTHEMIA
ERYTHROCYTOSIS
Secondary polycythemia is due to an increase in erythropoietin production to
compensate for hypoxia. This reactive erythrocytosis leading to disturbances
of normal cellular growth.This reactive erythrocytosis has been described in
people who live at high altitudes with low atmospheric pressure and in
people with chronic pulmonary disease, congenital heart disease (right toleft shunt), and renal disease (hydronephrosis). Pheochromocytoma and
other endocrine disorders also have been described as possible causes of
erythrocytosis.
APPARENT POLYCYTHEMIA
Apparent polycythemia, characterized by an increased hemoglobin
concentration and packed-cell volume but normal RBC mass, is caused by a
reduction in plasma volume. Apparent polycythemia most commonly affects
middle-aged obese men with hypertension and a significant social history of
smoking and high alcohol consumption. Some cases are associated with
diuretic therapy.Treatment is usually geared toward the underlying disorder;
however, more aggressive measures may be taken in patients with definite
cardiovascular risks.16
To prevent complications, it is recommended that the hemoglobin be
reduced below 16 g/dL and the hematocrit to below 47% as these are the
thresholds at which medical management is instituted. Patients with this
disease require special attention to local hemostasis. Preoperative
myelosuppressive treatment should be considered prior to dental treatment
when the blood counts are not controlled with phlebotomy alone.
25

ANEMIA
Introduction
Anemia is defined as an abnormal reduction in number of circulating red
blood cells, the quantity of hemoglobin and volume of packed red cells in
given unit of blood.20 This reduction in hemoglobin may result from blood
loss, as in common iron deficiency anemia, from increased destruction of red
blood cells, as in the hemolytic anemias, from decreased production of red
cells, as in pernicious and folic acid deficiency anemias, or from
combinations of these three.When there is a combination of causes, one
mechanism usually predominates. Anemias also may be classified according
to

their

pathophysiologic

macrocytic)of

the

red

basis:
cells

size

or

their

(microcytic,

normocytic,

hemoglobin

or

concentration

hypochromic,normochromic. The term hyperchromic is seldom used, but


it refers to a macrocytic cell with normal hemoglobin concentration that,
because of its large size, has an increased hemoglobin content.
General symptoms of all anemias include pallor of the skin, palpebral
conjunctiva, and nail beds; dyspnea; and easy fatigability. Fatigue and
decreased resistance to infection are common systemic symptoms. The nail
beds and oral mucosa exhibit pallor. This pallor is a common and easily
recognizable feature of anemia.
Oral manifestations
Mucosal conditions, such as glossitis, recurrent aphthae, candidal infections,
and angular stomatitis, may be more common in patients with anemia.
Glossitis may be the first sign of folate or vitamin B12 deficiency. The tongue
appears reddened, and the papillae are atrophic, producing a smooth (bald)

26

appearance. Angular stomatitis is commonly caused by a candidal infection,


and it has been linked to iron deficiency. If the anemia persists, resistance to
infection may be decreased.The main complication for oral health care is
risk from genral anaesthesia.
HAEMOLYTIC ANAEMIA
I Common Causes of Hemolytic Anemia
Extracorpuscular factors
Overwhelming infections and toxins
Cardiac valvular prostheses
Hypersplenism
Rh factor incompatibility (hemolytic disease of newborn, erythroblastosis
fetalis)
Chronic liver disease
Autoimmune hemolytic disease (eg, as in systemic lupus erythematosus)
Transfusion reactions
II Intracorpuscular defects
Abnormal shape of the erythrocytes
Hereditary spherocytosis
Hereditary elliptocytosis
III Erythrocyte enzyme deficiencies
Glucose-6-phosphate dehydrogenase deficiency
Pyruvate kinase deficiency
IV Abnormal hemoglobins (hemoglobinopathies)
Sickle cell anemia and sickle cell trait
27

Thalassemia
Other hemoglobinopathies (eg, hemoglobin C and F)
V Erythrocyte defects associated with other disease
Folic acid and vitamin B12 deficiency anemias
ANEMIA OWING TO BLOOD LOSS
IRON DEFICIENCY ANEMIA
Iron is essential for synthesis of heme portion of haemoglobin. Iron
deficiency anaemia is caused by imbalance between iron intake and loss of
inadequate utilization.
Etiology
Inadequate intake of iron, malabsorption of iron, increased requirement of
iron in growing child and pregnancy, chronic blood loss such as menstrual
and menopausal bleeding.
Clinical features
Iron deficiency anemia (blood loss anemia, hypochromic microcytic anemia)
is the most common of all anemias, affecting approximately 30% of the
worlds population and accounting for up to 500 million cases worldwide. It
occurs chiefly in women in 4th and 5th decades of life. Nails become brittle
and flattened and often show spoon shape (koilonychias)17

Causes

28

Iron deficiency anemia may result from chronic blood loss, such as occurs in
menstrual or menopausal bleeding, parturition, bleeding hemorrhoids, or a
bleeding malignant lesion or ulcer in the gastrointestinal tract. It also may
develop in patients from a variety of causes that may decrease the rate of
absorption of iron, such as subtotal or complete gastrectomy, or a habit of
clay eating, or as part of malabsorption syndromes.18
Oral manifestations
The major oral sign of iron deficiency anemia is pallor of the mucosa due to
lack of oxygenated blood in capillary bed in lamina propria and is associated
with lower levels of hemoglobin. In addition, the oral epithelial cells become
atrophic, with loss of normal keratinization. The tongue may become smooth
due to atrophy of the filiform and fungiform papillae, and glossodynia can
be a presenting or associated symptom. In long-standing cases, esophageal
strictures or webs can develop, resulting in dysphagia. Recent clinical
investigation has shown lingual signs and symptoms to be much less
common than was previously believed of skin extending up to and beyond
mucocutaneous junction. Recurrent apthous ulceration and candidal lesions
can also occur in iron deficiency anaemia.
Histologic examination of the tongue mucosa shows a reduction in
epithelial thickness, with a reduction in the number of cells in spite of an
increase in the progenitor cell layer. The cell size is decreased in the
maturation layers (in males), and the nucleocytoplasmic ratio is higher than
normal. Lingual mucosal atrophy may occur in the absence of other clinical
findings.
COLOR PLATE-II

29

IRON DEFFICIENCY ANEMIA


(Atrophy of tongue papillae)

Diagnosis
30

Diagnosis is based on a lowered hemoglobin in routine blood counts, on a


peripheral smear, the cells are microcytic and hypochromic.When the
anemia is well developed, the mean corpuscular hemoglobin, the mean
corpuscular hemoglobin concentration, and the mean corpuscular volume are
decreased. Whenever the hemoglobin value is less than 11 g/dL, it is of
definite clinical significance. The patient with iron defi-ciency anemia will
have low serum iron concentrations and a high serum iron-binding capacity.

Dental Considerations
Dental patients presenting with symptoms of anemia or oral signs suggestive
of this condition should have a complete blood count (CBC) with
differential. If significantly lowered hemoglobin values are obtained, the
patient should be referred to his or her physician for a more thorough
medical history, laboratory diagnosis, and treatment. Elective oral surgical or
periodontal procedures should not be performed on patients with marked
anemia because of the potential for increased bleeding and impaired wound
healing.When hemoglobin levels fall below 10 g/dL, the low oxygen tension
affects the rheologic interactions between the cellular components of blood,
mainly platelets and endothelium, decreasing their ability to clot effectively.
General anesthesia should not be administered unless the hemoglobin is at
least 10 g/dL. The patient should never be treated with iron until the cause of
the microcytic hypochromic anemia is found and corrected or until a
thorough search for the cause has proved fruitless.

Treatment
31

The diagnosis of iron deficiency anemia is made either by demonstration of


an iron deficient state or by evaluation of the response to therapeutic iron
replacement. The single most important aspect of treatment is identification
of the cause, especially a source of occult blood loss.19
PLUMMER VINSON SYNDROME(Paterson-Brown Kelly Syndrome)
First described by Plummer and Vinson, this syndrome is characterized by
dysphagia and a microcytic hypochromic anemia. A smooth and sore tongue,
dry mouth, spoon-shaped nails, and angular stomatitis are common findings.
There is atrophy of the tongue papillae, but it is less severe than in
pernicious anemia. There are atrophic changes in the oral mucosa, the
pharynx, the upper esophagus, and the vulva. These tissues are dry, inelastic,
and glazed in appearance. In addition, general symptoms include
listlessness, pallor, ankle edema, and dyspnea, all related to the anemia.
Many patients with this syndrome are edentulous, having lost their teeth
early in life. Complaints of a sore mouth and an inability to wear dentures
are frequent. In addition, patients with Plummer-Vinson syndrome often
complain of a spasm in the throat or of food sticking in the throat. The
dysphagia, which represents an important feature of this condition, appears
to be the result of muscular degeneration in the esophagus, and stenoses or
webs of the esophageal mucosa.
The diagnosis of this syndrome can be made on the basis of the history and
hematologic

findings.

The

esophageal

lesions

are

demonstrable

radiologically (barium swallow) or by esophagoscopy. Relative degrees of


achlorhydria are usually present.

32

SICKLE CELL DISEASES


It was first described by Herrick in 1910. In sickle cell disease, an autosomal
recessive disorder, an abnormality in the chain of hemoglobin is present in
which valine is substituted for the normal glutamic acid residue on sixth
position. This relatively minor biochemical change results in profound
undesirable physical characteristics in the hemoglobin. In the presence of
either a lowered blood oxygen tension or an increased blood pH, the
hemoglobin forms a sickle-shaped crystal (a tactoid) within the erythrocyte.
This sickling of the erythrocyte leads to stasis and hemolysis of the red cells,
especially in end-capillary circulation. The stasis then results in an even
lower oxygen tension, an increased pH, and further sickling. The disease is
hereditary and may manifest itself as the sickle cell trait or as sickle cell
anemia. Patients with sickle cell disease or trait are abnormally susceptible
to

infection,

particularly

pneumococcal

or

meningococcal,

and

osteomyelitis. Sickling crises can be precipitated and painful crises caused


by blockage of blood vessels and bone marrow infarcts can affect the jaws,
particularly the mandible. They can cause severe pain and infracted tissues
forms a focus susceptible to infection. Salmonella osteomyelitis is a
recognizable hazard.
General Manifestations
It is common in females and mostly clinical symptoms are evident before
age of 30 years. Clinical manifestations begin only after several months as
fetal Hb protects against sickling phenomenon. Precipitating factors are
dehydration, chills and infection but some time the attack occurs
spontaneously. There is fatigue, weakness and shortness of breath. Severe
33

abdominal pain, muscle and joint pan, at high temperature which may result
in circulalatory collapse. There is cardiomegaly, presence of leg ulcers and
gall stones. Most of persons expire before the age of 40. Sickle cell anaemia
should be suspected in black patients, particularly in those of afrocarribean
origin and investigated ,if anaesthesia is anticipated .if hemoglobin
concentration is less than 10gm/dl, then patient is probably a homozygote
with sickle cell disease, and hospitalization is necessary for anaesthesia .In
those with sickle cell trait the main precaution is that general anesthesia if
unavoidable should be carried out with full oxygenation .
Oral manifestations
Other than the jaundice and pallor of the oral mucosa, patients often show
delayed eruption and hypoplasia of the dentition secondary to their general
underdevelopment. Because of the chronic increased erythropoietic activity
and marrow hyperplasia, which are attempts to compensate for the
hemolysis, increased radiolucency resulting from the decreased number of
trabeculae is seen on dental radiographs. This change is noted especially in
the alveolar bone between the roots of the teeth, where the trabeculae may
appear as horizontal rows, creating a ladderlike effect . By contrast, the
lamina dura appears dense and distinct. In skull films, the diploe is
thickened, and the trabeculae are coarse and tend to run perpendicular to the
inner and outer tables, giving a radiographic appearance of hair on end.
The teeth do not present undue mobility.Areas of sclerosis or increased
radiopacity represent areas of past thromboses with subsequent bony
infarction. Patients with sickle cell anemia are particularly prone to develop
osteomyelitis, probably because of hypovascularity of the bone marrow
secondary to thromboses.
34

Diagnosis
FRESH BLOOD is sealed in a small chamber of microscopic slide with
metabisulfite (a reducing agent) for 1 hour and then observed for sickling.
Hemoglobin electrophoresis is less expensive, more accurate, and more
definitive in the diagnosis of sickle cell disease as it detects hemoglobin
S.10
Treatment
There is no treatment for sickle cell disease other than symptomatic
treatment. Regular health care and prompt antibiotic treatment of infections
are important. Painful bone infarcts should be treated with NSAID and fluid
intake should be increased . Patients with sickling disorders are more likely
to have pain which is indistinguishable from toothache presumably due to
pulpal infarcts. Therefore patients should be treated with analgesics in the
first instance unless an obvious carious lesion is present .Admission to
hospital is required for severe painful crises not responsive to analgesics .
THALASSAEMIAS(Cooleys anemia, Mediterranean anemia, and
Erythroblastic anemia)
The thalassemias are a group of congenital disorders characterized by a
deficient synthesis of either the or the chains of globin in the hemoglobin
molecule. As a result, the red blood cells are microcytic and hypochromic
with an aberrant morphology. Thalassemias are often considered among the
hypoproliferative anemias, the hemolytic anemias, and the anemias related
to abnormal hemoglobin. In -thalassemia (deficient or reduced chain)
intracellular inclusions, Heinz bodies are formed by the precipitation of the
chains that accumulate in excess following the impaired chain production. In
the most severe form of this disease, the fetuss red blood cells contain
35

hemoglobin composed of chains only. This condition is incompatible with


life, due to the hemoglobins lack of oxygen-carrying capacity. Clinical
signs in -thalassemia depend on the severity of the -chain production
deficiency. -Globin synthesis is impaired in -thalassemia with mutations
in the sequences of the -globin gene, leading to errors in the splicing of
messenger ribonucleic acid (mRNA).
Types
Alpha thalassemia-There is reduction or absence of alpha chain synthesis.
Beta thalassemia-There is reduction or absence of beta chains.
Homozygous -thalassemia-Thalassaemias major or cooleys anemia usually
homozygous.
Beta thalassemia
Haemolysis is not primarily due to lack of beta chains but it is because of
free alpha chains which forms insoluble aggregates that precipitate with in
RBCs and cause damage to cell membrane.
Clinical manifestations
Occurs between age of 6 to 24 month. The skin color becomes ashen-gray
due to the combination of pallor, jaundice, and hemosiderosis. Patients also
present with cardiomegaly, hepatomegaly, and splenomegaly. thalassaemia
is a characterized by severe hypochromic, microcytic anaemia, great
enlargement of liver and spleen and skeletal abnormalties due to
extramedullary erythropoiesis. There is failure to thrive early death if
repeated transfusion are not given. Regular transfusion are life saving and

36

prevent development of boney deformities but lead to increased deposition


of iron in tissues. Haemosiderosis is main cause of complications.
Oral manifestations
Bimaxillary protrusion and other occlusal abnormalities are frequent in
thalassemia major cases.Dental and facial abnormalities include poor
spacing of teeth, a marked opened bite, prominent malar bones, and a saddle
nose. In addition, the pneumatization of the maxillary sinuses is delayed.As
a result of these skeletal changes, the upper lip is retracted, giving the child a
chipmunk facies. The radiographic changes seen in the jaws include
generalized rarefaction of the alveolar bone, thinning of cortical bone,
enlarged marrow spaces, and coarse trabeculae, which are similar to the
changes observed in sickle cell disease patients. In the parietal bones, the
thin cortex covering the coarse vertical trabeculae and the enlarged diplo
produce a hair on end picture. Cranial nerve palsies have been described in
thalassemia due to the extramedullary hematopoiesis resulting in pressure
on the nerves. In -thalassemia major, there is no correlation between the
chronologic, skeletal, and dental developmental age. The skeletal retardation
increases with age due to hypoxia from severe anemia, endocrine
hypofunction secondary to iron deposition, or the toxic action of iron
enzyme systems leading to tissue injury. The dentin and enamel are
indicators of iron deposition, and deciduous and permanent teeth of patients
with thalassemia contain up to five times the iron concentration measured in
normal patients. The high concentration of iron explains the discoloration of
teeth in patients with -thalassemia major.

37

Diagnosis
Hemolytic anemia with hypochromic microcytic red blood cells that vary in
size and shape is characteristic of thalassemia major. The hemoglobin
electrophoresis shows increased amounts of fetal hemoglobin and variable
amounts of normal adult hemoglobin. In patients homozygous for thalassemia, there is no detectable hemoglobin A. Prenatal diagnosis of
thalassemia is facilitated by deoxyribonucleic acid (DNA) analysis of
amniotic fluid cells, and it plays an important role in genetic counseling.
Treatment
Patients with mild thalassemia ( trait or minor) are clinically normal and
require no treatment. In other cases, the patients survival depends on blood
transfusions. Prevention of a hemoglobin concentration decrease to under 10
g/dL improves the chances of normal development and survival into
adulthood. This hypertransfusion treatment results in iron overload with
hemosiderosis and iron deposition in all body tissues.
Dental Management
As in any patient with a chronic anemia, poor healing may ensue after
surgical dental procedures. The possibility always exists of exacerbating the
symptoms of cerebral or cardiac hypoxia if substantial bleeding occurs in a
patient who is already anemic. Surgery has been used successfully to treat
the facial deformities.
ANEMIA OWING TO DECREASED PRODUCTION OF RED CELLS
MEGALOBLASTIC ANEMIA
The term megaloblastic anemia is used to describe a group of disorders
characterized by a distinct morphologic pattern in hemapoietic cells. These
cells have small immature nuclei and large mature cytoplasms.
38

Microscopically, this nuclear-cytoplasmic asynchrony is described as


megaloblastic. This group of disorders chiefly affects cells with rapid
turnover. The most common form of vitamin B12 deficiency is pernicious
anemia it is also called as primary anemia, addisons anemia or biermers
anemia, which is due to atrophy of the gastric mucosa resulting in a lack of
intrinsic factor secretion. Intrinsic factor acts by binding to the vitamin B 12
molecule, forming a complex that crosses the ileal mucosa and protects the
vitamin from proteolysis. The disease can be the result of an autoimmune
reaction to either the gastric parietal cells or intrinsic factor and is often seen
in connection with other autoimmune diseases such as Graves disease.
Oral Manifestations
Glossitis and glossodynia are the classic oral symptoms of pernicious
anemia. The tongue is beefy redand inflamed,with small erythematous
areas on the tip and margins. There is a loss of filiform papillae, and, in
advanced disease, the papillary atrophy involves the entire tongue surface
together with a loss of the normal muscle tone also called as hunters
glosstis.The erythematous macular lesions also can involve the buccal and
labial mucosa.21 Patients may complain of dysphagia and taste aberrations.
Discomfort described by denture wearers who have pernicious anemia is
probably due to the weakened mucosal tissues. Although the burning
mouth sensation diagnosed in pernicious anemia can be due to a
neuropathy, other causes of oral burning, including candidiasis, should be
considered.

39

Color plate-III

Small erosions on buccal mucosa


due to vitB12 defficiency

PERNICIOUS ANEMIA
Atrophy of papillae and lobulations on tongue

40

SIDEROPENIC ANEMIA
It is certain pathological condition in which iron gets accumulated in
mitochondria and appears as a ring of granules round the nucleus. These are
called as ring sideroblast and chracterised cell of sideropenic anemia which
is either hereditary or acquired.
APLASTIC ANEMIA
It is rare disorder chracterised by peripheral blood pancytopenia (anemia,
leucopenia, thrombocytopenia) associated with bone marrow suppression
Fanconis anemia is an inherited anemia that manifests in early childhood.
chracterised by pancytopenia, bone marrow hypoplasia, and congenital
anomalies. The management is to stop any drugs that may be responsible
and to give antibiotic and transfusions.
Oral Manifestations
Oral mucosa shows pallor. In some cases spontaneous hemorrhage may
occur from gingiva. Petechiae are often present on soft palate and in severe
cases submucosal ecchymosis. Large ragged ulcers covered by gray or black
necrotic membrane may be present, which are the result of generalized lack
of resistance to infection and trauma.

41

Hematological findings
RBC count is remarkably diminished as low as 1 million cells/mm3.
WBC and platelet count is as low as 2000/mm 3. Bleeding time is prolonged
clotting time is normal. Anemia is normocytic with some degeree of
macrocytosis.
Dental management
Gingival bleeding can be reduced by antithrombolytic agent such as
aminocaproic acid and transexemix acid 20mg/kg QID 24 hrs before the
procedure and continued for three days.
WHITE BLOOD CELL DISORDERS
The three types of granulocytes are neutrophils, eosinophils, and
basophils.Neutrophils are the most dominant of all circulating phagocytes
Lymphocytes are the primary cells involved in immunity. They appear to
originate from pluripotential stem cells in the bone marrow and migrate to
other lymphoid tissues, including lymph nodes, spleen, thymus, and mucosal
surfaces of the gastrointestinal tract. There are two types of lymphocytes
thymus-dependent

lymphocytes

and

non-thymus-dependent

lymphocytes.Peripheral blood contains approximately 4,000 to 11,000


WBCs per cubic millimeter . Leukocytes protect against foreign invaders
such as fungi, bacteria, viruses, and parasites.

42

LEUKEMIA
Leukemia, originally described by Virchow in 1874 as white blood, is a
malignancy affecting the WBCs of the bone marrow. This neoplastic process
is characterized by differentiation and proliferation of malignantly
transformed hematopoietic stem cells, leading to suppression of normal
cells. The malignant cells replace and turn off the normal marrow elements,
causing anemia, thrombocytopenia, and a deficiency of normally functioning
leukocytes. In time, the leukemic cells infiltrate other body organs,
destroying normal tissue.
Any of the white blood cells may be involved by this disorder and for this
reason disease is often classified as:
1.Lymphoid (lymphoblastic,lymphocytic) leukemia-involving the
lymphocytic series.
2.Myeloid(myelogenous)leukemia-involving progenitor cell that gives rise
to terminally differentiated cells of myeloid series (erythrocyte,granulocyte,
monocyte and platelets)
The classification may be modified to indicate the course of disease by
application of terms acute, sub-acute, and chronic.
Etiology
Virus-Epstein-Barr virus, herpes like virus and HTLV (human T cell
leukemic virus) have been considered to be the etiological agents
responsible for leukemia. Radiation and atomic energy over the dose of 100
rads, it is known to significantly increase the risk of leukemia. Leukemia
among radiologists and Japanese exposed to the atomic blast are more, as
compared to other population. Chronic exposure to aniline dyes, benzene
and phenylbutazone have been recognized to be associated with
43

leukemia.Usually in these patients pancytopenia due to marrow hyperplasia


occurs prior to leukemia. Patient treated with anticancer drug like melphalan
and chlorambucil have an increased risk of developing leukemia, usually of
acute myelocytic variety. Presence of certain genetic and chromosomal
factors like a philadelphia chromosome is found in about 15 percent of
cases of acute lymphocytic leukemia.
ACUTE LEUKEMIA
Acute leukemia is a disorder in which there is a failure of maturation of
leukocytes. As a result there is an accumulation of immature cells within the
bone marrow and later in the blood. It is the most common type of leukemia,
except in children (in whom acute lymphoblastic leukemia is more
common).
Pathophysiology
There is a block in differentiation of leukemic and stem cells and leukemic
blasts have prolonged. Thus accumulation of leukemic blast in acute
leukemia results primarily from failure of maturation into functional stage.
As leukemic blast accumulates in the marrow, they suppress the normal
hematopoietic stem cells.
Clinical features
It is more common in children and young adults between the age of 15 and
39 years. Males are affected more commonly than females with a ratio of
3:2. There is abrupt stormy onset with pyrexia and enlargement of spleen.
Symptoms usually result from bone marrow suppression and infiltration of
other organs and tissues by leukemic cells. Weakness, fever, headache,
generalized swelling of lymph nodes, petechiae or hemorrhage in skin and
mucous membrane are seen. There is pain in bones and tenderness, resulting
from marrow expansion, with infiltration of subperiosteum.Central nervous
44

manifestations such as headache, vomiting, nerve palsies resulting from


meningeal spread is more common in children than in adults, and more
common in ALL than AML. The clinical features are due to anemia and
thrombocytopenia viz. pallor, dyspnea, fatigue, petechiae, ecchymosis,
epistaxis and melena. Hepatosplenomegaly is present in later stages.
There is an increased susceptibility to infection. Cervical lymphadenopathy,
secondary to pharyngeal sepsis is seen. Intracranial and subarachnoid
hemorrhage

may

result

from

thrombocytopenia

and

leukostasis

(intravascular clumping of leukemic blasts in the small blood vessels of


brain).There is recurrent infection of lungs, urinary tract skin, mouth, rectum
and upper respiratory tract, which may result in fever. Localized tumors
consisting of leukemic cells called chloromas, surface of which turn green
when exposed to light because of the presence of myeloperodioxase.
Oral manifestations
The submental, cervical and pre and postauricular lymph nodes may be
enlarged and tender. Paresthesia of lower lip and chin may be present. There
may be toothache due to leukemic cell infiltration of dental pulp. The oral
mucous membrane shows pallor, ulceration with necrosis, petechiae,
ecchymosis and bleeding tendency. There may be massive necrosis of
lingual mucosa with sloughing. Gingiva shows hypertrophy and cyanotic
discoloration. The hypertrophy may be due to leukemic cell infiltration
within gingiva or due to local irritants. The gingiva appears boggy,
edematous and deep red bleeds easily due to ulceration of sulcus epithelium
and necrosis of underlying tissue. Mobility of permanent teeth may be
present. Oral infections (candidal, viral and bacterial) are serious and
potentially fatal complication in leukemic patients.

45

COLOR PLATE -IV

Acute Leukaemia,
Gingival Enlargement and Ulcerations

46

Hematological findings
The total WBC count may vary from a very low count less than 1 x 10 6per
cu mm to as high as 5000 x 10 6per cu mm or more. The peripheral smear
shows significant number of immature granulocytes or lymphatic precursors
or even stem cells. Bone marrow is hypercellular with replacement of
normal marrow elements by leukemic blast cells in varying degree.
There is an associated normochromic anemia, thrombocytopenia and
decrease in normally functioning neutrophils.
Management
First phase is phase of induction, pateint is treated using combination of
vincristine (1.4 mg/m2 every week of 1 month), L-asparaginase (600 units/m2
biweekly for 1 month) and prednisone (40 mg/m 2 orally daily for 1month).
As the leukemic cells regress, regrowth of normal cells occurs and the
patient goes rapidly into remission. Phase of consolidation in this, drugs
used include daunorubicin, mercaptopurine, cytarabine, and methotrexate
with intra-thecal therapy using the last two drugs, together with irradiation
of

the

cranium

to

eradicate

the

disease

from

central

nervous

system.Radiation reduces the risk of relapse in central nervous system when


given with methotrexate. Phase of maintenance, in this phase, patient
receives a repeating cycle of above drugs until two or three years have been
completed. Allogenic bone marrow transplantation from HLA identical twin
is done. Ablative therapy has been utilized to eradicate the patient's residual
leukemic cells and normal cells with intensive irradiation and chemotherapy.
After this reconstruction of the hemopoietic tissue is done with precursor
cells from the donor. Acute non-lymphoblastic leukemia is treated with
daunorubicin, cytarabine and 6-thioguanine. All these drugs are very toxic to
the normal as well as leukemic cells and therefore, treatment is given in
47

pulses to reduce toxicity. Catabolic products of leukemic cells produce uric


acid and cause hyperuricemia, which is prevented by allopurinol. In
supportive therapy transfusion of red cells and platelets may be required in
cases of severe anemia and thrombocytopenia.Combination of higher
antibiotics like aminoglycosides with cephalosporin, allopurinol, before
starting anti-leukemic agents are given to prevent hyperuricemia. Topical
treatment to stop gingival bleeding includes removing obvious local irritants
and direct pressure. Use of absorbable gelatin or collagen sponge topical
thrombin is helpful. The management of oral ulcers includes topical
antibacterials with povidone iodine solution, chlorhexidine rinses or
tetracycline rinses. Psychological support is very important as delusion and
hallucinations are not uncommon during periods of severe bone marrow
failure.

CHRONIC LEUKEMIA
Chronic leukemias are characterized by the presence of large leukemic cells
and differentiated WBCs in the bone marrow, peripheral blood and other
tissues. It has a prolonged clinical course even without therapy.

CHRONIC MYELOID LEUKEMIA


Pathophysiology
It is associated with the presence of a distinctive chromosomal abnormality,
i.e. Philadelphia chromosome.
Clinical features
The disease occurs chiefly between the age of 35 to 60 years. The disease
may be discovered during routine examination, when splenomegaly or an
elevated count is noted. There may be slowly advancing anemia with loss of
weight, prominence of abdomen and disscomfort in the left upper quadrant

48

due to splenomegaly. Attacks of acute left upper abdominal pain may


develop due to infarction of spleen. Anemia causes weakness, fatigue and
dyspnea on exertion. As the disease progress thrombocytopenia can cause
petechiae, ecchymosis as well as hemorrrhage from the skin and mucous
membrane. Liver may be enlarged but lymph nodes are normal.
Hematological finding
Examination of blood shows a normocytic and normochromic anemia.
WBC count is considerably increased and may be between 50 x 106 to
500 X 106 cells per cu mm. Peripheral smear shows mature leukocytes but,
few immature forms may also be present. The platelet count is often high
initially but with treatment, it comes down.
Management
The treatment of choice is chemotherapy using the drug busulphan given
orally in a dose of 4 mg daily or in large doses of 50-100 mg spaced 2 to 3
weeks apart. The treatment is continued for 12 to 18 weeks and should be
discontinued when WBC count is between 10 x 106 and 20 x 106per cu mm,
other wise busulphan may cause aplasia of the bone marrow.A combination
chemotherapy using a small dose of busulphan 2 mg daily along with
mercaptopurine 50mg daily or thioguanine 80 mg daily. Radiotherapy and
splenectomy are other treatment of choice.

49

CHRONIC LYMPHATIC LEUKEMIA


Chronic Lymphatic Leukemia is a slowly progressing malignancy involving
lymphocytes.
Pathophysiology
It is characterized by the accumulation of long lived, non functional B
lymphocytes.
Clinical features
It occurs more frequently in males and majority of the patients are over 45
years, the onset is very insidious. Tiredness and ill health are common,
although some patients are symptom free and the disorder is found
incidentally. Bone marrow infiltration causes anemia and thrombocytopenia
and results in pallor, weakness, dyspnea and purpura. There is a moderate
enlargement of lymph nodes which are firm, rubbery and discrete. Liver and
spleen are usually enlarged and palpable. There is an increased susceptibility
to infection as the leukemic B cells are non-functional. Leukemic infiltration
results in skin nodules, intestinal malabsorption, pulmonary obstruction or
compression of the central or peripheral nervous system. The most common
groups of lymph nodes involved are cervical, axillary and inguinal group.
Clinical staging
Stage A-Lymphocytosis is less than three areas of lymphoid enlargement, no
anemia or thrombocytopenia.
Stage B- More than three areas of lymphoid enlargement, no anemia or
thrombocytopenia.
Stage C-Anemia or thrombocytopenia, regardless of number of area of
lymphoid enlargement.

50

Oral manifestations
The most common oral finding is hypertrophy of gingiva. There may be
ulceration with necrosis and gangrenous degeneration, a dark brown exudate
and foul fetor oris are present. Tongue is frequently swollen and dark.
Regional lymphadenopathy is seen. Rapid loosening of teeth due to necrosis
of periodontal ligament has been reported. Destruction of alveolar bone also
occurs in some cases.
Hematological findings
Peripheral blood smear shows mild anemia and a large number of small
lymphocytes. Lymphoblasts are rare but increase in the terminal stages of
disease. WBC count may increase up to 1000 x 106 per cu mm.
Management
General measure to maintain good health, adequate rest, good food and
exercise should be advised. In chemotherapy, chlorambucil 6 to 10 mg/day
for 14 days with break of 14 days and cyclophosphamide 2 to 3 mg/kg IV
for 6 days. Combination therapy of cyclophosphamide, doxorubicin,
vincristine, and prednisone have been recommended.Radiotherapy with very
small doses, of only 150 rads over a period of five weeks, is very effective
and may induce satisfactory remission. Steroids are given if the bone
marrow is severely involved initial treatment with prednisone 40 mg daily
and 25-50 mg daily later should be given.
Radiographic features of leukemia
It affects the entire body as it is malignancy of bone marrow. It is presented
as ill defined patchy radiolucent area. There is destruction of alveolar,bone
loss may be in form of transverse lines of increased radiolucency or irregular
areas and loss produces the so called, moth eaten appearance. Sclerosis of
bone may be presented alone or in combination with destructive lesion. In
51

Onion peel appearance there is formation of bone beneath the periosteum.


The new bone takes the form of a thin white line parallel with the shaft of
the bone and sometimes separated from it by a thin dark line (onion peel
effect). Skull is rarely involved and it may reveal areas of bone
destruction.The developing teeth may be displaced from their normal
position.There is also genralized loss of lamina dura with loosening of teeth.
Generalized bone loss may be seen.
HAIRY LEUKEMIA
It a variant of chronic lymphatic leukemia in which there is splenomegaly,
severe neutropenia, monocytopenia and the characteristic appearance of
hairy cells in blood and bone marrow. These hairy cells appear to be a cross
between the lymphocytes and monocytes. It occurs mainly in adults and
show male predilection. Manifestations result from infiltration of bone
marrow, liver, spleen. Splenomegaly is massive and hepatomegaly is less
common. Hairy cell can be identified on the peripheral smear.
PROLYMPHOCYTIC LEUKEMIA
It is another variant of chronic lymphatic leukemia in which there is massive
splenomegaly with little lymphadenopathy and a very high WBC count.
The characteristic cell is a large lymphocyte with prominent nucleus.

52

ALEUKEMIC LEUKEMIA
It is the sub-leukemic form of leukemia in which the WBC count of the
peripheral blood is normal or even subnormal and abnormal or immature
leukocytes may be present.
Dental Considerations
Topical treatment to stop gingival bleeding like removal of local irritants,
direct pressure and use of absorbable gelatin, collagen sponge, topical
thrombin and placement of microfibrillar collagen. If these local measures
are not successful platelet transfusion is given. Platelet transfusion and
intravenous combination of antibiotics is required before any dental
treatment.
Oral Ulcers
Oral mucosal ulcers are common findings in leukemic patients taking
chemotherapy and are frequently caused by the direct effect of
chemotherapeutic drugs on the oral mucosal cells. The ulcers are
characteristically large, irregular, and foul smelling, and are surrounded by
pale mucosa caused by anemia and a lack of normal inflammatory
response. The most common cause of oral ulcers in leukemic patients
receiving chemotherapy is recurrent HSV infections. These infections
involve the intraoral mucosa and the lips. Lesions frequently begin with the
classic cluster of vesicles typical of recurrent HSV and quickly spread,
causing large ulcer. The management of non-HSV oral ulcers in leukemic
patients should prevent the spread of localized infection, minimize
bacteremia, promote healing, and reduce pain. The ulcers in hospitalized
leukemic patients taking chemotherapy may be infected with organisms not
commonly associated with oral infection, particularly gram-negative enteric
bacilli. Topical antibacterial treatment can be attempted with povidone53

iodine

solutions,

bacitracin-neomycin

ointments,

or

chlorhexidine

rinses.Kaolin and pectin plus diphenhydramine oral rinses can be used to


reduce pain.
Oral infections
Candidiasis is a common oral fungal infection, but infections with other
fungi, such as Histoplasma, Aspergillus, or Phycomycetes, fungi, also may
begin on the oral tissues.When these lesions are suspected, a biopsy
specimen, a fine-needle aspiration, or a cytology smear must be obtained
because a culture alone is not a reliable test for these organisms. Diagnosis
of dental infection, particularly periodontal and pericoronal infections, is
difficult in neutropenic leukemic patients because normal inflammation is
absent.
LEUKOPENIA
Leucopenia is deficiency of white cells, which can be a chance
haemotological finding and may cause no symptom until it becomes so
severe as to impair defence against infection.
AGRANULOCYTOSIS
It is also called as granulocytopenia, agranulocytic angina. It is a serious
disease characterized by marked leukopenia with reduction and absence of
neutrophilic leukocytes.

54

PRIMARY AGRANULOCYOSIS
The etiology of primary agranulocytosis is unknown. Secondary
agranulocytosis is used when cause is recognized. Mild neutropenia when
1000/mm3 to 2000/mm3 neutrophils are present. Moderate neutropenia when
500/mm3 to 1000/mm3 neutrophils are present. Idiosyncrasy or sensitization
to certain drugs like aminophylline, chlorpromazine and phenylbutazone,
benzene, bismuth, chlorampheenicol, sulfonamides and use of cytotoxic
drugs or antimetabolics, deficiency of vitamin B12 and folic acid. Certain
infections decrease the number of neutrophils in circulating blood because of
increased migration of neutrophils into the tissue, destruction of neutrophils
or direct effect of microorganism and its toxins on the bone marrow.
Infection with hepatitis A and varicella zoster virus infection are commonly
associated with neutropenia. Overwhelming bacterial infection, particularly
septicemia can be accomplished by neutropenia because cells are used at
rapid rate to overcome infection. Diseases causing sequestration of
neutrophils includes systemic lupus erythematosus and Feity's syndrome. It
can be associated with leukemia, pancytopenia and hypersplenism.
Hemodialysis patient experience decrease in neutrophil owing destruction by
complement activated by the dialysis membrane. Irradiation can cause
neutropenia due to direct toxic effect on division of bone marrow cells.
Clinical features
It can occur at any age but it somewhat more common in adults, particularly
in woman. It is also common in professional and in hospital as they have
easy access of the offending drugs and often use drug sample injudiciously.
Symptoms may be sudden or gradual. The condition begins with sore throat,
55

high fever and often rigors, which may be followed by prostration. Skin
appears pale and anemic and in some cases, jaundiced. There is rapidly
advancing necrotic ulceration of throat and mouth with little evidence of pus
formation In most of the cases patient dies within 3 to 5 days due to toxemia
and septicemia.

Oral manifestations
The most common sites are gingiva and palate, tonsil and pharynx.
There may be associated pain, excessive salivation and spontaneous oral
hemorrhage. The oral lesions appear as necrotizing ulcerations of oral
mucosa, tonsils and pharynx. The lesions appear as ragged and necrotic and
are covered with a gray black membrane. The necrotic tissue is often foul
smelling. On margins of lesion there is lack of inflammation.The disease
spreads quickly in gingival tissues causing destruction of supporting
structures and inevitable loss of deciduous and permanent teeth.
Supporting alveolar bone is rapidly destroyed, so that teeth are denuded of
bone and are supported only by soft tissues. Very rarely, infection spreads to
deep into the marrow to cause osteomyelitis.
Hematological findings
Majority of patients show a leukocyte count below 2000 cells per cu mm 3
and granulocyte count below 100 cells per cu mm3. Hemoglobin and platelet
counts are normal.

56

CYCLIC NEUTROPENIA
In cyclic neutropenia there is fall in the number of circulating neutrophils at
regular intervals of 3-4 weeks. It is therefore necessary to monitor the white
cell count daily for several weeks inorder to diagnose the condition. It may
cause oral ulceration and periodontal breakdown. Etiology is drugs and
chemicals infections and long term exposure to radiation. In Oral cavity
spontaneous hemorrhage may occur from gingiva. Petechiae may be seen in
soft palate.
Treatment
The universally accepted treatment for most cases of cyclic neutropenia is
careful monitoring of the patient for infection during neutropenic periods
and vigorous early management of infection. In some patients, use of
corticosteroids, adrenocorticotropin, or testosterone modulates the sharp
reduction in marrow function.Unfortunately, these drugs are not successful
for all patients. The use of granulocyte colony-stimulating factor (G-CSF)
has been employed to boost neutrophil levels. Unlike with congenital
agranulocytosis, G-CSF therapy in cyclic neutropenia is not associated with
the development of acute myeloid leukemia or myelodyplasia.24
Oral and Dental Considerations
Oral lesions are common in cyclic neutropenia and may be the major
clinical manifestation of the disease. The two most common oral
manifestations are oral mucosal ulcers and periodontal disease. The oral
ulcers recur with each new bout of neutropenia and resemble the large deep
scarring ulcers seen in major aphthous stomatitis. The periodontal

57

manifestations range from marginal gingivitis to rapidly advancing


periodontal bone loss caused by bacterial infection of the dental supporting
structures.

QUALITATIVE LEUKOCYTE DISORDERS


CHEDIAK-HIGASHI SYNDROME
Chediak-Higashi
characterized

by

syndrome

is

rare

oculocutaneous

autosomal

albinism,

recessive

progressive

defect

neurologic

abnormalities, and large blue-grey granules in the cytoplasms of neutrophils,


eosinophils, basophils, and platelets.Abnormal granules also have been
observed in renal tubular cells, nerve cells, and fibroblasts. The abnormal
granules seen in all blood granulocytes result in neutrophils with decreased
chemotactic and bactericidal ability, although phagocytosis remains intact.
The abnormality in bactericidal activity is thought to be caused by an
inefficient use of lysosomal enzymes resulting from a mutation in the
lysosomal trafficking regulator, or LYST gene.25 This leads to defective T-cell
signaling and the potential for an associated lymphoproliferative syndrome.26
Patients develop severe neutropenia as a result of ineffective granulopoiesis,
and most die in childhood from infections or advanced lymphoproliferative
syndrome.
Clinical Manifestations
Hypopigmentation resulting from the pigment dilution is noted in skin and
hair during infancy. The hair will have gray streaks. Neuropathy and ataxis
are prominant features in some patients.

58

ORAL MANIFESTATIONS
The gingivae appear intensely red, despite the neutropenia, with
granulomatous margins. Severe gingival recession is common, and early
severe periodontal disease with advanced bone loss, mobility, denuded roots,
and loss of teeth. These patients may also report recurring oral ulcerations
that may correspond to neutrophilic count.
LYMPHORETICULAR MALIGNANCY
Primary malignant changes in lymphoreticular tissue is of two main types:
Hodgkins disease accounts for about 20% of cases and non hodgkins
lymphoma for about 80%. The presentation is usually enlargement of the
lymph nodes with a rubbery consistency. Oropharyngeal involvement is rare
in hodgkins disease less than 1%of cases but nonhodgkins lymphoma more
commonly presents in the mouth and can be oral manifestation of HIV
disease
Types
1.Hodgkin's lymphoma
2.Non-Hodgkin's lymphoma

HODGKINS LYMPHOMA
It was first described by British pathologist Thomas Hodgkin in 1832. It is
characterized by painless enlargement of lymphoid tissue throughout the
body.
Etiology
Particularly herpes and oncorna virus are being investigated as possible
etiological agents. Sometimes, it can occur without any etiological factor.
59

Clinical features
It is characterized by a bimodal age incidence, peak one in young adults and
the second in the 5th decade of life with equal distribution between sexes.
The onset is insidious, usually with enlargement of one group of superficial
nodes. The cervical lymph nodes are usually the first to be involved but the
disease may start in the mediastinal, axillary, abdominal, pelvic or inguinal
lymph nodes. The involved nodes are painless. Generalized weakness, loss
of weight, cough, dyspnea and anorexia are seen.Pain in back and abdomen
owing to splenic enlargement, due to pressure of enlarged nodes or
involvement of vertebrae. The lymph nodes are discrete and rubbery in
consistency with overlying skin being freely mobile. Splenomegaly is
usually seen in later stage. Some patients may manifest pruritis.
Characteristic features of this disease are Pel-Ebstein fever, a cyclic spiking
of high fever and generalized severe pruritis of unknown etiology. Pressure
of enlarged lymph nodes on adjacent structures may cause dyspnea,
dysphagia, venous obstruction, jaundice and paraplegia.
Clinical stages (ANN Arbor staging)
Stage I- involvement of single lymph node region or extra-lymphatic sites.
Stage II- involvement of two or more lymph node regions or an extra
lymphatic site and lymph node region on the same side of diaphragm.
Stage III- involvement of lymph node region on the both sides or without
extralymphatic involvement or involvement of spleen or both.
Stage IV-diffuse involvement of one of more extralymphatic tissues e.g.
liver or bone marrow.
Such stages are subdivided into A and B categories depending on whether
they have systemic symptoms such as weight loss, fever, night sweats.

60

Oral manifestations
Primary jaw lesions are uncommon. Secondary effect can be seen in oral
cavity in the form of infection due to reduced host immune response.It may
appear in the oral cavity as an ulcer or a swelling or as an intra-bony lesion
which presents as a hard swelling.
Histopathological features
It is characterized by replacement of normal lymph node architecture by an
admixture of malignant lymphoid cells and non-neoplastic inflammatory
cells. Reed-Sternberg cells which are sheets of lymphoid cells with
interposed

vacuolated

spaces

containing

characteristic

bi-nucleated

mononuclear cells are seen.


Histological types
Lymphocyte predominant-Abundant lymphocytes, few plasma cells,
occasional Reed-Sternberg cell, localized involvement on one side of
diaphragm and most favorable prognosis.
Mixed cellularity-Lymphocytes, plasma cells, eosinophils, easily identified
Reed-Sternberg cell.
Nodular sclerosis-Sparse lymphocytes, stromal cell, fibrosis and numerous
but bizarre Reed-Sternberg cell, poor prognosis.
Lymphocyte depletion-Lymphocytes, plasma cells, eosinophils with
localized involvement.
Radiographic features
It is rarely seen in jaws. The common regions are the posterior maxilla and
mandible.There are radiolucent areas separated from each other by normal
appearing bone which later become connfluent, unless treatment is carried
out. Typically, the radiolucent lesions have diffuse ill defined margins which
suggest infiltration of bone. Osteoblastic type is uncommon in jaws, but it is
61

seen in the vertebrae and pelvis. In it, there is frank sclerosis with filling of
the marrow spaces by bone. It presents as greyness or whiteness which is
abnormal. The margins may be well defined and sharp or irregular and
trailing off gradually into the normal bone.
Laboratory investigations
Anemia which is normocytic and normochromic is a common finding. The
total WBC count is normal but there may be mild eosinophilia. In the
terminal stage there, may be leukopenia and thrombocytopenia. ESR is
raised. Liver function may be abnormal due to infiltration in liver. LDH is
raised level is an adverse prognostic factor. Chest radiography is done to
permit staging.
Management
Radiotherapy irradiation treatment 3500-4000 rads/week over, the involved
region plus all adjacent sites been given in stage I and II. It is also given
after chemotherapy, to sites where there was originally bulk disease.
Chemotherapy is given in stage III and IV. Usually combination is given.
First combination is MOP, i.e. mustine HCl (6 mg/m 2 IV on day 1 and day
8), oncovin which is also called as vincristine (1.4 mg/m 2 IV on day 1 and
8), procarbazine (100 mg/m2) orally from day 1 to 14) and prednisone (40
mg/m2 orally from day 1 to 14). MOPP combination given in six courses
with no drugs is given from day 15 to 28. Second combination is ABVD
regimen, i.e. adriamycin (25 mg/m 2 IV bolus on day 1,8 and 14), bleomycin
(10 mg/m2 bolus on day 1,14) vinblastine (6 mg/m 2 IV bolus on day 1,14)
and decarbazine (375 mg/m2 IV bolus on day 1,14). The cycle should be
repeated on 20th day. A combination of radiotherapy and chemotherapy may
increase the overall response and long-term survival but, it is associated with
62

delayed complications like leukemia, gonadal atrophy and avascular necrosis


of bone. Splenectomy is advocated in many patients, except with stage IV
disease.

Non-Hodgkin's Lymphoma
It is also called as lymphosarcoma. In this group, there is neoplastic
proliferation of lymphoid cells, usually affecting the B-lymphocytes. Unlike
Hodgkin's lymphoma, the disease is frequently widespread at the time of
diagnosis, often involving not only the lymph nodes but also bone marrow,
spleen and other tissue. Early involvement of bone marrow is typical of this
lymphoma.
Types
1. Nodular
2. Diffuse
Etiology
The etiology is unclear but herpes viral etiology has been suggested. There
may be induced immunologic effect permitting a malignant clone to
proliferate.
Clinical Features
It affects persons of all ages from infants to the elderly.But is commonest in
middle age group. Males are affected more commonly than the females.
In the oral cavity it frequently occurs in tonsils. The other sites affected are
salivary glands or jaws. The onset of symptoms may be insidious.
Painless lymph node enlargement of abdominal and mediastinal region is the
most common finding. Very often the first group of lymph nodes affected
may be cervical, axillary or inguinal. The patient complains of tiredness, loss

63

of weight, fever and sweating. Pain is the main symptom of bone


involvement which may present as a pathological fracture. Patient may
complain abdominal pain, nausea, vomiting, diarrhea or intestinal
obstruction which may occur due to involvement of gastrointestinal tract.
Pressure effect of lymphoma may cause dysphagia, breathlessness, vomiting,
intestinal obstruction or ascites and paraplegia. If liver and spleen are
involved hepatosplenomegaly is present. The growth is fleshy and is prone
to ulceration.
Oral manifestations
Occurrence of malignant lymphoma in oral cavity is rare, when present it is
more often found to arise from the tonsils, although other oral tissue may
also be involved. Palatal lesions have been described as slow growing,
painless, bluish soft tissues mass which may be confused with minor
salivary gland tumors. Paresthesia of mental nerve has been reported.
Sometimes there is pain and neuralgia in the region of 2nd and 3rd division
of Vth cranial nerve. In rare cases necrotic proliferation of palate may also be
seen. The swelling may ulcerate and discolor in some cases.
Radiographic features
As the disease progresses small radiolucent foci scattered throughout the
area may be seen. Subsequent radiographs of the expanding lesion will show
that these small foci have coalesced to form large multilocular moth eaten
radiolucency with poorly defined margins. Lesions may cause marked
expansion of bone. Erosion and perforation of cortex may occur.
If the lesion involves maxillary sinus, possible opacification with breached
cortical walls and associated para-central or intra central masses is seen.
Cortices of unerupted tooth buds and lamina dura of adjacent teeth are lost.

64

COLOR PLATE-V

HODGKINS LYMPHOMA soft tissue swelling


showing ulceration and denuded bone

NON HODGKINS LYMPHOMA of palate


showing swelling and ulceration

65

Histopathological features
In the nodular pattern the neoplastic cells tend to aggregate in such a way
that large clusters of cells are seen. Diffuse pattern is characterized by a
monotonous distribution of cells with no evidence of nodularity or germinal
center pattern.
Laboratory investigations
Blood count usually shows normal levels but if there is associated
hypersplenism or hemolytic anemia the reduced WBC and RBC counts are
seen along with reduced hemoglobin levels and reticulocytosis. In some
cases there may be slight increase in lymphocytes and thrombocytopenia.
Moderate degree of anemia will also present when there is considerable bone
marrow involvement. Some very aggressive high grade non-Hodgkin
lymphomas are associated with very high urate levels which can precipitate
renal failure.
Management
No treatment is necessary, if disease is not advanced. When diagnosed in late
stages, chemotherapy is the treatment of choice. In most cases single agent
chemotherapy

(chlorambucil)

is

usually

given.

Combination

with

prednisolone is also useful. A combination of cyclophosphamide,


doxorubicin, vincristine, bleomycin with prednisolone is commonly used.
Radiotherapy is used to treat local disease and the patient is given a total
dose of 150 rads spread over a period of five weeks. Transplantation studies
of autologous stem cell transplantation are in progress.

66

PLASMA CELL TUMOURS (MYELOMA)


Multiple myeloma (MM)
It is a malignant neoplasm of plasma cells that is characterized by the
production of pathologic M proteins, bone lesions, kidney disease,
hyperviscosity, and hypercalcemia.
CLINICAL FEATURES
Human leukocyte antigen studies suggest a genetic predisposition to the
disease, which occurs equally in both sexes, most often in patients older than
50 years of age. Skeletal pain is the most common presenting symptom and
is caused by bone lysis that may result either directly from accumulation of
tumor cells indirectly from osteoclast-activating factors secreted by the
malignant myeloma cells. Pain in involved bone may be aggravated by
exercise and relieved by rest. Swelling over the areas of bone may be
detectable.
Oral Manifestations
Approximately 5% to 30% of myeloma patients have jaw lesions, and
accidental discovery of lesions in the jaws may be the first evidence of this
disease. The patient may experience pain, swelling, numbness of the jaws,
epulis formation, or unexplained mobility of the teeth. Skull lesions are
more common than jaw lesions. The mandible is more frequently involved
in MM because of its greater content of marrow. Lesions are most common
in the region of the angle of the jaw, where red marrow generally is present.
In most instances, the lesions appear unassociated with the apices of the

67

teeth. Tongue biopsy is an excellent method of diagnosis. Clinically, the


tongue may be enlarged and studded with small garnet-colored
enlargements, including nodes on the cheeks and lips.
Radiographic Features
The most common radiographic abnormality is the presence of punchedout radiolucent lesions (plasmacytomas), but generalized osteoporosis may
occur in the absence of these discrete punched-out lesions
Laboratort Diagnosis
It is based on serum M proteins demonstrated with serum protein
electrophoresis or immunoelectrophoresis, or on Bence Jones proteins,
which are monoclonal immunoglobulin light chains detected in 24-hour
urine specimens. Bone marrow biopsy results reveal atypical plasma cells.
Complications
Hypercalcemia due to mobilization of calcium from skelton resulting in
nephrocalcinosis, lethargy, drowsiness, and eventually coma. Cause of death
is renal failure caused by accumulation of abnormal protein in renal tissue.
Amyloidosis occurs in 6 to 15% of patients with MM and may be detected
intissue specimens with use of a Congo red stain or electron microscopy.
The most common site of involvement is the tongue and usually follow skin
lesions. The commonest oral sign is gingival bleeding, but post extraction
haemorrhage and ulceration also occur.

68

PLATELET DISORDERS
PLATELET DISORDERS ARE CLASSIFIED AS
A.PURPURA
Idiopathic thrombocytopenic purpura
Secondary thrombocytopenic purpura
Congenital purpura
Thrombocytopathic purpura
Von willebrands disease
Bernard-soulier syndrome
Aldrich syndrome
B. Thrombocytosis
PURPURA
It is defined as purplish discoloration of the skin and mucous
membrane due to subcutaneous and submucus extravasation of blood.
Purpura may be due to defective platelets or due to an unexplained
increase in capillary fragility.
IDIOPATHIC THROMBOCYTOPENIC PURPURA

69

It is also called as Werlhofs disease, purpura, hemorrhagic, and primary


thrombocytopenic purpura.It is a disease in which there is abnormal
reduction in number of circulating blood platelets with normal or raised
number of megakaryocytes in the bone marrow.It is thought to be an
autoimmune disorder in which a person becomes immunized and develops
antibodies against his own platelets.It can be a result of decrease in
production of platelet or increased destruction of platelets or both. Clinical
features and oral manifestation are spontaneous appearance of purpuric
haemorrhagic lesion of skin, which vary from red pin point petechiae to
large purplish ecchymoses and sometimes even massive hematoma .Pateint
also exhibits a bruising, tendency, epistaxis, hematuria, melena are common
findings. Intracrania hemorrhage is rare but can be seen in children and the
symptoms are headache, dizziness and confusion.
Oral Manifestations
First oral manifestation that can be seen in oral cavity in the form of
excessive bleeding after tooth extraction. Submucous petechiae and
ecchymosis commonly occur specially at junction of hard and soft palate.It
appears as numerous tiny grouped clusters of redish spots only a millimeter
or less in diameter. Petechiae do not blanch on pressure which is
distinguishing feature between telangiectasia and purpura. In severe cases
extensive spontaneous bleeding may be seen and this may form foci of
secondary infection.

Treatment

70

Management is corticosteroids, splenectomy if there is no response to


prednisolone in 3 to 4 days. Platelet transfusion can be given.Spontaneous
gingival hemorrhage can be often be controlled by local use of haemostatics
such as gel foam, or absorbable cellulose with thrombin.
SECONDARY THROMBOCYTOPENIA
It is caused mainly due to drugs barbiturates analgesics or antihistamines,
infections like viral and bacterial .Clinical features are similar to idiopathic
thrombocytopenic purpura. Here prognosis is much better provided the
underlying cause is removed and transfusion is given as required.
CONGENITAL PURPURA
It may result from placental transfer of platelet antibodies. Such antibodies
may arise from active immunization of mother by fetal antigens or from
passive transfer of auto antibodies present in maternal circulation. In infants
it is seen at about one to two weeks of age. Bleeding is seldom or even life
threatening and the disorder is frequently mild or even subclinical. Some
cases show genralised petechiae and ecchymosis.
THROMBOTIC THROMBOCYTOPENIC PURPURA
It is characterized by occlusion of small arterioles and capillaries of many
organs by thrombi formed of fibrin and platelets.

Clinical features

71

It generally occurs in young adults and more commonly in females than in


males. There is thrombocytopenia, hemolytic anemia, fever, transitory
neurologic dysfunction and renal failure.
Treatment
Corticosteroids, platelet aggregation inhibitors, splenectomy and exchange
transfusion.

VON WILLEBRANDS DISEASE


It is also called as pseudohemophilia, vascular hemophilia and vascular
purpura. It is a rare disorder which is inherited as an autosomal dominant
trait in which there is defect in all three components of the hemostatic
mechanism; the capillaries, platelets and coagulation mechanism. It is most
common hereditary clotting disorder. In it, there is quantitative and
qualitative deficiency in larger molecule portion of factor VIII molecule. von
Willebrand's factor activity is responsible for platelet adhesion to
subendothelium, regulation of the plasma level of factor VIII coagulant
activity and thereby normal hemostatis.
Clinical features
Excessive bleeding either spontaneously or following even minor trauma, is
the chief feature of the disease. The most common sites of bleeding are nose,
skin and gingiva. Bleeding into the gastrointestinal tract, epistaxis and
severe menorrhagia are also common. Bleeding tendencies usually appear
early in childhood and decrease in middle and old age.

Oral manifestations
72

Gingival bleeding and postextraction bleeding are the most common oral
manifestations. The disease may be discovered after dental extraction.
Hematological findings
Prolonged bleeding time, normal platelet count, failure of aggregation of
platelets impaired adherence of platelets and depressed levels of factor VlII
are suggestive of this disorder. Low AHG levels and abnormal platelet
retention to glass beads. The platelet count and prothrombin consumption
are normal. The clotting time usually is normal but capillary fragility is
increased.
Management
Bleeding episode is best controlled by transfusion of plasma and or
cryoprecipitate and by local control of homeostasis. Patients with von
Willebrand's disease should not be given aspirin because of prolongation of
the bleeding time that may occur.
BERNARD-SOULIER SYNDROME
It is transmitted as an autosomal dominant trait and is characterized by
prolonged bleeding time and defective aggregation of platelet. The only
treatment is platelet transfusion during acute bleeding episodes.
ALDRICH SYNDROME
It is also called as Wiskott-Aldrich syndrome. It is X linked recessive
condition.
Clinical features
73

It is characterized by thrombocytopenia, eczema, increased susceptibility to


infection and a prolongel bleeding time. Patients commonly manifest boils,
otitis media. bloody diarrhea and respiratory infection. There is common
occurrence of malignant lymphoma, which is an important feature of this
disease. Bleeding occurs from nose, skin and gastrointestinal tract.
Oral manifestations
Palatal petechiae are frequently present. Spontaneous bleeding from the
gingiva.
Laboratory findings:
Prolonged bleeding time and there is considerable anisocytosis, alternation
in the size and shape of platelets with most platelets smaller than normal
There is decreased production and defective maturation of platelets since
normal megakaryocytes may be seen in the marrow.
FAMILIAL THROBASTHENIA
It is also called as Glanzmann's disease. It is hereditary, chronic hemorrhagic
disease transmitted as an autosomal recessive trait.
Clinical features
There is excessive bleeding, either spontaneous or following minor trauma.
Both sexes may be affected and onset of menarche may be a critical event.
Purpuric hemorrhages of skin are common, as are epistaxis, gastrointestinal
bleeding. Hemoarthrosis is also noted in some cases.
Oral manifestations
Spontaneous bleeding from the oral cavity particularly gingival bleeding.
74

Laboratory finding
Bleeding time is prolonged while clot retraction is impaired. Platelet count
is normal as the clotting time. The aggregation of platelet by epinephrine,
ADP and thrombin is defective.
Management
No specific treatment but patient in oral surgery can be given microfibriallar
collagen preparation with fibrinolytic inhibitors.

THROMBOCYTOPATHIC PURPURA
It occurs due to qualitative defect in platelets.
Clinical features
They have severe bleeding tendency and bruise easily after minor trauma.
Spontaneous ecchymosis is common. Epistaxis and bleeding into
gastrointestinal tract are common findings.
Oral manifestations
Spontaneous gingival hemorrhage with mucosal ecchymosis occasionally
occur. Excessive and prolonged bleeding form dental extractions may pose
serious management problems.
Laboratory findings
Platelet count is normal but bleeding time is either normal or prolonged,
which is due to defective platelet aggregation, so that normal capillary
plugging is impaired.
Management

75

There is no specific treatment, although blood transfusion can be given and


it will aid in controlling the prolonged bleeding.

THROMBOCYTOSIS OR THROMBOCYTHEMIA
It is characterized by an increase in the number of platelets in the blood in
excess of 1000 x 106/dl. It is of two types, i.e. primary and secondary.
Causes
Polycythemia and myeloid leukemia, anemia, tuberculosis and sarcoidosis.
Hyperadrenalism, rheumatoid arthritis and bronchial carcinoma.
Clinical features
It is a rare disorder of the elderly associated with a tendency to bleed and to
have thrombic episodes. Epistaxis, bleeding into the gastrointestinal tract as
well as bleeding into the genitourinary tract and central nervous system is
common. Hemorrhages in skin are also common.
Oral manifestations
Spontaneous gingival bleeding and excessive and prolonged bleeding after
extraction of tooth is also common.
Laboratory findings
The platelet count is increased and there is abnormal aggregation in response
to several aggregating agents.

The clotting time, prothrombin time are

normal but bleeding time is frequently prolonged.


Management
Certain cytotoxic drugs, heparin, corticosteroid and aspirin in small dose
may help to counter act the thrombactive tendency. It responds to radioactive
phosphorus.

76

Color plate-VI

THROMBOCYTOPENIA,
purple colored petechiae and echhymosis

77

THROMBASTHENIA

HEMORRHAGIC DISORDERS
HEMOPHILIA A
It is a hereditary disorder of blood coagulation characterized by excessive
hemorrhage due to a prolonged coagulation time. Deficiency of factor VIII
or antihemophilic factor is the cause of hemophilia. It is transmitted as Xlinked recessive character carried on X-chromosome. The males are
clinically affected and the females are carriers of the trait. Hemophilia A
occurs 10 times more commonly than hemophilia B.
Types
Mild-less than 4 percent of AHG
Moderate-1 to 3 percent of AHG
Moderate to severe-O.O% to 0.9% of AHG
Severe-O% of AHG
Clinical features
Bleeding manifestations usually begin after 6 months of age, when the child
begins to move about and tends to fall and sustain injuries, i.e. when
spontaneous hemorrhage is noted by the parents.The most common
manifestation is hemorrhage into joints which is spontaneous and associated
with warmth and muscle spasm. Repeated episodes cause damage to the
joint with wasting of the related muscle, leading to deformity and crippling.
Hemorrhage into subcutaneous tissues, internal organs and musculature also
are frequent and potentially disabling complications. Superficial trauma

78

gives rise to uncontrolled bleeding. Intracranial bleeding is relatively rare


unless associated with trauma.

Oral manifestations
Traumatic injury of the oral cavity may lead to the diagnosis of hemophilia.
The anatomic sites involved in persistent oral bleeding are the frenum of lip
and the tongue. There is prolonged bleeding after tooth extraction.
Hematoma of the floor of mouth may occur and blood may spread via the
fascial spaces and produce a hematoma of the larynx, with consequent
respiratory embarrassment. Physiological processes of tooth eruption and
exfoliation may be associated with severe and prolonged hemorrhage.
Gingival hemorrhage is extremely rare and when it does occur, it is the result
of gingival injury.
Hematological findings
Clotting time is prolonged, but however the bleeding time, platelet count and
prothrombin time are all normal.The prothrombin consumption time and the
partial thromboplastin time may be prolonged in severe cases.
Management
The main aim is to raise the factor VIII levels which can arrest bleeding.
Replacement therapy-various forms of replacement therapy are available
like plasma cryoprecipitate and factor VIII concentrates. Hypovolemia,
allergic reaction, transfusion hepatitis, hemolytic anemia and development
of factor VIII antibodies are complications with fresh frozen plasma.
Factor VIII concentrates-the dose and duration of administration of factor
VIII concentrates are planned, taking into consideration the site and the type
of bleeding.Intraligamentary injection in hemophilia does not cause
79

hemorrhage, even if replacement therapy has not been given prior to


injection. To reduce complications caused by cryoprecipitate or plasma
various drugs are used instead of factor VIII products, before dental
extraction, e.g. a synthetic analogue of anti-diuretic I-deamino 8arginine
vasopressin (DDAVP) in combination with tranexamic acid and Epsilonaminocaproic acid (EACA) can be given.

CHRISTMAS DISEASE or HEMOPHILIA B


It occurs due to hereditary deficiency of factor IX or functionally defective
factor IX. It is transmitted as X-linked recessive character through
chromosome. It is very rare, compared to hemophilia A. Clinical features are
same as hemophilia. In the laboratory hemophilia A may be differenntiated
from hemophilia B by modification of the prothrombin consumption time or
the partial thromboplastin time.
Dental management of Hemophilia A and Hemophilia B
Anesthesia-Local anesthesia is contraindicated in severe hemophiliac
patients with prior replacement therapy. If to be given, it should be
intrapulpal anesthesia, periodontal ligament and papillary injection. Sedation
with diazepam or NO2/O2 can be given.
Endodontic therapy-Common endodontic procedure are quite acceptable
provided care is taken not to exceed beyond the apex of tooth. Hemorrhage
into the canal can usually be controlled with 1: 1000 aqueous epinephrine on
an endodontic paper point.
Restorative procedures can be carried out in hemophiliac patient, but the
rubber dam must be used to prevent trauma to gingiva and other soft tissues.
When use of rubber dam is not practical, an epinephrine impregnated
hemostatic cord is placed in the gingival sulcus before preparation of the
crown or inlay margins.
80

Prosthodontic therapy- Complete dentures are well tolerated in hemophilic


patients. Partial dentures are also well tolerated, as long as the patient
maintains meticulous oral hygiene because clasp can trap food debris,
resulting in gingivitis and subsequent hemorrhage.
Periodontic therapy- Conservative periodontic treatment is generally more
desirable than gingival and osseous surgery because of hospitalization and
extensive amount of replacement therapy necessary with surgery.
Oral surgical procedure: Local homeostatic agents and techniques include
pressure surgical packs, oxidized cellulose saturated with bovine thrombin
solution, vasoconstrictors, suture, topical thrombin and use of absorbable
homeostatic. After packing, the tooth socket must be protected by
mechanical splint to prevent disturbance to the clot. Posttoperative use of
antifibrinolytic agent and adherence to soft diet are further advocated to
support clot maintenance. Aspirin and other NSAIDs are avoided in patients
with bleeding disorders owing to inhibition of their platelet function.
Intramuscular injection should also be avoided because of risk of hematoma
formation. Preoperative factor level should be 30 to 40 percent of normal
activity. Electro surgery is not recommended because it causes tissue
necrosis and possible subsequent hemorrhage.
Factor V Deficiency or Parahemophilia
It is a rare hemorrhagic disorder, clinically similar to hemophilia, caused by
a deficiency of factor V or proaccelerin.
Clinical features
It is inherited as an autosomal dominant trait affecting both sexes.
Spontaneous epistaxis, bleeding into the gastrointestinal tract and
menorrhagia are common. Cutaneous ecchymosis and hamartomas are

81

frequently seen, although petechiae are rare. Intraocular hemorrhage and


hemorrhage into the central nervous system have been also reported.

Oral manifestations
Spontaneous gingival bleeding occurs in some cases and prolonged bleeding
after extraction of tooth is observed.
Laboratory findings
Both clotting and prothrombin time are prolonged but, bleeding time is
normal. The basic defect is reduction in plasma proaccelerin.
Management
Transfusion and freshly frozen plasma are given when there is excessive
hemorrhage.
Anticoagulant Treatment
Coumarin anticoagulants such as warfarin are used for prevention e.g. of
thromboembolic disease, which can complicate atrial fibrillation or insertion
of prosthetic heart valves. The underlying condition may therefore influence
oral health care management more then anticoagulant treatment. The latter
should be checked regularly to maintain prothrombin time, which is reported
as international normalized ratio of 2-3 in most cases but 3-4.5 for those
with prosthetic valves. Short term anticoagulation with heparin is given
before renal dialysis session. Heparin is effective only for about 6hrs.
Extraction or other surgery can therefore be delayed for 12-24hr after the
last dose of heparin, when the benefits of dialysis are also maximal.

82

ENDOCRINE DISORDERS
HYPOTHALAMUS AND ANTERIOR PITUITARY
Introduction and Pathophysiology
DISEASES OF PITUTARY GLAND
HYPERPITUITARISUM
Gigantisum
Acromegaly
HYPOPITUTARISUM
THYROID DISEASE
General Description
Pathophysiology
Hyperthyroidisum
Hypothyroidisum
Management
Prognosis
Oral Health Considerations
PARATHYROID DISEASE
Hyperparathyroidisum
Hypoparathyroidisum
DISEASE OF PANCREATIC GLAND
Diabetese mellitus
Type-I(IDDM)
Type-II(NIDDM)
ADRENAL GLAND DISORDER
Addisons Disease
Cushings Syndrome
Adrenal Insufficiency

83

HYPOTHALAMUS AND ANTERIOR PITUITARY


Pituitary disease can present with either overt disease or subtle findings to
the oral health clinician. Patients with hormonal dysfunctions caused by
pituitary disease may be found to have significant abnormalities on head and
neck examination. Large pituitary adenomas frequently present with changes
in vision and loss of visual-field integrity, and the oral health clinician may
be the first medical professional to note these diseases. For example, in
active Graves disease (one of the conditions causing excessive function of
the thyroid), defects in the motor function of cranial nerves III, IV, and VI
may be observed. In acromegaly and in Cushings disease, pituitary
adenomas secrete active hormones, causing gradual changes in facial
features and orofacial structures. In addition to the changes an oral health
clinician can observe and document on physical examination, patients with
disease caused by pituitary adenomas often have alterations in the blood
levels of several circulating hormones. 27 Notably, abnormal hormone levels
may also be the result of previous medical or surgical therapy for underlying
pituitary disease.Normally, blood levels of hormones secreted by the
pituitary are exquisitely regulated.28 Disruption of pituitary function can
produce lifethreatening conditions, adversely affecting the safety of patients
during all but the most minor clinical interventions. Prompt recognition of
pituitary dysfunction can prevent complications of dental treatment and can

84

provide a safe setting for clinical and therapeutic interventions in these


patients. Even after definitive medical or surgical treatment of pituitary
disease, patients may require lifelong replacement of several hormones.
Replacement therapy may be indicated after partial resection or partial
destruction of pituitary tissue.
Occasionally, oral changes can lead to diagnosis of unsuspected endocrine
disease. Patients with Addison disease, diabetes mellitus and thyrotoxicosis
in particular also need special care when having oral health care operations,
and genral anaesthetics should be avoided.

DISEASES OF PITUTARY GLAND


HYPERPITUITARISM
It results from hyperfunction of anterior lobe of pitutatry gland, most
significantly with increased production of growth harmone.
Types
1.Gigantisum-If the increase occurs before epiphysis of long bone are
closed.
2.Acromegaly-if the increase occurs later in life after epiphysis closure.

GIGANTISUM
Clinical Features
Generalized overgrowth of most tissue in childhood. Most of the soft tissue
and bones respond to the excess hormone by enlarging. Excessive
generalized skeletal growth. Patient may often have of height to 7 to 8 feet.
Patients achieve monstrous size because of tumors of the pituitary gland.
Later in life it may show genital underdevelopment and excessive
perspiration and they complain of headache, lassitude, fatigue, muscle and
joints pain and hot flashes. There is increase in size of calvarium which may
85

lead to change in the hat size. Pituitary tumors may also induce deficiency of
other pituitary hormones causing signs of hypogonadism including
decreased libido and menstrual problems in women.

ACROMEGALY
It is more common in males and occurs most frequently in 3rd decade.
Bone overgrowth and thickening of the soft tissue cause a characteristic
coarsening of facial features termed acromegaly. Hand and feet become
large, with clubbing of the toes and fingers due to enlargement of the tufts of
the terminal phalanges. There is temporal headache, photoophobia and
reduction in vision. The terminal phalanges of the hands and feets become
large and the ribs also increase in size.
Oral Manifestations
Teeth
Teeth in gigantism are proportional to the sized of jaw and the rest of the
body and root may be longer than normal. The teeth become spaced, partly
because of enlargement of the tongue and party because upper teeth are
situated on the inner aspect of the lower dental arch, due to disproportionate
enlargement of the two jaws
Jaw bone
Mandibular condylar growth is very prominent. Overgrowth of mandible
leading to prognathism. Mandible may be of extraordinary proportions
creating a major discrepancy between the upper and lower jaws and a
pronounced class III malocclusion. In some cases the growth at the condyle
exceeds that of the alveolar processes, so that increased in vertical depth of
the ramus is greater than that of the body of the jaw, consequently the upper
86

and lower teeth fail to come into proper occlusion.The palatal vault is
usually flattened and the tongue increase in size and may cause crenation on
its lateral border. The lips become thick and Negroid. In edentulous patients
enlargement of the alveolus may prevent the comfortable fit of complete
dentures.

Radiographic Features
Skull changes
Enlargement of sella turcica, enlargement of paranasal sinus and excessive
pneumatization of temporal bone squames and petrous ridge. Diffuse
thickening of outer table of skull. Enlargement and distortion of the pituitary
fossa. Air sinus-the air sinuses are really prominent in acromegaly rather
than in gigantism.
Teeth
Increased tooth size especially root due to secondary cemental hyperplasia.
Diastema between teeth due to lengthening of dental arch. Increase in
thickness and height of alveolar process.
Jaw bone
In acromegaly the angle between the ramus and body of mandible may
increase, which results in anterior tooth root push forward so they appear as
fan out. There is also lengthening of condylar process, class III skeletal
relationship. The new bone laid down on the condyle results in an increase
in the vertical length of the ramus as well as overall length of whole bone.
It is greater on the tip and posterior aspect of the coronoid processes, on the
posterior border of the ramus and on the chin. Enlargement of the mandible
is common finding as the length of the horizontal and ascending rami both
87

are increased causing it to become prognathic with an increase obliquity of


the angle and with loss of the antegonial notch. There is also enlargement of
inferior dental canal.Thickening and enlargement of the alveolar bone with
spacing and fanning out of the teeth, particularly anteriorly resulting in an
open bite.
COLOR PLATE-7

88

Diagnosis

89

It can be made from the characteristic clinical and radiographic findings.


Growth hormone concentration can be measured by radioimmunoassay
technique.
Management
Surgical mangement-Trans-sphenoidal surgery may result in cure of GH
excess especially in patients with macroadenoma.
Medical mangement -Octreotide, a long acting analogue of somatostatin,
lowers GH. It is administered subcutaneously 2 to3 times/day. Dopamine
antagonists are also used.
Radiotherapy-External radiotherapy stops tumor growth and lowers GH
levels. GH levels fall slowly and there is a risk of hypopituitarism.
HYPOPITUITARISM
It results due to reduced secretion of pituitary hormone which may occur due
to pituitary adenoma that compresses the pituitary gland. It is often the
consequence of growth of pituitary gland or interference with stalk function.
It results in pituitary dwarfism . Pathologic changes can result from a variety
of pituitary gland malfunction. Total absence of all pituitary secretions is
known as panhypopituitarism. Hypopituitarism which commences after
puberty is called as Simmond's disease.
Causes
Congenital or due to destructive disease of pituitary gland such as infarct
occurring before puberty. Space occupying lesions involving the sella turcica
like craniopharyngioma, adenomas and sarcoidosis. Sheehan's syndrome is a
form of hypopituitarism caused by infarction of the pituitary associated with
postpartum hemorrhage.
Clinical Features
90

Stature of individual-The underdevelopment is symmetrical, individual is


very small and in some cases there may be a disproportional shortening of
the long bones. The hallmark of this condition is that the growth is retarded
to a greater degree than is bone and dental development. Hypocalcemia, it
may occur because of growth hormone and cortisol deficiency. Lack of
gonadootrophin delays the onset of puberty.
Diabetic insipidus-The presence of diabetes insipidus associated with
deficient secretion of vasopressin is suggestive of pituitary dysfunction.
Growth hormone secretion is lost resulting in lethargy, muscle weakness and
increase fat mass in adults. After luteinizing hormone (LH) secretion
becomes impaired, in the male loss of libido and impotence and in female
oligomenorrrhea or amenorrhea. The male produces gynecoomastia and skin
becomes fair and wrinkled.
Skull-The skull and facial bone are small and there is delay in maturation of
the skeleton and epiphysis may remain ununited throughout the life.
Oral Manifestations
Marked failure of development of maxilla and mandible with lack of
condylar growth with short ramus and this can lead to severe malocclusion
and crowding of the teeth. The two important hormones excreted by this
gland-the somatotrophic and the thyrotrophic are responsible for the normal
eruption of teeth and the alveolar growth. Thus, in case of hypoofunction
this gland the tooth eruption is hampered. The dental arch is smaller than
normal and thus cannot accommodate all the teeth resulting in crowding and
subsequent malocclusion. The clinical crown appears smaller than normal
because even through eruption does occur it is not complete. Eruption is
delayed and so the shedding of the deciduous teeth.
Radiographic Features
91

Complete absence of third molar bud. Roots of teeth are short and apices are
wide open and pulp canal is toward the apex. There is loss of alveolar bone.
Management
It is usually directed towards removal of the cause or replacement of the
pituitary hormone or those of its target glands.

DISEASES OF THYROID GLAND


THYROID DISEASES
After diabetes mellitus, thyroid disease is the most common endocrine
problem in the general population.29 Many signs and symptoms of thyroid
disease are observable during examination of the orofacial complex.
Furthermore, under- or overactivity of the thyroid gland can cause lifethreatening cardiac events.Thyroid diseases often require long-term
treatment, are frequently intermittent diseases, and worsen during life
stresses such as childbirth or depression. 3032 Thyroid diseases occur more
often in women and most often in women older than 50 years of age. It has
been estimated that the lifetime risk of thyrotoxicosis (eg, clinically
significant hyperfunction of the thyroid gland) is 5% for women and 1% for
men.33,34 Routine screening for thyroid disease in an older (> 50 years of age)
population of women will detect an unsuspected symptomatic thyroid
dysfunction in 1 in 71 women.31 The second most common thyroid disease is
found in the neonatal population.35,36 Congenital hypothyroidism is caused
by a clinically significant defect in thyroid hormone production at birth.
Congenital hypothyroidism occurs in 1 in 3,500 newborns, affects females
twice as often as males, and is one of the common preventable causes of
mental retardation.33 In the newborn with hypothyroidism, no clinical

92

features are specific, but there is an inverse relationship between the age at
which treatment is started and the degree of mental retardation.
The signs and symptoms of hyperthyroidism are the result of increased
secretion of T4 by the thyroid gland, but many are identical to the signs and
symptoms of anxiety. In the dental patient in pain, signs of hyperthyroidism
may coexist with and exacerbate the patients normal response to pain and
anxiety. In addition, routine examination of the head and neck may disclose
signs of thyroid disease, including changes in oculomotor function,
protrusion of the eyes, excess sweating, enlargement of the thyroid or the
tongue, lingual thyroid tissue, and difficulty in swallowing. Treatment of
thyroid disease can accelerate the protrusion of the eyes and can cause
agranulocytosis.29Atrial fibrillation, increasing thyroid size, and swings in
thyroid hormone levels to symptomatic hypothyroid or hyperthyroid status
are also possible during medical therapy for underlying thyroid disease.
Pathophysiology
The thyroid is a unique endocrine gland that depends on dietary iodine
intake to produce the hormone thyroxine. Thyroxine regulates the pace of
metabolism in all cells through interactions with mitochondrial, nuclear and
extramitochondrial processes.37 Dietary iodine intake modulates the
functional activity of the thyroid gland, directly altering thyroid sensitivity
to TSH as well as producing an inhibitory effect on thyroid function
independent of TSH.38 Iodine deficiency results in increases in thyroid gland
size (goiter) and hypothyroidism. The major circulating form of thyroid
hormone is T4, but T3, the tri-iodinated variation of thyroxine, is the active
intracellular form of the hormone.37 The location of the thyroid gland (at the
base of the neck, just superior to the sternal notch) permits easy observation
93

and examination by the oral healthcare practitioner. Autoimmune disease


and the excess production of TSH by a pituitary adenoma also causes goiter.
The two most common autoimmune diseases of the thyroid are Graves
disease and Hashimotos thyroiditis.39,40 Graves disease presents most often
with hyperthyroidism, goiter, and eye symptoms, which are linked to the
etiology of the disease, namely, the production of autoantibodies that mimic
the action of TSH atthe TSH receptor on the cellular membrane of the
thyroid cell.41
An antigenically related site that interacts with anti-TSH receptor antibodies
is also present in orbital muscle tissue.39,4647 Hashimotos thyroiditis, which
may present clinically with either hypothyroid or hyperthyroid symptoms
and laboratory results, is an intermittent disease that is often exacerbated by
intercurrent viral infection.45 Sjogrens syndrome has been suggested to have
the same immunologic etiology and to coexist with autoimmune thyroid
disease.46 The co-incident diseases suggest that related immune defects may
contribute to a common etiology.39 In addition, environmental factors have
been linked to autoimmune thyroid diseases.45,48 Thyroglobulin, a protein
synthesized in the thyroid, not only binds T4 but also acts as a storage and
maturation protein.49 Thyroglobulin is recycled through the follicular lumen
of the thyroid gland until the poorly iodinated prohormone bound to the
protein is further matured; T4, containing four iodine molecules, is the major
product.49 This micromanagement of hormone production by protein
transportation within the gland is unique to the thyroid and represents an
additional layer of control of prohormone trafficking. levels as an indicator
of disease .39 The control of thyroid hormone maturation by thyroglobulin is
disrupted in thyroid cancer cells.Patients with thyroid cancer have

94

abnormalities of prohormone maturation and a defective iodine interaction


with thyroglobulin, which can be demonstrated in the thyroid cancer cells.42

HYPERTHYROIDISM
It is also called as thyrotoxicosis and it is a syndrome in which there is
excessive production of thyroxin in thyroid gland. It is associated with
diffuse toxic goiter and less frequently with toxic nodular goiter or toxic
adenoma. Excessive thyroxin causes generalized increase in metabolic rate
of all body tissues. In patient with thyrotoxicosis, dental treatment can
precipitate an acute emergency like thyroid crisis or thyroid storm.
Definition
Hyperthyroidism is excessive functional activity of the thyroid gland that
can be caused by Graves' disease, excessive replacement of or overdose of
thyroid hormone.
Causes
Exophthalmic goiter-It is characteristic by diffuse hyperplasia of the thyroid
and by eye signs.
Toxic adenoma-It is the result of hyperfunction which

originates by a

benign tumor of the thyroid gland.


Ectopic thyroid tissue-Graves disease, multinodular goiter, thyroid
adenoma.

95

Clinical Features
It has predilection for females between 20 and 40 years of age. Thyroid is
diffusely enlarged, smooth, possible asymmetrical and nodular, a thrill may
be present, may be tender. Abdomen, liver and spleen may be enlarged.
Neuromuscular-It includes nervousness, fine tremors, and muscle weakness,
mood swings from depression to extreme euphoria, emotional liability,
hyper-reflaxia, ill sustained clonus, proximal myopathy, bulbar myopathy
and periodic paralysis.
Gastrointestinal
Weight loss despite normal or increased appetite, diarrhea, bowel alterations,
anorexia, vomiting and hyperdefecation.
Cardiorespiratory
Palpitation, excessive perspiiration, irregular heart beat. Increased metabolic
activity leads to increased circulatory demands, tachycardia and increased
pulse pressure and sometimes congestive cardiac failure. Exertional dyspnea
and ankle edema, blood pressure normal, systolic hypertension may be
present. Angina and cardiomyopathy and exacerbation of asthma.
Ocular
In thyrotoxicosis patient may have bulging eye and partial paralysis of the
ocular muscles, retraction and jerky movement, corneal ulceration, optic
neuritis, ocular muscle weakness, papillooedema, loss of visual activity,
exophthalmos.
Reproductive
Amenorrhea, oligomenorrhea, infertility, spontaneous abortion and loss of
libido, impotence.

96

Dermatological
Increases sweating, pruritus, oncholysis, pigmentation, vitiligo, digital
clubbing and pretibial myxedema (bilateral nonpiiting edema).
Other features include heat intolerance, sweaty and warm extreemities, thin
shiny skin, pretibial myxedema, increased PR and early fatigue,
lymphadenopathy, thirst and osteoporosis.
Oral Manifestations
Advanced rate of dental development and early eruption with premature loss
of primary teeth. Generalized decrease in bone density or loss of some areas
of edentulous alveolar bone. Early jaw development and alveolar bone
atrophy.
Radiographic Features
In older children and adults well marked generalized osteoporosis is
sometime appears but it is not revealed in the jaw. In some cases there may
be alveolar resorption and in some cases there may be greater density of the
trabeculae. .
Laboratory Investigation
Plasma levels of T3 and T4 are increased, free thyroxin index is raised in this
disorder. Thyroid stimulating hormone (TSH) is decreased. Anemia may be
moderate to severe degree and is seen in patient with prolonged duration of
the disease. The anemia is hypochromic and abnormal forms of RBC may be
seen.
Management
Antithyroid drugs-It would be appropriated to give antithyroid drugs for 12
to 18 months to those in whom a single episode was anticipated.
Carbimazole-For 0 to 3 weeks-40 to 60 mg daily in divided doses, for 4 to 8

97

weeks-20 to 40 mg daily in divided doses and for maintenance phase-5 to 20


mg daily.
Subtotal thyroidectomy-The antithyroid drug is stopped 2 weeks before
surgery and replaced by potassium iodate 170 mg daily orally.
Radioactive iodine-I131acts either by destroying functioning thyroid cells or
by inhibiting their ability to replicate. Dose-185 to 370 mEq (5-10 mCi) is
given orally.
-adrenoreceptor

antagonist-selective

receptor

antagonist

such

as

propranolol (160 mg daily in divided doses or nadolol 40 to 80 mg once


daily) will elivate but not abolish symptoms of , hyperthyroidism within 24
to 48 hours.

HYPOTHYROIDISUM
It is caused by insufficient secretion of thyroxin by the thyroid gland. As
failure of thyrotrophic function on the part of the pituitary gland or an
atrophy or destruction of the thyroid gland leads to an inability of the thyroid
to produce sufficient hormone to meet the requirement of the body.
Definition
Decreased or deficient secretion of thyroid hormones caused by, thyroiditis,
insufficient thyroid replacement, postthyroidectomy, postradioactive iodine
therapy.
Types
Cretinism-If failure of hormone occurs in infancy.
Juvenile myxedema-If it occurs in childhood.
Myxedema-If it occurs after the puberty. In it there is subcutaneous
deposition of hydrophilic mucoopolysaccharides.

98

CRETINISM AND JUVENILE MYXEDEMA


Clinical Features
It may be present at birth or become evidence within the first few months
after birth. Hoarse cry, constipation, feeding problems in neonates, retarded
mental and physical growth. Delayed fusion of all body epiphysis and
delayed ossification of paranasal sinus, partially pneumatization. There is
protuberant abdomen with umbilical hernia. The hairs are sparse and brittle,
the finger nails are brittle and the sweat glands are atrophic.
MYXEDEMA
Early symptoms includes weakness, fatigue, cold intolerance, lethargy,
dryness of skin, headache, menorrhagia, and anorexia. Late symptoms
includes slowing of intellectual and motor activity, absence of sweating,
modest weight gain, constipation, peripheral edema, pallor, hoarseness,
decreased sense of taste and smell, muscle cramps, aches and pains,
dyspnea, anginal pain and deafness. Dull expressionless face, periorbital
edema, sparse hair and skin that feels droughty to touch. Temperature
normal and the patient may be disorientated which may indicate impending
myxedematous coma, pulse decreased, blood pressure normal, diastolic
hypertension may be present. Facial pallor, puffiness of face and eyelids
(myxedema), occasional purpura, thickened nose and lips in more advanced
cases, note scars in neck from thyroidectomy. Thyroid gland may be
enlarged, thin brittle nails, coarse thin hair, dry rough skin, displaced apical
beat may be present. Delayed return of deep tendon reflexes, pleural effusion
may be present. There are also watery eyes, brittle hair and patchy alopecia.

99

Oral Manifestations
Cretinism and juvenile myxedema
Teeth
Dental development delayed and primary teeth slow to exfoliate. Enamel
hypoplasia can also be seen. Abnormalities of dentin formation lead to
enlarge pulp chamber.
Jaw bone
Maxilla is overdeveloped and mandible is underdeveloped. Retarded
condylar growth leads to characteristic micrognathia and open bite
relationship.
Tongue
It is enlarged by edema fluid and may protrude continuously and such
protrusion may lead to malocclusion of teeth.
The base of skull is shortened leading to a retraction of the bridge of the
nose with flaring. Face is wide and fails to develop in longitudinal direction.
Lips are puffy, thickened and protruding.
Myxedema
Tongue and lip-Macroglossia and enlarged lip are seen as a result of the
deposition of water and protein including facial swelling of non pitting type
and mandible is underdeveloped. There is greater tendency to periodontal
disease, with alveolar destruction and loosening of the teeth.
Radiographic Features
Skull bones show delayed closing of the frontanels and epiphysis, numerous
wormian bones. There is transverse line of increased density involving the
metaphysical regions. Teeth reveal thinning of lamina dura. Delayed dental
eruption, short tooth root. Separation of teeth as a result of enlargement of
tongue, periodontal diseases, loss of teeth and external root resorption. The
100

alveolar processes are relatively large as compared to body of bone which is


smaller than in normal individuals.
Laboratory Findings
Thyroid stimulating hormone (TSH) increased and T3 and T4 decreased.
In ECG, a classical sinus bradycardia with low voltage complexes and ST
wave abnormalities. There is raised cholesterol and triglycerides level and
low serum sodium.
Complications
Common complications include coronary artery disease, congestive heart
failure. Increased susceptibility to infection, mental disturbances including
depression.
Diagnosis
Clinical signs and symptoms and radiographic features along with laboratory
test revealing reduction in serum T3 and T4 levels are confirmatory.
Management
Patients are managed by thyroid preparation. Mainly use is levothyroxin,
which is available as 25, 50 and 100mg tablets. It is customary to start
slowly and a dose of 50mg/ day should be given for 3 weeks and finally to
150mg/day. In the elderly and in patient with ischemic heart disease the
initial dose should be 25ug/day. In children it should start as early as
possible to avoid major developmental and intellectual abnormalities.
Dental Consideration of Thyroid Disorders
In dentistry the use of sedative and analgesic are dangerous as these agents
tend to precipitate coma in patient with hypothyroidism.In patients with
severe hyperthyroidism the emergencies likely to occur are thyroid crisis,
emotional disturbances, cardiac difficulties. Treatment by the dentist should

101

consist of medication to sedate the patient, application of cold packs to


lower

COLOR PLATE-8

102

body temperature. Oxygen is given if necessary. If severe, patient should be


immediately hospitalized.
Clinical and Laboratory Findings for thyroid diseases
THYROID FUNCTION TESTS
Normal radioactive iodine(RAIU) uptake is 5-30% in 24-hr
ThyroxineT4 levels in serum is 4-12g/dl
T3(Triiodothyronine) is 80-100mg/dl
TSH(Thyroid Stimulating Harmone) Levels in serum is 0.4-5 IU/ml
Screening for thyroid disease can be divided into two categories
(1) screening of newborns for congenital hypothyroidism and (2) screening
of adult patients seen for non-thyroid- related reasons, using the 1998
primary care guidelines formulated by the American College of Physicians. 33
Screening for neonatal hypothyroidism relies on TSH testing, an abnormally
high TSH result requires follow-up by a T4 determination to confirm the
hypothyroid condition. Screening for thyroid dysfunction in adults can
identify four disease conditions: overt hypothyroidism and hyperthyroidism
and subclinical hypothyroidism and hyperthyroidism. For adults, the primary
screen is the TSH level, which, if abnormal, is followed by a determination
of free T4 (ie, circulating T4 that is not bound to serum proteins).31 If the TSH
level is abnormally low, clinically significant hyperthyroid disease would be
confirmed by an elevated level of free T4. If the TSH level is abnormally
high, a subnormal level of free T4 would indicate clinically significant
hypothyroidism. Subclinical disease for hypothyroidism is diagnosed by the
combination of a high TSH level and a normal T4 level whereas a low TSH
103

level and a normal T4 level represents subclinical hyperthyroidism.


Screening is indicated for women over 50 years of age and for all patients
presenting with any of the following signs or symptoms like thyroid
enlargement, eye signs compatible with thyroid disease, new onset of atrial
fibrillation, and a history of previous thyroid disease and new symptoms of
either hypo- or hyperthyroidism. A new finding of asymmetry of the thyroid
gland on routine examination of the head and neck requires referral and
follow-up by an internist or endocrinologist. Whether the cause of the
abnormality is multinodular goiter, nonfunctioning thyroid nodules or cysts,
or thyroid cancer, the prognosis is good for early intervention and treatment
in all cases except those of anaplastic thyroid carcinomas, which have a 10year survival rate of 2%.50 Diagnosis of a pathologic lesion in an abnormal
gland is often a noninvasive procedure using fine-needle biopsy with
aspiration cytology of the affected region.51 Other diagnostic methods
include ultrasonography, computed tomography, magetic resonance imaging,
and nuclear scintigraphy with radioactive iodine.52 Classification of thyroid
cytology from fine-needle aspiration biopsy specimens is well developed
and is often diagnostic. Papillary thyroid cancer is the most common
epithelial tumor and accounts for 80% of all thyroid cancers. 50 Thyroid
cancers are treated by excision and by radiation. Recurrence of the cancer
after excision or radiation therapy may be followed with serum or tissue
thyroglobulin determinations.53 Rarely, thyroid cancers are metastatic.
Metastases are seen especially with medullary thyroid cancer, a cancer
linked to a rare autosomally dominant inherited defect of the RET protooncogene, which causes the familial syndromes that are called multiple
endocrine neoplasia.50 More common than thyroid cancer, solitary benign
nodules of the thyroid are a frequent final diagnosis after the clinical finding
104

of thyroid gland asymmetry. The treatment of these lesions is controversial


and may include long-term T4 therapy.54

DISEASE OF PARATHYROID GLAND


HYPERPARATHYROIDISM
It is an endocrine disorder in which there is an excess of circulating
parathyroid hormone. Excess PTH stimulates osteoclast to mobilize calcium
from skeleton leading hypercalcemia in addition to PTH increased renal
tubular reabsorption of calcium. Following is the sequence of event which
gives an idea of the reaction promoted by this hormone. The bone and the
kidney are the target organs of parathyroid hormone which mediates the
osteoclast to resorb bone actively. When the bone is resorbed, calcium is
released in the extracellular fluid and the serum calcium level is elevated.
The parathyroid hormone acts on the epithelium of kidney tubules causing
diuresis of phosphorus resulting in decrease in serum phosphorus level. At
the same time it induces an increase in calcium reabsorption from
glomerular filtrate. Parathyroid hormone may also increase the absorption of
calcium from the intestine but this is not definitely established. Hence in a
healthy person injection of parathyroid hormone produces an elevated
plasma calcium level, a decreased plasma phosphorus level and an increased
alkaline phosphatase level.
Types
Primary-There is autonomous secretion of parathyroid hormone (PTH) by
hyperplasia, benign and malignant tumor of one or more of the four
parathyroid glands.

105

Secondary-Compensatory increase in output of PTH in response to


hypocalcemia. The underlying hypocalcemia may result from an inadequate
dietary intake or poor absorption of vitamin D or from deficient metabolism
of vitamin D in the liver or kidney. It affects to restore serum calcium level
at the expense of the lots of calcium in bone.
Tertiary-Occasionally parathyroid tumor after long standing secondary
hyperparathyroidism

develops

this

condition

known

as

tertiary

hyperparathyroidism. The increased parathyroid level produces increased


bone resorption and a resultant hypercalcemia.
Ectopic-Due to excessive parathyroid hormone synthesized in patient with
malignant disease.
Clinical Features
Female to Male ratio is 3:1. Mainly in 30 to 60 years of age. Renal calculi,
and hematuria, back pain, urinary tract infection and hypertension are
common. Peptic ulcer, psychiatric effect like emotional instability, bone and
joint pain, and sometime pathologic fractures occur.
Gastrointestinal difficulties such as anorexia, nausea, vomiting and crampy
pain may be present. Bone deformities occur such as bending of long bone
including occasional fracture and collapse of vertebrae and formation of
pigeon chest. Hyeprcalcemia is associated with muscle weakness, fatigue,
weight loss, insomnia, headache, polydipsia and polyuria.
Oral Manifestations
Gradual loosening drifting and loss of teeth, malocclusion. Jaw bone-there is
pathological fracture of bone. Cystic lesion involving jaws are seen over 10
percent of cases.
106

Radiographic Features
Demineralization of skeleton bone matrix contains less than normal amounts
of calcium producing unusually radiolucent skeletal image. There is lack of
normal contrast in the radiograph resulting in over all grayness, often
associated with a granular appearance in the bone. The rarefaction is of
homogeneous nature and there may be normal, granular or ground glass
appearance.Sometimes rarefaction gives a mottled or moth eaten appearance
with varying density. Osteitis fibrosa generalisata localized destruction of
bone is produced by osteoclastic activity leaving residual area of fibrosis. In
some cases moth-eaten appearance can be seen.
Brown tumor
It may develop peripherally or centrally, it appears radiographically as ill
defined radioolucency called as brown tumor, as gross specimen is brown or
reddish brown. In it, trabeculae are completely missing. It may occur in
pelvis, ribs or femur but are most commonly found in facial bones and jaws.
These lesions may be multiple within the single bone or they may be
polyostotic. They appear as unilocular or multilocular with variably defined
margin and may produce cortical expansion.
Pathological calcification-Punctuate and nodular calcifications occasionally
occur in kidneys and joints. Earliest change is subtle erosion of bone from
subperiosteal surface of phalanges of hand.
Skull bones-Entire calvarium has granular appearance caused by loss of
central trabeculae and thinning of cortical tables. Evidence in the skull vault
of osteopenia producing a fine overall stippled pattern to the bone, hence it
107

is called as pepper-pot skull. Demineralization of inferior border of


mandibular canal, thinning of outlines of the maxillary sinus are the
common findingsin jaw bones.If the alveolus is severely affected the teeth
may become mobile and migrate.
The radiopaque cortical plate outlining the bones and anatomic regions may
be thinned or lost entirely. Loss of lamina dura which may be seen around
one tooth or all remaining teeth. It may be complete or partial.
Laboratory Findings
The serum calcium level is raised and serum phosphorus level is decreased
and

serum

alkaline

phosphatase

level

is

elevated

in

primary

hyperparaathyroidism and in secondary hyperparathyroidism the serum


calcium level is decreased whereas the serum phosphorus and alkaline
phosphatase level are elevated.
Diagnosis
Serum alkaline phosphatase and serum calcium level is increased. Decreased
blood phosphorous level. Increase in circulating hormone demonstrated by
radioisotope studies.
Management
It often regresses without surgery and the rarefaction disappears. The oral
administration of vitamin D in secondary type can prevent skeletal
demineralization in most of the cases. Surgical management includes
excision of adenoma.

108

HYPOPARATHYROIDISM AND
PSEUDOHYPOPARATHYROIDISM
It is an uncommon condition in which there is insufficient secretion of
parathyroid hormone. Pseudohypoparathyroidism is a condition in which
there is defect in the response of tissue target cell to normal level of
parathyroid hormone.
Etiology
Surgical damage to parathyroid gland and their vascular supply during
thyroid gland procedure. Parathyroid damage from radioactive iodine 131.
Autoimmune destruction of parathyroid gland.
Clinical Features
Hypocalcemia-it can lead to tetany in the form of carpopedal spasm of the
wrist and ankle joint including stiffness in hands, feet and lips. There is also
paresthesia of hand, feet and around the mouth. Tingling in the circumoral
area, fingers ad toes. Patients may complain of anxiety, depression, epilepsy
and chorea. Reduction in intellectual capacity due to calcification within the
brain.
Pseudohypoparathyroidism
Patient with pseudohypoparathyroidism manifests short stature due to early
closure of certain bony epiphysis. The face is round and the hand shows
shortening of the metacarpal bones, so that fingers are short.
Trousseau's sign

109

It is elicited by occluding blood flow to the forearm for 3 minutes with


sphygmomanometer cuff applied to the arm and raising the pressure above
systolic level. This will induce carpopedal spasm.
Oral Manifestations
Hypoplasia of enamel, delayed eruption, external root resorption and root
dilacerations. There is also blunting of molar roots.
Chvostek sign
A sharp tap over the facial nerve in front of ear causes muscle twitching of
facial muscle around the mouth.
Chronic candidiasis is also some time present.
Radiographic Features
Calcification of basal ganglion which appears flocculent and paired with the
cerebral hemisphere on PA view. Radiograph of jaw may reveal enamel
hypoplasia, external root resorption, delayed eruption or root calcification.
Diagnosis
The serum calcium level is decreased usually below 7 mg/dl. Serum
phosphate level correspondingly elevated.
Urinary calcium is low or absent.
Management
Supplemental calcium and vitamin D depending on severity of the
hypocalcaemia and the nature of the associated signs and symptoms.
In severe cases intravenous administration of calcium gluconate is the
treatment of choice.

110

COLOR PLATE-9

111

DISEASE OF PANCREATIC GLAND


DIABETES MELLITUS
It may cause by autoimmune response. Principal laboratory signs are
hypercalcemia. It is common endoocrine disorders characterized by chronic
hyperglycemia and abnormalities in carbohydrate and lipid metabolisum.
Definition
Inappropriate hyperglycemia due to tissue resistance to insulin action,
reduced insulin secretion or both.
Etiology
Caused by a disorders of carbohydrate metabolisum resulting from insulin
deficiency or ineffectiveness, producing hyperglycemia and glycosuria.
Types
1. Primary
-Type I or insulin dependent (lDDM)
-Type II or non insulin dependent (NlDDM)
-Maturity onset diabetes of the young (MOOY)
2. Secondary
-Pancreatic disease
-Endocrine disease-excess of harmonal anagonist eg. growth hormone in
acromegaly
-Drug induced like corticosteroid,thiazides diuretics and phenytoin.

112

-Genetic syndrome like Down syndrome, Klinefelter's syndrome and Turner


syndrome
3. Impaired glucose tolerance
4. Gestational diabetes
Etiology
Type I Diabetes Mellitus
Viruses
Several viruses are implicated including infection with mumps coxsackie B4,
retrovirus, rubella and cytomegalovirus and Epstein-Barr virus. Virus
particle known to cause cytopathic autoimmune damage to beta cells have
been isolated from the pancrease.
Diet
Bovine serum albumin (BSA) a major constituent of cow's milk has been
implicated in triggering type-I diabetes. It has been shown that a child has
taken cow's milk early in infancy has been m prone to develop type I
diabetes mellitus compared to other who has taken breast milk.
Stress
It may precipitate the development of Type I diabetes by stimulating the
secretion of counter regulatory hormones and possibly by modulalating
immune activity.
Immunological factors
There is evidence that Type I diabetes is a T cell mediated autoimmune
disease. There is also HLA linked genetic predisposition. Monocular cell
infiltration of pancreatic islets restoration in selective destruction of insulin
secreting cells and induction of remission by immunosuppressive drugs such
as cyclosporine suggest it immunological etiology.
113

Type II Diabetes Mellitus


Genetic
The majority of cause of type II diabetes are multifactorial. Various types are
associated with it like hepatocyte nuclear factor, glucokinase, and
mitochondrial DNA and insulin receptors.
Environmental factors
Overeating, especially when combined with obesity and under activity is
associated with developmental of type II diabetes.
Malnutrition
It is proposed that malnutrition in utero and the infancy may damage beta
cell development at a critical period predisposing to type II diabetes later in
life.
Age
Age is an important risk factors for type II diabetes as it is principally
disease of middle aged and elderly affecting 10 percent of the population
over the age of 65.
Pregnancy
During normal pregnancy, insulin sensitivity is reduced through the action of
placental hormone and this affects glucose tolerance. The term gestational
diabetes refers to hyperglycemia occurring for the first time during
pregnancy.
Insulin resistance occurs in type II diabetes is due to an abnormal insulin
molecule, an excessive amount of circulating antagonists and target tissue
defect.
Clinical Features
Polydipsia-Excessive intake of fluid.
Polyuria-Excessive urine passage.
114

Polyphagia-Excessive hunger.
Breathe-Presence of acetone breathe.
Visual activity-Visual difficulty ranging from proogressive color blindness
to total blindness that have disease more than 20 years.
Atherosclerosis-Coronary

artery

disease

and

stroke

are

frequent

complication.
Diabetic neuropathy-It can cause marked irritability.
Infection-Recurrent vaginal (yeast) infections, recurrrent urinary tract
infections, recurrent skin infections (especially of feet) and reversible
paresthesia of fingers or toe.
Other symptoms inclue nocturia, weight loss, fatigue, obesity usually present
in older age group, nausea; vomiting. Temperature, blood pressure may be
elevated and peripheral pulses may be reduced.
Oral Manifestations
Gingival and periodontal disease
It will influence the onset and course of periodontal disease. Patient with
diabetes are more prone to develop periodontal disease than are those with
normal glucose metabolism. The patient may exhibit a fulminating
perioodontitis with periodontal abscess formation and inflamed painful
abscess and even hemorrhagic gingival papillae, this factor culminated and
give rise to tooth mobility, i.e. loose teeth. It will show more severe and
rapid alveolar bone resorption and are more prone to develop periodontal
abscess. Insulin dependent diabetic children tend to have more destruction
around the first molars and incisors than elsewhere. As such diabetes
mellitus does not cause periodontal disease directly but it alters the response
of the periodontal lesion to local irritants, hastening bone loss and retarding
115

postsurgical healing of the periodontal lesions. Gingival fluid in the diabetes


has more glucose level which favors the growth of microflora.Diabetes is
considered to be factor for median rhomboidal glossitis as frequency of
abnormal blood sugar level and predisposition of these subjects to
candidiasis. There is also impairment of blood supply to dorsum of tongue
due to arteriosclerosis changes in the blood vessels supplying the area.
Impairment of local immune mechanism which decreases the concentration
of Langerhans of cells in the lesion.
Oral candidiasis
It is infection with Candida albicans which occur due to encouragement of
local multiiplication of Candida albicans due to impaired glucose level and
immune mechanism.
Localized osteitis
Dry socket develops in diabetes hence they show delayed healing and
impaired immunological balance.
Burning mouth
It is often associated with variety of otherwise unexplained oral symptoms
such as burning sensation, atypical paresis, dysetheria and dysgeusia.
Trigeminal nerve involvement
Diabetes neuropathy is recognized as polymorphic condition as when
manifested as polyneuropathy on the assumption the trigeminal nerve might
be involved.
Other features include increased caries activity, due to excessive fluid loss
patient complained of xerostomia. There is also atrophy of lingual papillae
with fissuring and dry tongue. There is delay in healing of oral wound due to
decreased polymorphonuclear chemotaxis. There is also angular cheilosis,

116

altered taste sensation, oral lichen planus, and diffuse enlargement of parotid
gland.

COLOR PLATE-10
LESIONS IN DIABETES MELITUS

117

Radiographic Features

118

Slight discontinuity or blurring of the cortex of alveolar crest to wide


destruction of lamina dura.
Horizontal and vertical bone loss.
Diagnosis
It is often made from clinical symptoms but laboratory confirmation of
hyperglycemia is essential for diagnosis.
Plasma glucose concentration
Unequivocal elevation of plasma glucose concentration greater than 140
mg/dl.
The glucose tolerance test
Plasma Glucose concentration is 200 mg/dl.
Taste paper strip
Strips are available for direct estimation of blood glucose level.
Blood
Random glucose elevated, fasting glucose elevated, 2hr postprandial glucose
elevated.
Management
Diet control
The patient with NIDDM, particularly those who are obese, dietary control
toward a balanced calorie intake and exercise leading to weight loss is the
sole treatment require. In diabetic patient it is recommended that the
percentage of calories derives from carbohydrates should be increased and
that from fat reduced. A suitable diet for diabetic person 50 percent of the
daily caloric intake should be derived from carbohydrates of which
significant amounts should be in the form of nonstarch polysaccharides.

119

Fat intake should be reduced; the use of monounsaturated oils in the diet
(e.g. olive oil, peanut oil) is beneficial.
Reduced intake of sodium (no more than 6 g/ day), alcohol abstinence.Low
calories and sugar free drink are useful for patients with diabetes.
Oral hypoglycemic drugs-if dietary management proves ineffective in
controlling hyperglycemia. hypoglycemic drugs like insulin or oral
hypoglycemic are prescribed.
Sulfonylurea
First generation sulfonylurea in which tolbutamide is nowadays is given in a
dosage of 25 or 500 mg 8 or 12 hourly. It is useful in the elderly in whom the
risk and the consequence of inducing hypoglycemia are increased. In second
generation sulfonylurea, gliclazide and glizipide are widely used.
Biguanides
They are less widely used than sulfonylurea because of their higher
incidence of side effects. Mechanism of action is by increasing insulin
sensitivity and peripheral blood glucose uptake. Metformin in dose of 500
mg 12 hourly. Its use is contraindicated in persons with impaired renal or
hepatic function and in those who take alcohol in excess because of risk of
lactic acidosis.
Alfaglucoside inhibitors
They delay carbohyydratesabsorption in the gut by selectively inhibiting
disaccharides. Acrabose is currently available in a dose of 50 to 100 mg with
each meal.

Insulin therapy

120

The duration of action of short acting unmodified insulin, which is a solution


can be extended by addition of protamine and zinc at neutral pH. Insulin is
injected subcutaneously into recommended sites namely anterior abdominal
wall, upper arms, outer thighs and buttocks. Short acting insulin has to be
injected at least 30 minutes before a meal to allow adequate time for
absorption. Side effects of insulin are hypoglycemia, weight gain, peripheral
edema, insulin antibodies; local allergy and lipodystrophy.
Dental Consideration
Emergency can occur due to diabetes coma or insulin shock.
Pretreatment History
If the patient takes large daily dose of insulin there is possibility of diabetic
coma or insulin shock. If the patient complains of being thirsty, nausea and
shortness of breath and has warm dry skin, the patient is most likely
hyperglycemic and should be reffered to physician.
Dental Management
Deliver treatment in such a way so as to minimize disturbances of metabolic
balance. Appointment should be of short duration and in the morning.
Encourage to maintain their standard regimen.
Glucose drink should be available if patient complains of hypoglycemia.
Use local anesthesia without epinephrine in the dental procedure.
Increased incidence of dry socket mainly associated with mandibular
extraction is due to decreased blood supply to mandible caused .by
arteriosclerosis in long-standing diabetes. Epinephrine will further reduce
blood supply which further increases chances of dry socket. Following
extraction suturing of the socket should be done to aid homeostasis.
Physician advice should be taken before arranging GA for dental treatment.
121

Antibiotic prophylaxis before dental surgery to prevent subsequent infection.


Complicated oral procedure in dental emergencies should be avoided
whenever possible in uncontrolled diabetics until stabilization of blood
glucose level is achieved.
Complications
Ketoacidosis, coronary artery disease, peripheral vascular disease.
Recurrent skin and urinary infections, renal and retinal changes, cataracts.
Peripheral neuropathy, premature mortality, hyperosmotic nonketotic coma.
DIABETIC INSIPIDUS
Causes
It occurs due to insufficiency of the posterior pituitary hormone.
Traumatic episodes, such as head trauma or surgical procedures carried out
near the pituitary region, can often lead to destruction of the posterior lobe
of the pituitary. In these patients there is damage to the neuroohypophyseal
mechanism for the production of vasopressin.
MANAGEMENT
Administration of vasopression (desmopression)5 to 10mg once or twice
daily

122

ADRENAL GLAND DISORDERS


ADDISON'S DISEASE
It is also called as chronic adrenal insufficiency of the adrenal cortex. It was
first described by Addison in 1855.
Causes
Autoimmune-sporadic and polyglandular syndrome.
Tuberculosis, metastatic carcinoma, intradermal hemorrhage, amyloidosis,
Hemochromatosis, adrenal infarction and congenital adrenal hypoplasia.
Drugs which can cause Addison's disease are aminoglutethimide,
ketoconazole and etomidate. It may cause by bilateral destruction of the
suprarenal glands.
Clinical Features
It is more common in males and, while found in all age groups, it is most
frequently seen in the 3rd and 4th decades.
Feeble heart action, general debility, vomiting, and diarrhea and severe
anemia. Patient complains of postural hypotension. The disease is
characterized by bronzing of skin, a pigmentation of the mucous membrane.
Decrease cortisol level interferes with the manufacture of carbohydrates
from protein, causing hypoglycemia and diminished glycogen storage in the
liver. Neuromuscular function is inhibited, producing muscle weakness.
There is also reduced resistance to infection, trauma, and stress.

123

Oral Manifestation
The pale brown or deep chocolate pigmentation of the oral mucosa,
spreading over the buccal mucosa from the angle of the mouth and/or
developing on the gingiva, tongue, lips may be first evidence of disease.
Laboratory Investigation
The associated anemia is normocytic and normochromic associated with
reticulocytosis. There is reduction in the red cell mass. There is high blood
levels potassium and low concentration of sodium and chloride. Elevated
blood urea nitrogen.
Management
Glucocorticoids replacement-Cortisol is the drug of choice. In patients who
are not critically ill hydrocortisone 15 mg on waking and 5 mg at 6 PM in
evening. Supplement mineralocorticoid can be given.

CUSHING'S SYNDROME
Cushing's syndrome arises from excess secretion of glucocorticoids by the
adrenal glands. It was described by Harvey Cushing in 1932.
Etiology
Cushings syndrome is mainly seen in cases of adrenal adenoma, adrenal
carcinoma, adrenal hyperplasia and basophilic adenoma of the anterior lobe
of pituitary gland. Pateint under medication of exogenous corticosteroid.
In cases of ACTH secreting tumor of the anterior pituitary associated with
adrenal cortical hyperplasia, in ectopically located adrenal like tumor like in
ovary and in alcoholics, major depressive illness and primary obesity.
Clinical Features
124

Female to male ratio is 3:5, seen in 3rd and 4th decades.


Moon face
Rapidly acquired obesity about upper portion of the body and rounded moon
face.
Buffalo hump
There is truncal obesity with promiinent supraclavicular and dorsal cervical
fat pads giving rise to the 'buffalo hump' appearance at the base of neck.
The distal extremities are usually thin. Weakness, hypertension, or
concurrent diabetes is usually present.Alternation in hair distribution.There
is also weight loss, menstrual irregularity, hirsutism, backache, obesity,
hypertension can also occur.
Oral Manifestations
In children growth and development including skeletal and dental age may
be retarded. In some instances there may be osteoporosis of the jaws.
Radiographic Features
Generalized osteoporosis is present. The bone likely to involve are the
vertebrae and the ribs although the long bones may be affected. There is
osseous demineralization with pathological fractures, often superimposed.
Skull may show diffuse thinning and have mottled appearance. Jaw may
show areas of loss of lamina dura.
Management
If the lesion in the pituitary gland is the cause, therapy usually consists of
combination of surgery and radiotherapy.

COLOR PLATE-11

125

Drugs
126

Metyrapone in dose of 2 to 6 gm per day in divided doses by mouth. Other


drug which is given is aminoglutethimide which is anticonvullsant, and it
acts by blocking steroid synthesis.
Radiotherapy
In Cushing's syndrome due to adrenocortical hyperplasia pituitary irradiation
is the best treatment.
Surgery
Tumors involving the adrenal cortex are removed surgically and often
require postoperative administration of corticosteroids to maintain normal
glucocorticosteroicis level.

127

IMMUNOLOGIOCAL DISORDERS
Immunologic Disease
PRIMARY IMMUNODEFICIENCIES
Oral Manifestations
Dental Management
CONNECTIVE-TISSUE DISEASES
Systemic Lupus Erythematosus
Scleroderma
Dermatomyositis
Rheumatoid Arthritis
Miscellenous
Angiodema
Orofacial Granulomatosis

128

Many of the immunologically mediated diseases have some oral health care
relevance. Immunological disease will be considered under the headings of
allergy, atopic disease and autoimmune disease. The immune response, so
necessary for protection against disease, can also cause disease or other
undesirable consequences when it reacts against tissues.
IMMUNODEFFICIENCY DEFECT WITH PRIMARY DEFECT
IN CELLULAR IMMUNITY
DIGEORGE SYNDROME (VELOCARDIOFACIAL SYNDROME)
DiGeorge syndrome has recently been shown to be one of a group of
disorders caused by a deletion on chromosome 22q11. 55This genetic defect
results in abnormal development of the facial and neural crest tissues,
causing abnormal development of derivatives of the third and fourth
pharyngeal pouches. The result of this defect in embryonic growth are
abnormalities of the thymus, the parathyroid glands, and the great vessels of
the heart. The subsequent malfunction of these organs accounts for the
respective features of DiGeorge syndrome
Clinical features
Variable

immunodeficiency,

neonatal

hypocalcemia

secondary

to

hypoparathyroidism, and congenital cardiac defects. Abnormal ear, palatal


(cleft palate), maxillary, and mandibular development define the
characteristic facies of this disorder. These features include short palpebral
fissures, a small mouth, and a prominent forehead. 56. The immunodeficiency
associated with DiGeorge syndrome becomes apparent during the first few
months of life. Most patients have normal leukocyte function and normal
129

humoral immunity but a nearly total lack of cellular immunity. As a result,


patients have an increased susceptibility to infections with viruses and fungi.
Infections with Candida albicans are especially prominent. DiGeorge
syndrome was important in the development of the concept of separate
immune systems for humoral and cellular hypersensitivity because
hypoplasia of the thymus produced impairment of only cellular immunity.
The T-cell deficiency is variable, depending on how severely the thymus is
affected. It is now believed that the thymus is completely absent in less than
5% of patients with 22q11 deletion syndrome, but maldescent of the thymus
leads to an absence of thymus tissue in the mediastinum in most cases. 57
Partial DiGeorge syndrome exists with partial aplasia of the thymus and
parathyroid glands. Spontaneous improvement in the immunologic defect of
DiGeorge syndrome has been described.Transplantation of fetal or
postneonatal thymic tissue may restore immune function.
SEVERE COMBINED IMMUNODEFICIENCY
Severecombinedimmunodeficiency(SCID)(Swiss-typeagammaglobulinemia)
is a genetic disease that can be inherited as either a sex-linked or autosomal
recessive trait that causes a variety of molecular defects. 58 Because over 50%
of cases are caused by a genetic defect on the X chromosome, SCID is more
common in male infants than in female infants (a ratio of 3:1). The
remaining cases of SCID are due to recessive genes on other chromosomes,
one-half of these patients have a genetic deficiency of adenosine deaminase
or purine nucleoside phosphorylase. A deficiency of these purine
degradation enzymes results in the accumulation of metabolites that are
toxic to lymphoid stem cells. These patients have low peripheral lymphocyte
counts, a severe deficiency of immunoglobulins, and a lack of cellular
immunity. The symptoms of this disease begin in the first few weeks of life
130

and include bacterial, viral, and fungal infections. Localized or systemic


candidiasis is common. Cutaneous granulomas may also occur.59 Infants are
also at risk for lethal graft-versus-host disease (GVHD) if given transfusions
with nonirradiated blood products, and they can die of progressive infection
if vaccinated with live organisms. The severity of these immunologic
disorders has made them logical candidates for treatments such as bone
marrow transplantation and gene replacement therapy.Gene therapy has
shown limited success in individuals with adenosine deaminase deficiency.
Early diagnosis and the availability of matched donors for bone marrow
transplantation remain the most important factors in a hopeful prognosis for
patients with this group of disorders.
Partial Combined Immunodeficiencies
ATAXIA TELANGIECTASIA
Ataxia telangiectasia (AT) is a disorder characterized by cerebellar ataxia,
oculocutaneous telangiectasia, and immunodeficiency.The ataxia usually
begins in infancy and is progressive. Telangiectasias of the skin and eyes
become apparent between 3 and 6 years of age. Though not all patients with
AT have immunodeficiency, AT is clinically manifested by recurrent and
chronic sinopulmonary infections. AT is inherited as an autosomal recessive
trait. The AT gene (ATM), identified in 1995, encodes a protein involved in
the repair of double-strand breaks in deoxyribonucleic acid (DNA). 60 Since
radiosensitivity is a characteristic of AT in vitro, understanding the
mechanism of action of ATM may provide additional information on
radiation signaling in human cells, it may be possible to sensitize tumor cells
to radiation and subsequently increase the therapeutic benefit of
radiotherapy.21 In addition, the ATM locus is a common event in some tumor
types, suggesting a general role for ATM in cancer. Defective
131

DNA repair mechanisms common to these patients may account for the high
incidence of malignancies. The ATMgene, therefore, has the potential for
wide-ranging roles such as detecting DNA damage, preventing genomic rearrangements in malignancy, and preventing programmed cell death. The
immunologic abnormalities of AT include T-cell and B-cell deficiencies,
causing both an abnormal cellular response and a deficiency of
immunoglobulins. Due to a markedly hypoplastic thymus, the peripheral Tcell pool is frequently reduced in size. Although the number and class
distribution of B lymphocytes are usually normal, about 70% of AT patients
are serum IgA deficient and can also be deficient in IgG2 and IgG4. These
immunologic abnormalities may be the result of cells that exhibit
chromosomal breaks (usually in chromosomes 7 and 14) at the sites of the Tcell receptor genes and the genes that encode the heavy chains of
immunoglobulins. Treatment for AT is limited to supportive care as no cure
is available. Unless a severe IgG deficiency is present, therapy with gamma
globulin is not indicated.Due to the highly variable incidence of infection,
bone marrow transplantation is usually not advised.
WISKOTT-ALDRICH SYNDROME
Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by
lymphocytes and platelets that are faulty due to an altered cell surface
glycoprotein they share. The classic clinical features include a microcytic
thrombocytopenia, severe eczema, and pyogenic and opportunistic
infections. The immunologic findings of WAS are a result of both T-cell
defects and abnormal immunoglobulin levels. The T cells have a uniquely
abnormal appearance due to a cytoskeletal defect. Moreover, the T cells are
defective in function, and this malfunction becomes progressively worse.

132

Impaired response to polysaccharide antigens, elevated serum IgA and IgE


levels, normal levels of IgG, and decreased amounts of IgM are among the
variable effects on humoral immunity. In addition, the collaboration among
immune cells is also faulty in patients with WAS.During the normal
collaboration of T cells and B cells in antibody formation, the cytoskeleton
of the T cells becomes polarized toward the B cells. This reorientation of T
cells to B cells fails to occur in patients with Wiskott-Aldrich syndrome,
most likely because of the cytoskeletal defect in the T cells. The end result is
a poorly collaborated immune response.
Oral Manifestations
Patients with T-lymphocyte abnormalities have a higher incidence of oral
disease than patients with B-lymphocyte disorders have. T-lymphocyte
abnormalities lead to chronic fungal and viral infections, which are more
likely to occur in the oral mucosa than are the bacterial infections seen in
Blymphocyte deficiencies.22 A consistent oral sign noted in patients with Tcell diseases such as thymic hypoplasia or AT is chronic oral candidiasis.
Herpes simplex virus infections are also common in patients with T-cell
disease. The infections may be localized to the mouth but frequently become
disseminated and are potentially lethal if not treated with antiviral
medication.23 Other oral signs seen with T-cell deficiencies include the
dermal and mucosal telangiectases of AT. Congenital defects of the mouth
and jaws (including cleft palate, micrognathia, bifid uvula, and short
philtrum of theupper lip) have also been seen in patients with thymic
hypoplasia. In patients with AT, hypotonia of facial muscles and atrophy of
the skin gives rise to a characteristic dull expression, drooling can also be a
problem.24 The major sign in patients with B-cell abnormalities is recurrent
bacterial infections25 that frequently involve the respiratory tract. The most
133

common of these infections that comes to the attention of dentists is chronic


maxillary sinusitis. The weight of evidence indicates that patients with
primary immunoglobulin deficiencies do not have an increase in dental
caries or periodontal disease.64,65 Although oral ulceration has been
occasionally described in patients with CVID and IgA deficiency, it is not a
characteristic finding.66 Neutropenia and neutrophil dysfunction syndromes
commonly cause oral ulcers, but immunoglobulin deficiencies do not.
Factors other than primary immunodeficiency may cause candidiasis and
maxillary sinusitis, but for patients with these infections who are not
successfully treated by antibiotic or antifungal therapy or who have a history
of other recurring infections, immunodeficiency should be ruled out. This
should be done with a careful history that includes past episodes of
pneumonia, recurrent otitis media, autoimmune disease, severe asthma,
malabsorption syndrome, and pyoderma. Laboratory studies should be
performed when the history suggests immunodeficiency.With rare
exceptions, a deficiency of humoral immunity is accompanied by diminished
serum concentration of one or more classes of immunoglobulin. Laboratory
studies to rule out B-lymphocyte dysfunction should include a quantitation
of the major immunoglobulins, using immunodiffusion techniques. In
questionable cases, the clinical immunologist will test the patients ability to
synthesize specific antibodies after immunization with standard antigens.
Estimation of numbers of circulating B lymphocytes has also been of great
value in determining the pathogenesis of certain types of immunodeficiency.
Screening for T-lymphocyte dysfunction must be performed by a clinician
who is experienced in performing such tests. Normal levels of serum
immunoglobulins and antibody responsiveness are reliable indices of intact
T-helper-cell function. T-cell function can be measured directly by delayed
134

hypersensitivity skin testing, using a variety of antigens such as purified


protein derivative (PPD) of tuberculin, Candida, andTrichophyton. Negative
reactions to these antigens suggest a defect of cellular (T-cell) immunity.
Laboratory studies that are used to check T-cell activity include lymphocyte
proliferation, T-cell subset quantification, and T-cell cytotoxicity assays.
Dental Management
Dental treatment for patients with primary immunodeficiency must
minimize the chances of local infection or bacteremia. Patients with
symptomatic B-cell abnormalities are usually given monthly therapy with
concentrated human gamma globulin that has been screened for hepatitis B
and HIV.29 Prior to instituting dental treatment, the gamma globulin level
should be checked to ensure that it is at least 200 mg/dL.When oral surgery
is necessary, an extra dose of gamma globulin should be administered the
day before surgery, in a dose usually between 100 and 200 mg/kg of body
weight.30,31 Unusual transfusion reactions occur in patients with primary
immunodeficiency and must be taken into account when using blood
replacement therapy. Patients with B-cell deficiency resulting in the absence
of particular immunoglobulins may experience severe transfusion reactions
when receiving blood from a patient who has normal immunoglobulin
levels. The immunoglobulin acts as a foreign protein and causes an allergic
response. For this reason, the patient with selective IgA deficiency must be
given IgA-depleted blood.32. A culture and sensitivity for bacteria and fungi
should be taken prior to instituting antibiotic therapy. Few dentists do this
routinely for normal patients with abscesses, but it is particularly important
for immunodeficient patients because these patients get unusual infections
with fungi and gram-negative bacteria.71

135

CONNECTIVE-TISSUE DISEASES
Connective-tissue diseases are customarily grouped together under names
such as collagen disease, collagen vascular disease, hyperimmune disease, or
autoimmune

disease.

rheumatoid

arthritis,

They

include

scleroderma

systemic

lupus

(progressive

erythematosus,

systemic

sclerosis),

dermatomyositis, and polyarteritis nodosa. Rheumatic fever is also


sometimes classified with these disorders. The term autoimmune has been
used to describe this group of diseases because autoantibodies that react with
normal tissue in vitro have been detected in significant quantities in patients
with

these

diseases.

In

connective-tissue

diseases,

the

term

immunocomplex more accurately describes the source of most of the


tissue damage although autoantibodies appear to cause some hematologic
changes. In immunocomplex disease, a nonspecific inflammatory response
results from the accumulation of antigen-antibody complexes rather than
from specific destruction by antibodies. The stimulus that causes the
formation of the abnormal antibodies that trigger the immunocomplexes is
unknown,

but

some

investigators

microorganisms are responsible.

136

believe

that

viruses

or

other

SYSTEMIC LUPUS ERYTHEMATOUS


Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease
characterized by the production of numerous autoantibodies. Organ injury is
secondary to either the direct binding of autoantibodies to self-antigens or
the deposition of immunocomplexes in vessels or tissues. It is estimated that
15% to 17% of lupus cases occur prior to the age of 16 years, 72 with the peak
incidence being in the age range of 20 to 40 years. SLE occurs ten times
more frequently in females and has a higher incidence among black people.
The autoantibodies of SLE may be directed against nucleoproteins,
erythrocytes, leukocytes, platelets, coagulation factors, and organs such as
the liver, the kidneys, or the heart. SLE therefore has a variety of clinical
manifestations.
Nomenclature (Subtypes)
Over the years, the classification of lupus has been modified to include
additional forms. Discoid lupus erythematosus (DLE) is confined to the skin
and mucosa; only approximately 10 to 20% of patients with DLE develop
systemic manifestations later in the course of the disease. The skin lesions of
DLE begin as erythematous scaling lesions with sharp borders that slowly
expand forming telangiectasias and (eventually) depigmented scars.
Follicular plugging that extends down into the skin follicles can be observed
when the scale is removed. The malar or so-called butterfly rash is common,
but does not always occur and is not pathognomonic for DLE as it is also
seen in other dermatologic diseases such as seborrheic dermatitis. Chronic
cutaneous lupus erythematosus and subacute cutaneous lupus erythematosus
are mainly dermatologic diseases that are almost always restricted to the
skin (most often the face and scalp) and to the oral mucosa. Neonatal lupus
erythematosus is most often a transient self-limited disease. Dermatologic,
137

hepatic, and hematologic involvement usually disappears at the age of about


6 months, in parallel with the decline in maternal antibodies in the neonatal
circulation. Drug-induced lupus erythematosus has many features incommon
with SLE and characteristically develops in people who have no history of
systemic rheumatic disease. By far, the drugs with the highest risk are
procainamide and hydralazine, with incidences of approximately 20% for
procainamide and 5% to 8% for hydralazine. The risk for developing lupus
like disease with other drugs is much lower, quinidine can be considered a
moderate-risk drug, whereas sulfasalazine, chlorpromazine, penicillamine,
methyldopa, carbamazepine, acebutalol, isoniazid, captopril, propylthiuracil,
and mincycline are relatively low-risk drugs.73
Etiology And Pathogenesis
The specific etiology of SLE is not known with certainty, but
immunocomplexes, autoantibodies, and genetic, infectious, environmental,
and endocrine factors play significant roles.
Genetic factors
Relatives of SLE patients have higher incidences of autoantibodies,
immunodeficiency, and connective-tissue disease. Genes that increase the
risk of SLE have been identified (specifically, HLA-DR2 and HLADR3).Genetic linkage analyses yield consistent findings for linkage of SLE
on chromosome 1.74
Infectious and Environmental Factors
Virus like particles of ribonucleic acid RNA viruses have been detected in
tissues of SLE patients and are thought by some to initiate the abnormal
immune response. Epstein-Barr virus, Cytomegalovirus, varicella-zoster
virus, and other endogenous/ exogenous retroviruses have been reported to
occur with increased frequency in patients with SLE. This association could
138

result from the intrinsic susceptibility of lupus patients to these infections, or


virus-infected individuals may simply be prone to developing lupus.
Endocrine Factors
A hormonal component to SLE is suggested by its high incidence in women
in their childbearing years, the many reports of remission during pregnancy,
and the finding of increased estrogen levels in SLE patients.
Immunocomplexes and Autoantibodies
Immunocomplexes consisting chiefly of nucleic acid and antibody account
for the majority of the tissue damage seen in SLE. These complexes set off
immunologic reactions that activate complement and attract neutrophils and
macrophages. The result is vasculitis, fibrosis, and tissue necrosis. Patients
with increased circulating immunocomplexes have more severe disease,
particularly of the kidney. Immunocomplexes also account for tissue damage
in the central nervous system, skin, and lungs. The autoantibodies in SLE
patients could be the actual pathogenic agents of tissue destruction, or they
could be the consequence of tissue damage.75 Autoantibodies are a cause of
the hemolytic anemia, thrombocytopenia, and lymphopenia seen in SLE
patients. The formation of autoantibodies is thought to be related to the
decreased functioning of suppressor T lymphocytes and hyperreactive B
lymphocytes. A unified theory that accounts for many of the findings
described above has been developed. In this theory, many factors acting
together result in SLE.An individual with a genetic predisposition develops
a chronic viral infection that releases nucleic acid antigens. Sunburn or
damage from chemicals may also contribute to antigen release. A lack of
normal suppressor T-lymphocyte function and B-lymphocyte hyperactivity
leads to the formation of autoantibodies and immunocomplexes; widespread
tissue damage results.
139

Clinical Manifestations
SLE is a disease with multiorgan involvement. Immunocomplex deposition
causes small-vessel vasculitis, which then leads to renal, cardiac,
hematologic, mucocutaneous, and central nervous system destruction. In
addition, inflammation of the serous membranes results in joint, peritoneal,
and pleuropericardial symptoms. As there is no typical pattern of
presentation, one patient may present with dermatitis and kidney disease
whereas another may present with arthritis, anemia, and pleurisy. Thus,
whenever a patient demonstrates signs and symptoms of multiorgan
involvement, SLE should be considered in the differential diagnosis,
especially for a female who is 20 to 40 years of age. The following is a brief
overview of the most frequently encountered clinical manifestations.
Renal Manifestations
Kidney involvement in the form of glomerular destruction is seen in
approximately 50% of patients. The glomerulonephritis results from the
deposition of complement and immunocomplexes in the basement
membrane of the glomerulus. Five to twenty-two percent of SLE patients
progress to end-stage renal disease and require hemodialysis or
transplantation.77 Nephrotic syndrome results from massive destruction and
is a common cause of death in SLE patients. The severity of kidney disease
is often a good indication of the overall prognosis of the patient.
Cardiac Manifestations
Accelerated atherosclerosis and valvular heart disease constitute the primary
cardiac manifestations of SLE. The most common of all cardiac lesions in
SLE patients involves the endocardium and was originally described (by
Libman and Sacks) as verrucous valvular lesions. Lupus-related valvular
pathoses can include valve leaflet thickening,with or without regurgitation.
140

Hematologic Manifestations
The primary hematologic diseases among SLE patients are leukopenia,
anemia, and thrombocytopenia. Leukopenia (< 4,000/mm3) is common and
usually reflects lymphopenia but can also be due to immunosuppressive
therapies. Anemia of chronic disease occurs in most patients during periods
of disease activity but is also often due to hemodialysis.Hemolytic anemia
occurs in a small proportion of patients with positive Coombs test results.
Thrombocytopenia (< 100,000/mm3) results from increased phagocytosis of
autoantibody-coated platelets by spleen, liver, bone marrow and lymph node
macrophages and can occur in up to 25% of patients.When antiphospholipid
antibodies or the lupus anticoagulant and anticardiolipin antibodies are
present, patients are prone to episodic thrombosis, thrombocytopenia, and
spontaneous abortion.
Mucocutaneous Manifestations
The cutaneous manifestations of SLE include photosensitive rashes,
alopecia, Raynauds phenomenon, and skin ulceration secondary to
vasculitis. Cutaneous involvement does not necessarily correlate with
increased systemic disease. The malar or butterfly rash (which affects
fewer than half of SLE patients) and the discoid rash are the two most
characteristic rashes of SLE. The malar rash is a fixed flat or raised
erythematous rash over the cheeks and bridge of the nose, often involving
the chin and ears. It is usually exacerbated by ultraviolet light. A more
diffuse maculopapular rash, mainly in sun-exposed areas, is also common.
Vasculitic skin lesions include subcutaneous nodules, ulcers, and infarcts of
skin or digits. Oral mucosal lesions can be found as annular leukoplakic
areas and/or erythematous erosions or chronic ulcerations, often resembling
lichen planus.
141

Musculoskeletal Manifestations
Arthritis and arthropathies are the primary musculoskeletal disorders
associated with SLE. Arthralgia with morning stiffness is the most common
initial manifestation of SLE.More than 75 % of SLE patients develop a true
arthritis, which is symmetrical and non-erosive and which usually involves
the hands,wrists, and knees. Deforming arthritis is uncommon in SLE
patients.
Central Nervous System Manifestations
Significant neuropsychiatric signs and symptoms are found in 10% to 20%
of patients who have SLE.78 Diffuse and focal cerebral dysfunctions
(including psychoses, seizures, and cerebrovascular accidents) in addition to
peripheral sensorimotor neuropathies, account for more than 60% of
neuropsychiatric manifestations.79 Central nervous system involvement is a
poor prognostic sign.
Diagnosis And Laboratory Evaluation
The most important diagnostic laboratory test for SLE is the test for
antinuclear antibody (ANA) in the serum, which is positive for 96% to 100%
of patients with SLE. The clinician should remember that the ANA test is
also positive in a minority of patients with scleroderma or rheumatoid
arthritis, therefore, the diagnosis must be made on the total clinical picture,
not on a single laboratory test. In addition, SLE is characterized by the
production of numerous autoantibodies, including ANAs, antinative DNA,
rheumatoid factor, antibody to Smith (Sm) antigen, antibody to Ro (SS-A)
antigen, and antibody to La (SS-B) antigen. Many of these autoantibodies
produce specific laboratory and clinical abnormalities and can also be seen
in a variety of other rheumatologic diseases. An individual with elevated
142

ANA and antinative DNA most likely has lupus. Important findings on
routine laboratory tests include anemia, thrombocytopenia, (which may
occasionally be severe enough to cause purpura), increased levels of
globulins, and a biologic false-positive result on the serologic test for
syphilis (STS). Depressed complement levels (particularly C3 and C4),are
also common.
Oral Manifestations
Patients with SLE are affected by a variety of orofacial disorders, including
characteristic oral lesions, nonspecific ulcerations, salivary gland disease,
and temporomandibular disorders. The reported incidence of these
manifestations varies considerably, depending on the criteria of the
investigators. The first report of oral manifestations of SLE in the American
dental literature was in 1931, by the dermatologist Monash, who reported a
50% incidence of oral lesions.45 More recently, Rhodus and Johnson
reported a higher incidence (81.3% to 87.5%) of various oral lesions,
including ulceration, angular cheilosis,mucositis, and glossitis. They also
reported a high incidence (75.0% to 87.5%) of signs and symptoms of oral
conditions, including glossodynia, dysgeusia, dysphagia, and dry mouth.46
The oral lesions of SLE are caused by vasculitis and appear as frank
ulceration or mucosal inflammation. Some individuals with SLE or discoid
lupus have discoid-appearing oral lesions.82 The lip lesions often have a
central atrophic and occasionally ulcerated area with small white dots,
surrounded by a keratinized border composed of small radiating white striae.
The intraoral lesions are somewhat different because of the thinner
epithelium; they are composed of a central depressed red atrophic area
surrounded by a 2 to 4 mm elevated keratotic zone that dissolves into small
white lines. The oral lesions of SLE are easily confused with the lesions of
143

lichen planus, both clinically and histologically. The World Health


Organization established criteria for the histologic diagnosis of oral SLE, but
these criteria often do not adequately distinguish lupus from lichen planus.
Karjalainen and Tomich48 compared 17 cases of SLE with 17 cases of
lichen planus and described five histologic criteria to distinguish these two
disorders by light microscopy: (1) vascularization of keratinocytes, (2)
subepithelial presence of patchy periodic acidSchiff (PAS)-positive
deposits, (3) edema in the upper lamina propria, (4) PAS-positive thickening
of blood vessel walls, and (5) severe deep or perivascular inflammatory
infiltration. Sanchez and colleagues demonstrated that the inflammatory
infiltrate in the oral lesions of SLE consists primarily of helper or inducer T
lymphocytes.47 Direct fluorescent antibody staining of biopsy specimens
has become an important aid in the diagnosis of the mucosal or skin lesions
of SLE.More than 90% of patients with either DLE or SLE have deposits of
immunoglobulin and C3 in the basement membrane zone. This lupus band
test is an excellent means of differentiating lupus lesions from lichen planus,
which is often clinically and histologically indistinguishable from other
forms of leukoplakia. Immunoglobulin deposits are detected in oral lesions
of SLE and DLE whereas those deposits are rare in lichen planus or
leukoplakia. There are a small number of cases, however, in which DLE and
lichen planus overlap. Another oral sign of SLE is xerostomia secondary to
Sjgrens syndrome.49 Xerostomia can significantly increase the occurrence
of dental caries and candidiasis, especially when patients are being treated
with steroids or immunosuppressive agents. Temporomandibular-joint
involvement commonly occurs in SLE patients sometime during the course
of their disease and may cause pain and mechanical dysfunction.

144

Treatment
With regard to the management of the oral lesions of SLE, there have been
no reports involving the treatment of a large series of patients. In general, the
oral ulcerations of SLE are transient, occurring with acute lupus flares.
Symptomatic lesions can be treated with high-potency topical corticosteroids
or intralesional steroid injections. Discoid lupus lesions on the lower lip. A
chronic palatal lesion (the initial sign of systemic lupus erythematosus in
this patient). Chronic lesion of the dorsal tongue in a patient with systemic
lupus.
Dental Consideration
Because SLE can be a widespread disease affecting many organ systems, the
dental management of an SLE patient requires a good understanding of
general medicine. The more common problems seen in SLE patients are
discussed below.
Adrenal Suppression
Patients with SLE may be taking adrenal-suppressive doses of
corticosteroids, which makes these patients susceptible to shock.
Glucocorticosteroid therapy will cause adrenal suppression that affects
adrenal function for up to 12 months, but the patients stress response will
return within 14 to 30 days. There is no need for replacement therapy for
dental treatment in patients who have not taken glucocorticosteroids during
the preceding 30 days. Patients who are receiving alternate-day therapy can
be treated on an off day without supplementation if they have been on the
alternate-day regimen for at least 2 weeks. Patients who are receiving daily
low-dose corticosteroid therapy (< 30 mg hydrocortisone equivalent) will
not need replacement therapy. Patients who are receiving daily high-dose
corticosteroid therapy (> 30 mg hydrocortisone equivalent) should be treated
145

as if they were completely adrenally suppressed and were without a normal


stress response. The dose will need to be doubled on the day of treatment.
The patients primary care physician should be consulted if the replacement
dosage is uncertain or when highly stressful procedures are to be done (eg,
general anesthesia)85
Infection
Patients who are taking cytotoxic or immunosuppressive agents are at an
increased risk of infection. Patients with an absolute neutrophil count of
between 500 and 1,000 cells/mm3 will need perioperative prophylactic
antibiotics. Although infection due to opportunistic pathogens should be
considered in patients who are on high steroid dosages (especially patients
who are on adjuvant immunosuppressive therapy), no protocol has been
established for the prophylactic use of antibiotics.
Hematologic Abnormalities
Patients with SLE can frequently develop normochromic normocytic
anemia, hemolytic anemia, leukopenia, and thrombocytopenia. The presence
of an elevated partial thromboplastin time can result from circulating
anticoagulant. Prior to any extensive dental procedures, a preoperative
complete blood count can screen for thrombocytopenia, anemia, and
leukopenia,

and

prothrombin

time/partial

thromboplastin

time

measurement can screen for a coagulopathy.


Cardiac Disease
Libman-Sacks vegetations under the mitral-valve leaflets may occur in
patients with SLE. These vegetations rarely affect function but can lead to
bacterial endocarditis. Patients with SLE and heart murmurs should have
antibiotic prophylaxis prior to dental treatment that is likely to cause
bacteremia.
146

Renal Disease
Renal disease is common in SLE patients and ranges from an asymptomatic
state to frank renal failure, therefore, the dentist should be aware of the
patients renal function (ie, creatinine clearance, serum creatinine, and blood
urea nitrogen). Patients who are undergoing hemodialysis should receive
dental treatment on nondialysis days.86
Exacerbation by Surgery
The dentist should proceed with caution in performing elective surgery or
dental procedures, especially in patients who have a history of postsurgery
lupus flares.
Exacerbation by Drug Therapy
Drugs that have been related to acute lupus flares include penicillin,
sulfonamides, and nonsteroidal anti-inflammatory drugs (NSAIDs) with
photosensitizing potential. All of these should be used judiciously.

147

SCLERODERMA
It is also called as Systemic Sclerosis or Hidebound disease. It is a
multisystem connective-tissue disease that involves hardening of the skin
and mucosa, smooth-muscle atrophy, and fibrosis of internal organs. The
prevalence of scleroderma is estimated to be about 250 per million,with
women being affected significantly more frequently than men.87 Several US
studies have suggested that black patients have a higher age-specific
incidence rate and more severe disease than have white patients.88
Nomenclature (Subtypes)
Localized scleroderma refers to scleroderma primarily involving the skin,
with minimal (if any) systemic features. Only rarely have patients with
localized scleroderma developed systemic sclerosis. Three major types of
localized scleroderma exist: morphea, generalized morphea, and linear
scleroderma. Morphea begins with violaceous skin patches that enlarge,
become indurated, and eventually lose hair and the ability to sweat. Later in
the course of the disease, the lesion burns out and appears as a hypo- or
hyperpigmented area depressed below the level of the skin.89 A small number
of patients develop numerous larger lesions that coalesce, and these
patients are said to have generalized morphea. Patients with either type of
morphea usually have a benign course characterized by the softening of the
lesions over time. Linear scleroderma is a form of the localized disease that
may develop during childhood and that usually involves the arms, legs, or
head. This form of the disease develops as a thin band of sclerosis that may
run the entire length of an extremity, involving underlying muscle, bones,
and joints.When the disease crosses a joint, limitation of motion is possible,

148

along with growth abnormalities. The lesion of linear localized scleroderma


of the head and face is called en coup de sabre, and these lesions may result
in hemiatrophy of the face. Scleroderma localized to the hands is called
acrosclerosis.
PROGRESSIVE SYSTEIC SCLEROSIS (PSS)
It is a multisystem disease characterized by the inflammation and fibrosis of
many organs. PSS occurs three to four times more frequently in females,
with its highest incidence occurring between the ages of 25 and 50 years.
There are two major subsets: limited cutaneous scleroderma (previously
called calcinosis cutis, Raynauds phenomenon, esophageal dysmotility,
sclerodactyly, and telangiectasia [CREST syndrome]) and diffuse
cutaneous scleroderma. The major difference between limited and diffuse
scleroderma is the pace of the disease. Patients with limited scleroderma
often have a long history of Raynauds phenomenon before the appearance
of other symptoms. They have skin thickening limited to hands and
frequently have problems with digital ulcers and esophageal dysmotility.
Although generally a milder form of disease than diffuse scleroderma,
limited scleroderma can have life-threatening complications. Diffuse
scleroderma patients have a more acute onset, with constitutional symptoms,
arthritis, carpal tunnel syndrome, and marked swelling of the hands and legs.
They also characteristically develop widespread skin thickening (progressing
from the fingers to the trunk) as well as internal organ involvement
(including gastrointestinal and pulmonary fibrosis) and potentially lifethreatening cardiac and renal failure. Other possible variants are an
overlapping syndrome with SLE, Sjgrens syndrome, rheumatoid arthritis,
and dermatomyositis.

149

Etiology and Pathogenesis


The etiology of PSS is unclear, but the pathogenesis is characterized by
vascular injury as well as the overproduction of normal collagen.Vascular
wall fibrosis of small and medium size arterioles is a prominent alteration in
PSS and likely plays a crucial role in the pathogenesis of pulmonary
hypertension, renal crisis, myocardial dysfunction, and digital gangrene in
this disease.55 Excessive collagen deposition in affected tissues is also a
central event in the pathogenesis of PSS and is responsible for most of the
clinical manifestations of this disease. The up-regulation of collagen gene
expression in PSS fibroblasts and the aberrant expression of cytokines that
positively or negatively influence fibroblast collagen synthesis appear to be
critical events in the development of the pathologic tissue fibrosis that is
characteristic of PSS.90 A role for environmental factors in the pathogenesis
of PSS is suggested by an increased rate of PSS and PSS-like disease
detected in individuals who are exposed to silica dust, vinyl chloride,
benzene, and tryptophan.91
Clinical Manifestations
PSS sclerosis is a chronic multisystem disorder characterized, morphea of
the face, skeletal muscles, and internal organs. The following is an overview
of frequently encountered clinical manifestations.
Raynauds Phenomenon
Raynauds phenomenon, a paroxysmal vasospasm of the fingers that results
in a change in the color of the fingertips as a response to cold or emotion, is
the most common finding of PSS.More than 95% of scleroderma patients
eventually experience the characteristic digital cyanosis and blanching that
results from intimal hyperplasia.92 Raynauds phenomenon may be nothing
150

more than a nuisance, but some patients have recurrent episodes that are
associated with digital pitting scars, nail fold infarcts, or digital ulcers.
Cutaneous Manifestation
The thickening of the skin of PSS patients always begins in the fingers.
Early skin changes, starting with pitting edema, often involve the whole
hand and the extremities. In several months, the edema is replaced by a
tightening and hardening of the skin, which results in difficulty in moving
the affected parts.Hyperpigmentation, telangiectases, and subcutaneous
calcifications may also occur, leading to deformity and severe cosmetic
problems.
Musculoskeletal Manifestations
Polyarthralgias and morning stiffness affecting both small and large joints
are frequent in patients with scleroderma. Inflammatory joint pain with
markedly swollen fingers often appears to be true synovitis and can lead to
the premature diagnosis of rheumatoid arthritis.
Gastrointestinal Manifestations
Distal esophageal motor dysfunction is the most frequent gastrointestinal
finding; it results from weakness and incoordination of esophageal smooth
muscle and leads to distal dysphagia. Intestinal fibrosis leading to severe
intestinal malabsorption can also occur.
Cardiac Manifestations
Clinical evidence of myocardial involvement in scleroderma cases is
uncommon, but such involvement is more frequent in patients with diffuse
scleroderma. The clinical presentations of cardiac involvement can include
pericarditis, conduction problems, and congestive

heart failure. Patchy

replacement of the myocardium and the conduction system by fibrous tissue


occurs in most patients.
151

Pulmonary Manifestations
Pulmonary interstitial fibrosis is now the most frequent cause of death in
patients with scleroderma since renal disease has become a treatable
complication. Patients with either limited or diffuse scleroderma can develop
interstitial disease although it tends to be more severe in patients with
diffuse scleroderma. In patients with severe fibrosis, the greatest damage
occurs during the first 5 years of illness, often when there are no pulmonary
symptoms. Pleural thickening, pleural effusions, and pneumothorax are less
frequent manifestations of lung disease in patients with scleroderma.58
Renal Manifestation
Until recently, renal involvement was the most dreaded and deadly
complication of scleroderma. The use of high-dose corticosteroids for the
treatment of scleroderma has been implicated in precipitating renal crisis in
some patients. In addition, pathologic changes due to the disease itself
typically show alterations resembling hypertensivenephrosclerosis as well as
mucinoid hyperplasia and vascular fibrinoid necrosis in the interlobar
arteries.Renal crisis is characterized by malignant hypertension, which can
rapidly progress to renal failure. The use of angiotensin-converting enzyme
inhibitors has helped to make renal disease due to scleroderma a very
treatable condition.

152

Laboratory Evaluation
ANAs are present in approximately 90% of scleroderma patients and are
characteristically antinucleolar or anticentromere antibodies. There are a few
other important ANAs that are specific for scleroderma but are not yet
commercially available. Anti-ribonucleic acid (RNA) polymerase III may be
the most common antibody found in patients with scleroderma. Other
laboratory findings include anemia, an elevated erythrocyte sedimentation
rate, and hypergammaglobulinemia.
Treatment
The treatment of PSS depends on the extent and severity of skin and organ
involvement. D-penicillamine, a drug effective for both rheumatoid arthritis
and Wilsons disease, has shown promise in the management of PSS by
decreasing both skin thickening and organ involvement. This drug has two
mechanisms of action: interference with cross-linking of collagen and
immunosuppression. Nifedipine is a calcium channel blocker that has been
shown to be effective in managing Raynauds phenomenon and myocardial
perfusion.94 Extracorporeal photochemotherapy has also shown promise in
reversing cutaneous sclerosis in patients in the early stages of PSS.95
Oral Findings
The clinical signs of scleroderma of the mouth and jaws are consistent with
findings elsewhere in the body. The lips become rigid, and the oral aperture
narrows considerably.96 Skin folds are lost around the mouth, giving a mask
like appearance to the face. The tongue can also become hard and rigid,
making speaking and swallowing difficult. Involvement of the esophagus
causes dysphagia.97 Oral telangiectasia is equally prevalent in both limited
and diffuse forms of PSS and is most commonly observed on the hard palate
and the lips.98 When the soft tissues around the temporomandibular joint are
153

affected, they restrict movement of the mandible, causing pseudoankylosis. 64


The linear form of localized scleroderma may involve the face as well as
underlying bone and teeth. Dental radiographic findings have been reported
and widely described; these classic findings (which include uniform
thickening of the periodontal membrane, especially around the posterior
teeth) are found in less than 10% of patients. Other characteristic
radiographic findings include calcinosis of the soft tissues around the
jaws.The areas of calcinosis will be detected by dental radiography and may
be misinterpreted as radiographic intrabony lesions. A thorough clinical
examination will demonstrate that the calcifications are present in the soft
tissue. When the facial tissues and muscles of mastication are extensively
involved, the pressure exerted will cause resorption of the mandible. This
resorption is particularly apparent at the angle of the mandible at the
attachment of the masseter muscle. The coronoid process, condyle, or area
of attachment of the digastric muscles may also be damaged by the continual
pressure. Patients may also have oral disease secondary to drug therapy or
xerostomia. Gingival hyperplasia can result from the use of calcium channel
blockers; pemphigus, blood dyscrasias, or lichenoid reactions may result
from penicillamine use. Salivary gland hypofunction that frequently
correlated with keratoconjunctivitis sicca occurred in 14 of 32 patients
studied by Nagy and colleagues.96 Although some such patients have
overlapping Sjgrens syndrome and have antiSS-A antibody and a lip
biopsy which shows inflammation, most simply have fibrotic glands that
cause the lack of saliva or tears.Xerostomia results in an increased
susceptibility to dental caries, Candida infections, and periodontal disease.

154

Dental Management
The most common problem in the dental treatment of scleroderma patients is
the physical limitation caused by the narrowing of the oral aperture and
rigidity of the tongue. Procedures such as molar endodontics, prosthetics,
and restorative procedures in the posterior portions of the mouth become
difficult, and the dental treatment plan may sometimes need to be altered
because of the physical problem of access. The oral opening may be
increased an average of 5 mm by stretching exercises. One particularly
effective technique is the use of an increasing number of tongue blades
between the posterior teeth to stretch the facial tissues. In addition,
mechanical devices that assist the patient in performing the stretching
exercises are available. If these approaches are insufficient, a bilateral
commissurotomy may be necessary. When treating a patient with diffuse
scleroderma, the extent of the heart, lung, or kidney involvement should be
considered, and appropriate alterations should be made before, during, and
after treatment. Patients with extensive resorption of the angle of the
mandible are at risk for developing pathologic fractures from minor trauma,
including dental extractions. Patients with Sjgrens syndrome should have
daily fluoride treatments and make frequent visits to the oral hygienist.

155

DERMATOMYOSITIS
Dermatomyositis (DM) is a rare inflammatory degenerative disease
characterized by skin lesions and progressive muscle atrophy. The disease
occurs most frequently during childhood and between the fourth and sixth
decades of life. The true incidence and prevalence are difficult to ascertain
because of the rarity of the disease and the lack of consistent diagnostic
criteria. Most studies have found a preponderance of female patients over
male patients. Skin manifestations have been identified in 30% to 40% of
adult patients and in 95% of affected children.97 DM is classified with the
connective-tissue diseases because of many overlapping clinical features and
the fact that it is frequently seen together with scleroderma, SLE, rheumatoid
arthritis, or Sjgrens syndrome.
Nomenclature (Subtypes)
The three types of idiopathic inflammatory myopathies are DM,
polymyositis (PM), and inclusion body myositis. Specific subtypes of DM or
PM can be categorized as adult idiopathic, juvenile, or amyopathic DM.
There is also a form of DM that is associated with connective-tissue disease
or malignancy.
Etiology AND Pathogenesis
The etiology of DM is unknown, but genetic, immunologic, and
environmental factors are likely to play an important role. Studies of
histocompatibility antigen prevalence have demonstrated that human
leukocyte antigens HLA-B8, HLA-B14, and HLA-DR3 are associated with
dermatomyositis, but these studies have failed to link HLA haplotype with
disease.67Immune mechanisms play a significant role in the onset of the
disease, particularly circulating immunocomplexes, cellular immunity, and
autoantibodies to skeletal-muscle myoglobin or myosin. The onset of the
156

disease has been associated with infections such as influenza, hepatitis,


coxsackie virus infection, and infection with the protozoan Toxoplasma
gondii.DM has also been linked to drug therapy and cancer.
Clinical Manifestations
DM usually begins with a symmetric and painless weakness of the proximal
muscles of the arms, legs, and trunk. The weakness is progressive and
characteristically spreads to the face, neck, larynx, pharynx, and heart.
Muscle involvement may become severe enough to confine the patient to
bed or to cause death due to failure of the respiratory muscles. The primary
classic skin lesion is a violaceous macular erythema distributed
symmetrically. As the disease progresses, the erythema may become
progressively indurated due to mucin deposition. The pathognomonic skin
manifestations, occurring in approximately 70% of patients, are Gottrons
papules, which are violaceous papules overlying the dorsal elbow, knee, or
interphalangeal or metacarpophalangeal joints. Facial changes may take on
the butterfly distribution associated with SLE or may primarily involve the
eyelids and the forehead. Other skin changes are nonspecific diffuse
erythema, erythematous plaques, macules, papules, telangiectases, and
Raynauds phenomenon. Diagnosis from skin lesions alone is rarely
possible. Noncutaneous manifestations of DM include interstitial lung
disease, cardiac conduction abnormalities, conjunctival edema, and renal
damage.
Oral Manifestations
Oral involvement is rarely a part of the disease process of DM. The most
common clinical manifestations in the head and neck include weakness of
the pharyngeal and palatal muscles, which causes difficulty in swallowing
(dysphagia) and nasal speech (dystonia). The muscles of mastication and the
157

facial muscles may also be involved, causing difficulty in chewing.


Involvement of the oral mucosa has been described, but the lesions are not
diagnostic. These lesions include shallow ulcers, erythematous patches, and
telangiectasis. More characteristic are the facial skin lesions, which may
present as a butterfly rash (similar to the lesions of SLE) or as a swelling
of the eyelids, face, or lips. Lilac-colored eyelids secondary to stasis of
blood in multiple telangiectasias is also a common finding. Calcinosis of the
soft tissues is seen, especially in children. These calcified nodules may
appear in the face and may show up on dental radographs, leading to
misinterpretation. The tongue may also become rigid due to severe
calcinosis.
Diagnosis and Laboratory Evaluation
A diagnosis of definite PM or DM is given if any four of the following
criteria are met:
1. Proximal symmetric muscle weakness, progressing
from weeks to months
2. Evidence of an inflammatory myopathy on muscle biopsy
3. Elevation of serum muscle enzymes
4. Electromyographic features of myopathy
5. Cutaneous eruption that is typical of DM
A diagnosis of probable PM or DM is given if three criteria are met, and a
diagnosis of possible PM or DM is given if two criteria are fulfilled.
Laboratory reports show evidence of muscle destruction by elevated levels
of aspartate aminotransferase (formerly called serum glutamic-oxaloacetic
transaminase), lactate dehydrogenase, alanine aminotransferase (formerly
called serum glutamic- pyruvic transaminase), and creatine phosphokinase.

158

Treatment
An underlying carcinoma should be ruled out in all cases of DM since it is
present in 10 to 25% of patients. Initial therapy consists of bed rest
combined with high doses of systemic corticosteroids. In resistant cases,
plasmapheresis or immunosuppressive drugs such as methotrexate or
azathioprine have been helpful.98
Dental Management
The disease process of DM poses no significant challenge to the dentist. The
same precautions as are necessary for all patients who are taking high-dose
long-term steroids and antimetabolites should be taken.

159

RHEUMATOID ARTHRITIS
Rheumatoid Arthritis (RA) is a disease characterized by inflammation of the
synovial membrane. Women are approximately three times more likely to be
affected than men, and 80% of people with RA develop signs and symptoms
of the disease at between 35 and 50 years of age. Epidemiologic studies
suggest that the incidence of the disease is declining in younger age groups
because of unknown environmental factors.99 Unlike degenerative joint
disease (osteoarthritis), which is localized to the joints in middle-aged and
elderly individuals, rheumatoid arthritis affects people of all age groups and
affects other organs, including muscles and the hematopoietic system.
Although this disease is called arthritis, there are frequent extra-articular
manifestations.
Nomenclature (Subtypes)
Several variations of RA exist. Feltys syndrome accounts for less than 5%
of the total cases. In addition to having the usual manifestations of RA,
patients with Feltys syndrome also have splenomegaly and leukopenia, with
neutrophils showing the greatest decrease. In severe cases, recurrent
bacterial infection is a common cause of death. Another variant is juvenile
RA (Stills disease), which is thought by some rheumatologists to be a
separate disease and not just a simple variation of adult RA. 70 Systemic
extra-articular symptoms are prominent, including fever, lymphadenopathy,
hepatosplenomegaly, carditis, and rash.Visual impairment secondary to
iridocyclitis (inflammation of the iris and ciliary body) may also occur. In
50% of patients, growth and sexual maturation are delayed during active
stages of the disease.

160

Etiology and Pathogenesis


The pathogenesis of RA is unknown, but it appears to be multifactorial,
involving genetic,immune, and infectious etiologies.
Genetic Factors
Studies of identical twins demonstrate that genetic factors play an important
role in the pathogenesis of RA. This is confirmed by the findings of the
HLA-DR4 major histocompatibility complex in up to 70% of RA patients.
Immune Factors
Most of research into the cause of RA involves studies of the immune
system. The inflammatory response that causes joint and other injury is
immune in nature. RA is believed to be a T-lymphocyte-driven disease in
which a sudden influx of T cells into the affected joint(s) is followed by an
increased number of macrophages and fibroblasts.
The initiating factor of this immune response is unknown. The evidence of
immune features in this disease includes the following:
1. The presence of rheumatoid factors (antigammaglobulin antibodies that
form soluble complexes, measured in the serum by coating latex particles
with IgG and testing the agglutinating properties of the patients serum)
in the serum and synovial fluid of affected patients
2. Extensive collections of plasma cells and lymphocytes found on
histologic examination of affected tissues
3. Decreased complement levels in the synovial fluid of affected patients
(suggests complement use during hypersensitivity reactions)
4. The overlap of RA with SLE and other diseases suspected of an immune
pathogenesis.

161

Infectious Factors
Several infectious agents (including both bacteria such as streptococci and
Mycoplasma, as well as viruses such as Epstein-Barr virus) have been
suggested to cause the initial T-cell influx.
Clinical Manifestations
The initial symptom in a majority of patients with RA is nonspecific
weakness and fatigue, which may precede joint symptoms by several
months. This is followed by symmetric polyarthritis characterized by a
complaint of stiffness and a finding of a spindle-shaped swelling of the
involved joints. The proximal interphalangeal joints of the fingers and
metacarpophalangeal joints of the hands are most commonly involved the
wrists, elbows, knees, and ankles also are frequently affected. In some
patients, all joints may be involved, including the temporomandibular joint
and the cricoarytenoid joint of the larynx. The joints that are affected with
RA become red, swollen, and warm to the touch.Muscle atrophy around the
affected

joint

is

common.

Extracapsular

manifestations

include

subcutaneous nodules (especially over pressure points), which occur in 20


to 25% of patients; enlargement of the lymph nodes and spleen; chronic skin
ulcers from a diffuse arteritis; pleural effusion; and pulmonary fibrosis.
Rheumatoid granulomas may affect the heart, the eyes, or the brain. Some
patients may have a short course of nondisabling disease whereas others
have an unrelenting downhill course of crippling and severe disability. A
fluctuating course of remissions and exacerbations is seen in many patients,
and this unpredictable course makes the choice of therapeutic regimens
difficult.

162

Oral Manifestations
The treatment of RA can cause oral manifestations. The longterm use of
methotrexate and other antirheumatic agents such as D-penicillamine and
NSAIDs can cause stomatitis. Cyclosporine may cause gingival overgrowth.
Direct effects of the disease are also seen. Patients with long-standing active
RA have an increased incidence of periodontal disease, including loss of
alveolar bone and teeth. Similarities in the host immune responses of RA
and periodontal disease, involving reduced cellular and enhanced humoral
activity, have been reported102 although the increased dental and periodontal
disease may be chiefly related to a decreased ability to maintain proper oral
hygiene. Sjgrens syndrome is a common complication of RA.
JUVENILE RHEUMATOID ARTHRITIS
It is also called as Still's disease and juvenile polyarthritis. It is defined as a
chronic synovitis with or without extraaarticular manifestations, but it is
accompanied by more systemic features than for adults.
Clinical Features
Age and sex-it occurs in children and has its peak between 1 and 3 years.
Joint involved-initial bilateral polyarthritis of both small and large joints
including the cervical spine. Signs-splenomegaly, lymphadenopathy,
leukoocytosis, pyrexia and rash.
Symptoms
Neck pain and a limited range of movement.
Restricted opening of the mouth.
TMJ involvement-one or both TMJ are involved.
Micrognathia-it may cause interference with normal condylar growth,
leading to micrognathia. This. is seen in at least 20 percent of cases.

163

Persistence leads to deterioration of jaw movement. Radiographic features


and treatment planning are same as rheumatoid arthritis.
Radiological Features
Joint space-the pannus may destroy the disc and due to this, the joint space
is reduced slightly or substantially, depending on the severity of the
condition and the length of time. There is flattening of the head of the
condyle. Erosion of the condyle can be seen. In condyle, hollowing out
appearance of the cartilage is seen.As the disease continues, the condylar
outline becomes increasingly irregular and ragged. In most severe cases,
condyle may be completely resorbed, resulting in loss of vertical support and
anterior open bite. Sharpened pencil or mouthpiece of flute appearance in
advanced stages, due to erosion of anterior and posterior condylar surface at
the attachment of the synovial lining occurs. Others features are subchondral
sclerosis and flattening of articular surface may occur with subchondral cyst
and osteophytic formation. Bone destruction which occurs in articular
eminence may be slight or confined to the posterior face or to the inferior
convexity. Most of the eminence may be destroyed in severe long continued
cases.
Radiological

progression

in

Temporomandibular Joint Disorders


Stage I - Periarticular osteoporosis
Stage II - Loss of aliicular cartilage
Stage III - Erosion
Stage IV - Subluxation and ankylosis.

164

rheumatoid

arthritis

in

Investigations
Diagnosis and Laboratory Evaluation
Rose-Waaler test is positive in 70 percent of the patients with rheumatoid
arthritis.

Antinuclear

immunofluorescence.

antibodies

are

detected

by

indirect

Analysis of synovial fluid is essential for the

immediate diagnosis of joint infection, inflammation and degenerative


disease.
The diagnosis is based on satisfying at least four of the following seven
criteria: (1) morning stiffness, (2) arthritis of three or more joint areas, (3)
arthritis of the joints of the hand, (4) symmetric arthritis, (5)rheumatoid
nodules, (6) serum rheumatoid factor, and (7) radiographic changes. The first
four criteria must be present for at least 6 weeks, and the second through
fifth must be observed by a physician. 101 Autoantibodies (such as ANA and
rheumatoid factor) are respectively found in 30% to 60% and 72% to 85% of
adult patients.However, these autoantibodies are not specific to RA and are
found in patients who have a number of other conditions, such as SLE and
scleroderma. Rheumatoid factor, particularly in high titers, adds weight to
the diagnosis of RA and is associated with more destructive disease and a
worse prognosis. Other associated laboratory findings include an elevated
erythrocyte sedimentation rate and normochromic normocytic anemia. Some
tests may be helpful in excluding RA by indicating an alternative diagnosis.
For example, antibodies to DNA would indicate SLE whereas anti-Ro (SSA) or anti-La.
Management
Adequate rest to the joint, soft diet is advocated. Treatment should be given
for suppression of the active process, preservation of function and
165

prevention of deformities.Local injection of long acting steroids such as


methyl prednisolone acetate (20-80 mg for large joint and 4 to 10 mg for
small joint) or triamcinolone hexaacetomide (10-40 mg for large joint and 2
to 6 mg for small joint) are given. Nonsteroidal antiinflammatory drugs are
used these drugs are inhibitory to prostaglandins, these are used for
symptomatic relief. Salicylates (for pain) and antiiinflammatory agents like
phenyl butazone indomethacin, ibuprofen, diclofenac, and piroxicam can be
used. Immunomodulator like azathioprine is found to be effective in both,
high and low doses. Slow acting antirheumatic drugs, these are the
antimalarials like hydroxyl chloroquine sulfate, sulphasalazine (500 mg/day)
and methotrexate (O-penicillamine and parenteral gold). Local treatment it is
done with heat, diathermy, jaw exercise or a mouth stretcher. Muscle
strengthening exercise and hydrotherapy is used in some patients. Medical
synovectomy, synovial obliteration is achieved with osmic acid or variety of
radiocolloids, if pain is present even after injection of steroids. Erbium
acetate is used for small joints, while yttrium silicate is used for large joints.
Surgical synovectomy accounts for removal of synovial membrane which is
responsible for enzymatic destruction of cartilage
Complications
Ankylosis, subluxation, secondary arthritis, muscular atrophy and bird like
face can occur.

166

ANGIODEMA
It is also called as Angioneuratic edema, Quinckes edema, Giant cell
urticaria) it is a diffuse edematous swelling of soft tissue commonly
involving the subcutaneous and submucosal connective tissue.Angiodema
may be hereditary, acquired or idiopathic in nature.
Heridetery angiodema: It is a rare autosomal dominnat genetic disorder
due to a C1 esterase inhibtor defect this leads to an unimpeded complement
response in inflammation, causing oedema due to stress , allergy or trauma.
Acquired angiodema: It can rise due to abnormal antibodies against C1
esterase inhibtor, or more commonly as a reaction to drugs such as
angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory
drugs, food additives or latex rubber. Because of potential seriousness of
condition, patients require urgent management with airway maintenance to
treat the acute attack. Patients should then be refferd to a specialist. Those
with heridetery angiodema can be treated prophylactically with stanzol or
fresh frozen plasma (containing C1 esterase inhibtor), and those with
acquired angiodema require avoidance advice and the availability of self
administered steroids, adrenaline or antihistamines.
Clinical features
Clinically, there is a recurrent non-itchy oedema commonly affecting the
face,tongue,pharynx and larynx. This can lead to respiratory embarrassment,
and in severe cases, death. Angiodema manifests as a soft, nontender, diffuse
edematous swelling of relatively rapid onst, which may be solitary or
multiple, most commonly involving the face around the lips,tongue, pharynx
167

and larynx. Eyes may be swollen shut and lips extremely puffy. The skin
may be normal color or slightly pink. A feeling of tenseness or an itching or
prickly sensation sometimes precedes the swelling. In heridetery form
patients become symptomatic at second decade of life and this form is more
dangerous due to involvement of respiratory and gastrointestinal symptoms.
Treatment
When the etiological factor such as food can be discovered its elimination
from diet will prevent recurrent attacks. Antihistaminic drugs should be
administered. If the attack is not controlled or if laryngeal involvement is
present intramuscular epinephrine is given.

168

COLOR PLATE-12

Angiodema swelling of lower lip

Periocular angiodema

169

OROFACIAL GRANULOMATOSIS
Orofacial granulomatosis also can be called as orofacial lymphoedema.Signs
and symptoms are lip swelling, facial swelling, angular chelitis, mucosal
tags cobblestoning ulceration, apthae, full thickness gingivitis and palatal
hyperplasia. The lip and facial swelling is permanent but may increase or
decrease dramatically in response to exposure to allergens. When the lip
swelling worsens, tissues become more turgid due to oedema in the tissues,
and the lip swelling becomes exaggerated. There is almost always an
associated bilateral angular chelitis which improves with steroid therapy.
The intraoral buccal cobblestoning and mucosal tagging is also the result of
intence lymphoedema. The ulceration may be typically apthous in nature,
especially if there is concururrent nutrition deficiency (which is common, for
example, in intestinal crohns disease, or there may be deep intransigent
ulceration which persists indefinitely without healing. The full thickness
gingivitis and less commonly hyperplastic palatal inflammation, is due to
granulomatous inflammation, and is particularly severe in the mixed
dentition phase. Soft tissue swellings occasionally arise due to areas of
nonspecific infection, and may cause severe pain. The condition affects
individual of all ages but is particularly prevalent in children and
adolescents, when the emotional sequelae of facial deformities are
particularly severe.
Diagnosis
The diagnosis is clinically obvious, but biopsy is confirmatory. Biopsy must
be deep if non-caseating granulomas are not to be missed. Other histological
infilteration and intercellular oedema. Tuberculosis should be excluded. A
170

number of other investigation are needed for successful management of


orofacial lymphoedema. These include careful history of gastrointestinal
symptoms, an any one with intestinal symptoms such as pain, rectal bleeding
or diarrhoea should be investigated by gastroenterologist to exclude
intestinal disease. In children, leucocyte labeling is a non-invasive method of
assessing gastrointestinal inflammation. Angiotensin-converting enzyme
levels are raised in sarcoidosis, and so this is also useful screening test in
addition to chest radiography.As alluded to above, the central abnormality
appears to be granuloma formation in orofacial tissues which interfere with
proper lymphatic drainage. When food allergy is superimposed on this
problem, the condition becomes clinically obvious. About 85% of patients
with orofacial lyphoedema who are patch tested will show a reaction to
benzoates(E additives) or cinnamon aldehyde, as compared to 25%of
controls without orofacial lymphoedema.
Treatment
Dietary manipulation, if this is successfully implemented, will cause
significant improvement in many cases. Strict oral hygiene measures are
also important and empirical therapy with erythromycin for 3 months is
occasionally helpful. Steroid therapy, either intestinal or systemic, is
sometimes required to control the clinical features.

171

NUTRITIONAL DEFFICIENCY
Introduction
Development of Nutrient Deficiencies
Malnutrition and Periodontal Diseases
Oral Manifestations of Nutrient Deficiencies
Angular Stomatitis and Cheilosis
Altered Taste
Xerostomia
Changes in Tongue
Systemic Diseases Associated with Oral Manifestations and Nutrient
Deficiencies
BERI-BERI
PELLAGRA
SCURVY
RICKETS
OSTEOMALACIA

Patients with nutritional deficiency are common in the developing world but
are rarely seen elsewhere. Those most liable to be affected in the west are
the elderly, food cranks and alchohlics living on grossly unbalanced diet, or
patients with malabsorption. The relationship between nutrition and oral
health is multifaceted. Nutrition has both local and systemic impacts on the
oral cavity . While diet and eating patterns have a local effect on the teeth,
172

saliva and soft tissues, the systemic impact of nutrition also has considerable
implications and it too merits assessment as a component of comprehensive
care. The systemic effect is the impact of the nutrients consumed as they
assume their biological functions in relation to the development and
maintenance of the extra- and intra-oral structures and secretions . An
adequate supply of nutrients is essential to the growth, development, and
maintenance of tissues, effectiveness of the immune system, prevention of
cell damage and, in general, to increased resistance to many chronic, and
some infectious diseases . The oral cavity is often one of the first sites where
nutrient deficiencies can be clinically noted. Clinical manifestations of
nutrient deficiencies can have a significant impact on the function of the oral
cavity. Functional properties of the oral cavity include taste, salivation,
mastication, and swallowing food. Any alterations in the structure and
function of the oral cavity may compromise intake and contribute to the
development of a nutrient-deficiency state. When the associated oral
structures are affected, these alterations may be compounded even further,
leading to subsequent inadequate dietary intake and compromised nutrition
status.
Development of Nutrient Deficiencies
Nutrient deficiencies result from an imbalance of supply and demand, that
is, when the supply of nutrients is inadequate to meet the demands of the
body . The imbalance may result from one of three primary causes:
inadequate intake, impaired digestion and absorption, or increased losses. A
deficiency of any one nutrient may in turn contribute to subsequent
deficiencies of other nutrients. Clinical manifestations of deficiencies occur
once tissue stores are depleted. They may present as symptoms reported by
173

patients as well as by physical observations notable on examination.


Extraoral manifestations include alterations in appearance and integrity of
the skin, while intra-oral manifestations may be reflected in altered integrity
and appearance of the teeth, soft tissue, and tongue. Left untreated,
deficiency symptoms may progress to deficiency diseases. Different Oral
Cavity Area will exibit different clinical manifestations due to different
nutrition deficiencies. On Face region there will be Malar pigmentation,
Bitemporal wasting, Nasolabial seborrhea, Edema, Lack of color due to
Protein-energy Malnutrition, Niacin, riboflavin,B6, Iron deficiency. On Lips
Cheilosis Angular fissures due to riboflavin, Niacin, B 6 ,riboflavin, iron.
Gingiva

becomes Spongy, bleeding gums, abnormal redness due to

defficiency of vitamin C. Tongue will show symptoms of glossitis (red, raw,


fissured) due to folate niacin iron b 6 and b12 defficiencies. It will appear pale
atrophic smooth and slick( filliform papillary atrophy) due to iron and folate
defficiency and the tongue will appear magenta color due to riboflavin
deficiency.
Once a negative nutritional imbalance has occurred, depletion of tissue
levels and body stores occur. This is evidenced by depleted serum levels of
nutrients and/or altered response to diagnostic tests. Serum levels may not
always reflect nutrient stores. Once body stores are depleted, biologic and
physiologic performance and cell functions of those cells dependent on the
specific nutrient become altered. Following altered biologic and physiologic
performance, clinical manifestations typically appear in the development of
a deficiency. Once clinical symptoms become apparent, morbidity and
mortality rise. Careful review of the medical history and presenting
symptoms with physical examination is critical to detecting deficiency
conditions and possible etiologies. Illness and infection can increase nutrient
174

needs and thereby contribute to a deficiency. Bacterial and fungal infections


in the oral cavity may alter tissue integrity, increase nutrient utilization, and
compromise intake. The end result is twofold, with increased needs and
decreased dietary intake. Inflammatory bowel disease may cause
deficiencies of water soluble vitamins including B6, B12, folate, trace
elements, calcium, zinc, and magnesium due to altered digestion and
absorption. Inadequate intake may be due to functional difficulties such as
poor dentition, tooth loss, ill-fitting dentures, xerostomia, and systemic
disease, as well as psychosocial problems including lack of income,
homelessness, depression, and anorexia. A prolonged poor dietary intake due
to ill-fitting dentures and difficulties with mastication has been
shown to result in inadequate intake of zinc, calcium, and B6.

Malnutrition and Periodontal Diseases


Periodontal diseases, a group of infectious diseases which are mostly
chronic, affect the supporting tissues of the teeth. Compromised host defense
responses associated with malnutrition may make the periodontium more
susceptible to infectious organisms that are a normal component
of the oral flora. The acute phase protein response to tissue injury is
impaired to varying degrees in malnourished individuals. During periods of
malnutrition, the magnitude of the inflammatory response is limited,
resulting in an impaired host response. This could result in a greater amount
of periodontal destruction, leading to a compromised dentition. Along with
dental and/or pharmacological treatment of the underlying local etiologic
factors, nutritional management goals focus on provision of adequate
calories, protein and nutrients to promote tissue repair, restoration of the host
175

defense mechanisms, and overall well being. Controversy exists regarding


the relationship between nutrition status and periodontal disease . It is
important to note that although some nutritional deficiencies (notably
vitamin C and folate) can alter the disease process, periodontal diseases are
not caused by these deficiencies nor can they be cured by nutrient
supplementation alone. Gingivitis, a form of periodontal disease, refers to
inflammation of the soft tissue component of the periodontium. There are
multiple causes of gingivitis including: chronic diseases such as diabetes;
medications including phenytoin and calcium channel blockers; pregnancy;
and nutrient deficiencies. Spongy, red, bleeding and painful gingiva are also
noted in scurvy, an advanced vitamin C deficiency disease. In severe
gingivitis, the easy bleeding and soreness of the gingiva may make eating
difficult and contribute to poor intake. Soft, nonirritating, temperate and
mildly flavored foods and fluids should be provided to meet energy and
nutrient needs. Historically, vitamin A deficiency was cited as a cause of
periodontal disease. Clinical manifestations folate deficiency, however, may
include gingivitis.
Oral Manifestations of Nutrient Deficiencies
While nutrient deficiencies may contribute to abnormal color, topography,
size and sensations in the oral cavity, other causes of abnormal findings such
as glossodynia and glossopyrosis (painful and burning tongue and soft
tissue), dysgeusia (altered taste), angular cheilitis (painful, dry cracked
corners of the mouth), and changes in appearance and texture of the tongue
must also be evaluated. Abnormal findings may reflect oral manifestations
of a myriad of systemic diseases, medications, disorders unique to the oral
cavity, or a nutrient deficiency. Three possible categories of etiologies
176

include: oral manifestations of a nutrient deficiency, oral manifestations of a


systemic disease that impacts on diet and nutrition status, and local oral
disorders that interfere with dietary intake.

Angular Stomatitis and Cheilosis


Angular stomatitis (painful fissures at the corners of the mouth) and
cheilosis (dry scaling of the lips and corners of the mouth) are common
findings in riboflavin deficiency. Similar findings may be noted with niacin
and B6 deficiency states. The similarity of these findings may be due to
riboflavins role in B6 and tryptophan (which is converted to niacin)
metabolism. Angular stomatitis, however, may be associated with iron
deficiency anemia. Angular cheilitis, however, is often associated with
fungal infections, lip-sucking, and dehydration. Treatment must focus on
correcting the deficiency state and providing adequate energy, protein, fluids
and nutrients to promote healing. When angular cheilitis is due to
opportunistic infections brought on by decreased resistance secondary to
nutrient deficiencies, treatment should focus on antifungal therapy,
correction of the nutrient deficiency, and diet modification to make eating a
more comfortable experience. Temperate, non-spicy foods and fluids should
be used to avoid further irritation to the lips and mouth. At least 68 cups of
fluid per day should be encouraged. Individuals with angular stomatitis or
cheilosis may experience difficulty and pain when they try to open their
mouths wide to laugh or eat. They will lick their lips repeatedly with their
tongues to moisten them, a habit that should be discouraged to prevent
further irritation and infection.

177

Changes in the Tongue


There are several changes that can occur on the tongue during nutrient
deficiency states. A painful, magenta colored, atrophic, smooth tongue is
noted during a riboflavin deficiency. Glossitis may also be evidence of a
vitamin B6, folate or B12 deficiency. However, during a chronic folate
deficiency, the tongue papillae will become atrophied, resulting in a shiny,
smooth surface appearance. Glossitis with loss of filiform papillae may also
be seen in individuals with iron-deficiency anemia. A niacin deficiency
results in a raw beefy, bright red, swollen, and painful tongue. Glossodynia
may also be present in diabetes, resulting in painful mastication and
swallowing. Medical nutrition management focuses on correcting the cause
of the deficiency, provision of adequate calories, protein and nutrients for
healing, and a nonirritating diet consisting of liquids and soft solid foods
moderate in temperature and mild in taste.
Altered Taste
Hypogeusia, or diminished taste, is noted in zinc deficiency. Other nondeficiency state causes of altered taste include radiation to the head and
neck, diabetes mellitus, and Sjgrens syndrome. Taste tests should be
conducted to determine which taste sensations remain. Diets should be
tailored to highlight the remaining taste sensations and limit those foods or
flavorings which are offensive. Dysgeusia refers to altered taste, which may
also affect appetite and intake.
Xerostomia
Xerostomia is rarely due to a nutrient deficiency. It may be seen in severe
vitamin A deficiency states and in protein calorie malnutrition. The primary
178

causes of xerostomia include medications, Sjgrens syndrome, diabetes


mellitus, and radiation to the head and neck. Altered taste sensations are
frequently reported by individuals with xerostomia. Artificial salivas may be
used. However, they may also contribute to altered taste. Inadequate salivary
flow can also contribute to oral infections, including dental caries and
glossopyrosis. Moist, non-spicy foods and temperate fluids should be
provided; fluids are particularly important at mealtime. Individuals with
xerostomia should be encouraged to use tart or citrus flavored sugar-free
gums and candies to increase salivary flow. Oral hygiene is very important
to reduce risk of dental caries, particularly following meals and snacks.
Systemic Diseases Associated with Oral Manifestations and Nutrient
Deficiencies are
-Beri-beri
-Pellagra
-Scurvy
-Osteomalacia

179

BERI-BERI
A prolonged gross deficiency of vitamin B1 i.e. thiamine causes beriberi.
There are three types of beriberi
-Wet beriberi
-Dry beriberi
-Infantile beriberi
Other diseases, which can be associated with it, are
- Wernicke's encephalopathy
-Peripheral neuritis
-Korsakoff's psychosis.
Wet beriberi
It is marked by cardiac dilation with four chamber enlargement, pallor and
flabbiness of myocardium.
Etiology
It is caused due to eating diets in which calories are derived from polished
rice. It is commonly seen in chronic alcoholics due to their poor nutrition in
general and also because alcohol interferes with intestinal absorption of
thiamine. It is often precipitated by infection, pregnancy and lactation.
Pathogenesis
Deficiency of thiamine will cause incomplete metabolism of glucose and
accumulation of pyruvic acid and lactic acid in tissue and body fluid which
leads to dilation of peripheral blood vessels and fluid may leak out through
capillaries, producing edema and high cardiac output.
Clinical features
There is pain in legs after walking due to accumulation of lactic acid. There
is tachycardia and increased blood pressure, cardiomegaly and palpitations.
There is also presence of sinus tachycardia and inverted T waves. Skin is
180

warm due to vasodilation. Edema may develop rapidly to involve leg, face
and trunk.
DRY BERI BERI
Clinical features
It is a peripheral neuropathy. In long-standing cases, there is degeneration
and demyelination of both sensory and motor nerve fibers resulting in severe
wasting of muscles. Blood pyruvate levels are normal.
Oral manifestations
There is hypersensitivity of oral mucosa. Pain in the tongue, teeth, jaws and
face.
Management
Complete rest. Thiamine 50 mg IM for 3 days then 10 mg 3 times daily by
oral route. Infantile beriberi is treated via mother's milk. Mothers should
receive 10,000 mcg twice daily. In addition, infants should be given
thiamine in doses of 10,000 to 20,000 mcg IM once in a day for 3days.
Wernicke's Encephalopathy
It is commonly seen in alcoholics with persistent vomiting.
There is a classical triad of ocular abnormalities, ataxia and confusion. There
are facial symmetrical areas of grayish discoloration. There is also bilateral
symmetrical ophthalmoplegia and ataxia. Histologically, there is
hypertrophy and hyperplasia of small blood vessels. Injection of thiamine
should be given 50 mg by slow intravenous injection followed by 50 mg
daily by oral route for a week.
Korsakoff's Psychosis
In it there is a predominant abnormality in mental function which is memory
defect. There is profound impairment of memory recall and new learning
ability.
181

Pellagra
Causes of pellagra are tryptophan deficiency,if insufficient tryptophan is
available for synthesis of niacin. Dietary deficiency of niacin. High dietary
levels of amino acid lucine antagonize the synthesis of NAD and
NADP(Nicotinamine Adenine Dinucleoide Phosphate). Chronic alcoholism,
diarrhoea and carcinoid syndrome can also cause pellagra.
Clinical features
It can be developed in 3 weeks with prodromal symptoms of loss of appetite,
vague gastrointestinal disturbances and numbness or burning in various
locations. It is called as disease of 3-Ds
-Dermatitis
-Diarrhea
-Dementia.
There is an erythema on skin resembling severe sunburns which appears
symmetrically overall parts of the body exposed to sunlight and especially
on the neck. Affected area is well demarcated from the normal. In acute
cases, skin lesions may produce vesiculation, cracking, exudation, crusting
with ulceration and secondary infection. In chronic cases, dermatitis occurs
as roughening and thickening of skin with brown pigmentation.
Alimentary tract is also affected it causes anorexia, nausea, dysphagia and
glossitis that precedes the skin lesions. Noninfective inflammation may
extend through the gastrointestinal tract. Diarrhea is caused by atrophy of
gastric epithelium followed by submucosal inflammation which is then
followed by ulceration.

182

Delirium is the most common mental disturbance in the acute form and
dementia in chronic cases. There is also loss of appetite, irritability and
burning sensation in different areas of the body.
Oral manifestations
Entire oral mucosa becomes fiery red and painful and salivation is profuse.
The epithelium of the entire tongue is desquamated. The filiform papillae are
most sensitive and disappear first, the fungiform papillae may become
enlarged. The tongue becomes red swollen and beefy and in animals the
deficiency leads to black tongue. In early stages, only the tip and margins of
the tongue are swollen and red. In advanced cases, the tongue losses all the
papillae and the reddening becomes intense.
In this stage, the tongue becomes so swollen that indentation from the teeth
are found along the borders of the tongue. The mouth is sore and shows
angular stomatitis, cheilitis. Tenderness, pain and ulceration begin at the
interdental papillae and spreads rapidly. Superimposed ANUG or Vincent's
infection involving the gingiva, tongue and mucosa is common.
Management
Niacin 10 mg or 10,000 mg per day. Vitamin B complex should be given and
if alcoholic patient should be adviced to stop the habit.

183

Scurvy
Prolonged deficiency of vitamin C may result in scurvy. It is characterized
by weakened blood vessels particularly micro vessels having least muscular
supports, defective synthesis of osteoid which is derivative of collagen and
impaired wound healing.
Pathogenesis
There is defective formation of collagen in connective tissues because of
failure of hydroxylation of proline to hydroxyproline which is a
characteristic amino acid of collagen. There is also increase permeability of
capillary (hemorrhage), anemia due to erythropoiesis and defective collagen
formation.
Clinical features
In infantile scurvy there is lassitude, anorexia, painful limbs and
enlargement of costochondral junction. Hair follicle rises above skin and
there are perifollicular hemorrhages, i.e. tiny points of bleeding occurring
around the orifice of hair follicles with heaping of keratin like material.
Hemorrhage may occur in the joint, into nerve sheath under the nails or
conjunctiva. Petechial hemorrhage occurs in buttocks, abdomen, legs, arms,
ankle and nail beds. Scorbutic child usually assumes a frog like position and
this may reflect as subperiosteal hemorrhage. Epistaxis, anemia and delayed
wound healing are common features. Edema of the limbs and face is a
frequent finding in severe ascorbic acid deficiency. It may lead to premature
aging, thyroid insufficiency and lower resistance to all infections.

184

Oral manifestations
It occurs chiefly involves gingiva and periodontal region. Interdental and
marginal gingiva is bright red, swollen, smooth with shiny surface producing
an appearance known as scurvy bud. In fully developed scurvy, the gingiva
becomes boggy, ulcerated and bleeds easily. Color of gingiva changes to
violaceous red. Typical fetid breath of the patient with fusospirochetal
stomatitis. In severe cases, hemorrhage and swelling of periodontal ligament
membrane occurs followed by loss of bone and loosening of teeth which are
exfoliated.
Histopathological features
Osteoblasts fail to form osteoid and cartilage cells of epiphyseal plate
continue to proliferate in normal fashion and salts are deposited in the matrix
between the columns of cartilage cells. The calcified matrix material is not
destroyed so the wide zone of calcified but nonossified matrix, called the
scorbutic lattice develops in the metaphysie.As the lattice increases in width
a more and more fragile zone develops, so that eventually complete fracture
of the spicule occurs with separation and deformity of the cartilage shaft
joint.
Laboratory features
Anemia in scurvy is mild to moderate but may be severe.It is usually
normocytic, normochromic, associated with leucopenia,
thrombocytopenia,reticulocytosis and normoblastic hyperplasia of the bone
marrow.
Management
Vitamin C 250mg three times daily can be given .

185

COLOR PLATE-13

NIACIN DEFFICIENCY,
loss of papillae and swollen red tongue

SCURVY,severe gingival eroison

186

Vitamin D Deficient Rickets


The word 'rickets' refers to any disorder in vitamin D calcium phosphorous
axis which results in hypomineralised bone matrix that is failure of
endochondral calcification. It develops in an area where sunlight is deficient.
It results from inadequate extracellular level of calcium and inorganic
phosphate, mineral necessary for new bone to calcify. Osteoid builds in
excessive amounts because it fails to mineralize properly. Rickets occur in
infants and children and osteomalacia common in adults.
Pathogenesis
There is overgrowth of epiphyseal cartilage due to inadequate provisional
calcification and failure of cartilage cells to form a matrix and disintegrates.
There is persistence of distorted, irregular masses of cartilage many of which
projects into the marrow cavity. Deposition of osteoid matrix on
inadequately mineralized cartilaginous remnants.Disruption of the orderly
replacement of cartilage by osteoid matrix with enlargement and lateral
expansion of osteochondral junctions. There is abnormal growth of
capillaries and fibroblasts in the disorganized zone because of microfracture
and stresses on inadequately mineralized, weak, poorly formed bone.
Deforming of skeleton due to loss of structural rigidity of the developing
bone.

187

Clinical features
It occurs in infants and children. In the first 6 month of life, tetany,
convulsions are common manifestations due to hypocalcemia. The wrist and
ankles are typically swollen and the changes in bone are found in the
epiphyseal plates, metaphysis and the shaft. Localized area of thinning are
sometimes present in the skull, so that a finger can produce indentation. This
condition is called as 'craniotabes'. There is softening of posterior part of
the parietal bone, which may be first sign of the disease. Patients have a
short stature and deformed extremities. Children with rickets show bowing
of legs. Excess of osteoid produces frontal bossing and squared .appearance
to the head. Deformation of chest results from over growth cartilage or
osteoid tissue at the costochondrial junction producing 'rickety rosary'.
The weakened metaphyseal areas of the ribs are subject to pull of the
respiratory muscles and thus bend inwards creating anterior protrusion of the
sternum resulting in a pigeon breast deformity. The inward pull at the
margins of diaphragm creates Harrison's grooves, girdling the thoracic
cavity at the lower margin of the rib cage. When an ambulatory child
develops rickets, deformities are likely to affect the spine, pelvis and long
bones causing 'lumbar lordosis'.
Oral manifestations
Developmental abnormalities of dentin and enamel, delayed eruption and
malalignment of teeth.There is higher caries index in rickets as compared to
normal. There may be hypoplasia of enamel and enamel may be mottled,
yellow gray in color. There are large pulp chamber, high pulp horns and
delayed closure of root apices. The osteoid is so soft that teeth are displaced
leading to malocclusion of the teeth .

188

Radiographic features
The earliest and prominent manifestation is widening and fraying of
epiphysis of the long bones. Bowing is a characteristic deformity seen in the
weight bearing areas, fine trabeculae are reduced in number. Green stick
fractures will be noted in many cases in children.A thinning of jaw cortical
structure such as the inferior mandibular canal, the lamina dura and the
follicular walls of developing teeth has been described in rickets. The
trabeculae become reduced in number. In severe cases, jaws appear
completely radiolucent, so that teeth appear to be suspended in air.
If the disease occurs before 3 years of age, enamel hypoplasia is fairly
common. The pulp cavities of deciduous teeth are grossly enlarged.
The dentin is reduced to a thin margin separating the pulp cavity from
enamel and cementum. The density of existing dentin appears to be normal
and margins of pulp cavities are well and sharply defined. There is
narrowing of the periodontal ligament space.

Osteomalacia
It is also known as adult rickets and only flat bones and diaphyses of long
bones are affected. It is most commonly seen in postmenopausal females
with a history of low dietary calcium intake and little exposure to UV light.
Clinical features
It is seen in adults and pelvic deformities are commonly seen in females.
Remodeling of bone occur in the absence of adequate calcium resulting in
softening and distortion of the skeleton.The majority of patients have bone
pain and muscle weakness of varying severity. There is increased tendency

189

towards fracture, peculiar waddling or penguin gait. Tetany and green stick
bone fractures are also seen in some cases.
Oral manifestations
There is incidence of severe periodontitis in some cases of osteomalacia.

Radiographic features
A poorly calcified ribbon like zone extending into bone at approximately
right angles to the periosteal margin. They are partial or complete fracture
without displacement in which callus has been formed but there is no
calcium available to be deposited, thus healing process is not complete and
fracture remains apparent radioographically. It is also called as Looser's
zone. Osteoid tissue is formed in the defect but there is no calcium available
to be deposited in the osteoid. Pseudofracture of the jaws near the angle has
also been noted. Individual bony trabeculae may be sparse and unusually
coarse in intraoral periapical radiograph. The lamina dura may be thin or
absent in long-standing and severe cases of osteomalacia.
Biochemical changes
Elevation of serum alkaline phosphatase to three or more times its normal
levels. Serum phosphorus is low due to increased phosphorus excretion in
response to reduction of serum calcium. Serum calcium levels are usually on
the lower side.
Management of rickets and osteomalacia
Dietary enrichment of vitamin D in the form of milk. If tetany is present,
calcium gluconate IV Daily dose between 1000-2000 IU of vitamin D
190

combined with 500-1000 mg of calcium is given. Hormonal therapy like


f1ucytosin can be given . Curative treatment includes 2000 to 4000 IU of
calcium daily for 6 to 12 weeks followed by a daily maintenance dose of
2000 to 4000 IU for a prolonged period. Patients with osteomalacia due to
intestinal malabsorption require a larger dose of vitamin D and calcium, i.e.
40,000 to 1, 00,000 IU of vitamin D and 15 to 20 gm of calcium lactate per
day.
Hence,the comprehensive management of patients with systemic diseases
requires a coordinated team approach of the physician, dentist, registered
dietitian and other health professionals. Medical, dental and nutritional
management of the disease and associated sequelae are essential to
maximize disease management and minimize the often harmful side effects
of disease. Medical management should include reinforcement of medical
nutrition therapy and oral hygiene. Medical and dental professionals should
screen and identify patients at nutrition risk and refer patients to a physician
for comprehensive medical nutrition therapy.

191

RENAL DISORDERS
RENAL FAILURE
Acute Renal Failure
Chronic Renal Failure
Clinical Features
Oral Manifestations
Radiographic Features
Laboratory Diagnosis
RENAL FAILURE
Classification of renal failure is based on two criteria
The onset (acute versus chronic failure) and the location that precipitates
nephron destruction (prerenal, renal or instrinsic, and postrenal failure).
Chronic renal failure is a slow, irreversible, and progressive process that
occurs over a period of years whereas acute renal failure develops over a
period of days or weeks. The distinction between acute and chronic disease
is important, acute disease is usually reversible if managed appropriately
whereas chronic renal failure is a progressive and irreversible process that
leads to death in the absence of medical intervention.
ACUTE RENAL FAILURE
Acute renal failure (ARF) is a clinical syndrome characterized by a rapid
decline in kidney function over a period of days to weeks, leading to severe
azotemia (the building up of nitrogenous waste products in the blood).
Medications, surgery, pregnancy-related complications, and trauma are the
most common causes of ARF.

192

CHRONIC RENAL FAILURE


Chronic renal failure (CRF) can be caused by many diseases that devastate
the nephron mass of the kidneys. Most of these conditions involve diffuse
bilateral destruction of the renal parenchyma. Some renal conditions affect
the glomerulus (glomerulonephritis), others involve the renal tubules
(polycystic kidney disease or pyelonephritis), while others interfere with
blood perfusion to the renal parenchyma (nephrosclerosis).
Clinical Features
Respiratory Symptoms
Kussmauls respirations (the deep sighing breathing seen in response to
metabolic acidosis) is seen with uremia. Initially, however, dyspnea on
exertion is a more frequent and often overlooked complaint in patients with
progressing disease. The other respiratory complications, pneumonitis and
uremic lung, result from pulmonary edema associated with fluid and
sodium retention and/or congestive heart failure.
Immunologic Changes
The significant morbidity experienced by patients with renal failure can be
attributed to their altered host defenses.Uremic patients appear to be in a
state of reduced immunocapacity, the cause of which is thought to be a
combination of uremic toxemia and ensuing protein and caloric malnutrition
compounded

by

protein-restricted

diets.

Uremic

plasma

contains

nondialyzable factors that suppress lymphocyte responses that are


manifested at the cellular and humoral levels, such as granulocyte
dysfunction, suppressed cell-mediated immunity, and diminished ability to
produce antibodies.103 In addition, impaired or disrupted mucocutaneous
barriers decrease protection from environmental pathogens.Together, these
193

impairments place uremic patients at a high risk of infection, which is a


common cause of morbidity and mortality.
Myopathy
Muscle cramps are more common, RESTLESS LEG SYNDROME, where
patients legs jump at night.
Neuropathy
Sensory neuropathy will occur that cause paresthesia.autonomic neuropathy
may cause delayed gastric emptying, diarrhea and postral hypotension.
CVS Efects
Hypertension results in 80% of patients. This is due to sodium retention and
increased secretion of rennin, angiotensin-I and aldosterone.
Other effects invove gradual softening and bowing of bones and acidosis.

Oral Manifestations
With impaired renal function, a decreased GFR, and the accumulation and
retention of various products of renal failure, the oral cavity may show a
variety of changes as the body progresses through an azotemic to a uremic
state. In studies of renal patients, up to 90% were found to have oral
symptoms of uremia. Some of the presenting signs are an ammonia-like taste
and smell, stomatitis, gingivitis, decreased salivary flow, xerostomia, and
parotitis. As renal failure develops, one of the early symptoms may be
a bad taste and odor in the mouth, particularly in the morning. This uremic
fetor, an ammoniacal odor, is typical of any uremic patient and is caused by
the high concentration of urea in the saliva and its subsequent breakdown to
ammonia. Salivary urea levels correlate well with the BUN levels, but no
fixed linear relationship exists.An acute rise in the BUN level may result in
uremic stomatitis, characterized by red mucosa covered with a thick exudate
194

COLOR PLATE-14

UREMIA,erthmatous
pseudomembranous uremic stomatitis

195

and a pseudomembrane or as an ulcerative form characterized by frank


ulcerations with redness. In all reported cases, intraoral changes have been
related to BUN levels > 150 mg/dL and disappear spontaneously when
medical treatment results in a lowered Blood Urea Nitrogen level. Although
its exact cause is uncertain, uremic stomatitis can be regarded as a chemical
burn or as a general loss of tissue resistance and inability to withstand
normal and traumatic influences.White plaques called uremic frost and
occasionally found on the skin can rarely be found intraorally. This uremic
frost results
from residual urea crystals left on the epithelial surfaces after perspiration
evaporates or as a result of decreased salivary flow.A more common oral
finding is significant xerostomia, probably caused by a combination of direct
involvement of the salivary glands, chemical inflammation, dehydration, and
mouth breathing (Kussmauls respiration). Salivary adenitis can occasionally
be seen.Another finding associated with increased salivary urea nitrogen,
particularly in children, is a low caries activity. This is observed despite a
high sugar intake and poor oral hygiene, suggesting an increased
neutralizing capacity of the urea arising from ureal hydrolysis. With the
increased

availability

and

improved

techniques

of

dialysis

and

transplantation, many of the oral manifestations of uremia and renal failure


are less commonly observed.
Other oral manifestations of renal disease are related to
Renal Osteodystrophy (RO). These manifestations usually become evident
late in the course of the disease. The classic signs of RO in the mandible and
maxilla are bone demineralization, loss of trabeculation, ground-glass
appearance, total or partial loss of lamina dura, giant cell lesions or brown
tumors, and metastatic calcification. These changes appear most frequently
196

in the mandibular molar region superior to the mandibular canal.


Hypocalcemia

occurs

due

to

impaired

calcium

absorption

and

hyperphosphatemia due to reduction in renal phophorus secrtion.


Hypocalcemia results in secondary hyperparathyroidisum with increasd
level of parathyroid harmone.

Radiographic manifestations
Demineralization of bone is seen, loss of bony trabeculation which leads to
Ground-glass appearance. There is loss of lamina dura. Socket sclerosis,
pulpal narrowing and calcification. Giant cell lesions,brown tumors are seen
these are radiolucent lesions of hyperparathyroid harmone are calledbrown
tumors because they contain areas of old hemorrhage and appear brown on
clinical inspection. Arterial and oral calcifications is also evident .
Laboratory Investigations
Serum Chemistry

In the presence of renal dysfunction, changes in homeostasis are reflected in


serum chemistry. Sodium, chloride, blood urea nitrogen (BUN), glucose,
creatinine, carbon dioxide, potassium, phosphate, and calcium levels provide
a useful tool to evaluate the degree of renal impairment and disease
progression. Serum creatinine and BUN are often important markers
to the GFR.
Normal Glomerular filtration rate is 100150 mL/min and level in symptomatic renal
failure is < 610 mL/min
Normal Blood urea nitrogen is 818 mg/dL and in renal failure is > 50 mg/dL
Normal Serum calcium 8.510.5 mg/dL in renal failure cases it is Depressed

197

Creatinine Clearance Test


The glomerular filtration rate assesses the amount of functioning renal tissue
and can be calculated indirectly by the endogenous creatinine clearance test.
Creatinine is a breakdown product of muscle, liberated from muscle tissue
and excreted from the urine at a constant rate. This results in a steady plasma
concentration of 0.7 to 1.5 mg/dL (often slightly higher in men because of
increased muscle mass). Creatinine is 100% filtered by the glomerulus and is
not reabsorbed by the tubule. The creatinine clearance test is performed by
collecting a 24-hour urine specimen and a blood sample in the same 24-hour
period. In chronic renal failure and in some forms of acute disease, the GFR
is decreased below the normal range of 100 to 150 mL/min.
Renal ultrasonography
Following the intravenous (IV) injection of a contrast Ultrasonography of
the kidneys finds its usefulness in the enhanced ability to distinguish solid
tumors from fluid-filled cysts. This diagnostic procedure uses high
frequency sound waves (ultrasound) directed at the kidneys to produce
reflected waves or echoes from tissues of varying densities, thereby forming
images (sonograms).
Biopsy
The development and growing use of renal biopsy has considerably
advanced the knowledge of the natural history of kidney diseases.
Management
Plasma calcium and potassium are kept as near as normal. Hypocalcemia is
corrected

by

giving

hydroxylated

synthetic

analogue

of

vit-D.

hyperphophatemia is caused by dietery restriction of foods with high


phosphate content like milk, cheese, eggs and use of phosphate binding
drugs.

198

INFECTIOUS DISEASES
BACTERIAL INFECTIONS
Tuberculosis
Leprosy
Tularemia
Tetanus
NOMA
VIRAL and FUNGAL INFECTIONS
Herpes simplex
Herpangioma
Chicken pox
Herpes zoster
Mumps
Actinomycosis
Mucoromycosis

TUBERCULOSIS
TB is the most common cause of death from a single microbial agent.TB is
responsible for almost 1 in 4 preventable deaths in the world.The World
Health Organization estimates that worldwide there are approximately 20
million active TB cases. Approximately 3 million people die each year from
TB, with 80% of this total occurring in developing countries.

199

ETIOLOGY AND PATHOGENESIS


The genus Mycobacterium contains a variety of species, ranging from
human pathogens to relatively harmless organisms. As the major cause of
TB, a chronic communicable disease, M. tuberculosis is by far the most
historically prominent member of this group of bacteria. In addition to their
very slow growth on special enriched media, these aerobic slender rods are
characterized by their acid-fast staining feature. The unusually high lipid
content of the cell wall confers the organisms with an ability to strongly
retain a red dye (carbolfuchsin) after treatment with an acid-alcohol solution.
This unique structure also allows the bacteria to survive outside a hosts
body, suspended in airborne microdroplet nuclei for extended periods
of time. The overwhelming majority of primary human infections involve
inhalation of mycobacteria-laden respiratory microdroplets. 104,105 The
diameter of these aerosolized droplets ranges from 1 to 5 microns. Dispersal
of M. tuberculosis occurs via these droplets as a result of coughing,
sneezing, or even speaking. Microdroplet nuclei are small enough to bypass
protective host bronchial mucocilliary defenses, leading to mycobacteria
subsequently replica The organisms oxygen requirement predisposes the
lungs as primary infection sites, with the potential for subsequent
dissemination to other tissues. Onset of clinical disease is characterized by
gradual

infiltration

of

neutrophils,

macrophages,

and

lymphocytes.Distinctive granulomatous TB lesions called tubercles may


appear anywhere in the lung parenchyma however, they are most evident in
the periphery . Because TB is the prototype microbial infection for inducing
protective cellular immunity, the immunocompetence of the affected host
plays a significant role in controlling the extent and severity of resultant
disease.15,16 It is important to remember that most people infected with M.
200

tuberculosis develop a positive type IV hypersensitive skin test reaction


when challenged but do not progress to clinical disease. For those infected
individuals who develop clinical symptoms, fatigue, malaise, weight loss,
night sweats, and fever are most commonly noted in addition to positive
chest radiograph manifestations. Pulmonary manifestations most frequently
are chest pain, bloody sputum, and the presence of a prolonged productive
cough of greater than 3 weeks duration. Initial mycobacterial infection may
progress to several different states depending on the extent of M.
tuberculosis exposure and resistance of the patient. These include (1)
asymptomatic primary tuberculosis, (2) symptomatic primary tuberculosis,
(3) progressive primary tuberculosis, and (4) reactivation tuberculosis. The
ability of an infected individual to develop dual cellular and humoral
immune responses against M. tuberculosis antigens thus greatly influences
disease onset and progression.
Asymptomatic Primary Tuberculosis: Individuals may be infected with
M. tuberculosis without apparent clinical manifestations. When skin tested,
individuals with asymptomatic primary tuberculosis display a positive
tuberculin reaction indicating that they have been infected and have
developed cell-mediated immunity against the bacteria.
Symptomatic Primary Tuberculosis: In symptomatic primary tuberculosis,
M. tuberculosis is spread via the lymphatics to cause granulomatous
inflammation in both the lung periphery and hilar nodes, and it is
accompanied by respiratory symptoms. The Ghon complex, a remnant of
this infection, most often occurs in infants and children and is comprised of
small calcified lung nodules and lymphadenopathy of the hilar lymph nodes.
Progressive Primary Tuberculosis: A much more serious disease may
develop in those individuals who are less resistant to tubercle bacilli. In
201

these patients, microorganisms may spread throughout the body either (1) by
means of the blood, resulting in miliary tuberculosis,(2) via the respiratory
tissues, inducing a bronchopneumonia,or (3) through the gastrointestinal
tract as a result of the organisms being coughed up. In miliary tuberculosis,
foci of infection occur in distant organs and tissues but most frequently
develop in the meninges, lungs, liver, and renal cortex.
Reactivation Tuberculosis: Reactivation tuberculosis occurs in individuals
who have developed primary tuberculosis and who are asymptomatic, but
who still carry the bacteria within tubercles. These patients exhibit positive
tuberculin skin tests and thus demonstrate cellular immunity.Infection is
characterized by tubercle formation, caseation, fibrosis, and further
extension of the lesion.

Clinical Features
Patient may suffer episodes of fever and chills, easy fatigability and malaise.
There may be gradual loss of weight accommpanied by persistent cough
with or without hemoptysis. Local symptoms depend upon the tissue or
organs involved. Tubercular lymphadenitis may progress to acute abscess or
remain as granulomatous lesion. In any case, swelling of neck is present
which is tender, painful and often show inflammation of the overlying skin.
When abscess forms, it perforates and discharges pus.
Pulmonary tuberculosis
A persistence cough, hemoptysis abundant sputum is usual features of
pulmonary tubercuulosis. There is also evening rise in temperature of 0.5 to
2Fand night sweats. Scrofula is grandular form of disease resulting in
marked enrgement of the cervical lymph nodes with caseation and frequent
breakdown of the gland. Such tuberculosis infection is called as 'scrofula'

202

.The chronicity of the infection and the lack of marked pain or acute
inflammatory symptoms have resulted in the term 'cold abscess'.
They are relatively uncommon and seen in middle and older age groups. As
cleansing action of saliva and its antibacterial properties, in general, also
provide protection against tubrcle bacilli. Tongue is most commonly affected
followed by palate, lips, buccal mucosa and gingiva.Majority of oral lesions
are secondary to infection in some other parts of body.
Oral Manifestations
Oral manifestations of tuberculosis occur in approximately 3% of cases
involving long-standing pulmonary and/or systemic infection. 106,107 The
bacteria can infect oral tissues and lymph nodes (scrofula).Within the oral
cavity, lesions can occur in the soft tissues and supporting bone and in tooth
extraction sites, and may even affect the tongue and floor of the mouth
When reviewing this information, it becomes apparent that progression of
infection with tubercle bacilli to more severe disseminated stages occurs in
the absence of adequate cellular immunity to infection. Thus, the ability of
an infected individual to develop a dual immune response against M.
tuberculosis antigens greatly influences disease onset and progression. These
crucial protective responses are (1) acquired immunity to infection and (2)
development of tuberculin hypersensitivity.
Ulcer
The lesion may be preceded by an opalescent vesicle or nodule. A result of
caseation necrosis. It breaks down into an ulcer which is usually superficial
or deep and painful. It tends to increased slowly in size. In area of trauma
may be mistaken as traumatic ulcer or carcinoma. Ulcers are nonspecific in
their clinical presentation and for this reason they are overlooked by the
203

COLOR PLATE-15

PATHOGENESIS OF TUBERCULOSIS

MONTOUX TEST

TUBERCULOUS ULCER ON TONGUE


(painless irregular with thin undermined borders)

204

clinician Two main types of oral tuberculosis infection occur-one is primary


and other is secondary.
Primary lesion: It develops when bacteria are directly inoculated in the oral
tissue of a person who has not acquired immunity to the disease. It involves
gingiva, tooth extraction socket and buccal fold.
Secondary lesion: Infection is carried in by hematogenous route or through
break in the tissue surface, is deposited in the submucosa, subsequently
proliferates and ulcerates the overlying mucosa. It occurs more frequently in
cases of extrapulmonary tuberculosis. The typical tuberculosis lesion is an
irregular lesion with ragged undermined edges, minimum induration and
often with yellowish granular base. The mucosa surrounding the ulcer is
inflamed and edematous.
Sentinel tubercle: Tiny, single and multiple nodules called 'sentinel tubercle'
may also be seen surrounding the ulcer.
Mucocutaneous junction: At the mucocutaneous junction, tubercular ulcers
are usually extremely shallow with granulating base. Crusting and oozing is
seen when the lesion involves adjacent cutaneous surface. They are usually
painful.
Nodular form: The nodular form of tuberculosis presents as single or
multiple nodules of variable sizes, which initially may appear a
semitransparent lesion of pinhead size.
Miliary tubercle: Miliary tubercle of oral mucosa are occasionally seen in
miliary tuberculosis which is a result of acute dissemination of the infection
through hematogenous and lymphatic channel. The oral lesion appears as
small, gray tubercle with the tendency to break down and ulcerate.
Periapical tissue: Tubercle involvement of the periapical tissue and tooth
socket have been reported. The socket may be filled with so called
205

tuberculosis granulation tissue, consisting of many small, pink and red


elevations.
Tuberculosis gingivitis: Tuberculosis gingivitis is an unusual form which
may appear as diffuse, hyperemic or nodular papillary proliferation.
Jaw involvement: It may involve maxilla or mandible.
Diagnosis
MANTOUX TEST (Tuberculin skin test): this test is done by intradermal
injection of 0.1ml of tuberculoprotien, PPD profied protein derivative. It is
positive if induration is seen after 48-72hrs.Maximum diameter of the
induration measured by palpation and not redness. More then 15mm or
ulceration strongly positive more then 10mm positive and less then 5mm
negative .A diagnosis of infection with M. tuberculosis relies on (1)
development of a positive delayed hypersensitivity (tuberculin) skin reaction
to purified protein derivative (PPD), a mycobacterial antigen isolated from
bacterial cultures, and (2) demonstration of acid-fast mycobacteria in clinical
specimens. Information obtained while collecting a patients medical history
can provide evidence for suspicion of TB.
Chemotherapy for Tuberculosis
Combination therapy: usually 34 drugs to prevent resistance, chosen from
the following: isoniazid, rifampin, ethambutol, rifabutin, streptomycin,
pyrazinamide Prolonged therapy6 mon minimum indicated for slow
growth rate of bacteria,and increasing incidence of Mycobacterium
tuberculosis drug resistance.

206

Tuberculosis Vaccines
Bacille Calmette-Gurin (BCG), an attenuated strain of Mycobacterium
bovis, has been used for more than 80 years to protect humans against TB.
0.05 ml BCG vaccine is given intradermally to new born at the time of birth
at oter upper left arm or shoulder120.

LEPROSY (Hansen's Disease)


Leprosy is a chronic granulomatous infection caused by an acid-fast
bacillus, Mycobacterium leprae. The disease is only slightly contagious.
Although rare in the United States, it reaches endemic proportions in some
parts of the world.
Clinical Features
The most recent standarized classification of leprosy is that of Ridley and
Jopling, who have divided the disease into two polarized categories,
tuberculoid leprosy (TT) and lepromatous leprosy (LL) with three
intermediate groups: borderline tuberculoid (BT), borderline leprosy (BB)
and borderline lepromatous (BL).
The tuberculoid lesions are characterized by single or multiple macular,
erythematous eruptions, with dermal nerve and peripheral nerve trunk
involvement resulting in loss of sensation. The lepromatous lesions develop
early erythematous macules or papules that subsequently lead to progressive
thickening of the skin and the characteristic nodules. These may develop in
considerable numbers on any skin area and produce severe disfigurement.
Facial

paralysis

occurs

with

some

207

frequency

due

to

nerve

involvement.Although the disease is a crippling and disfiguring one, it runs


a chronic course and seldom causes sudden death.

Oral Manifestations
The oral lesions that have been reported have generally consisted of small
tumor-like masses called lepromas, which develop on the tongue, lips or
hard palate. These nodules show a tendency to break down and ulcerate.
Gingival hyperplasia with loossening of the teeth has also been described,
but Reichart and his associates found that most of the gingival and
periodontal changes occurring in a group of 30 leprosy patients were
nonspecific. Skeletal changes involving face are rhinomaxillary changes
termed facies leprosa consists of atrophy of anterior nasal spine, atrophy and
recession of maxillary alveolar process confined to incisor region and
endonasal inflammation. Collapse of nose saddle nose is also seen.
Loss of lateral portion of eyebrow is common. Much latter, the skin of face
and forehead become thickened and corrugated (Leonine facies) and ear
lobe becomes pedunculous, nasal stiffness, epistaxis, hoarseness of voice is
seen
Histologic Features
The typical granulomatous nodule shows collection of epitheloid cells and
lymphocytes in a fibrous stroma. Langerhans type giant cells are variably
present. Vacuolated macrophages called lepra cells are scattered throughout
the lesions and often contain bacilli.

208

COLOR PLATE-16

LEPROSY, nodular infiltrate on


right buccal mucosa and commisure

209

Treatment
Specific

long

term

chemotherapy

is

initiated

upon

diagnosis.

Dapsone(100mg once daily) is effective choice of drug. If patient develops


resistance to this drug then newer drugs such as clofazamine, rifampicin,
prothionamide are used in combination to treat this disease.

NOMA
It is also called as Cancrum oris, gangrenous stomatitis. It is rapidly
spreading gangrene of oral and facial tissues occurring usually in debilitated
or nutritionally deficient person. Predisposing Factors are persons who are
undernourished. debilitated from infections such as diphtheria, dysentery,
measles, pneumonia, scarlet fever, syphilis, tuberculosis and blood
dyscrasias. It originates as a specific infection by Vincent's organisms.
Miscellaneous factors such as leukemia, sickle cell trait, stress and
chemotherapeutic agents can cause noma.
Clinical Features
It is seen chiefly in children, but can be found in adults in certain conditions
like in malnourished states. Common sites are areas of stagnation around
fixed bridge or crown. The commencement of gangrene is denoted by
blackening of skin. Small ulcers of gingival mucosa spread rapidly and
involve the sorrounding tissues of jaws, lips and cheeks by gangrenous
necrosis. Foul odour is present. Patients have high temperature during the
course of the disease, suffer secondary infection and may die from toxemia
or pneumonia.
Overlying skin is inflamed, edematous and finely necrotic which results in
formation of line of demarcation between healthy and dead tissue. In
advanced stage, there is blue black discoloration of the skin. As gangrenous
210

process advances, slough appears and soon separated, leaving a perforating


wound in the involved area. In jaw large masses may be sloughed out
leaving the jaws exposed.

Management
Parenteral fluid should be given urgently to correct dehydration and
electrolyte balance. Blood transfusion helps in improving the clinical state of
the patient, who is usually anemic and toxic. The specific drug of choice is
penicillin although sulphonamides also yield good results. Reconstructive
surgery is necessary to lead near normal life.

NOMA, destructive
necrosis of oral and facial structures

211

SCARLET FEVER
Predominately occurs in children during winter months, caused by infection
with group-A streptococci of beta hemolytic type that elaborate erythrogenic
toxins.
Clinical Features
Incubation period is of 3 to 5 days. The desquamation of skin begins around
the middle of the second week after the onset. Patient exhibits severe
pharyngitis and tonsillitis, chills, fever and vomiting. Throat becomes highly
erythematous and exudation is common. There may be enlargement and
tenderness of regional lymph nodes.
Skin becomes bright scarlet to dusky red, skin rash may appear on the
second or third day of the illness. After 3 to 4 days, the rash fades. This rash
is due to toxic injury to the vascular endothelium which produces dilation of
the small blood vessels and consequent hyperemia.
Oral Manifestations
Stomatitis scarlatina accounts for the chief oral manifestation of scarlet
fever. Mucosa of palate may appear congested and throat is often fiery red.
Face, especially the temples and cheeks are flushed and red, but pale area of
circumoral pallor is often seen around the mouth. Tonsil and faucial pillars
are usually swollen and sometimes covered with grayish exudate.
Strawberry tongue exhibits white coating and fungiform papillae are
edematous and hyperemic, projecting above the surface as small red knobs
and it is called as 'strawberry tongue'.
Coating of tongue is soon lost, beginning at the tip and lateral margins and
the organ becomes deep red, glistening and smooth, except for swollen

212

hyperemic papilla. The tongue in this phase is called as 'raspberry tongue'.


Oral mucosa is uniformly congested and the breath is fetid. In severe cases
of scarlet fever, ulceration of buccal mucosa and palate have been reported.
In some cases hypoplasia of teeth is seen in permanent teeth, if conditions
occur at the time of tooth developments.
Complications
Localized or generalized bacterial dissemination or hypersensitivity reaction
to the bacterial toxins.Peritonsillar abscess, rhinitis, sinusitis, otitis media
and mastoiditis.Meningitis, pneumonia, glomerulonephritis, rheumatic fever
and arthritis can occur.Oral complications include cancrum oris, ulceration
with

perforation

of

palate.Osteomyelitis

and

involvement

of

the

temporomandibular joint can also take place.


Laboratory Diagnosis
Swab culture of oropharynx disclose the presence of hemolytic streptococci
and antistreptolysin-O titer is elevated.
Management
Antibiotics-Penicillin is the drug of choice, since group A streptococci are
generally, highly sensitive to this antibiotics. The species are also sensitive
to other antibiotics like erythromycin, tetracycline and chloramphenicol.

DIPTHERIA
It is an acute contagious disease caused by gram +ve bacillus
Corynebacterium diphtheriae, also called as klebs loeffler bacillus.
Transmission
It is transmitted by droplet infection or direct contact.
213

Pathogenesis
The portal of entry is the upper respiratory tract and rarely skin, genitalia,
eye and middle ear. The bacilli settle on the mucous membrane or upper
respiratory tract and lead to inflammation and necrosis of mucosal cells. The
infection may spread to adjacent areas. In the primary invasive region, it
forms a thick, firm, leathery, blue white pseudomembrane composed of
bacteria, necrotic epithelium, macrophages and fibrin. A narrrow zone of
inflammation surrounding the area is seen.When the diphtheria bacteria
multiply in the local tissues, they produce powerful exotoxins. This exotoxin
diffuses through the body through a hematogenous route. Heart, muscle,
kidney, peripheral nerves and adrenal glands are thus involved. Death may
be caused by heart failure, airway obstruction which is caused by edema or
by the effect of toxin.
Clinical Features
It occurs most frequently in children, during the fall and winter months
Listlessness, malaise, headache, fever and occasional vomiting.
Within a short time, patient complains of sore throat. Mild redness and
edema of pharynx with cervical lymphadenopathy. There may be swelling of
the neck, called as bull neck. Nasal regurgitation of liquids during drinking.
Larynx is edematous and is covered by pseudomembrane.There is
generalized polyneuritis with weakness, paresthesia may follow in the next
10 to 14 days.
Oral Manifestations
There is formation of patchy 'diphtheritic membrane' which begins on tonsils
and enlarges, becoming confluent over the surface. It is thick and grayish in
color. It tends to adhere and leave a raw bleeding surface on removal. Soft
palate shows temporary paralyses usually during 3rd and 5th weeks ofthe
214

disease. The paralysis usually disappears in a few weeks or few months, at


the most.
Prevention
The disease may be prevented by prophylactic active immunization with
0.5ml DPT (Diphtheria-Tetanus-Pertusis) given IM at 6,10,14 weeks of age
at outer mid thigh in infants and oter upper arm in older.120
Complications
The common complications are myocarditis, polyneuritis, acute intestinal
nephritis
Management
The patient should be isolated and bed rest is very essential. It is treated with
diphtheria antitoxin. Mild cases treated with 10,000 to 20,000 units of
antitoxin.
Moderate cases with 20,000 to 40,000 units and severe cases with 50,000 to
100,000 units of antitoxin. Along with antitoxin antibiotics like penicillin
and erythromycin should be given.

215

TULAREMIA
It is caused by gram-negative bacillus Francisella tularensis. It is contacted
through infected rabbits, muskrats, ground squirrels and other wild germ,
particularly of rodent family.
Types
-Cutaneous
-Ophthalmic
-Pleuropulmonary
-Oral
-Abdominal
Clinical Features
Incubation period is up to seven days. Patient usually suffers a sudden
headache, nausea, bony pain, profuse sweat, vomiting, chills and fever.
A single cut or sore on the skin develops into a suppurative ulcer.
Lymph nodes become swollen and painful and the lymph nodes are
remarkably enlarged.Eyes are also involved with conjunctivitis developing
through localization of disease in the conjunctival sac.
Complications
Tularemic pneumonia and pleuritis are complications of this disease.
Oral Manifestations
Primary infection of the mouth usually occurs from eating infected meat.
It is common on soft palate, tongue gingiva and angle of mouth.
It is usually accompanied by severe pain. Ulcer is shallow with whitish
fibrinous pseudomembrane, but may extend more deeply with superinfection
of Vincent's organism. Generalized stomatitis may develop. Single nodular
masses eventually develops into abscess. The tonsil, posterior pharyngeal
wall, soft palate, base of the tongue and buccal mucosa may be covered by a
216

grayish white membrane simulating the appearance of diphtheria. Regional


lymphadenitis may arise in submaxillary and the cervical groups of nodes.
Cervical lymph nodes are tender, enlarged and may suppurate.
Laboratory Diagnosis
Agglutination test is used to demonstrate a rising titer of antibody in the
serum of patients of F. tularensis. Intradermal injection of an extract of F
tularensis gives a positive delayed hypersensitivity reaction in 1st or 2nd
week of illness.
Management
Antibiotics of choice are streptomycin and tetracycline, either alone or in
combination.
TETANUS
It is also called as lock jaw. It is a disease of nervous system characterized
by intense activity of motor neurons and resulting in severe muscle spasm. It
is caused by anaerobic gram-positive bacillus Clostridium tetani, which acts
at the synapse of the interneurons of inhibitory pathways and motor neurons
to produce blockade of spinal inhibition.
Transmission
It can enter the body through even the most trivial injury. It is often reported
amongst intravenous drug abusers. It is transmitted through contaminated
soil dust or wood splinters. Carious teeth may rarely act as port of entry for
the organism. Infection of the cut surface of umbilical cord or circumcision
wound. Due to use of unclean instruments or dressing, may result in tetanus
of the newborn which is called as tetanus neonatorum.

217

Types
Local tetanus
Cephalic form
Generalized form
Neonatal tetanus
Chronic tetanus
Clinical Features
It is more common in young males during their accident prone years.
Local tetanus
It is characterized by muscle spasm near the site of entry of bacilli. In some
cases it may proceed to generalized form. Mortality rate is less than 1
percent in this form.
Cephalic form
In some cases bacilli are introduced through the wounds in the head and
neck region. Cranial nerve palsy occurs with cranial nerve, most commonly
the 7th cranial nerve.
Generalized form
Pain and stiffness in jaw, neck muscles with muscle rigidity producing
trismus and dysphagia. Rigidity of facial muscles may also occur producing
the typical risus sardonicus. Sometimes, entire body may be affected with
contraction of all groups of somatic muscles leading to characteristic
opisthotonos. Reflex spasm frequently develops after stimuli. Acute trismus
may stimulate acute oral infection, trauma, temporomandibular dysfunction
and even hysteria. The temperature is usually raised due to increase
metabolic rate. When spasm of intercostal pharyngeal and diaphragmatic
muscle occurs adequate ventilation becomes impossible and the resultant
anoxia causes death. Death in patients with tetanus is generally related to
218

pulmonary complications including bronchopneumonia and pulmonary


embolism.
Neonatal tetanus
The incubation period of neonatal tetanus is 3 to 10 days. It has high fatality
rate. The disease is characterized by difficulty in suckling and excessive
crying in early stage. As the disease progresses, variable degree of muscular
spasm develops. Death is usually due to inadequate ventilation and asphyxia.
Chronic tetanus
Cause of it is due to the persistence of focus of infection and fibrosis from
inadequately controllled spasms. It may persist for many years. Clinically,
there are features of generalized tetanus to intermittent spasm of individual
muscles.
Management
Antimicrobial drugs, active and passive immunization, surgical wound care
and anticonvulsants. Neutralizing the toxin is achieved by administered of
human

tetanus

immunoglobulin.

1,000,000

units

of

penicillin

intravenously, every 6 hours, for 10 days must be administered to kill


vegetative form of Clostridium tetani. Sedation of patient should be done
with diazepam. Supportive care includes providing proper nutrition. Specific
therapy includes immediate intravenous injection of immune serum
containing 20,000 IU of antitoxin.

Vaccination
Tetanus toxoid(TT) vaccine is administered every 10 years and as early as
possible in pregnancy 0.5ml IM at upper arm region.120
219

VIRAL INFECTIONS
Herpes simplex
Herpangioma
Chicken pox
Herpes zoster
Mumps

HERPES SIMPLEX INFECTION


All herpes viruses contain DNA nucleus which can remain latent in host
neural cells, thereby evading host immune response. HHV-6 is a newly
discovered virus and can infect T4-lymphocytes and is a possible factor in
HIV infection. It is the most common viral disease affecting men.
Epidemiology
HSV I-Infections above the waist is caused by HSV I.
HSV II-Infections below the waist is caused by HSV II.
Both HSV I and II can be transmitted sexually.
Occur in early childhood.
Preschool period is more prone due to frequent exchange of salivary and
nasal secretions.
Primary Herpes Simplex Infection
It is also called as acute herpetic gingivo-stomatitis, herpes labialis, fever
blister,cold sore and infectious stomatitis. It occurs in patients with no prior
infection with HSV-I. HSV reaches nerve ganglion supplying the affected
area, presumably along nerve pathways and remains latent until reactivated.

220

The usual ganglion involved is the trigeminal for HSV-l and lumbosacral, for
HSV-2.
Transmission
It occurs during close personal contact.
Primary infection of newborn is believed to be caused by vaginal secretions
during birth, which results in viremia and disseminated infection of brain,
liver, adrenals and lungs.
Dentist may experience primary lesion of fingers from contact with lesions
of the mouth or saliva of the patients who are asymptomatic carriers of HSV,
called as herpetic whitlow.
Clinical Features
Incubation period is 5 to 7 days, but may range from 2 to 12 days. It
develops in both, children and young adults. Prodromal symptoms precede
local lesion by 1 to 2 days and it includes fever, headache, malaise, nausea,
vomiting and within a few days, mouth becomes painful. There is also
irritability, pain upon swallowing and regional lymphadenopathy. Small
vesicles, which are thin walled, surrounded by inflammatory base are
formed. They quickly rupture leaving small, shallow, oval shaped discrete
ulcers. The base of the ulcer is covered with grayish white or yellow plaque.
The margins of the sloughed lesions are uneven and are accentuated by
bright red rimmed, well demarcated, inflammatory halos. The individual
ulcer differs in size from 2 to 6 mm. As the disease progresses several
lesions may coalesce, forming larger, irregular lesions. Lips in severe cases,
excoriation involving the lips may become hemorrhagic and matted with
serosanguinous fibrin like exudate and parting of the lips during mastication
and speech, may become extremely painful and difficult.Acute marginal
gingivitis, entire gingiva is edematous and swollen and small gingival ulcers
221

are

seen.

Posterior

pharynx

reveals

inflammation,

cervical

and

submandibular lymphadenopathy is also seen. Lesions begin healing in a


week to 10 days and leave no scar.
Nonvenereal, acute ulcerative herpetic gingivostomatitis in children
An acute febrile episode with sore mouth and refusal of food intake occurs
in ulcerative gingivostomatitis. It is self limiting infection. Disseminated
skin infection is rare. Spread occurs to genital areas from mouth by infected
oral secretions transferred on hands. Recurrence occurs by latent virus
infection of sensory ganglion of nerve that supplies each area involved in the
original infection.
Primary herpes simplex gingivostomatitis and pharyngitis among high
school and college students
Accounts for 40 percent of acute pharyngitis in college students. Kissing,
petting and developing actual sexual contact accounts for it. Patients with
HIV pharyngitis may have associated cervical lymphadenopathy and
constitutional symptoms.
Primary herpes simplex infection of oropharynx in older patients
Seen in patients who do not acquire HSV infection and immunity during
childhood. In such cases, primary herpes simplex infection is often acquire
via new sexual partner and primary HSV gingivostomatitis and pharyngitis
can occur. It occurs usually due to HSV I.
Herpetic genitalis-Caused by HSV-II common in uterine cervix, vagina,
vulva and penis. It develops 3 to 6 days after exposure as vesicular lesions
that are often preceded by burning and pricking sensation. Lesions may
occur on penis, vulva, perianal areas or anus. Lesions are more likely to
occur on vascular, well keratinized areas such as shaft of penis but may pass,
more or less rapidly, into superficial erosions that are very painful when
222

touched or contaminated with urine. Urethra may be involved and extremely


painful

dysuria

may

develop,

espeecially

in

women.

Regional

lymphadenopathy, fever, malaise and anorexia may develop.


Genital herpes in HlV patients
The lesion of genital herpes in immunocompromised patients and HIV
infected patients are larger, deeper and are likely to persist and release virus
for periods as long as 30 days. Antibodies to the virus develop 4 to 6 weeks
after primary infection.
Herpetic meningoencephalitis
Serious form characterized by sudden fever and symptoms of increased
intracranial pressure. Paralysis of various muscle groups with convulsion
and even death may ensue.
Herpetic conjunctivitis
Swelling and congestion of palpebral conjunctiva, keratitis and corneal
ulceration.Recurrent lesions can lead to serious corneal scarring, which may
produce blindness.
Herpetic eczema (Kaposi variceliform eruption)
It is epidermal form of herpetic infections superimposed upon a pre-existing
eczema and is characterized by diffuse vesicular lesions of skin. The patient
usually exhibits a high fever coincident with typical umbilicated vesicles as
well as other systemic manifestation.
Disseminated herpes simplex infection of newborn
It is uncommon and they acquired it during passage through the birth canal
of mother suffering from herpetic vulvovaginitis. The newborns exhibit a
wide variety of signs and symptoms of the disease and with few exceptions,
die on the ninth or twelfth day of life.

223

Histopathological Features
Intraepithelial blisters filled with fluid. Intranuclear inclusions, Lipschutz
bodies which are eosinophilic, civoid, homogenous structure within the
nucleus, tend to displace the nucleolus and nuclear chromatin peripherally.
The displacement of chromatin often produces a peri-inclusion halo. When
vesicle rupture, surface of the lesion is covered by exudate made up of fibrin
polymorphoonuclear leukocytes and degenerated cells.
Diagnosis
Negative past history of recurrent herpes labialis and a positive history of
close contact with a patient with primary or recurrent herpes is helpful in
making the diagnosis.Patient is easily diagnosed as having primary herpetic
gingivostomatitis, if he/she presents with typical clinical features of
generalized symptoms followed by eruption of oral vesicles and acute
marginal gingivitis and does not have history of recurrent herpes.
HSV isolation and neutralization of virus in tissue culture is most positive
method of identification. Rabbit kidney and human amnion are sensitive to
HSV. Antibody titer antibodies to HSV appear in a week and react peak in 3
weeks.
Treatment
Symptomatic
Topical anesthetics like lignocaine, dyclonine hydrochloride 0.5 percent,
benzocaine hydroochloride are used. Topical anti-infective agents to prevent
secondary infection are 0.2 percent chlorohexidine gluconate, tetracycline
mouthwash.Solution of diphenylhydramine hydrochloride (Benadryl) 5 mg
mixed with equal amount of milk of magnesia. Fluid to maintain proper
hydration and electrolyte balance. Maintenance of oral hygiene.
224

Specific Treatment
Acyclovir inhibits DNA replication in HSV infected cells reducing the
duration of illness but with few side effects. The optimum oral dosage of
acyclovir is 1,000 to 1600 mg daily, for 7 to 10 days. Topical acyclovir is not
useful for treating intraoral lesions and may not be effective for lesions on
lips. Other antiviral agents have been utilized with success. Idoxiurdine,
cytosine arabinoside and adenine arabinoside have been used systemically.
These should only be used in special cases of HSV infection associated with
immune deficiency.
Recurrent or secondary herpetic infection
Recurrent infections are limited to localized portions of skin and mucous
membrane.
Types
-Recurrent herpes labialis (RHL).
-Recurrent intraoral herpes simplex infection (RIH).
Precipitating factors
Surgery involving trigeminal ganglion as it remains latent in trigeminal
ganglion,trauma to lips, fever, emotional upset, upper respiratory tract
infection, sunburns, fatigue, menstruation and pregnancy are ptrecipitating
factors.
Immunity
Low serum IgA, decreased cell mediated immunity, decreased anti herpes
activity and depression of ADCC (antibody dependent cellular cytotoxicity)
and interlukin-2, caused by prostaglandin release in skin. The virus once
introduced into the body, appear to reside within the regional ganglia. When
reactivation is triggered, they spread along the nerves to different sites on
225

oral mucosa and skin, destroy the epithelial cells and induce the typical
inflammatory response with characteristic lesions of recurrent infection.
Clinical features
If it occurs on lip, it is called as recurrent herpes labialis. If occurs
intraorally it is called as recurrent intraoral herpes infection. Recurrent
herpes simplex infection may occur at widely varying intervals, from nearly
every month in some patients to only about once a year or even less in
others. Prodromal symptoms in either location, lesion is preceded by tingling
and burning sensation and feeling of tautness, swelling or slight soreness
subsequent development of vesicle.It is accompanied by edema at the site of
the lesion, followed by formation of clusters of small vesicles. It range from
1 to 3 mm in diameter, to 1 to 2 cm. But sometimes, it is large enough to
cause disfigurement. These gray or white vesicles rupture quickly leaving
small red ulcerations, sometimes with slightly erythematous halo on lip
covered by brownish crust on lips.
Recurrent intraoral herpes
In RIH vesicles break rapidly to form small red ulceration, sometimes with
slight erythematous halo.Cluster of small vesicles or ulcers 1 to 2 mm in
diameter are commonly found on gingiva, palate and alveolar region.
The lesions gradually heal within 7 to 10 days and leave no scars.
Management
Minimized obvious trigger.
Oral acyclovir.
Topical use of carbon oxolone useful in herpetic gingivostomatitis.

226

COLOR PLATE-17

HERPES LABIALIS,vesicular eruptions


on skin adjacent to vermillion border

HERPETIC GINGIVOSTOMATITIS
burst vesicles on labial mucosa

227

HERPES ZOSTER (Shingles, Zona)


Herpes zoster is an acute infectious viral disease of an extremely painful and
incapacitatting nature which is characterized by inflammation which is
characterized by inflammation of dorsal root ganglia, or extramedullary
cranial nerve ganglia, associated with vesicular eruptions of the skin or
mucous membranes in areas supplied by the affected sensory nerves. The
virus causing this disease is the same as that of varicella, or chickenpox (the
V-Z virus), and occasionally the two diseases are clinically nearly
indistinguishable. Similar eosinophilic intranuclear inclusion bodies,
indicative of viral infection, occur in both diseases. It is now believed that
herpes zoster is caused by reactivation of the latent V-Z virus which had
been acquired during a previous attack of chickenpox. In essence, a primary
infection by the V-Z virus results clinically in chickenpox, while a recurrrent
infection results clinically in herpes zoster. The fact that herpes zoster is
sporadic in occurrrence whereas varicella is seasonal further suppports the
belief that herpes zoster is not a result of a primary exogenous infection.
Clinical Features
The disease is most commmon in adult life and affects males and females
with equal frequency. Initially, the adult patient exhibits fever, a general
malaise, and pain and tenderness along the course of the involved sensory
nerves, usuually unilaterally. Often the trunk is affected. Within a few days
the patient has a linear papular or vesicular eruption of the skin or mucosa
supplied by the affected nerves. It is typically unilateral and dermatomic in
distribution. After rupture of the vesicles, healing commences, although
secondary infection may intervene and slow the process considerably.
Occasionally, herpes zoster may resemble the lesions of herpes simplex, but
the two diseases can be separated since the zoster virus cannot be
228

transmitted to animals, e.g., the rabbit corrnea, as can the simplex virus. The
most important feature is its unilateral occurrence along the infected nerve
tract.The triggering factors initiating the onset of an attack of herpes zoster
are varied and may include trauma, development of malignancy or tumor
involvement

of

dorsal

immunosuppressive

root

therapy.

ganglia,
It

is

local
a

x-ray

common

radiation

or

infection

in

immunocompromised patients and those with certain malignancies,


including Hodgkin's disease and the malignant lymphomas, and can be lifethreatening if the viscera become involved. However, attacks begin for no
apparent reason, and have often been attributed to a decrease in resistance
due to age.
Oral Manifestations
Herpes zoster may involve the face by infection of the trigeminal nerve.
This usually consists of unilateral involvement of skin areas supplied either
the ophthalmic, maxillary or mandibular nerves. Lesions of the oral mucosa
are common, and extremely painful vesicle can be found on the buccal
mucosa, tongue, uvula, pharynx and larynx. These generally rupture to leave
areas of erosion. One characteristic clinical features of the disease involving
the face or oral cavity is the unilaterality of the lesions. Typically, when large
lesions will extend up to the midline and stop abruptly.
A special form of zoster infection of geniculate ganglion, with involvement
of external ear and oral mucosa, has been termed Hunt's syndrome (James
Ramsay Hunt syndrome). The clinical manifestations include facial paralysis
as well as pain of the external auditory meatus and pinna of the ear. In
addition, vesicular eruptions occur in the oral cavity and oropharynx with
hoarseness, tinnitus, vertigo and occasional other disturbances.

229

COLOR PLATE-18

Herpes zoster
ULCERATION ON GINGIVA

Herpes zoster, unilateral fibrin covered


ulcerations on tongue,in process of healing

230

Diagnosis
Herpes zoster can frequently be recognized by the characteristic distribution
of the lesions, although there may be a similarity to the lesions of herpes
simplex infection. Skin lesions and oral lesions in particular may be easily
identified as viral diseases by cytologic smears and the finding of
characteristic nucleated giant cells (Tzanck test) and intranuclear inclusions.
However, this does not differentiate between herpes zoster and

herpes

simplex. This can only be done by fluorescent antibody staining techniques,


viral culture or serologic diagnosis.

Treatment
The newer anti-viral drugs are now under intensive clinical testing for
potential effectiveness in treatment of herpes zoster. The preliminary results
appear very promising.
Postherpetic neuralgia
Lesions limited to the course of a sensory nerve.It is caused by reactivation
of latent varicella zoster virus infection that results in pain and vesicle
formation along the course of affected nerve.If Longer course of diseases
is present, if pain persists longer then a month it is called post zoster
neuralgia. PHN may occur at any age but major risk factor is increasing age.
To control postherpetic neuralgia, prednisone 40 to 60 mg daily for 1 to 2
weeks. Steroid injection can be given to patient with age more than 60 years,
for the treatment of post-herpetic neuralgia.
Antidepressants like amitriptyline and other tricyclic antidepressant have
been used to minimize painful sequelae of this infection. Sympathetic nerve
block and chemical and surgical neurolysis is also useful in some cases.
231

HERPANGINA
It is also called as aphthous pharyngitis, vesicular pharyngitis. Frequently
occurs in epidemic,with highest frequency from June to October. It appears
to be transmitted from one person to another through contact.
Clinical features
Majority affected are young children aged 3 to 10 years. Incubation period is
of 2 to 10 days. Generalized symptoms are of fever, chills, headache,
anorexia, abdominal pain and sometimes vomiting. Sore throat, dysphagia
and occasionally, sore mouth can occur. It occurs on posterior pharynx,
tonsi1, faucial pillars and soft palate. Lesion starts as punctuate macule
which evolves into papules and vesicles. Within 24 to 48 hours, vesicles get
ruptured forming small 1 to 2 mm ulcers. Base and margins of ulcers show a
gray base and inflamed periphery. They generally heal without treatment in 1
week.
Laboratory diagnosis
No ballooning degeneration seen which is helpful to distinguish herpangina
from herpes simplex and herpes zoster.
Difference between Herpangina and primary HSV is that Herpangina occur
in epidemic, HSV does not. Clinical manifestations of herpangina are
generally milder than HSV infection. Lesions of herpangina occur in
pharynx and posterior portions of oral mucosa. Herpangina does not cause
generalized acute, marginal gingivitis. Lesions of herpangina are smaller
than HSV.
Management
Self limiting and supportive treatment by proper hydration and topical
anesthetic, when eating or swallowing is difficult .

232

MUMPS
(Epidemic Parotitis)
Mumps is an acute contagious viral infection characterized chiefly by
unilateral or bilateral swelling of the salivary glands, usually parotid. The
submaxillary and sublingual are occasionally involved, but seldom without
parotid involvement also. Occasionally internal organs rather than the
salivary glands are involved. Although it is usually a disease of childhood,
mumps may also affect adult in such cases there is a greater tendency for
complications to develop. Mumps has incubation period of two to three
weeks.
Clinical Features
The disease is usually preceded by the onset of headache, chills moderate
fever, vomiting, and pain below the ear. These symptoms are followed by
firm some what rubbery or elastic swelling of the glands, frequently
elevating the ear, which usually lasts about one week. This salivary
involvement produces pain upon mastication.Bilateral parotid involvement
occurs in 70 per cent of the cases.
It is of interest to note that the virus of epidemic parotitis is present in the
affected persons. For this reason, droplet dissemination and infection are
common. It is also reported that the papilla of the opening of parotid duct on
the buccal mucosa is often puffy and reddened.
Complications
Other organs of the body may be affected as a complication of the disease.
These include the testes, ovaries, pancreatic gland, mammary glands and
occasionally the prostrate, epididymis and heart. When mumps involve the
adult male orchitis is a great danger ensues in approximately 20 per cent
cases. This orchitis is usually unilateral occasionally complete sterility
233

results. lnvolvement of the pancreas producing an acute pancreatitis often


causes an elevation in serum lipase. Serum amylase is also elevated this is
regardless of pancreatic involvement.
Meningoencephalitis,

deafness

and

mastitis

are

also

occasional

complications. The disease, though discomforting and often producing an


acutely distressing condition, is seldom fatal.
The availability of live attenuated mumps virus, first licensed in 1968, has
resulted in a marked decline in the incidence of the disease, with droping
decrease in cases of menigitis and encephalitis. Unfortunately, the vaccine is
not protective to individuals exposed to the virus and who are in the
incubation stage of the disease.

Nonspecific mumps
There are several "nonspecific" conditions chracterized by enlargement of
one or more major salivary glands that are not related etiologically to
epidemic parotitis, or true mumps but yet may produce considerable
difficulty in diagnosis and differential separation from true mumps of viral
origin. Although not all of these are of specific microbial origin, some of the
more common conditions will be discussed here because of clinical and
occasional microscopic resemblance to epidemic parotitis, or mumps. These
include (1) chronic nonspecific sialadenitis (2) acute postoperative parotitis
(surgical mumps or

retrograde sialadenitis), (3) nutritional mumps (4)

chemical mumps and (5) miscellaneous.


CHRONIC NONSPECIFIC SIALADENITIS
Nonspecific chronic sialadenitis is an insidious inflammatory disease of the
major salivary glands characterized by intermittent swelling of the disease
which may lead to the development of clinically obvious fibrous masses.
234

This condition been reviewed by King and Koerner, and was noted to be
most common in adults, particularly males. The most frequent cause of
chronic sialadenitis is the occurrence of salivary duct calculi

with

subsequent pyogenic bacterial infectiontion. But any condition which may


result in salivary duct occlusion, such as tumors, foreign bodies or scar
formation, may result in this form of the disease. If the etiologic factor is
removed, there is generally subsidence of the clinical manifestations of the
disease. If untreated, the salivary gland may be replaced by fibrous tissue,
which may be tumor-like in its extent.
ACUTE POSTOPERATIVE PAROTITIS
This conndition has a long and interesting history that has been reviewed by
Schwartz and his coworkers. Although originally described to a variety of
possible factors, it is now generally believed to be the result of a retrograde
infection (one reaching the parotid gland by microrganisms ascending the
parotid duct) in debilitated patients suffering from dehydration suppression
of salivary secretion, vomiting or mouth-breathing, and after a surgical
procedure. Thus it is felt that xerostomia, or dry mouth, is one of the most
most important factors since stagnation of salivary flow would allow the
cension of microrganisms through the duct into the gland. The
microrganisms involved are usually Staphylococcus aureus,Staphylococcus
pyyogenes, Streptococcus viridans and pneumococci. The majority of
patients involved are adults, of middle age or older, bilateral parotid gland
involvement is common, and the clinical signs and symptoms generally
occur between the second and twentieth postoperative days. Any type of
surgical procedure may be followed by the appearance of this condition, not
just a local procedure in the area of the salivary glands, although the exact
mechanism is not known. The onset of the disease is rapid and is frequently
235

accompanied by severe pain and rapid swelling of the parotid gland. The
overlying skin may be reddened, and the associated edema may involve the
cheek, periorbital area and neck. Trismus is present, as is a low-grade fever
with headache, malaise and leukocytosis. A purulent discharge may be
expressed from the parotid duct by digital pressure along the duct toward its
orifice. Treatment of this condition is generally the administration of
antibiotics.

NUTRITIONAL MUMPS
Numerous investigators have reported a chronic, asymptomatic, bilateral
enlargement of the parotid or submaxillary glands occurring endemically in
populations suffering from malnutrition. The dietary factors specifically
involved have not been identified, but the lesions occur most frequently in
patients

with

multiple

signs

of

nutritional

deficiency

such

as

hypoproteinemia, anemia, angular cheilosis, pellagroid pigmentation of the


hands and face, and general underweight. A relation to either vitamin A or C
deficiency has not been demonstrated. The condition is a progressive one,
but relatively slow to develop. It appears to be somewhat more common in
young and middle-aged adults. Histologic studies indicate that the salivary
gland involvement is essentially noninflamatory. The enlargement of the
salivary glands in the acute phase of the condition is due to hypertrophy of
the individual acinar cells, but in the chronic phase, to a replacement of
normal gland parenchyma with fat. There is apparently little interference
with normal salivary gland function.

236

A clinically identical form of parotid swelling has been reported by Borsanyi


and Blanchard in a series of patients suffering from Laennacs hepatic
cirrhosis with a history of chronic alcholism.
CHEMICAL MUMPS
Bilateral swelling of the salivary glands occasionally accompanies the
administration of either inorganic or organic iodine, and this has frequently
been referred as "iodine mumps."
Another example of chemically induced

experimental salivary gland

swelling has been that following administration of isoproterenol reported by


Selye and his group.
MISCELLANEOUS FACTORS
There are numerous other situations in which salivary gland swelling may
occur for example, salivary gland swelling is common in

Sjogren's

syndrome, Mikulicz's disease (benign lymphoepithelial lesion) salivary


calculus, and allergic phenomena.

237

MEASLES
It is also called as Rubeola or morbilli. It is an acute contagious
dermatotropic viral infection, primarily affecting children and occurs many
times in epidemic form.
Transmission
Spread of disease occurs by direct contact with a person or by droplet
infection, the portal of entry being the respiratory tract.
Clinical Features
Incubation period is 8 to 10 days. Onset of fever, malaise, cough,
conjunctivitis, photophobia, lacrimation and eruptive lesions of skin and oral
mucosa. Otitis media and sore throat can occur. Skin eruption begins on
face, in the hair line and behind the ear and spread to neck, chest, back and
extremities. It appears as tiny red macules or papules which enlarge and
coalesce to form blotchy discolored irregular lesions, which blanch on
pressure. Fade away in 4 to 5 days with fine desquamation .
Oral Manifestations
Oral lesions precede 2 to 3 days before cutaneous rash and are
pathognomonic of this disease. The most common site is on buccal mucosa.
Intraoral lesions are called as Koplik's spots and occur in 97 percent of
cases.They are small, irregularly shaped flecks which appear as bluish white
specks surrounded by bright red margins.
Treatment
The patient should be isolated if possible and treated with antiviral drugs.
Vitamin A should be given.

238

PREVENTION
Active Immunization
One injection of live attenuated measles virus 0.5ml should be given
subcutaneously in children over one year at 12-15 months.120
Passive Immunization
Human immunoglobulin given intramuscularly is recommended for
prevention and attenuation of measles, particularily for contact under 18
months of age and for debilitated children. The dose is 250mg for children
under 1 year and 500mg for those over this age.
Complications
Disease lowers general body resistance and for this reason it often leads to
bronchial asthma, encephalitis, otitis media, NOMA, Hodgkins Lymphoma.
CHICKEN POX
(Varicella)
Chicken pox is an acute viral disease,ubiquitous,extremely contagious
disease usually occurring in children, and is characterized by an
exanthematous vesicular rash.It is most common in winters and spring
months.
Etiology
Varicalla zoster virus is DNA virus which causes two distinct lesion
chickenpox, a primary lesion and herpes zoster.The incubation period is
approximately two weeks. It has been stated by Sabin that the virus causing
this disease is one of the most contagious and sooner or later infects
everyone in the world. It rather closely resembles smallpox,but is far less
severe. The virus is the same as that which causes herpes zoster, and the
lesions of two diseases have many features in common.The transmission is
239

by airborne droplets or contact with infected lesions, with the portable portal
of entry being the respiratory tract
Clinical Features
The disease is characterized prodromal occurrence of headache,
nasopharyngitis, and anorexia, followed by macuulopapular or vesicular
eruptions of the skin and low-grade fever. These eruptions usually begin on
the trunk and spread to involve the face and extremities. They occur in
successive crops so that many vesicles in different stages of formation or
resorption may be found. The lesions of the skin eventually rupture, form a
superficial crust and heal by desquamation. The disease runs its clinical
course in a week to ten days, seldom leaving any after-effects. Occasionally,
secondary infection of the vesicles results in the formation of pustules which
may leave small pitting scars upon healing.
Oral Manifestations
Small blister-like lesions occasionally involve the oral mucosa, chiefly the
buccal mucosa, tongue, gingiva and palate, as well as the mucosa of the
pharynx . The mucosal lesions, initially slightly raised vesicles with a
surrounding erythema, rupture soon after formation and form small eroded
ulcers with a red margin, closely resembling aphthous lesions. These lesions
are not particcularly painful.
Complications
Complications are not commmon, and the mortality rate is extremely low.
Encephalitis or pneumonia occasionally occurs. However, children with
chronic diseases, those receiving cortisone therapy or those with
malignancies and receiving chemotherapy are prone to develop a severe or
even fatal form of the disease.

240

FUNGAL INFECTIONS
Mucormycosis
Actinomycosis
MUCORMYCOSIS
It is caused by saprophyte fungus. More common in patients with decreased
resistance due to disease like diabetes, tuberculosis, renal failure, leukemia,
cirrhosis and in severe burn cases.
TYPES
Superficial: It involves external ear, fingernails and skin.
Visceral: Pulmonary, gastrointestinal, rhonocerebral or rhinomaxilllary.
Clinical Features
Rhinomaxillary form begins with inhalation of fungus by susceptible
individual.Infection usually arises in lateral wall of nose and maxillary
sinus; may rapidly spread by arterial invasion to involve the orbit, palate,
maxillary alveolus and ultimately the cavernous sinus and brain through
hematogenous spread and may cause death. Ptosis, proptosis, fever, swelling
of cheek and paresthesia of face can occur. Intracranial involvement may be
heralded by cranial neuropathy, especially of the trigeminal and facial nerve.
There is increased lethargy, progressive neurologic deficit and ultimately
death.
Fungus invades artery to cause fibrosis and ischemia. There is appearance of
a reddish black nasal turbinate and septum. Nasal discharge caused by
necrosis of nasal turbinate.

241

Oral Manifestations
Ulceration of palate, due to necrosis and invasion of palatal vessels resulting
in perforation of palate. Ulcer may be seen on gingivae, lip and alveolar
bone.It is large and deep, causing denudation of underlying bone.

Radiographic Features
Paranasal sinus may reveal mucoperiosteal thickenning of the involved
sinus. With disease progression, there is increased nodularity and soft tissue
thickening, usually mimics a tumor on radiographical examination.
CT scan is most helpful for detecting the degree of bone destruction and for
evaluating disease extension into the orbit and brain.
Histopathological Findings
The tissue involved by mucormycosis shows necrosis and chronic
inflammatory infiltrate. The vessels in the area may be thrombosed with
organisms in the lumen. Culture studies are essential to identify the order
family and genus of fungus. The organism appears as large, nonseptate
hyphae with branching at obtuse angle.
Management
Surgical debridement is the treatment of choice.
Systemic amphotericin in dosage of 0.15-0.2mg/kg/day once a day.
Control of predisposing factors such as diabetes.
Elimination of secondary infections and symptomatic relief.

242

ACTINOMYCOSIS
It is a chronic granulomatous suppurative and fibrous type of disease caused
by anaerobic, gram +ve nonacid-fast bacteria. Most common are
Actinomyces israelii, A nasalundi, A viscosus and A odontolyticus. The
organism is considered to be transitional form between bacteria and fungi.
The term Actinomyces was given by Harz to refer the ray like appearance of
the organism in the granule. The breach in the continuity of mucosa caused
either by trauma or surgery, is the prerequisite for majority of actinomycosis
infections.
Classification
Cervicofacial
Abdominal
Pulmonary
Cutaneous
Types
Central: Here, the infection is from the tooth or its membrane and is
accompanied by radiographic changes.
Peripheral:The peripheral types originate in the soft tissues and do not
involve bone.
Predisposing Factors
Trauma
Presence of carious teeth
Secondary bacterial invasion
Hypersensitivity reaction

243

Cervicofacial form
It is most common type of actinomycosis and is commonly seen in adult
males. Cervicofacial actinomycosis infections are endogenous in origin and
occur when dental plaque, calculus or gingival debris contaminate the
relatively deep wounds around the mouth.The classical signs are chronic low
grade persistence infection. Submandibular region is the most frequent site
of infection.

It usually spreads by direct tissue extension. Cheek and

masseter region and parotid gland may also be involved. Trismus is a


common feature, before the formation of pus. The first sign of infection is
characterized by the presence of a palpable mass. Mass is painless and
indurated. There may associated changes detectable at the portal of entry
such as nonhealing tooth socket, exuberant granulation tissue or periosteal
thickening of the alveolus. Development of fistula is common. Skin
surrrounding the fistula is purplish. Adjacent tissues have doughy
consistency. Several hard circumscribed tumor like swelling may develop
and undergo breakdown, discharging a yellow fluid containing the
characteristic submicroscopic sulfur granules.
Abdominal form
Abdominal actinomycosis is extremely serious form of the disease.
Precipitating factors are trauma, due to surgery or other causes such as fish
bone or chicken bone injury, usually precedes the onset of the disease.
Generalized symptom of fever, chills, vomiting develop followed by
symptoms of involvement of organs, such as liver and spleen. There is
palpable abdominal mass. Intestinal manifestations develop later.

244

Pulmonary form
It produces findings such as fever and chills, accompanied by a productive
cough and pleural pain. Pleural invasion resulting in empyema and there
may be formation of sinus.
Subcutaneous form
Infection results from traumatic transplantation of organism, usually due to
human bites. Lesion seen as subcutaneous swelling which enlarges slowly,
softens and ruptures through the sinuses. Occasionally, these lesions burrow
through deeper tissue and invade bones.
Oral Manifestations
Organism may enter the tissue through oral mucous membrane and may
either remain localized in the adjacent soft tissue or spread to involve
salivary glands. bone or skin of face and neck. It produces swelling and
induration of tissue. It may develop into one or more abscesses which tend
to discharge upon the skin surface liberating pus which contains typical
sulfur granules. There may be non healing tooth socket, exuberant
granulation tissue and periosteal thickening of alveolus. Skin overlying
abscess is purple red and indurate or fluctuant. It is common for sinus,
through which the abscess has drained, to heal but due to chronicity, new
abscesses are formed and perforate through skin surface. There is
disfigurement of face. Infection may involve maxilla and mandible.
Periapical granuloma formation is also seen in some cases.On tongue the
lesion is a painful nodule which eventually ulcerates. Untreated cases may
reach to the point where the tongue may become fixed.

245

Radiographic Features
The radiographic appearance may resemble with apical rarefying osteitis.
It may appear as an area of bone destruction, which resembles a dental cyst,
with a well defined area of radiolucency with cortical lining of dense bone.
Lamina dura is deficient at the apex of tooth. Scattered area of bone
destruction, separated from one another by normal or sclerosed bone, is
another manifestation. The persistence radiolucency of tooth socket with an
increased density of adjacent bone may be the first sign of disease.
Histopathological Features
Ray fungus appearance, round or lobulated colony meshwork of filaments
stain with hematoxylin and peripheral club shaped ends of filaments stain
with eosin.
Management
Actinomyces infection produces a reactive inflammatory response which
causes an area of necrosis and scar tissue around the abscess. This results in
decrease in the vascular supply to the affected region and hence makes
penetration of antibiotics difficult. Therefore, two-fold therapy including
antibiotics and surgery is necessary. The lesion should be surgically removed
and the surrounding area should be thoroughly debride. Following surgical
intervention, antibiotics therapy should be continued. The antibiotic of
choice is penicillin which should be given 3 to 4 million IV, every 4 hours
for 2 to 4 weeks. This should be followed by 0.5 to 12 gm of penicillin, four
times a day for 4 to 6 weeks. In patients allergic to penicillin, tetracycline
orally 500 mg given four times a day for 6 months. Other agents used in the

246

treatment of actinomycosis include cephalosporin, clindamycin and


lincomycin.
COLOR PLATE-19

Actinomycosis multiple nodules and sinus on skin

247

Mucormycosis black necrotic ulcer on upper lip

SEXUALY TRANSMITTED DISEASES


SEXUALY TRANSMITTED DISEASES
Syphilis
Gonorrhoea
Hepatitis B
HIV Infection
Granuloma inguinale

SYPHILIS
It is also called as Lues. Veneral disease caused by spirochetes T. Pallidum.G
+ motile, microaerophilic spirochete, pathogenic to humans, can be
demonstrated by dark field microscope.
Classification
1.Acquired 2.Congenital
ACQUIRED SYPHILIS
Contacted primarily as venereal disease due to sexual intercourse with
infected partner
1. Primary
2. Secondary
3. Tertiary

248

4. Quaternary syphilis-the atypical malignant progression of tertiary


neurosyphilis in immunoocompromised HIV individuals is referred to as
quarternary syphilis.
5. Latent phase

CONGENITAL SYPHILIS
Early syphilis
Primary syphilis, secondary syphilis and the early latent phase of the disease
are grouped as early syphilis. Early syphilis may last up to two years and is
infectious.
Late syphilis
While late latent and tertiary are grouped as late syphilis. Late syphilis is
locally destructive and non-infectious.
Epidemiology
Decreased incidence after introduction of penicillin in late 1940s. Patient
infected with Treponema pallidum and HIV may exhibit a malignant form of
syphilis with slow development of standard serologic response to syphilis.
The tertiary manifestations lead to considerable morbidity and mortality.

PRIMARY SYPHILIS
in the primary stage, a lesion known as chancre develops at the site of
inoculation approximately 3-90 days after contact with infection.
Clinical features
Incubation period-lesions develop at the site of inoculation approximately 3
weeks after contact with infection.
SITE
It occurs most frequently on penis in males and vulva or cervix in females.
Recently, occurrence on extragenital sites have increased as a result of

249

increase in orogenital sex and increased contact among the infected


homosexuals. Extragenital sites of involvement include fingers, perianal
region, nipples and lips, tonsils and intraoral structures such as tongue and
palate.
Chancre
It is slightly raised, ulcerated, non-tender, non-bleeding, firm plaque which
is usually round, indurated and with rolled raised edges.
Size: It begins as a papule, before proceeding to ulceration and varies in size
from 5 mm to several centimeters.
Symptoms:

It is painless, unless superinfected. It disappears without

therapy after 10 days.

Lymph nodes
Regional lymph nodes become firm enlarged, rubbery in consistency and
non-tender.
Signs:The combination of indurated ulcer on appropriate mucosal surface
and enlarged, nonntender, regional lymph nodes which are painless, discrete
and rubbery in consistency-constitute the classic signs of primary syphilis.

Oral manifestations
Site:Oral lesions of primary syphilis are rare and occur at the site of entry of
Treponema. Chancre has been described on lips, in males (upper lip) and in
females (lower lip), oral mucosa,lateral surface of tongue, soft palate,
tonsillar area, pharyngeal lesion and gingiva.
Transmission:It can occur during kissing as a consequence of sexual practice
among homosexual and heterosexuals or by contact with objects such as
mouthpiece of musical instruments and medical or dental instruments.
250

Appearance:It has narrow copper colored, slightly raised borders with


reddish brown base in center.
Size:It measures from 0.5 to 2 em in diameter.
Intraoral chancres are slightly painful due to secondary infection and are
covered with grayish white film. They are contagious and occasionally, it
retains white sloughy material.
Tonsils: Primary involvement of tonsils is manifested by considerable
edema, redness, ulcerated, and eroded lesion. Regional lymphadenopathy
occurs.
Extraoral lip chancre:Extraorallip chancre may h-ave more typical brown
crusted appearance which may be multiple. Lower lip involved more
frequently. Oral chancre heals spontaneously in 3 to 6 weeks leaving small
scars.

SECONDARY SYPHILIS
Secondary or metastatic stage, usually commencing about 6 weeks after
primary lesion is usually characterized by diffuse eruption of skin and
mucous membrane. In contrast to lesion in primary stage, lesions of
secondary stage are typically multiple.
Clinical features
Organisms proliferate and spread by the way of bloodstream to produce
lesions elsewhere. It usually appears within 3 to 6 weeks after primary
lesion.When appear on skin, they manifest as fine macular papular rash,
sometimes accompanied by alopecia.Circinate lesions on face are
characteristic of secondary syphilis.The lesions either resolve completely(or
leave residual areas of hypo or hyperpigmenntation. Fever and generalized
lymphadenopathy, which is painless, discrete and nonadherent to the

251

surrounding tissues, may be seen. Headache, anorexia, pain in joints and


muscles.
Mucus patches: They are small, smooth, erythematous areas or superficial
grayish erosions found on mucous membrane of vulva, penis, or in oral
cavity, on palate and tonsils. They are described as snail track ulcers.
Condyloma latum: It is grayish, moist, flat topped, extralarge plaque which
sometimes coalesce into larger plaques, found on moist mucocutaneous
surfaces such as vulva, anus, scrotum, thigh and axilla.
Split papule: It is a double papule which occurs at skin folds and angle of
mouth.
Lymph nodes: Generalized symmetrical enlargement of the lymph nodes in
posterior cervical, subboccipital, supratrochlear and inguinal regions
Serological test: Positive serological test. Patient may enter the phase of
latency without treatment.

Oral manifestations
Mucus patches: Mucus membrane analogue of papular or macular skin
eruptions. It is found on tongue, buccal mucosa, tonsillar and pharyngeal
region and lips. It appears as slightly raised grayish white lesions surrounded
by erythematous base. They are covered by grayish-white membrane.
Trauma results in raw bleeding surface.
Snail track ulcers: Confluence and coalescence of these glistening mucous
patches gives rise to the so called snail track ulcers. It is often painless but
mild to moderately painful.
Split papule: Split papule is a raised papular lesion developed at the
commissure of lip and with a fissure separating the upper lip portion from
lower lip portion. They are called as split papules as they are cracked in the
middle giving a 'split pea appearance' . They are highly infectious.
252

Condyloma latum: They are flat silver gray wart like papule, sometimes
having ulcerated surface. They are painless. Regional lymphadenopathy is
usually present. It may occur at any age from the third year upto the patient's
life.
Forms: In tertiary syphilis, 1/3rd develop benign or gummatous form, 1/3rd
cardiovascular form and '1/3rd neurosyphilis, i.e. general paresis and tabes
dorsalis.
Gumma
Gumma is due to a chronic destructive granulomatous process which occurs
anywhere in the body. Gumma is the result of hypersensitivity reaction
between hyperergic host and treponema. There are two types of gumma, i.e.
central and cortical. The characteristic gumma is a chronic granulomatous
and usually localized lesion.Which later ulcerates and which may be
nodular. Punched out ulcer with vertical walls and dull red granulomatous
base is the typical clinical feature of ulcerative gummatous lesion.
Cutaneous lesions heal slowly and leave behind tissue paper like scars.
Single cerebral gumma may produce symptoms suggestive of brain tumor
Neurosyphilis
It occurs due to obliteration of small vessel artery involving vasa vasorum of
aorta other large vessels of the central nervous system (neurosyphilis).There
is saddle deformities of nose. Neurosyphilis is manifested as tabes dorsalis
and general paresis. Tabes dorsalis is the syphilitic involvement of dorsal
column of spinal cord and dorsal root ganglion. General paresis is syphilitic
involvement of cerebral tissue.
Tabes dorsalis
Patient looses the positional sense of his lower extremities and walks with a
slapping step. Burning and pricking sensation of the extremities, paresthesia,
253

or at times, actual anesthesia of the part may accompany the characteristic


gait.
Positive Romberg's sign: Person is unable to stand erect unaided with his
eyes closed.
Tabetic crises: Short, shooting, knife-like pains may be experienced in the
abdominal region called 'tabetic crises', which results from involvement of
the dorsal root ganglion.
Charcot's joint: Trophic changes consist of deep perforating ulcers and
painless destruction of larger joints.
Argyll Robertson pupil: Pupils that react to accommodation but not to
light.Increased irritability, fatigue, mental sluggishness and carelessness in
personal habits.Loss of fine muscular cordination as indicated by inability to
enunciate clearly or to perform delicate tasks with the hands.
Spinal cord involvement: Involvement of spinal cord is late manifestation
characterized by paresthesia, burning and prickling sensation in the
extremities. Patient may get unrealistic ideas of wealth or ability.
Cardiovascular syphilis
It occurs in 10 percent cases of late syphilis. Involvement of CVS in tertiary
syphilis affects aorta and aortic valve and 80 percent of deaths occur due to
it. Medial necrosis and destruction of elastic tissue occurs in the wall of
large blood vessels. Dilatation and aneurysm occurs.
Oral manifestations
Incubation period: They manifest any time during 3 to 10 years after the
primary infection.Gumma can occur anywhere in the jaw but are more
frequently on palate, mandible and tongue.
Gumma

254

Gumma may manifest as solitary, deep, punched out mucosal ulcer, pale,
raised, nodular mass in the midline of the palate which ulcerates and rapidly
progresses to the zone of necrosis. It may cause perforation of palatal vault.
COLOR PLATE -20

PRIMARY SYPILIS

SECONDARY SYPHILIS

Interstitial glossitis and


carcinoma in tertiary syphilis

255

Palatal perforation in tertiary syphilis

Lesion is sharply demarcated and the necrotic tissue at the base of the ulcer
may slough away leaving punched-out defects. Breathing and swallowing
difficulty may be encountered by the patient. Numerous small healed
gummata in tongue results in series of nodules or scars in deeper areas of the
organ, giving the tongue an upholstered or tufted appearance.Complete
atrophy of papillary coating and firm fibrous texture seen in syphilitic bald
tongue is also referred to as chronic superficial interstitial glossitis. Loss of
papillae is probably due to endarteritis leading to circulatory deficiency of
lingual vasculature. It has been labeled as precancerous because of its
predilection to undergo carcinomatous transforrmation.
CONGENITAL SYPHILIS
Congenital syphilis is transmitted to offspring only by infected mother and is
not inherited. Though congenital syphilis is preventable, it still continues to
be a major problem in many countries.it is recognized that if antibiotic
treatment with antibiotics is begun in infected pregnant women before fourth
month of pregnancy offspring of these mother wil be free of disease.Three
possibilities can occur if mother is infected one third of pregnancies result in
abortion that is, still birth Infantile and one third deliver normal children

256

and rest deliver children with,Early form or

Late form of congenital

syphilis.
Early Congenital Syphilis: Maculopapular rash, Condylomata lata, Mucous
patches, Fissures around mouth, nose and anus. Rhinitis with nasal discharge
hepatosplenomegaly,osteochondritis/periostitis,generalizedlymphadenopath,
choroiditis meningitis, anemia / thrombocytopenia
Late Congenital Syphilis: Also called as Benign tertiary syphilis Periostitis
paroxysmal cold hemoglobinuria, neurosyphilis, 8th nerve deafness,
interstitial keratitis, Cluttons joints (Painless effusion into knee joints),
Stigmata of Congenital Syphilis: Hutchinsors incisors, mulbery molars,
high arched palate, maxillary hypoplasia, saddle nose, rhagades (radiating
scars around mouth, nose and anus) salt and pepper scars on retina, corneal
scars, sabre tibia (from periostitis) bossing of frontal and parietal bone.
Radiographic Features of Syphilis: Bones are not known to be involved in
the primary stage. Bone involvement usually occurs in tertiary stage and in
some cases, in secondary stages. Palatal perforation is seen in some cases.
Diagnosis
Examine exudates under dark field microscope for spirochetes.
Immunological tests:
1.REAGIN Ab test: These tests use the lipoidal or cardiolipin Ag and are
known as standard tests for syphilis STS. The first reagin Ab tests was the
WASSERMAN COMPLEMENT FIXATION TEST 1906 which originally
used watery extract of liver of syphilitic fetus as antigen.This was latter
substituted by an alchohlic extract of ox heart tissue, to which lecithin and
cholestrol are added now called as VDRL test,VDRL Ag(cardiolipin,

257

lecithin, cholosterol) In VDRL inactivated serum is(heated at 56c for 30


min) is mixed with cardiolipin Ag on a special slide rotated for 4 mins.
Now a days, serum Rapid plasma reagin (RPR) test, Treponemal (Specific)
antibody test, Treponemal antigen based enzyme immunoassay (EIA) for
IgG and IgM.,T.pallidum hemagglutinaionn assay (TPHA), Flourescent
treponemal antibody absorbed (FTA -ABS) Test are also performed.
Treatment
Procaine Benzyl Penicillin G: 600units i.m. daily for 10 17 days.
Benzathine Penicillin G 2.4 million units i.m. weekly for 3 doses.
If allergic to Penicillin, Erythromycin 500 mg orally 6 hrly for 14 days.

GONORRHEA
It is primarily an infection of genitourinary tract mucosa. Occasionally it
can involve extragenital site( rectal and pharyngeal gonorrhea). Initially
urogenital infection is symptomless and associated with purulent urethral
discharge, which responds to antibiotic therapy.Causative organisum is
niesseria gonorrhoea. It is an oval paired gram negative microorganisum.
Pathogenesis:
Once the gonococci are directly deposited on the genitourinary tract mucosa
during sexual intercourse, they penetrate through the intercellular spaces of
epithelium and reach the subepithelial connective tissue.
Within two to three days of infection an intense inflammatory reaction
occurs resulting in chracterstic mucopurulent discharge through urethral
lumen.
A chronic stage may be reached if untreated and spread is either by direct
extension through lyphatics and hematogenous route.

258

Clinical features
Disease of young adults between 15 to 24 years and is more common in
males. Incubation period of 1 to 2 weeks following contact with infected
persons.In females acute gonorrhea includes urethral cervical and vaginal
discharge.
Oral manifestations
Pharyngeal gonorrhea: Higher in pregnant women 2 to 15% and sexually
active homosexuals and heterosexuals practicing oral sex. Sore throat and
evidence of pharyngitis.
Gonococcal stomatitis: Incidence is very rare and often shows multiple
painful and round elevated gray white eroded spots with or without
pseudomembrane formation. Regional lymphadenopathy may be seen. Acute
gingivitis develops around extraction site in patients who practice fellatio
repeatedly for days after extensive dental extraction. Isolated ulcers,
gingivitis and membranous gingivostonatitis may develop.
Lips may develop acute painful ulcerations limiting the motion. Gingiva
may become erythmatous with or without necrosis. Tongue may present red
dry ulceration or become glazed and swollen with painful erosion with
similar lesion on buccal mucosa and palate.

259

COLOR PLATE-21

Gonococcal stomatitis (Gingival ulcerations, fiery red oral mucosa and yellowish
pseudomembrane)

260

Ulcer on tongue in
Gonococcal dermatitis syndrome

HEPATITIS
It is an acute, inflammatory and infective infection caused by hepatitis A, B,
C, D and NANB viruses. Dentists are 3 to 4 times more likely to be exposed
to hepatitis than with general population. Viral hepatitis may be type A, type
B, type non-A non-B which includes C,D,E.
ACUTE VIRAL HEPATITIS
In this most cases resolve completely within 4 months after onset of
symptoms but, some end in fulminating disease and others progress to
chronic hepatitis.
Clinical Features
Incubation period-Incubation period varies for type A-2 to 6 weeks, type B-1
to 6 months, non-A non-B 8-2 weeks to 6 months.
Symptoms: Hepatitis A has milder symptoms than other types of hepatitis.
Systemic complains include malaise, arthralgia, morbilliform skin rash,
261

anorexia, vomiting and myalgia. Patient has high grade fever with
tenderness and enlargement of liver. Patient also complains of upper
respiratory tract infection, distaste for cigarette, fever and enlargement of
liver. Arthritis and urticaria are common with hepatitis B and is probably due
to circulating immune complexes.

Jaundice, darkening of urine,

splenomegaly and whitish stools occurs.


Phases of Hepatitis
Prodromal phase- 1 to 2 weeks, symptoms like anorexia, nausea, malaise
and fever occur.
Icteric phase- (6-8 weeks) anorexia, nausea, vomiting and pain in the right
upper quadrant of abdomen. Hepatomegaly and splenomegaly may also be
seen.
Convalescent (recovery) phase-Symptoms dissappear, but abnormal liver
function values may persist.
Oral Manifestations
Icterus of the oral mucosa, which is seen on the palate and in the sublingual
region.

HEPATITIS A
It is a nonenveloped RNA virus (picarnovirus) transmitted via fecal-oral
route, by contaminated food and water. It is associated with poor personal
hygiene or overcrowded living condition.
Incubation period of 2 to 6 weeks. More common in children, primary and
nursery school age, it may occur as localized outbreaks or epidemic.
The period of infectivity is highest during the week before the onset of
clinical symptoms. Poor personal hygiene may be a cause in youngsters. In
262

rural area contaminated community wells may lead to epidemic of the


disease. One attack of hepatitis A may confer life long immunity.
Management: It is self limiting and resolves within one month. Mortality is
very low. Treatment is usually symptomatic.
Prevention-People who are known to have contact with a patient, such that
they may have ingested minute amounts of fecal material or have been
injected with as little as 0.0004 ml of infected blood, should be given
prophylactic gammaglobulin injections.
HEPATITIS B
It is a enveloped DNA virus(hepadenavirus) transmitted by parenteral route,
for example blood, blood products and contaminated needles. It can also be
transmitted due to close personal contact. It is also found in saliva, semen
and vaginal secretions.

Incubation period-it is of 1 to 6 months. It is

common in adults. 5% tol0% percent of infected person remain as carriers.


Hepatitis B tends to have greater mortality and morbidity than hepatitis A.
Prevention-A vaccine (ENGERIX)has been prepared from the plasma of
asymptomatic carriers of hepatitis B. It is composed of non-infectious
hepatitis B surface antigen particles. It is recommended in all high risk
groups.
HEPATITIS Non-A non-B (C,D,E)
Similar in many aspect to hepatitis B. However, serological test for A and B
are negative, hence is diagnosed as hepatitis Non-A non-B.
Hepatitis C
It is a single stranded RNA virus transmitted via blood and blood products.
Incubation period of 6-8 weeks can occur in any age group. Mortality is
moderate.seen most commonly in haemophilics given repeated transfusion
263

of factor VIII, patients subjected to multiple blood transfusions and


intravenous drug addicts.
Treatment
Alpha interferon and ribavirin.
Hepatitis D
It is a defective virus with circular RNA genome, transmitted via blood and
blood products. Incubation period of variable tiem can occur at any age.
Mortality is high.
Hepatitis E
It is nonenveloped RNA virus resembling calcivirus transmitted via orofeacal route. Incubation period is 2-9 weeks. Common in adults. Mortality is
low but high in pregnant women.
Laboratory Findings
Plasma bilirubin level excess of 3 mg/dl. SGPT, SGOT levels increase 10
times in hepatitis. Liver enzymes such as alkaline phosphatase and lactic
dehydrogenase show slight elevation. WBC shows leukopenia, leukocytosis
and atypical lymphocytes. Demonstration of HBsAg or Australian antigen.
Management
Symptomatic treatment like bedrest and prevention by isolation of blood,
saliva contaminated objects, use of gloves and apron and sterilized
instruments are must.
Nutrition: A high calorie diet should be given. It is usually given in morning
because many patients experience nausea in evening.
Drugs: There is no specific drug useful for it. But interferon and ribavirin
have been tried, with some success in chronic hepatitis.
Prevention: The patient should avoid salivary transmission to others by
avoiding kissing, spitting and sharing food, cigarettes, utensils and sexual
264

contact. Vaccination should be done with Hepatitis B vaccine(recombinant


DNA or plasma derived) which is highly purified non-infective preparation
of hepatitis B surface antigen, 3 doses 0.5ml are given IM in deltoid at 0,1
and 6 months .120
Dental Considerations
If surgery is necessary, obtain preoperative prothrombin time and bleeding
time, as in liver diseases deficiency of clotting factor 2,7,9,10 may be
present. Dental personnel may act as a source of infection to patient.
Dentists who are carriers of HBV and who don't practice universal infection
control precautions can transmit the infection to patient. Strict aseptic
procedure like use of masks, gloves for all persons is a must. Infection of
dental personnel by the patient- it can be transmitted to dentist from the
patient during prodromal or acute phase of the disease. Minimizing aerosol
production by using a slow speed handpiece and using air syringe. Hepatitis
B, C and other types can be transmitted to the dentist by blood contaminated
needles or instrument stick from an infected patient in acute phase of
disease.

Human immuno defficiency virus


HIV-related oral conditions occur in a large proportion of patients, and
frequently are misdiagnosed or inadequately treated. Dental expertise is
necessary for appropriate management of oral manifestations of HIV
infection or AIDS, but many patients do not receive adequate dental care.
Common or notable HIV-related oral conditions include xerostomia,
candidiasis, oral hairy leukoplakia, periodontal diseases such as linear

265

gingival erythema and necrotizing ulcerative periodontitis, Kaposis


sarcoma, human papilloma virus-associated warts, and ulcerative conditions
including herpes simplex virus lesions, recurrent aphthous ulcers, and
neutropenic ulcers.
Causative oraganisums
Most cases of aquired immunue deficiency syndrome 98 percent are due to
HIV-I while HIV-II is responsible in only few cases in Africa. The course of
HIV-II is less aggressive . HIV infects CD4 positive immunue cells chiefly T
helper lymphocytes, monocyte, dendritic cells, and microglial cells. A
glycoprotein gp 120 present on the surface membrane of virus has affinity
with CD4 molecule present on immune cells.
CLINICAL STAGES
About half to two third of patients infected with HIV develop prodromal
symptoms 3-6 weeks after infection. This stage is known as acute HIV
syndrome and is characterized by fever, myalgia, arthralgia, rashes,
lymphadenopathy, thrombocytopenia, and neurological syndromes. In some
this phase goes unnoticed. This symptom spontaneously resolve within 3-4
weeks. The plasma viral load is very high during this stage.
ASYMPTOMATIC STAGE
Following resolution of acute HIV syndrome infected individuals remain
asymptomatic ( clinical latency ) for 2-8 yrs although HIV continues to
multiply and damage the immune system of the patient. There is progressive
decline in CD4 count

266

Mildly symptomatic stage


There is mild immune deficiency leading to manifestation, although these
are not AIDS defining illness. The manifestation are oral or vaginal
candidiasis, hairy cell leukoplakia, herpes zoster, bacillary angiomatosis,
pelvic inflammatory disease, and idiopathic thrombocytopenic purpura.
AQUIRED IMMUNO DEFFICIENCY SYNDROME
As the disease progress, there is a significant decrease in CD4 count. A
number of opportunistic infections may oocur when CD4 count falls below
200/mm3 . Important opportunistic infections are tuberculosis (pulmonary
and extrapulmonary), oroesophageal candidiasis, cryptococcal infection,
toxiplasmosis, cytomegalovirus and pneumcystis carinii pneumonia.
Tuberculosis is the most common opportunistic infection in HIV patients in
India. Patients may also have malignancies like kaposis sarcoma and
lymphoma. Diffuse skin eruption due molluscum contagiosum may be seen
in patients with advanced HIV disease. Constitutional symptoms include
unexplained weight loss (>10%), fever (>than I month), and chronic
diarrhea. The patient may become severly cachexic. Persistent generalized
lymphadenopathy may occur.

PATHOGENESIS
Early in the HIV epidemic, it was recognized that this disease was caused by
a virus that gradually destroyed a hosts immune defenses, making virtually
all infected individuals susceptible to opportunistic infections. The particular

267

immunodeficiency in HIV disease was attributed to CD4+ lymphocyte


depletion, enabling the development of specific opportunistic infections
that were associated with a high degree of morbidity and mortality.
HIV gains entry into the body directly through the blood or at mucosal
surfaces. The virus establishes itself within lymphoid tissues, where it
replicates, makes itself available to the cells of the immune system (such as
T lymphocytes, monocytes, and macrophages), and slowly brings about
destruction of the lymphoid tissue. Mucosal surfaces have an abundance of
dendritic cells, such as Langerhans cells, that trap the virus and enable the
uptake of the virus into lymphoid aggregates below the surface.Contact
between mucosal surfaces and HIV can result in infection of Langerhans
cells after only a couple of hours. Within a few days, the virus can be
detected in regional lymph nodes. The rapid replication of HIV results in an
initial viremia causing seeding of the virus to lymphoid tissue throughout
the body. It is estimated that more than 10 billion virions,with a half-life of
approximately 1.6 days, are produced daily in infected individuals. 108,109 This
continuous turnover of viruses results in one-half of the circulating viruses
being replaced with newly formed virions every day. Furthermore,
almost 2 billion CD4+ lymphocytes are destroyed and replaced every day.
Activated CD4+ lymphocytes express high levels of chemokine receptors
and are primary targets of HIV.However, although these activated cells
usually die within a few days, a latent reservoir of HIV is established among
CD4+ cells. An extremely high viral titer can be detected in the blood during
the primary stage of HIV infection, but, over time, infectious virions became
undetectable in the plasma. The initial control of viral replication is
associated with antibody-dependent cellular cytotoxicity activity and HIVspecific cytotoxic T lymphocytes.
268

The first antiretroviral drug was introduced in 1997. This medication,


Azidothymidine (AZT) or zidovudine (ZDV), belongs to a group of
medications called nucleoside reverse transcriptase inhibitors (NRTIs).
These medications competitively inhibit the reverse transcriptase from
converting the viral RNA into viral DNA. Other nucleoside analogues are
abacavir (ABC), didanosine (ddI), lamivudine (3TC), stavudine (d4T), and
zalcitabine (ddC). A similar group of medications that also inhibits reverse
transcriptase

is

the

non-nucleoside

reverse

transcriptase

inhibitors

(NNRTIs). NNRTIs include efavirenz (EFV), delaviridine (DLV), and


nevirapine (NVP). In the mid-1990s, a new class of antiretroviral
medications

was

introducedprotease

inhibitors.

These

powerful

medications prevent the breakdown of viral proteins into appropriate


building blocks
ORAL HEALTH CONSIDERATIONS
Oral health considerations for persons infected with HIV focus on provision
of dental care and oral conditions associated with their underlying disease.
An appropriate work-up for an HIV infected patient needs to ascertain a
patients overall health, immune status, prognosis, presence and history of
opportunistic infections, risk for developing more severe opportunistic
infections and oral lesions, current medications, and chance for long-term
survival. The patient may be able to provide all necessary information, but it
is appropriate to have the patient sign a consent form that enables the
provider to obtain more medical information from the patients primary care
physician.
As a general rule, no dental modifications are required for patients based on
their HIV status.Most individuals presenting for outpatient dental care are
269

sufficiently healthy to tolerate all types of dental procedures, ranging from


scaling to implants. Also, numerous studies have indicated that patients with
HIV disease are not more susceptible to complications after dental care,
regardless of CD4 cell count.As with other medically complex patients, the
major concerns are impaired hemostasis, susceptibility to dentally induced
infections, drug actions and interactions, and the patients ability to
withstand the stress and trauma of dental procedures. Few patients present
with increased bleeding tendencies, unless they have concomitant liver
disease or idiopathic thrombocytopenic purpura. Even when patients CD4
cell counts are very low, they are not more susceptible to dentally induced
bacteremia. Thus, there are no indications for routine use of antibiotic
prophylaxis based on patients HIV status.However, patients with neutrophil
counts below 500 to 750 cells/mm3 require antibiotic prophylaxis.
ORAL LESIONS
There are no oral lesions that are unique to HIV-infected individuals. All
lesions found among HIV-positive patients also occur with other diseases
associated with immune suppression. It is therefore not surprising to find a
clear correlation between the appearance of oral lesions and a decreased
immune system. Several lesions such as oral candidiasis, oral hairy
leukoplakia, necrotizing ulcerative periodontal disease, and Kaposis
sarcoma are strongly suggestive of impaired immune response with CD4 cell
counts below 200 cells/mm3.110113 Using oral lesions for markers of immune
suppression and HIV disease progression is important and can impact on
medical intervention and treatment strategies. T-lymphocyte depletion
renders affected individuals more susceptible to fungal infections, viral
270

infections, and neoplastic growth. Some immune surveillance is also


diminished, enabling bacterial infections to flourish. Thus, it is not
surprising to find oral infections of these types in patients with HIV disease.

Fungal Infections
Candidiasis
Intraoral candidiasis, which is mainly caused by Candida albicans, is the
most common oral manifestation in patients with HIV disease. Although it is
not in itself pathognomonic for HIV disease, oral candidiasis may be an
indication of immune dete-rioration. A tentative diagnosis of oral candidiasis
is usually based on clinical appearance but should be confirmed by
laboratory tests. These tests include cytologic smears with potassium
hydroxide, biopsy for periodic acidSchiff and Gram staining for tissue
infiltration by spores and hyphae, or culture. In general, oral candidiasis has
four different clinical presentations, as follows:
1.Pseudomembranous candidiasis,or thrush
This condition is a common type of oral candidiasis. It manifests as white or
yellowish single or confluent plaques that can easily be rubbed off from the
oral mucosa. It is found on all oral surfaces and may leave an erythematous
or even bleeding underlying mucosa. Most patients are not aware of the
presence of this form
of candidiasis as pseudomembranous candidiasis is predominantly
asymptomatic. The condition is noticed most commonly when CD4 cells
counts drop below400 cells/mm3.
2.Erythematous or atrophic candidiasis
This condition appears on any mucosal surface as a reddish macular lesion,
atrophic patches, or depapillation on the dorsum of tongue . Erythematous
271

candidiasis

may

be

present

alone

or

in

combination

with

the

pseudomembranous type. Patients may complain of an occasional burning


sensation in the mouth. Long-standing lesions may even present as mucosal
ulcerations.
3.Hyperplastic or chronic candidiasis
This form of candidiasis is relatively uncommon and is found mainly in
persons who are severely immunocompromised. Hyperplastic candidiasis,
manifesting as white or discolored plaques that may be solitary or confluent
and cannot be wiped off the mucosa,may be confused with oral hairy
leukoplakia when located on the tongue only.Complaints of a burning
sensation, dysphagia, and a feeling of having a large piece of cotton in the
mouth are not unusual. This type of oral candidiasis is often present with
esophageal candidiasis.
4.Angular cheilitis
This condition, which is predominantly a mixed infection involving C.
albicans and Staphyloccocus aureus, manifests itself as red fissures
originating from the labial commissures of the mouth. Angular cheilitis may
be present with intraoral candidiasis. Concurrent oral dryness also is not
uncommon. Angular cheilitis has been associated with vitamin B deficiency
and decreased vertical dimension of occlusion from either periodontal
disease or ill-fitting dentures. Therefore, it is important to address concurrent
conditions as antifungal treatment is instituted.
Treatment

272

Treatment of oral candidiasis includes topical and systemic antifungal


medications.Appropriate treatment should be instituted to reduce symptoms
ranging from localized discomfort to significant dysphagia. Topical therapies
include mouth rinses, troches, ointments, and creams. These formulations
should be used concurrently with systemic agents to resolve the
infection when there is a risk of esophageal candidiasis. Since there is a high
sucrose content in these preparations, which predisposes patients to develop
dental caries, a strict oral hygiene program and daily flouride treatment
should be instituted while the patient is taking topical antifungal
medications. Topical antifungal therapies are most efficacious in patients
with CD4 counts above 150 to 200 cells/mm3. In patients with atrophic
candidiasis, troches should be used with care since they may aggravate
existing ulcerations through mechanical abrasion against the lesions.114
Common topical treatments include nystatin oral suspension (100,000
units/mL; 10 mL swished and swallowed four to five times per day) and
Colour Plate- 22

Pseudomembranous Candidiasis

Angular Cheilitis

273

Erythematous Candidiasis

Hyperplastic Candidiasis

nystatin troche (dissolved in the mouth four to five times per day).
Ointments and creams such as 1% clotrimazole ointment, 2% ketoconazole
cream, or nystatin cream are efficacious in treating angular cheilitis.
The efficacy of systemic antifungal medications may be significantly
reduced by impaired gastric acid secretion and by drug interactions with
medications such as rifampin. Furthermore, there exists a potential for liver
toxicity that needs to be addressed. Common systemic antifungals include
Ketoconazole(kenazole 200 mg tablets, one tablet twice a day with food),
fluconazole (flucot 100 mg tablets, 200 mg on day 1, followed by 100 mg
daily for 14 days), and itraconazole (itrole 100 mg tablets, 200 mg daily with
food). Resistance to fluconazole has been reported to occur in patients with

274

severe immune deficiency. Treatment of patients who are resistant to


fluconazole with a combination of fluconazole and terbinafine has been
successful. 180 It is also possible to increase the fluconazole dosage to 600 to
700 mg/day in order to improve efficacy. Another approach to treat
fluconazole resistant fungal infections is to add a topical medication such as
clotrimazole troches. This is successful if the resistance is owing to the
emergence of Candida krusei, a species resistant to fluconazole but
susceptible to clotrimazole. Protease inhibitor therapy has been associated
with a decreased incidence of oral candidiasis. This is owing mainly to
improved immune status but may also be a direct result of the protease
inhibitors.
Deep-Seated Infections
Intraoral manifestations of deepseated fungal infections, caused by
Cryptococcus neoformans, Histoplasma capsulatum, Geotrichum candidum,
and Aspergillus spp, are uncommon and are usually an indication of a
disseminated disease.116,117 Intraoral lesions associated with cryptococcosis,
histoplasmosis, and aspergillosis have been reported as being ulcerative,
nodular, or necrotic in nature, whereas geotrichosis lesions are described as
being pseudomembranous. Since oral lesions of this category are
nonspecific, definitive diagnosis requires histologic verification. Treatment
of these lesions is usually reserved for intravenous amphotericin B.
Viral Infections
Although there are no specific oral lesions caused by HIV infection, a
patient can display oral manifestations as an early sign of HIV infection.
Such oral symptoms may include nonspecific oral ulcerations, sore throat,

275

exudative pharyngitis, and oral candidiasis during the initial acuteinfection


state.These nonspecific manifestations disappear after the acute phase.
Herpesvirus
Oral herpes simplex virus (HSV) presents both as a local and a disseminated
infection. The presence of intraoral HSV-associated lesions is usually the
result of recurrent infections caused by reactivation of latent viruses. This
lesion is not specifically related to HIV, it is also a fairly common
occurrence among non-HIV infected individuals. However, HSV infections
among immunocompromised individuals may be more severe and manifest
differently than what is noticed in immunocompetent patients. Although
ulcerations caused by HSV-1 and HSV-2 are clinically indistinguishable,
HSV-1 is more frequently associated with oral lesions.However, oral lesions
caused by HSV-2 appear to have a higher recurrence rate and are associated
with a higher incidence of resistance to acyclovir.
HSV in the oral cavity manifests as single or coalescent crops of vesicles
with subsequent ulceration and healing. The ulcers are small, shallow, and
round to elliptical. In general, recurrent HSV infections occur primarily on
more keratinized epithelium such as the gingiva. However, there are
numerous reports of oral ulcerations caused by HSV infections on
nonkeratinized epithelium in HIV-infected patients. HSV associated
ulcerations are usually accompanied by increased pain during the acute
stage, which can affect an individuals nutritional intake. These ulcerations
tend to heal in 7 to 10 days, although this may be extended in
immunocompromised patients. In this particular patient population, lesions
tend to be larger and occur with increased frequency. Furthermore, in these
patients, recurrent HSV may exhibit clinical signs and symptoms that are

276

similar to those of primary HSV infection, such as malaise, cervical


lymphadenopathy, and intensely painful linear gingival erythema.1
Oral manifestations of HSV can be mistaken for other viral infections such
as Cytomegalovirus and varicella-zoster virus, infection or for aphthous
ulcers, and a definitive diagnosis should be made based on the clinical
history and laboratory tests, such as cytologic staining for Tzanck cells, viral
culture from the ulcer, biopsy, or HSV-1 detection via monoclonal-antibody
testing.Treatment for HSV-1 infections usually consists of acyclovir (200 mg
orally five times daily). Although famciclovir can also be used, valacyclovir
is a poor alternative because it may cause severe side effects in
immunocompromised patients.Foscarnet may be used for resistant
infections.
Cytomegalovirus
Oral manifestation of Cytomegalovirus (CMV) infection is only observed in
patients with CD4 counts below 100 cells/mm3. Lesions associated with
CMV are nonspecific ulcerations that usually appear as a single ulcer,
without preceding vesicles, on any oral mucosal tissue. These ulcers are
painful and tend to heal poorly. Differential diagnosis should include
recurrent aphthous ulcers and HSV-associated lesions. A definitive diagnosis
must include a biopsy specimen that shows basophilic intranuclear
inclusions of CMV, or CMV identification via monoclonal-antibody assay or
in situ hybridization. A recommended regimen for intraoral lesions is high
dose acyclovir therapy (800 mg orally five times a day) for a minimum of 2
weeks. Oral manifestations of CMV may be associated with disseminated
disease, and the patient needs to be evaluated for ophthamologic and other
CMVassociated diseases once an oral diagnosis is confirmed.
Epstein-Barr Virus
277

Epstein-Barr virus (EBV) infections have been associated with numerous


manifestations, including infectious mononucleosis, Burkitts lymphoma,
nasopharyngeal carcinoma, and oral hairy leukoplakia. Oral hairy
leukoplakia was initially described in individuals with HIV disease, but it
has since been found in many other patient populations. This lesion may be
present in all phases of HIV disease, but it is most commonly found in
individuals with CD4 cell counts below 200 cells/mm3. It manifests as an
asymptomatic white lesion, most frequently with vertical hyperkeratotic
striae that are usually seen on the lateral borders of the tongue. The lesion
may vary from linear striae to white patches that cannot be wiped off, and
they often have white hyperkeratotic hair like projections. Because of its
clinical characteristics, differential diagnosis should include hyperplastic
candidiasis. Although it is not thought that Candida albicans contributes to
the clinical appearance of oral hairy leukoplakia, C. albicans may be present
in more than 50% of oral hairy leukoplakia lesions. When definitive
diagnosis of oral hairy leukoplakia needs to be established, it is necessary to
verify the presence of EBV in the superficial layers of the involved
epithelium. Owing to the significant association between this lesion and
HIV, a biopsy is necessary to rule out oral hairy leukoplakia in patients yet to
be tested for HIV. In HIV-positive individuals, an empiric diagnosis can be
inferred when a clinical lesion resembling oral hairy leukoplakia does not
respond to antifungal medications. It is important to assure the patient that
the presence of oral hairy leukoplakia has not been associated with person-to
person transmission of EBV. Treatment of this lesion usually is not indicated
unless the patient complains of esthetic disfiguration or masticatory
functional impairment. Antiviral therapy (acyclovir (acivir) 800 mg orally

278

five times a day for 7 days). Prophylactic therapy with 800 mg acyclovir per
day may be necessary to prevent recurrence.
Varicella-Zoster Virus
There have been reports of increased incidence of human varicella-zoster
virus (HZV) infections among HIV-infected persons, relative to increased
age and degree of immunosuppression. Complications associated with HZV
in immunocompromised patients are common and can be severe, especially
for those individuals with CD4 counts fewer than 200 cells/mm3. 188
Clinically, oral HZV infection presents as vesicles that quickly rupture,
resulting in ulcerations. The ulcers are multiple, shallow, and small, with an
erythematous base, and are characteristically distributed unilaterally along a
division of the fifth cranial nerve. Patients frequently complain of pain,
neuropraxia, and tenderness. Although clinical presentation is distinct for
HZV infection, a definitive diagnosis should be confirmed by laboratory
tests such as histologic staining for multinucleated giant cells with
intranuclear inclusions, direct immunofluorescence, and cytology smears
taken from the lesion. Treatment usually is focused on supportive care and is
centered on the prevention of postherpetic neuralgia and dissemination.
High doses of oral acyclovir (800 mg orally five times a day), famciclovir
(virovir 500 mg orally three times a day), or valaciclovir (valcivir 500 mg
orally three times a day) have been efficacious in treating HZV infection.
Caution is needed when using valacyclovir in severely immunosuppressed
patients as this medication has been associated with hemolysis in this
particular patient population. For greatly immunosuppressed patients,
intravenous acyclovir therapy may be more appropriate. Foscarnet also may
be useful for acyclovir resistant herpes zoster.
Human Herpesvirus 8
279

Recently, human herpesvirus 8 (HHV8) has been linked to the etiology of


Kaposis sarcoma (KS). Most intraoral KS lesions are found on the hard and
soft palates, manifesting as red-blue or purple-blue macules or nodules. The
lesions are initially asymptomatic, but due to trauma and secondary
ulcerations, they can become symptomatic as they get larger in size. Large
lesions may interfere with the individuals ability to speak, swallow, and
masticate.Lesions on the gingiva and tongue are also common, however,
extrapalatal lesions are associated with a more rapid progression of KS, as
well as HIV disease. Oral KS is usually seen in patients with CD4 counts
below 200 cells/mm3 but can be seen in all stages of HIV disease. The
macular lesions can be confused with physiologic pigmentation, a
differential

diagnosis

should

also

include

bacillary

(epithelioid)

angiomatosis, lymphoma, and trauma. As KS is an AIDS defining lesion, a


definitive diagnosis requires a biopsy.
Treatment for KS includes:
1.Intralesional injections with chemotherapeutic agents such as vinblastine
sulfate (0.1 mg/mm2 ) or sodium tetradecyl sulfate (0.1 mg/mm2 ).
2.Radiation (800 to 2,000 rad) 3.Surgical excision
Intralesional injections are most effective for small nodular lesions and as an
adjuvant to radiation. It is important to realize that most of these treatments
do not result in a cure but are used to reduce the size and number of lesions.
Recent studies show some efficacy with antiangiogenesis agents, such as
thalidomide, and oral 9-cis retinoic acid.119No antiherpetic medications have
shown any benefit as prophylaxis or treatment for KS.
Human Papillomavirus
Oral

manifestations

with

papillomaviruses

are

similar

to

human

papillomavirus (HPV) infections at other sites. Infections with HPV may


280

cause different distinct appearances, including oral squamous cell


papilloma, verruca vulgaris, focal epithelial hyperplasia, and condyloma
acuminatum. Each lesion has a specific expression of an identified HPV
genotype. Oral squamous cell papillomas may present as exophytic
pedunculated papules with a cauliflower-like appearance.
Verruca vulgaris (the common wart) is a firm, sessile, exophytic, and
whitish lesion. This form of HPV presentation also has a hyperkeratinized
superficial epithelium with a slight invagination of the center of the lesion.
Focal epithelial hyperplasia (Hecks disease) may present as a single or
multiple, smooth or pebble-like, hyperplastic leukoplakic lesion. Focal
epithelial hyperplasia is commonly found on keratinized tissues such as the
alveolar mucosa and the lips.
Condyloma acuminatum presents as small white-to-pink nodules with a
pebbled surface and is most commonly found on the soft and hard palates
and the tongue.
The presence of HPVassociated lesions is not pathognomonic for HIV
infection or progression. However, an increase in the prevalence of oral
HPV infections among HIV infected persons has been reported since the
Color Plate-23

281

Kaposis Sarcoma

HPV associated Warts

Oral Hairy Leukoplakia

282

introduction of protease inhibitors. Although most of oral HPV


manifestations are asymptomatic, unless lesions are induced by trauma, they
can interfere with mastication and may raise cosmetic concerns.
Treatments for HPV include surgical removal, laser ablation, cryotherapy,
and topical application of keratinolytic agents. For smaller lesions, topical
application of 25% podophyllum resin may be used to reduce the size.A
more novel approach has been the use of intralesional injection of antiviral
agents. Interferon-(alferon in intralesional injections (1,000,000 IU/cm2
once weekly) and subcutaneous injections (3,000,000 IU/cm2 twice weekly)
have been shown to be effective in long-term resolution of lesions.196
Bacterial Infection
Periodontal Disease: The most common oral manifestations of bacterial
origin are associated with periodontal conditions. These conditions are
usually categorized by their clinical appearance and include linear gingival
erythema (LGE), necrotizing ulcerative gingivitis (NUG), and necrotizing
ulcerative periodontitis (NUP). It has also been noted that HIV-seropositive
patients with previous periodontal disease may show faster rates of
conventional periodontal deterioration as compared with those of HIVseronegative persons. The level of immune suppression, as demonstrated by
decreasing number of T-cell lymphocytes, in combination with the degree of
plaque accumulation, may explain periodontal conditions in HIV-infected
patients.
Linear gingival erythema is an atypical gingivitis that is depicted as a 2 to
3 mm distinct band of fiery redness at the marginal gingiva around the teeth.
Such erythema is not proportional to the plaque accumulation and seems to

283

Color Plate-24

Necrotizing Ulcerative Gingivitis

Linear Gingival Erethema

Necrotizing Ulcerative Periodontitis

284

only affect the soft tissue, without any ulcerations, increased pocket depths,
or any attachment loss. Patients with this condition are usually
asymptomatic.Differential diagnosis should include a localized erythema
due to dry mucosa associated with mouth breathing, lichen planus,mucous
membrane pemphigoid, or an allergic reaction. The most recent theory
regarding the pathogenesis of this lesion implicates subgingival candida
infection as a possible cause.
Treatments include improved oral home care and conventional dental
scaling and root planing, along with the use of chlorhexidine gluconate
(0.12%) mouth rinses (15 mL swished and expectorated twice a day) for up
to 3 months. Additionally, concomitant use of topical antifungal medications
may be beneficial. Manifestations of NUG and NUP are triggered by
changes in the immune status, most probably aggravated by intraoral
bacteria. The two entities may present as a continuum of the same disease
but also may appear as separate entities. NUG is limited to the gingiva,
whereas NUP is characterized by localized to generalized aggressive
alveolar bone and attachment destruction. Occurrence of NUG has been
associated with stress, anxiety, malnutrition, and smoking. Patients with
NUG complain of spontaneous gingival bleeding and mild to moderate
gingival pain. NUP is associated with complaints of deep-seated bone pain,
spontaneous gingival bleeding, halitosis, and tooth mobility. Clinically, these
conditions are presented with initial lesions of limited crater like necrosis of
gingival papillae. When untreated, NUP may progress at a rate of 1 to 2 mm
of soft- and hard-tissue destruction per week. NUP is mostly seen with
severe immune suppression, with CD4 counts below 100 cells/mm3.A
definitive diagnosis is based on clinical evaluation and radiologic evaluation
285

with panoramic radiographs or specific periapical dental radiographs.


Specific laboratory tests may be needed to rule out conditions and lesions
such as bullous lesions of benign mucous membrane pemphigoid, erythema
multiforme, acute forms of leukemia, and major aphthous ulceration.
Treatment for both NUG and NUP consists of debridement of necrotic soft
and hard tissue, antibiotic therapy with metronidazole(400mg 3 times a day)
or tetracycline (500 mg four times a day) for a week, and a follow-up with
scaling and dbridement. Due to the high risk for fungal infections in these
patients, an antifungal regimen may be prescribed together with the
antibiotics.

Chlorohexidine

gluconate

(0.12%)

mouth

rinses

are

recommended as maintenance therapy. Metronidazole should be used with


caution in patients who are taking lopinavir and retonavir.

Nonspecific Ulcerations
Necrotizing Stomatitis: Necrotizing stomatitis is a localized acute painful
ulcerative lesion on mucosal surfaces overlying bone. This condition
eventually leads to necrosis of tissue and subsequent bone exposure. No
specific microbial agent or mechanism has been linked to its etiology. This
condition is seen in patients with CD4 cells fewer than 100 cells/mm3.168
Differential diagnosis includes aphthous ulcer and NUP.Treatment consists
of careful debridement, local or systemic steroid therapy, antibiotics, and
institution of a soft-tissue stent to protect the affected area from further
trauma and for delivery of topical medications.201
Aphthous Ulcers:
Recurrent aphthous ulcerations (RAUs) are idiopathic oral ulcerations.
There are three disease entities of RAUs: minor, major, and herpetiform.
Diagnosis of RAUs is a diagnosis of exclusion, the clinical impression

286

should be confirmed with histologic examination and by response to


treatment.
Minor (recurrent) aphthous ulcerations are smaller than 10 mm in
diameter, well-circumscribed, round, sometimes covered by a yellow-gray
pseudomembrane, and surrounded by an erythematous halo. The
erythematous halo may be absent in severely immunocompromised patients
due to their lack of an intact inflammatory response.
Minor aphthous ulcerations are usually confined to the nonkeratinized oral
mucosa and tend to recur, often at the same site. Their duration is about 1 to
2 weeks, and healing occurs without scarring. Minor aphthous ulcerations
are prevalent in both nonHIVinfected populations and HIV-infected
populations. Differential diagnosis includes recurrent HSV infection.
Treatment is focused to provide symptomatic relief. An analgesic mouth
rinse, such as 2 to 4% viscous lidocaine solution (10 mL swished and
expectorated), is most commonly instituted for relief.
Major (recurrent) aphthous ulcerations are larger than 10 mm in diameter,
well-circumscribed, round, and shallow or deep with indurated margins. A
gray pseudomembrane covering the lesion may sometimes be present. Major
aphthous ulcerations can occur on any area of the oral mucosa. They are
usually single ulcerations, but in immunosuppressed individuals, groups of
up to 10 lesions have been observed. These ulcers tend to persist for more
than 3 weeks and to heal with a scar formation. In patients with HIV, major
aphthous ulcers have been associated with severe immune suppression, with
CD4 counts below 100 cells/mm3, and are markers for HIV disease
progression.

Treatment

for

major

aphthous

ulcerations

includes

administration of systemic corticosteroids. Topical formulations of


clobetasol or fluocinonide gel applied directly to the lesion, dexamethasone
287

mouth rinses (0.5 mg/5 mL), and systemic administration of 60 to 80 mg of


prednisone per day for 10 days have been used successfully. For steroidresistant patients, alternative therapy of 100 to 200 mg thalidomide may be
used. Thalidomide needs to be used with caution because of its severe
adverse side effects. However,despite its severe side effects, thalidomide has
been used with some success to treat both oral and esophageal ulcerations.
Refractory cases may be treated with other agents including colchicine or
levamisole.203 Antibiotics and antifungal agents may be used concurrently
when appropriate to prevent bacterial or fungal superinfections.
Herpetiform ulcers are the least common type of aphthous ulcers. These
ulcers are pinpoint (smaller than 1 mm in diameter) and round, with
perilesional erythema. They are usually found in batches of up to 100,
appearing on nonkeratinized mucosa such as the ventral surface of the
tongue and soft palate. Healing occurs without scarring. Treatments are
similar to those for minor aphthous ulcers and include symptomatic relief,
suppression of the local pathologic immune reaction, and treatment of any
concomitant superinfection.
Drug-Induced Ulcerations
Several medications that are frequently used for HIV-infected patients have
been associated with the development of oral ulcerations.204206 These
medications include zidovudine, zalcitabine, foscarnet, interferon, and
ganciclovir.207 Drug-induced ulcerations are mainly seen on nonkeratinized
mucosa, but they tend to affect keratinized mucosa in more severely
immunocompromised

patients.Certain

antiretroviral

therapies

induce

neutropenia and are thereby linked to the occurrence of oral ulcerations.

288

Administration of a growth factor such as granulocytemacrophage colonystimulating factor has shown to be successful in resolving ulcerations
associated with neutropenia.
Xerostomia
Xerostomia, or dry mouth, is a subjective symptomatic complaint that is
frequently noted by HIV-infected patients. It has been reported that reduced
salivary flow occurs in 2 to 10% of HIV-infected individuals.However, the
true prevalence is 80 to 90% of all patients taking HAART(Highly Active
Anti Retroviral Therapy). The effect of oral dryness on quality of life is
profound, and many patients with severe xerostomia sometimes opt to
change or stop their antiretroviral medications in order to regain better
salivary functions. The most common cause of decreased salivary flow in
HIVinfected patients is side effects of pharmocotherapeutic agents. Many
medications, such as antiretroviral medications (including nucleoside
transcriptase inhibitors, protease inhibitors) as well as antihistamines,
anticholinergics, antihypertensives, decongestants, narcotic analgesics, and
tricyclic antidepressants, have been associated with xerostomia. In addition,
xerostomia may be a result of HIV-associated salivary gland disease in this
population. The parotid glands are most frequently affected; however, minor
salivary glands can also be affected by viral infection such as with CMV.
Another cause of reduced salivary flow is radiation therapy to the head and
neck area, causing functional impairment of salivary glands in the radiated
area. Treatment for xerostomia focuses on symptomatic relief by
encouraging patients to hydrate themselves frequently and to minimize the
intake of caffeine and alcohol, which act as diuretics. Patients are also
recommended to use commercially available artificial saliva substitutes
289

(Xero-lube, Sali-synt,Moistir, Orex) to achieve relief. The use of pilocarpine


and bethanechol to stimulate salivary flow can also be useful. Ultimately,
discontinuation or substitution of xerostomia inducing drugs may be
necessary.
Oral Lesions in the Pediatric Population:
HIV-infected children may also develop a spectrum of oral lesions. These
lesions can affect children more severely than adults and can be a significant
source of pain with subsequent limitation of oral intake of nutrition and
medications. The most common oral manifestation in immunocompromised
children is candidiasis. The presence of oral candidiasis in HIV-infected
infants, as well as other clinical symptoms, is used as a clinical marker for
disease progression in a prognosis- based clinical staging system.Clinical
presentation of oral candidiasis in the pediatric population is similar to that
of the adult population. Some reports suggest that erythematous candidiasis
is more common than the pseudomembranous type in HIV-infected children.
A definitive diagnosis should be accompanied by laboratory tests, as
described previously. Both topical and systemic treatment with antifungal
medications can be used to treat oral candidiasis. Several reports have shown
that there are subtypes of Candida that are isolated in candidal lesions.
Therefore, it is not unreasonable to determine a specific subtype of Candida
and to select a specific antifungal agent directed toward the subtype. A report
has shown that fluconazole suspension (6 mg/kg loading dose followed by 3
mg/kg/d) has been highly effective and is superior to routine nystatin
rinses.213 In children who are fed by bottle, it is possible to place the
antifungal medication inside the nipple, as well as to cover the nipple with a
thin layer of topical medication. Several of the medications used by children
290

are made to taste better by the addition of sugar formulations, which also
make them syrupy and sticky. It is advisable to have children rinse their
mouths with water after administration of these medications in order to
reduce the incidence of tooth decay.

GRANULOMA INGUINALE
It is also called as granuloma venereum, donovanosis. It is found in inguinal
and anogenital region and is caused by Donovan granulomatosis and is a
chronic slowly progressing, mildly contagious disease.
Clinical Features
It chiefly affects adult black of either sex, but may occur in any race. Lesion
begins as a small papule that ulcerates, increases in size and eventually gives
rise to velvety, beefy, granulating and spreadin ulcerative lesion of inguinal
and anogenital region. Pseudo-bubo-inguinal ulceration is commonly
secondary to the genital lesion and arises initially as fluctuant swelling
known as pseudo-bubo. Metastatic spread to bone and soft subcutaneous
tissue has been reported.
Oral Manifestations
Oral lesion appears to be the most common extra genital form of granuloma
inguinale. Oral lesions occur either as a result of autoinoculation through
infected fingers or through oral coitus. It is most commonly found on lips,
buccal mucosa or palate or they may diffusely involve the mucosal surface.
Lesions of lip are characterized by extensive superficial ulceration with well
defined elevated, granulomatous margins.
Types may be of three types, i.e. ulcerative, exuberant and cicatrical.
Ulcerative-It is painful sometimes bleeding issassociated with it.

291

Exuberant-It appears as proliferative granular mass with an intact epithelial


covering. The mucous membrane is inflamed and edematous.
Cicatrical-Fibrous scar formation may become extensive.
Histopathological Features
Donovan bodies present in smears which are recognized as large, gramnegative oval bacteria with intense bipolar staining (safety pin appearance).
Management
Streptomycin or tetracycline is given. Treatment should continue until
healing is complete which usually takes 2 to 3 weeks. In chronic cases,
wound debridement followed by antibiotics therapy is helpful. Plastic
surgery is needed for correction of extensive scarring.

LYMPHOGRANULOMA VENEREUM
It is a venereal disease caused by one of the three strains of Chlamydia
trachomatis.
Clinical Features
There may be fever, chills, headache and malaise. It persists as firm, tender
enlargement of inguinal lymph nodes. Nodes are tender and adherent to the
underlying tissues.Enlargement of lymph nodes both above and below the
inguinal ligament, is characcteristic feature called as 'groove sign'. Overlying
skin becomes reddened and dusky and multiple purulent fistulae develop
over enlarged glands, In females, placenta is frequently involved.
Marked scarring and local edema frequently develops secondary to
suppurative lymphadenitis.
Diagnosis is done by complement fixation test.
Oral Manifestations
Results due to orogenital contact. Tongue is the most common site.
292

Lesion consists of small, slightly painful superficial ulceration with nonindurated borders which appear on lip.In long-standing infection, there is
zone of cicatrical refraction, dark red area with loss of superficial
epithelium, or opaque lichenoid grayish papules.
Dysphagia, red soft palate and small red granulomatous lesions accompanied
by regional lymphadenopathy, are commonly associated symptoms. Cervical
lymphadenopathy is present. Skin covering the swollen nodes is violaaceous
and indurated usually with one or more draining sinuses.
MANGEMENT
Antibiotic therapy of tetracycline and erythromycin.

293

BIBLIOGRAPHY
REFERENCES

1.Manfred Strassbung, disease of oral mucosa. A colour atlas 2nd


Quitencence books.Pg-154.
2. Lipsett J, Sparnon AL, Byard RW, et al. Embryogenesis of
enterocystomas-enteric duplication cysts of the tongue. Oral Surg Oral Med
Oral Pathol 1993;75:62630.
3.Gorlin RJ, Jirasek JE. Oral cysts containing gastric or intestinal mucosa:
unusual embryologic accident or heterotopia. J Oral Surg 1970;28:911
4.DeMeester SR, Campos GM, DeMeester TR, et al. The impact of an
antireflux procedure on intestinal metaplasia of the cardia. Ann Surg
1998;228:54756.
5.Wyngaarden JB, Smith LH. Cecil textbook of medicine. 16th ed.
Philadelphia (PA):W.B. Saunders; 1982;16(1):137082.
6. Richter JE. Typical and atypical presentation of gastroesophageal reflux
disease. Gastroenterol Clin North Am 1996;25(1):75102.
7. Richter JE. Short segment Barretts esophagus: the need for
standardization of the definition and of endoscopic criteria.
8. Yagiela JA,Neidle EA,Dowd FJ. Pharmacology and theraputics for
dentistry. 4th ed. St. Louis (MO):Mosby; 1998;44952.
9.Gastrointest Surg 1993;93:10336Pearson TC.Apparent polycythemia.
Blood Rev 1991;5:20513.
10.Arendt DM, Frost R, Whitt JC, Palamboro J.Multiple radiopaque masses
in jaws. J Am Dental Assoc 1989,118(3),349-51
11. Chen TS, Chen PS. Rise and fall of the Plummer-Vinson syndrome. J
Gastroenterol Hepatol 1994;9(6):6548.

294

12. Wescott WB, Correll RW. Oral and perioral pigmented macules in a
patient with gastric and intestinal polyposis. J Am Dent Assoc
1984;108(3):3856.
13. Mignogna MD, Lo Muzio L, Ruocco V, Bucci E. Early diagnosisof
multiple hamartoma and neoplasia syndrome (Cowden syndrome): the role
of the dentist. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1995;79(3):2959.
14. Porter S, Cawson R, Scully C, Eveson J. Multiple hamartoma syndrome
presenting with oral lesions. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1996;82(3):295301.
15. Katz JO,Chilvarquer LW,Terezhalmy GT. Gardners syndrome: report of
a case. J Oral Med 1987;42:2115. 3. Pearson TC.Apparent polycythemia.
Blood Rev 1991;5:20513.
16.3. Pearson TC.Apparent polycythemia. Blood Rev 1991;5:20513.17.4.
Cook JD, Skikne BS, Baynes RD. Iron deficiency: the global perspective.
Adv Exp Med Biol 1994;356:21928.
18.5. Provan D. Mechanisms and management of iron deficiency anemia. Br
J Haematol 1999;105 Suppl 1:1926.
19.7. Lindenbaum J.An approach to anemias. In: Bennett JC, Plum F,
editors. Cecil textbook of medicine. 20th ed. Philadelphia: WB Saunders
Co.; 1996. p. 823.
20.Shafer.W.G, Hine.M.K and Levy.B.M(1983) Dieases of blood and blood
forming

organs.In

textbook

of

oral

pathology(4the

719,W.B.Saunders,Philedelphia.
21. Greenberg MS. Clinical and histologic changes of the oral
mucosa in pernicious anemia. Oral Surg Oral Med Oral Pathol
1981;52:3842
295

edition)p-

22. Heaney ML.Myelodysplasias. N Engl J Med 1999;340:164960.


23. Lowenberg B, Downing JR, Burnett HA. Acute myeloid leukemia. N
Engl J Med 1999;341:105162.
24. Golub TR, Barker GF, Stegmaier K, Gilliland DG. The TEL gene
contributes to the pathogenesis of myeloid and lymphoid leukemias by
diverse molecular genetic mechanisms.Curr Top Microbiol Immunol
1997;220:6779.
25. Misumi DJ, Nagle DL, McGrail SH. The physical and genetic map
surrounding the LYST gene on mouse chromosome 13. Genomics
1997;40:14750.
26. Barrat FJ, LeDeist F, Bankerrov M, et al. Defective CTLA-4 cycling
pathway in Chdiak-Higashi syndrome: a possible mechanism for
deregulation of T lymphocyte activation. ProcNatl Acad Sci U S A
1999;96:864550.
27. Freda PU, Wardlaw SL. Clinical review 110: diagnosis and treatment of
pituitary tumors. J Clin Endocrinol Metab
1999;84:385966.
28. MacArthur L, Eiden L.Neuropeptide genes: targets of activitydependent
signal transduction. Peptides 1999,17:7218.
29.Hanna FWF Lazarus JH, Scanlon MF. Fortnightly review: controversial
aspects of thyroid disease. BMJ 1999;319:8949.
30. Harris B. Postpartum depression and thyroid antibody status. Thyroid
1999;9:699703.
31. Woeber KA. The year in review; the thyroid. Ann Intern Med
1999;131:95962.

296

32. Nobuyuki A, Tada H,Hidaka Y. Postpartum autoimmune thyroid


syndrome: a model of aggravation of autoimmune disease. Thyroid
1999;9:70513.
33. Anonymous. Clinical guideline part 1. Screening for thyroid disease.
American College of Physicians. Ann Intern Med 1998;129:1413.
34. Maussier M, DErrico G, Putignano P, et al. Thyrotoxicosis: clinical and
laboratory assessment. Rays 1999;24:26372.
35. LaFranchi S.Congenital hypothyroidism: etiologies, diagnosis and
management.Thyroid 1999;9:73540.
36. Weetman AP. Hypothyroidism: screening and subclinical disease BMJ
1997;314:11758.
37. Oppenheimer JH. Evolving concepts of thyroid hormone action.
Biochimie 1999;81:53943.
38. Filetti S, Bidart J-M,Arturi F, et al. Sodium/iodide symporter: a key
transport system in thyroid cancer cell metabolism. Eur J Endocrinol
1999;141:44357.
39. Krogh Rasmussen A, Hartoft-Nielsen ML, Feldt-Rasmussen U.Models
to study the pathogenesis of thyroid autoimmunity. Biochimie 1999;81:511
5.
40. Segni M, Leonardi E, Mazzoncini B, et al. Special features of Graves
disease in early childhood. Thyroid 1999;9:8717.
41. Di Cerbo A, Corda D. Signaling pathways involved in thyroid
hyperfunction and growth in Graves disease. Biochimie 1999;81:41524
42. Heufelder AE, Bahn RS. Evidence for the presence of a functional TSH
receptor in retroocular fibroblasts. Exp Clin Endocrinol 1992;100:627.

297

43. Heufelder A,Wenzel B, Bahn R. Cell surface localization of a 72


kilodalton heat shock protein in retroocular fibroblasts from patients with
Graves ophthalmopathy. J Clin Endocrinol Metab 1992;74:7326.
44. Heufelder AE,Kahaly GJ. Thyroid-associated orbitopathy. Exp Clin
Endocrinol & Diabetes 1999;107 Suppl:S15257.
45. Wiersinga WM.Environmental factors in autoimmune thyroid disease.
Exp Clin Endocrinol Diabetes 1999;107:S6770.
46. Kohriyama K,Katayama Y, Tsurusako Y. Relationship between primary
Sjogrens

syndrome

and

autoimmune

thyroiditis.

Nippon

Rinsho

1999;57:187881.
48. Baccarelli A. [Occupational agents and endocrine function:
updating of experimental and human data. Med Lav
1999;90:65070.
49. Dunn JT, Dunn AD. The importance of thyroglobulin structure
for thyroid hormone biosynthesis. Biochimie 1999;
81:5059.
50. Udelsman R, Chen H. The current management of thyroid
cancer. Adv Surgery 1999;33:127.
51. Fadda G, LiVolsi VA. Histology and aspiration cytology of
benign thyroid diseases. Rays 1999;24:18296.
52. Meller J, Becker W. Scintigraphy with 99mTc-pertechnetate
in the evaluation of functional thyroidal autonomy. Q J Nucl
Med 1999;43:17987.
53. Pacini F, Pinchera A. Serum and tissue thyroglobulin measurement:
clinical applications in thyroid disease. Biochimie
1999;81:4637.
54. Walsh RM,Watkinson JC, Franklyn J. The management of the
298

solitary thyroid nodule: a review. Clin Otolaryngol 1999;


24:38897.
56. Hillebrand G, Siebert R, Simeoni E, Santer R. DiGeorge syndrome with
discordant phenotype in monozygotic twins. J
Med Genet 2000;37:E23.
57. Weissman IL, Shizuru J. Immune reconstitution.N Engl J Med
1999;341:1227-9.
58. Rogers MH, Lwin R, Fairbanks L, et al. Cognitive and behavioral
abnormalities in adenosine deaminase deficient severe
combined immunodeficiency. J Pediatr 2001;139:44-50.
59. Savitsky K, Bar-Shira A, Gilad S, et al. A single ataxia telangiectasia
gene with a product similar to PI-3 kinase. Science
1995;268:1749-53.
60. Norhagen GE, Engstrom PE, Hammarstrom L, et al. Oral and
intestinal microflora in individuals with different immunoglobulin
deficiencies. Eur J Clin Microbiol Infect Dis 1990;9:631-3.
61. Greenberg MS. Oral herpes simplex infections in immunosuppressed
patients. Compend Suppl 1988;9:S28991.
62. Porter AR, Scully C. Orofacial manifestations in the primary
immunodeficiency disorders. Oral Surg Oral Med Oral Pathol
1994;78:413.
63. Spickett GP, Misbah SA, Chapel HM. Primary antibody deficiency in adults. Lancet 1991;337:281-4.
64. Tolo K. Periodontal disease mechanisms in immunocompromised
patients. J Clin Periodontol 1991;18:431-5.
65. Porter AR, Scully C. Orofacial manifestations in primary
immunodeficiencies: IgA. J Oral Pathol Med 1993;22:1179.
299

66. Porter AR, Scully C. Orofacial manifestations in primary


immunodeficiencies: common variable immunodeficiencies. J
Oral Pathol Med 1993; 22:1578.
67. Buckley RH. Advances in the diagnosis and treatment of primary
immunodeficiency diseases. Arch Intern Med
1986;146:377-84.
68. Huston DP, Kavanaugh AF, Rohane PW, Huston MM.
Immunoglobulin deficiency syndromes and therapy. J Allergy
Clin Immunol 1991;87:1-17.
69. Steihm ER. Appropriate therapeutic use of immunoglobulin.
Transfus Med Revi 1996;10:203.
70. Yu Z, Lennon VA.Mechanism of intravenous immune globulin
therapy in antibody mediated autoimmune diseases. N Engl
J Med 1999;340:227-8.
71. Arkachaisri T, Lehman TJ. Systemic lupus erythematosus and related
disorders of childhood. Curr Opin Rheumatol
1999;11:384-92.
72. Rubin RL. Etiology and mechanisms of drug-induced lupus.
Curr Opin Rheumatol 1999;11:35763.
73. McCurdy D. Genetic susceptibility to the connective tissue diseases.
Curr Opin in Rheumatol 1999;11:399-407.
74. Naparstek Y, Plotz PH. The role of autoantibodies in autoimmune
disease. Ann Rev Immunol 1993;11:79104.
75. Evans J.Antinuclear antibody testing in systemic autoimmune
disease. Clin Chest Med 1998;19:61325.
76. Mojcik CF, Klippel JH. End stage renal disease and systemic lupus
erythematosus. Am J Med 1996;101:1007.
300

77. De Rossi SS, Glick M. Lupus erythematosus: considerations for


dentistry. J Am Dent Assoc 1998;129:330-9.
78. Bluestein HG. The central nervous system in systemic lupus
erythematosus. In: Lahita RD, editor. Systemic lupus erythematosus.
New York: Churchill Livingstone; 1992. p. 639.
79. Monash S. Oral lesions of lupus erythematosus. Dent Cosmos
1931;73:511.
80. Rhodus NL, Johnson DK. The prevalence of oral manifestations of
systemic lupus erythematosus. Quintessence Int 1990;21:461-5.
81. Sanchez R, Jonsson R, Ahlfors E, et al. Oral lesions of lupus
erythematosus patients in relation to other chronic inflammatory oral
diseases: an immunologic study. Scand Dent Res 1988;96:569-78.
82. Karjalainen TK, Tomich CE. A histopathologic study of oral mucosal
lupus erythematosus. Oral Surg Oral Med Oral Pathol 1989;67:547-54.
83. Andonopoulos AP, Skopouli FN, Dimou GS, Drosos AA.
Sjgrens syndrome in systemic lupus erythematosus. J
Rheumatol 1990;17:201-4.
84. Glick M. Glucocorticosteroid replacement therapy: a literature
review and suggested replacement therapy.Oral Surg Oral
Med Oral Pathol 1989;67:61420.
85. De Rossi SS, Glick M. Dental considerations for the patient with renal
disease receiving hemodialysis. J Am Dent Assoc 1996;127:2119.
86. Mayes MD. Scleroderma epidemiology.Rheum Dis Clin North Am 1996;
22:75164.
87. Laing TJ, Gillespie BW, Toth MB, et al. Racial differences in
scleroderma among Michigan women. Arthritis Rheum 1997;40(4):734-42.

301

88.

Callen

JP.

Collagen

vascular

diseases.

Med

Clin

North

Am1998;82:121737.
89. Jimenez SA, Hitraya E, Varga J. Pathogenesis of scleroderma: collagen.
Rheum Dis Clin North Am 1996;22:64774.
90. Silver RM,Heyes MP,Maize JC, et al. Scleroderma, fasciitis and
eosinophilia associated with the ingestion of tryptophan. N
Engl J Med 1990;322:874-81.
91. Steen VD. Clinical manifestations of systemic sclerosis. Semin Cutan
Med Surg 1998;17:4854.
92. Steen VD,Conte C,Owens GR, et al. Severe restrictive lung disease in
systemic sclerosis. Arthritis Rheum 1994;37:12839.
93. Rademaker M,Meyric K, Thomas RH, et al. The anti-platelet effect of
nifedipine in patients with systemic sclerosis. Clin Exp Rheumatol
1992;10:57.
94. Rook AH, Freundlich B, Jegasothy BV, et al. Treatment of systemic
sclerosis with extracorporeal photochemotherapy: results of a multicenter
trial.Arch Dermatol 1992;128:337-46.
95. Nagy G, Kovacs J, Zeher M, et al. Analysis of the oral manifestations of
systemic sclerosis. Oral Surg Oral Med Oral Pathol 1994;77:1416.
96. Montesi A, Pesaresi A, Cavalli ML, et al. Oropharyngeal and esophageal
function in scleroderma.Dysphagia 1991;6:219-23.63101. Callen JP. Oral
manifestations of collagen vascular disease. Semin Cutan Med Surg
1997;16:3237.
97. Rubin MM, San Filippo RJ. Resorption of the mandibular angle in
progressive systemic sclerosis: case report. J Oral Maxillofac Surg
1992;50:75-7.

302

98. Wood KE, Lee P.Analysis of the oral manifestations of systemicsclerosis.


Oral Surg Oral Med Oral Pathol 1988;65:172.
99. Kovacs SO,Kovacs SC. Dermatomyositis. J Am Acad Dermatol
1998;39:899920.
100. Villalba L, Adams EM. Update on therapy for refractory
dermatomyositis and polymyositis. Curr Opin Rheumatol 1996;8:54451.
101. Michet C. Update in the epidemiology of the rheumatic diseases. Curr
Opin Rheumatol 1998; 10:12935. 70107. Gallagher KT, Bernstein B.
Juvenile rheumatoid arthritis.Curr Opin Rheumatol 1999;11:3726.
102. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism
Association 1987 revised criteria for the classification of rheumatoid
arthritis. Arthritis Rheum 1988;31:315-24.
103. Heinzelman M, Mercer-Jones MA, Passmore JC. Neutrophils and renal
failure. Am J Kidney Dis 1999;34(2):38499.
104. Centers for Disease Control and Prevention. Core curriculum on
tuberculosis. 3rd ed. Atlanta: US Department of Health and Human Services;
1994.
105. Bates JH, Stead WW. The history of tuberculosis as a global
epidemic.Med Clin North Am 1993;77:1205.
106. Orme IM, Anderson P, Boom WH. T cell response to Mycobacterium
tuberculosis. J Infect Dis 1993;167:148
107. Ellner JJ. The immune response in human tuberculosis: implications
for tuberculosis control. J Infect Dis 1997;176:1351.
108. Piatak M, Saag MS, Lang LC, et al. High levels of HIV-1 in plasma
during all stages of infection determined by competitive PCR. Science
1993;259:1749.

303

109. Perelson AS,Neumann AU,Markowitz M, et al. HIV-1 dynamics in


vivo: virion clearance rate, infected cell life-span, and viral generation time.
Science 1996;271:1582.
110. Glick M,Muzyka BC, Lurie D, et al. Oral manifestations associated
with HIV disease as markers for immune suppression and AIDS. Oral Surg
Oral Med Oral Pathol 1994;77:344.
111. Glick M,Muzyka BC, Salkin LM, et al. Necrotizing ulcerative
periodontitis: a marker for immune deterioration and a predictor for the
diagnosis of AIDS. J Periodontol 1994;65:393.
113. Patton LL. Sensitivity, specificity, and positive predictive value of oral
opportunistic infections in adults with HIV/AIDS as markers of immune
suppression and viral burden. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 2000;90:182.1998;27:1525.
114. Kademani D, Glick M. Oral ulcerations in individuals infected with
human

immunodeficiency

virus:

clinical

presentations,diagnosis,

management, and relevance to disease progression. Quintessence Int


1998;29:523.
115. Ghannoum MA, Elewski B. Successful treatment of fluconazole
resistant oropharyngeal candidiasis by a combination of fluconazole and
terbinafine. Clin Diagn Lab Immunol 1999,6:921
116. Glick M, Cohen SG, Cheney RT, et al. Oral manifestations of
disseminated Cryptococcus in a patient with acquired immunodeficiency
syndrome. Oral Surg Oral Med Oral Pathol 1987;64:454. with HIV disease.
Oral Surg Oral Med Oral Pathol 1994;77:116.
117. Heinic GS, Greenspan D,MacPhail LA, et al. Oral Geotrichum
candidum infection associated with HIV infection. A case report. Oral Surg
Oral Med Oral Pathol 1992;73:7268.
304

118. Glesby MJ,Moore RD,Chaisson RE. Clinical spectrum of herpes zoster


in adults infected with human immunodeficiency virus. Clin Infect Dis
1995;21:370.
119. Yarchoan R. Therapy for Kaposis sarcoma: recent advances
and experimental approaches. J AIDS 1999;21:S66.
120.Immunization in practice a practical guide for health staff by world
health organization .

305