A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 20

Volume 4 • Number 1 • December 1999

Non-Plaque-Induced Gingival Lesions

Palle Holmstrup*

* University of Copenhagen, Copenhagen, Denmark.

The origin of gingival inflammation is occasionally different from

that of routine plaque-associated gingivitis, and such non-plaque-
associated types of gingivitis often present characteristic clini-
cal features. Examples of such forms of gingivitis are specific
bacterial, viral, and fungal infections. Specific bacterial infec-
tions of gingiva may be due to Neisseria gonorrhea, Treponema
pallidum, streptococci, and other organisms. The most impor-
tant viral infections of gingiva are herpes simplex virus type 1

and 2 and varicella-zoster virus. Fungal infections may be caused
by several fungi, the most important of these being Candida
species including C. albicans, C. glabrata, C. krusei, C. tropicalis,
C. parapsilosis, and C. guillermondii. Gingival histoplasmosis is
a granulomatous disease caused by the fungus Histoplasma cap-
sulatum and, as for the other specific infections of gingiva, a con-
firmed diagnosis may require histopathologic examination and/or
culture. Atypical gingivitis may also occur as gingival manifes-
tations of dermatological diseases, the most relevant of these
being lichen planus, pemphigoid, pemphigus vulgaris, erythema
multiforme, and lupus erythematosus. Non-plaque induced gin-
gival inflammation can be caused by allergic reactions to den-
tal restorative materials, toothpastes, mouthwashes, and foods.
In addition, gingival inflammation may result from toxic reac-
tions, foreign body reactions, or mechanical and thermal trauma.
Ann Periodontol 1999;4:20-29.
KEY WORDS
Gingival diseases/etiology; gingival diseases/microbiology;
gingival diseases/classification; virus diseases; dermatologic
diseases; risk factors; trauma; hypersensitivity; foreign
bodies.
20
T
his review is limited to those lesions
that are most relevant to the peri-
odontist, who plays an important role
not only in diagnosing the various types of
gingival manifestations mentioned but also
in treating them. Although non-bacterial gin-
givitis is not caused by plaque and usually
does not disappear after plaque removal, it
should be emphasized that the severity of
the clinical manifestations often depends on
an interaction with the bacterial plaque pre-
sent.1
INFECTIOUS GINGIVITIS
Gingival Lesions of Specific Bacterial
Origin
Infective stomatitis and gingivitis have been
observed on rare occasions in both
immunocompetent and immunocompro-
mised individuals. Lesions occur when non-
plaque related pathogens overwhelm innate
host resistance.2 Gingival lesions may occur
due to infections with Neisseria gonor-
rhea,3,4 Treponema pallidum,2-5 strepto-
cocci, or other organisms.6,7
Gingival lesions may manifest as fiery red
edematous painful ulcerations, as asymp-
tomatic cancres or mucous patches, or as
atypical non-ulcerated, highly inflamed gin-
giva. Oral lesions may or may not be
accompanied by lesions in other body sites.
Viral Infections
Several viral infections are known to cause
gingivitis.8 The most important are the her-
pes viruses: herpes simplex viruses types 1
and 2 and varicella-zoster virus. These
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 21
Ann Periodontol
viruses usually enter the human body in childhood and
may give rise to oral mucosal disease followed by peri-
ods of latency and sometimes reactivation.
Herpes simplex virus types 1 and 2. Herpes sim-
plex virus type 1 (HSV-1) usually causes oral mani-
festations whereas herpes simplex virus type 2 (HSV-
2) is mainly involved in anogenital infections and only
occasionally is involved in oral infection. Sometimes
herpes simplex viruses may also play a role in recur-
ring erythema multiforme. Primary herpetic gingivo-
stomatitis is the classic initial manifestation of HSV-1
infection. It is mainly contracted by young children,
but may also be acquired by adults. The characteris-
tic manifestation is painful severe gingivitis with ulcer-
ations and edema accompanied by stomatitis. A char-
acteristic feature is the formation of vesicles which
rupture, coalesce and leave fibrin-coated ulcers.9,10
Fever and lymphadenopathy are other classic features.
It is presently unknown whether the virus plays a role
in other oral diseases, but herpes simplex virus has
been found in gingiva,11 acute necrotizing gingivitis,12
and periodontitis.13 Immunocompromised patients are
at increased risk of acquiring the infection.14 Reacti-
vation of the virus resulting in recurrent infections
occurs in 20 to 40% of individuals with the primary
infection15 and usually presents in the form of herpes
labialis. Factors triggering reactivation of latent virus
are trauma, ultraviolet light, fever, and others.8 Recur-
rent intraoral herpes typically presents a less dramatic
course than does the primary infection. A character-
istic manifestation is a cluster of small painful ulcers
in the attached gingiva. The diagnosis can be made on
the basis of the patient history and clinical findings
supported by isolation of HSV from lesions. This can
be achieved by cultures, enzyme-linked immunosor-
bent assays, and polymerase chain reaction (PCR)
methods.16-18 A reliable isolation is best obtained from
early vesicular lesions.
Varicella-zoster virus. Varicella-zoster virus causes
varicella (chickenpox) as the primary self-limiting
infection. It occurs mainly in children and later reac-
tivation of the virus in adults causes herpes zoster
(shingles). Both manifestations can involve the gin-
giva.4,19 Chickenpox is associated with fever, malaise,
and a skin rash. The intraoral lesions are small ulcers
usually on the tongue, palate, and gingiva.8,20 The
virus remains latent in the dorsal root ganglion from
where it can be reactivated.21 Later reactivation
results in herpes zoster, with unilateral lesions fol-
lowing the infected nerve.20 Reactivation of virus from
the trigeminal ganglion may result in intraoral lesions.
Initial symptoms are pain and paraesthesia which
may be present before lesions occur.15 The associ-
ated pain is usually severe. The lesions, which often
involve the gingiva, initiate as vesicles. They soon
rupture to leave fibrin-coated ulcers which often co-
Holmstrup
alesce to irregular forms.22 In immunocompromised
patients, including HIV-infected individuals, the infec-
tion can result in severe tissue destruction with tooth
exfoliation and necrosis of alveolar bone and high
morbidity.23,24 The diagnosis is usually obvious due
to the unilateral occurrence of lesions associated with
severe pain.
Fungal Infections
Fungal infection of the oral mucosa may be due to
infections with several fungi. The oral infections include
aspergillosis, blastomycosis, candidosis, coccid-
ioidomycosis, cryptococcosis, histoplasmosis, mucor-
mycosis, and paracoccidioidomycosis infections.8
Some of these infections are very uncommon and not
all of them manifest as gingivitis. The present review
is limited to candidosis and histoplasmosis.
Candidosis. Several species of Candida are recov-
ered from the mouth of humans. The most important
include C. albicans, C. glabrata, C. krusei, C. tropicalis,
C. parapsilosis, and C. guillermondii.25 C. albicans is
by far the most common. The prevalence of oral car-
riage of C. albicans in healthy adults range from 3 to
48%,26 the variation being due to differences in exam-
ined populations, isolation techniques, and time of
sampling. The most common fungal infection of the
oral mucosa is candidosis mainly caused by the organ-
ism C. albicans.8 Infection by C. albicans is consid-
ered opportunistic and usually occurs as a conse-
quence of reduced host defense posture.27 The
predisposing factors are, however, often difficult to
identify. Based on their site, infections may be defined
as superficial or systemic. Candidal infection of the
oral mucosa is usually superficial.
In otherwise healthy individuals, oral candidosis
rarely manifests in the gingiva, which is surprising
when considering the frequent isolation of C. albicans
in the subgingival flora of patients with severe peri-
odontitis.28 Gingival candidal infections may occur in
HIV-seropositive and other immunocompromised
patients. One manifestation of the infection shows ery-
thema of the attached gingiva, a finding sometimes
referred to as HIV-associated gingivitis or linear gingi-
val erythema.29 Usually there are no significant symp-
toms.30 Other types of oral mucosal manifestations
are pseudomembranous candidosis (also known as
thrush in neonates), erythematous candidosis, plaque-
type candidosis, and nodular candidosis.31,32 Pseu-
domembranous candidosis shows whitish patches,
which can be wiped off the mucosa with an instrument
or gauze leaving a slightly bleeding surface. The
pseudomembranous type usually has no major symp-
toms. Erythematous lesions can be found anywhere in
the oral mucosa. The intensely red lesions are usually
associated with pain, which is often severe. The plaque-
type of oral candidosis is a whitish plaque, which can-
21
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 22
Non-Plaque-Induced Gingival Lesions
not be removed. There are usually no symptoms and
the lesion is clinically indistinguishable from oral leuko-
plakia. Nodular candidal lesions are infrequent in the
gingiva. They are characterized by slightly elevated
nodules of white or reddish color.31 The diagnosis of
candidal infection can be based on culture, smear, and
biopsy. Since oral carriage of C. albicans is common
among healthy individuals, positive culture and smear
do not necessarily imply candidal infection.33 Quanti-
tative assessment of the mycologic findings and the
presence of clinical changes compatible with the above
types of lesions are necessary to obtain a reliable diag-
nosis, which can also be obtained on the basis of iden-
tification of hyphae or pseudohyphae in biopsies from
the lesions.
Histoplasmosis. Histoplasmosis is a granulomatous
disease caused by Histoplasma capsulatum, which is
a soil saprophyte found mainly in feces from bird and
bat. The infection occurs in the northeastern, south-
eastern, mid-Atlantic, and central states of the United
States. It is also found in Central and South America,
India, East Asia, and Australia. Histoplasmosis, which
is the most frequent systemic mycosis in the U.S., is
mediated by airborne spores from the mycelial form
of the organism.34 In the normal host, the course of the
infection is subclinical.35 The clinical manifestations
include acute and chronic pulmonary histoplasmosis
and a disseminated form, mainly occurring in immuno-
compromised patients.36 Oral lesions have been seen
in 30% of patients with pulmonary histoplasmosis and
in 66% of patients with the disseminated form.37,38 The
oral lesions may affect any area of the oral mucosa.39
They initiate as nodular or papillary and later become
ulcerative and painful. They are sometimes granulo-
matous, and the clinical appearance may resemble a
malignant tumor.40 The diagnosis is based on clinical
appearance and histopathology and/or culture.
DERMATOLOGICAL DISEASES
A number of dermatological diseases may present gin-
gival manifestations sometimes in the form of desqua-
mative lesions of the gingiva or gingival ulceration.
The most relevant of these diseases are lichen planus,
pemphigoid, pemphigus vulgaris, erythema multiforme,
and lupus erythematosus.
Lichen Planus
Lichen planus is probably the most common muco-
cutaneous disease manifesting on the gingiva. The dis-
ease may affect skin and oral as well as other mucosal
membranes in some patients while others may pre-
sent either skin or oral mucosal involvement alone.
Oral involvement alone is common and concomitant
skin lesions in patients with oral lesions have been
found in 5 to 44% of the cases.41,42 The disease may
be associated with severe discomfort and since it has
22
Volume 4 • Number 1 • December 1999
been shown to possess a premalignant potential,
although this is still a controversial issue,43 it is impor-
tant to diagnose and treat the patients and to follow
them at regular intervals.44
The prevalence of oral lichen planus (OLP) in var-
ious populations has been found to be 0.1% to 4%.45
The disease may afflict patients at any age although
it is seldom observed in childhood.46
A variety of clinical appearances is characteristic
of OLP. These include papular, reticular, plaque,
atrophic, ulcerative, and bullous lesions. Simultane-
ous presence of more than one type of lesion is com-
mon.47 The most characteristic clinical manifestations
of the disease and the basis of the clinical diagnosis
are white papules and white striations which often form
reticular patterns.47 Sometimes atrophic and ulcerative
lesions are referred to as erosive.48 OLP frequently
persists for many years.47 Any area of the oral mucosa
may be affected by OLP but the lesions may change
in clinical type and extension over the years. Such
changes may implicate the development of plaque-
type lesions which are clinically indistinguishable from
oral leukoplakia. This may give rise to a diagnostic
problem if other lesions more characteristic of OLP
have disappeared.47
OLP is frequently asymptomatic or associated with
minor discomfort only. This is especially true for papu-
lar, reticular, and plaque type lesions which are often
unnoticed by the patient. In contrast, atrophic and ulcer-
ative lesions may give rise to severe pain, particularly
related to food intake and oral hygiene procedures.
A striking histopathologic feature in OLP is a subep-
ithelial, band-like accumulation of lymphocytes and
macrophages characteristic of a type IV hypersensitivity
reaction.49 The epithelium shows hyperortho- or hyper-
parakeratinization and basal cell disruption with trans-
migration of lymphocytes into the basal and parabasal
cell layers.50 The infiltrating lymphocytes have been
identified as CD4+ and CD8+ positive cells.49,51,52
Other characteristic features are Civatte bodies which
are dyskeratotic basal cells. Common immunohisto-
chemical findings of OLP-lesions are fibrin in the base-
ment membrane zone, but deposits of IgM, C3, C4,
and C5 may also be found. None of these findings are
specific to OLP.49,53,54
The subepithelial inflammatory reaction in OLP
lesions is probably due to a so far unidentified anti-
gen in the junctional zone between epithelium and
connective tissue or to components of basal epithe-
lial cells.52,55,56 A lichen planus specific antigen in
the stratum spinosum of skin lesions has been
described,57 but this antigen does not appear to play
a significant role in oral lesions since it is rarely iden-
tified there. It is still an open question whether OLP
is a multivariant group of etiologically diverse dis-
eases with common clinical and histopathological fea-
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 23
Ann Periodontol
tures or a disease entity characterized by a type IV
hypersensitivity reaction to an antigen in the base-
ment membrane area. The clinical diagnosis is based
on the presence of papular or reticular lesions. The
diagnosis may be supported by histopathologic find-
ings of hyperkeratosis, degenerative changes of basal
cells and subepithelial inflammation dominated by
lymphocytes and macrophages.
The uncertain background of OLP results in numer-
ous border-zone cases of so-called oral lichenoid
lesions (OLL) for which a final diagnosis is difficult to
establish. The most common OLLs are probably lesions
in contact with dental restorations.58 Other types of
OLL are associated with various types of medications
including antimalarials, quinine, quinidine, non-steroidal
anti-inflammatory drugs, thiazides, diuretics, gold salts,
penicillamine, beta-blockers, and others.45 Graft-ver-
sus-host reactions are also characterized by a lichenoid
appearance,59 and a group of OLL is associated with
systemic diseases such as hepatitis C.60-62 This appears
to be particularly evident in Southern Europe and Japan
where hepatitis C has been found in 20 to 60% of OLL
cases.62-64
Pemphigoid
Pemphigoid is a group of disorders in which autoanti-
bodies towards components of the basement mem-
brane result in detachment of the epithelium from the
connective tissue. Bullous pemphigoid predominantly
affects the skin, but oral mucosal involvement may
occur.65,66 If only mucous membranes are affected,
the term benign mucous membrane pemphigoid
(BMMP) is often used. The term cicatricial pemphigoid
is also used to describe subepithelial bullous disease
limited to the mouth or eyes and infrequently other
mucosal areas. The use of this term is a problem
because oral lesions rarely result in scarring, though
this is a danger for ocular lesions.8 The majority of
affected patients are females with a mean age of onset
of 50 years or older.67
Oral involvement in BMMP is almost inevitable and
usually the oral cavity is the first site of involve-
ment.68,69 Any area of the oral mucosa may be
involved in BMMP, but the main manifestation is
desquamative lesions of the gingiva presenting
intensely erythematous attached gingiva.68,70 Rubbing
of the gingiva may precipitate bulla formation.71 The
intact bullae are often clear to yellowish or they may
be hemorrhagic. This is due to the separation of epithe-
lium from connective tissue at the junction resulting in
exposed vessels inside the bullae. Usually, the bullae
rupture rapidly leaving fibrin-coated ulcers. Sometimes,
tags of loose epithelium can be found due to rupture
of bullae. Some patients have involvement of other
mucosal surfaces. Ocular lesions are particularly impor-
tant because scar formation can result in blindness.72
Holmstrup
The separation of epithelium from connective tis-
sue at the basement membrane area is the main diag-
nostic feature of BMMP. A nonspecific inflammatory
reaction is a secondary histologic finding. In addition,
immunohistochemical examination can help distin-
guish BMMP from other vesiculobullous diseases.
Deposits of C3, IgG, and sometimes other immuno-
globulins as well as fibrin are found at the basement
membrane zone in the vast majority of cases.73-75 It
is important to involve peri-lesional tissue in the biopsy
because the characteristic features may be lost within
lesional tissue.76 Circulating immunoglobulins are
found only occasionally in BMMP by indirect immuno-
fluorescence.77
It is now evident that BMMP comprises a group of
disease entities characterized by an immune reaction
involving autoantibodies directed against various base-
ment membrane zone antigens.78 These antigens have
been identified as hemidesmosome or lamina lucida
components.75,79-82 In addition, complement-mediated
cell destructive processes may be involved in the
pathogenesis of the disease.83 The trigger mechanisms
behind these reactions, however, have not yet been
identified.
Pemphigus Vulgaris
Pemphigus is a group of autoimmune diseases char-
acterized by formation of intraepithelial bulla in skin
and mucous membranes. The group comprises sev-
eral variants, pemphigus vulgaris (PV) being the most
common and most serious form.84
PV affects individuals of Jewish or Mediterranean
background more often than others, which verifies a
strong genetic background of the disease.85 The dis-
ease can occur at any age, but is typically seen in the
middle-aged or elderly. It presents with widespread
bulla formation often including large areas of skin, and
untreated the disease is life-threatening. Intraoral onset
of the disease with bullae formation is very common
and lesions of the oral mucosa including the gingiva
are frequently seen. Gingival involvement may pre-
sent as painful desquamative lesions of the gingiva or
as erosions or ulcerations which are remains of rup-
tured bullae.86,87 Involvement of other mucous mem-
branes is common.70 The ulcers heal slowly, usually
without scar formation and the disease runs a chronic
course with recurring bulla formation.87
The diagnosis is based on the characteristic histo-
logic feature of PV; that is, intraepithelial bulla forma-
tion due to destruction of desmosomes resulting in
acantholysis. The bullae contain non-adhering free
epithelial cells (Tzank cells), which have lost their inter-
cellular bridges.88,89 The associated inflammatory reac-
tion is dominated by mononuclear cells and neu-
trophils. Immunohistochemistry reveals pericellular
epithelial deposits of IgG and C3. Circulating autoan-
23
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 24
Non-Plaque-Induced Gingival Lesions
tibodies against interepithelial adhesion molecules are
detectable in serum samples of most patients, but at
the initial stage of intraoral affection antiepithelial anti-
body may not be elevated.24,75,90,91 The background
of bulla formation in PV is damage to the intercellular
adhesion caused by autoantibodies to cadherin-type
epithelial cell adhesion molecules (desmoglein 1 and
3).88,92 The mechanism by which these molecules trig-
ger the formation of autoantibodies has not yet been
established.
Erythema Multiforme
Erythema multiforme (EM) is an acute, sometimes
recurrent, vesiculobullous disease affecting mucous
membranes and skin. The involvement of skin and
mucous membranes varies. Two forms of the disease
have been described: a minor form with only moder-
ate involvement and a major form (Stevens-Johnson
syndrome) with widespread mucous membrane and
skin lesions.93-95
EM may occur at any age but most frequently
affects young individuals. It may or may not involve
the oral mucosa, but oral involvement occurs in as
much as 25 to 60% of cases96 and sometimes is the
only involved site. The characteristic oral lesions com-
prise swollen lips often with extensive crust formation
of the vermilion border. The basic lesions, however,
are bullae which rupture and leave extensive ulcers
covered by yellowish fibrinous exudates sometimes
described as pseudomembranes. Such lesions may
also involve the buccal mucosa and gingiva.10,93,96,97
The skin lesions are characteristic due to the iris
appearance with a central bulla formation surrounded
by a blanched halo with an erythematous zone beyond
that. Similar intraoral lesions do occur but they are
infrequent. The disease is usually self-limiting but recur-
rences are common. Healing of the lesions may require
several weeks.98
The histopathologic findings of EM are characterized
by intra- or subepithelial separation of epithelium from
connective tissue with nonspecific inflammation.99
Immunohistochemical findings are nonspecific and in
most instances the diagnosis relies on the clinical find-
ings. The pathogenesis of EM remains obscure, but
the disease appears to be an immune reaction pre-
cipitated by a wide range of factors including herpes
simplex virus,100-103 Mycoplasma pneumoniae,104,105
and various drugs.106,107
Lupus Erythematosus
Lupus erythematosus (LE) is a group of autoimmune
connective tissue disorders in which antibodies form
to various cellular constituents including nucleus, cyto-
plasma membrane, and others. LE is divided into 2
major forms: discoid LE (DLE) and systemic LE (SLE)
which may involve a range of organ systems includ-
ing kidney, heart, central nervous system, vascular
24
Volume 4 • Number 1 • December 1999
system, and bone marrow. The prevalence of LE has
been estimated at 0.05 %.108
DLE is a mild chronic form which involves skin and
mucous membranes, sometimes involving the gingiva
as well as other parts of the oral mucosa.109,110 The
typical lesion presents a central atrophic area with
small white dots surrounded by irradiating fine white
striae with a periphery of telangiectasia. The lesions
can be ulcerated or clinically indistinguishable from
leukoplakia or atrophic oral lichen planus (OLP).109
Ulcerations may be a sign of SLE,110 which demon-
strates oral lesions in 25% to 40% of the patients.111,112
The characteristic “butterfly” skin lesions are photo-
sensitive, scaly, erythematous macules located on the
bridge of the nose and the cheeks.113
The diagnosis is based on clinical and histopatho-
logical findings. The epithelial changes, characteristic
of oral LE lesions, are hyperkeratosis, keratin plug-
ging, variation in epithelial thickness, liquefaction
degeneration of basal cells, and increased width of the
basement membrane. The subepithelial connective tis-
sue harbors inflammation, sometimes resembling OLP
but often with a less distinct band-shaped pattern.114
Immunohistochemical investigation reveals deposits
of various immunoglobulins, C3, and fibrin along the
basement membrane.115 The etiology of LE remains
unknown, but deposits of antigen-antibody complexes
appear to play a role in the tissue damage character-
istic of the disease.116
ALLERGIC REACTIONS
Manifestations of allergy in the oral mucosa are uncom-
mon and have been subjected to relatively few inves-
tigations. Several mechanisms may be involved in
allergy, which are exaggerated immune reactions. Usu-
ally these reactions are divided into 4 types, I through
IV. Oral mucosal reactions are type I (immediate type),
which is mediated by IgE, or more often type IV
(delayed type) mediated by T-cells. The rare intraoral
occurrence may be due to the fact that much higher
concentrations of allergen is required for an allergic
reaction to occur in the oral mucosa than in skin and
other surfaces.117,118 The present review includes aller-
gies to dental restorative materials, toothpastes and
mouthwashes, and food.
Dental Restorative Materials
Type IV allergy (contact allergy) is characterized by
clinical manifestation after a period of 12 to 48 hours
following contact with the allergen. The oral mucosal
affections have been denoted contact lesions and prior
contact with the allergen resulting in sensitization is
prerequisite for these reactions to occur.58 Reported
oral mucosal reactions to restorative materials include
reactions to mercury, nickel, gold, zinc, chromium,
palladium, and acrylics.119-123 The mucosal contact
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 25
Ann Periodontol
lesions which may also affect the gingiva resemble
oral lichen planus affections or oral leukoplakia. They
are reddish or whitish, sometimes ulcerated lesions,
but one of the crucial diagnostic observations is that
the lesions resolve after removal of the offending mate-
rial. Additional patch testing to identify the exact aller-
gen gives supplementary information, but for dental
amalgam it has been shown that there is no obvious
correlation between the result of an epicutaneous patch
test and the clinical result after removal of the fill-
ings.124 The diagnosis in these cases is based on the
clinical manifestation confined to the area of contact
with the offending restorative material and the result
after replacing this material.
Toothpastes and Mouthwashes
Although rare, contact hypersensitivity has been re-
ported to occur both after the use of toothpastes125,126
and mouthwashes.126 The constituents responsible of
the allergic reactions may be flavor additives, for
instance, carvone and cinnamon127 or preservatives.128
The above mentioned flavoring constituents may be
used in chewing gum and produce similar forms of gin-
givostomatitis.129 The clinical manifestations of allergy
include a fiery red edematous gingivitis sometimes with
ulcerations or whitening. Similar affections may involve
the labial, buccal, and tongue mucosa and in addition
cheilitis may be seen. The clinical manifestations are
characteristic and form the basis of the diagnosis which
may be supported by resolving of the lesions after ces-
sation of using the allergen-containing agent.
Foods
Allergy to food can manifest both as type I and type
IV reactions. Type I reactions with severe swelling have
been described after intake of food components such
as peanuts and pumpkin seed. Birch pollen allergy is
associated with some types of oral mucosa allergy,
and more than 20% of patients with oral allergy may
be hypersensitive to kiwi, peach, apple, chestnut, and
salami.130-136 Another food allergen resulting in gin-
givitis, gingivostomatitis or so-called plasma cell gin-
givitis is the red pepper.137,138 The diagnosis is diffi-
cult to establish unless it has been demonstrated that
the lesions resolve after removal of the allergen.
TOXIC REACTIONS
Toxic gingival reactions are due to external toxic injury
to the tissue as seen in surface etching by toxic prod-
ucts. Examples of such reactions are chlorhexidine-
induced mucosal desquamation,139,140 acetylsalicylic
acid burn,141 cocaine burn,142 and slough due to den-
tifrice detergents.143 Another chemical injury to the
gingival tissue may be caused by incorrect use of caus-
tics by the dentist. Paraformaldehyde used for pulp
mummification may give rise to inflammation and
Holmstrup
necrosis of the gingival tissue if the cavity sealing is
insufficient.144 Usually, the diagnosis is obvious from
the clinical findings and the patient history.
FOREIGN BODY REACTIONS
Another type of tissue reaction is established through
epithelial ulceration which allows entry of foreign mate-
rial into gingival connective tissue. This can happen via
abrasion or cutting,145 a route of tissue injury which
is best exemplified by the amalgam tattoo.146 Gingi-
val inflammation associated with foreign bodies has
been termed foreign body gingivitis. A clinical study
of this condition has shown that it often presents as a
red or combined red/white painful chronic lesion fre-
quently misdiagnosed as lichen planus.147 An X-ray
microanalysis of foreign body gingivitis showed that
most of the identified foreign bodies were of dental
material origin, usually abrasives.145 Another way of
introducing foreign substances into the tissues is self-
inflicted injury, for instance, due to chewing on sticks or
due to self-induced tattooing.148 It is uncertain whether
the inflammatory reaction in such cases is due to a
toxic or in some instances an allergic reaction.
MECHANICAL TRAUMA
Physical injuries to gingival tissues can occur due to
accidental, iatrogenic and factitious occurrences.
Among these, oral hygiene agents and procedures can
be injurious to gingival tissues. The damage varies
from superficial gingival laceration to major loss of tis-
sue resulting in gingival recession.149,150 Abrasivity of
dentifrice, great brushing force, and horizontal move-
ment of the toothbrush contribute to the gingival injury
even in young patients. Characteristic findings in these
patients are extremely good oral hygiene, cervical tooth
abrasion, and unaffected tops of the interdental papil-
lae in the site of injury. The disease has been termed
traumatic ulcerative gingival lesion.150 Gingival ulcer-
ation and inflammation primarily affecting the top of
the interdental papillae may, on the other hand, be
caused by dental flossing. The prevalence of such find-
ings, however, is unknown.151 An important differen-
tial diagnosis is necrotizing gingivitis.152 The diagno-
sis is made on basis of the clinical findings.
A special type of mechanical trauma to the gingi-
val tissues is expressed by the self-inflicted lesions,
sometimes termed gingivitis artefacta. A common type
of lesion shows ulceration of the gingival margin often
associated with recession. The lesions are most com-
mon in children and young individuals and two-thirds
appear to involve female patients. The lesions are usu-
ally produced by picking at or scratching the gingiva
with a finger or a fingernail. Sometimes the lesions
have been produced by instruments.153 It is often dif-
ficult to establish the correct diagnosis based on clin-
ical findings and identification of the offending agent.
25
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 26
Non-Plaque-Induced Gingival Lesions
THERMAL TRAUMA
While extensive thermal burns of the oral mucosa are
very rare, minor burns particularly from hot beverages
are seen occasionally. Their predilection by site is the
palatal and labial mucosa but any part of the oral
mucosa can be involved including the gingiva.154 The
area involved is painful, red and may slough the coag-
ulated surface. Vesicles may also appear155 and some-
times the lesion present as petechiae or erosion. Obvi-
ously, the history is important to establish the correct
diagnosis. Common causes are hot coffee, pizza, and
melted cheese, but dental treatment involving improper
handling of hot hydrocolloid impression material, hot
wax, or cautery instruments is another cause.154
NOT OTHERWISE SPECIFIED
The intent of this section is to indicate that there may
be some forms of gingivitis that do not neatly fit under
other items discussed above.
REFERENCES
1. Holmstrup P, Schiøtz AW, Westergaard J. Effect of den-
tal plaque control on gingival lichen planus. Oral Surg
Oral Med Oral Pathol 1990;69:585-590.
2. Rivera-Hidalgo F, Stanford TW. Oral mucosal lesions
caused by infective microorganisms. I. Viruses and bac-
teria. Periodontol 2000 1999;21:106-124.
3. Siegel MA. Syphilis and gonorrhea. Dent Clin N Am
1996;40:369-383.
4. Scully C. Infectious diseases: review of the literature. In:
Millard HD, Mason DR, eds. 2nd World Workshop on
Oral Medicine. Ann Arbor: University of Michigan,
1995;3:7-16.
5. Ramirez-Amador V, Sierra Madero JG, Esquivel Pedraza
LE, et al. Oral secondary syphilis in a patient with
human immunodeficiency virus infection. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 1996;81:652-
654.
6. Littner MM, Dayan D, Kaffe I, et al. Acute streptococ-
cal gingivostomatitis. Report of five cases. Oral Surg
Oral Med Oral Pathol 1982;53:144-147.
7. Blake GC, Trott JR. Acute streptococcal gingivitis. Dent
Pract Dent Rec 1959;10:43-45.
8. Scully C, Monteil R, Sposto MR. Infectious and tropical
diseases affecting the human mouth. Periodontol 2000
1998;18:47-70.
9. Miller CS, Redding SW. Diagnosis and management of
orofacial herpes simplex virus infections. Dent Clin N
Am 1992;36:879-895.
10. Scully C, Epstein JB, Porter SR, Cox MF. Viruses and
chronic diseases of the oral mucosa. Oral Surg Oral
Med Oral Pathol 1991;72:537-544.
11. Ehrlich J, Cohen GH, Hochman N. Specific herpes sim-
plex virus antigen in human gingiva. J Periodontol 1983;
54:357-360.
12. Contreras A, Falkler WA Jr., Enwonwu CO, et al.
Human Herpesviridae in acute necrotizing ulcerative
gingivitis in children in Nigeria. Oral Microbiol Immunol
1997; 12:259-265.
13. Parra B, Slots J. Detection of human viruses in peri-
odontal pockets using polymerase chain reaction. Oral
Microbiol Immunol 1996;11:289-293.
14. Holmstrup P, Westergaard J. HIV infection and peri-
odontal diseases. Periodontol 2000 1998;18:37-46.
26
Volume 4 • Number 1 • December 1999
15. Greenberg MS. Herpes virus infections. Dent Clin North
Am 1996;40:359-368.
16. Gominak S, Cros D, Paydarfar D. Herpes simplex labi-
alis and trigeminal neuropathy. Neurol 1990;40:151-
152.
17. Kriesel JD, Pisani PL, McKeough MB, Baringer JR,
Spruance SL. Correlation between detection of herpes
simplex virus in oral secretions by PCR and suscepti-
bility to experimental UV radiation-induced herpes labi-
alis. J Clin Microbiol 1994;32:3088-3090.
18. Steiner I, Kennedy PGE. Herpes simplex virus latent
infection in the nervous system. J Neurovirol 1995;1:19-
29.
19. Straus SE, Ostrove JM, Inchauspé G, et al. Varicella-
zoster virus infections. Biology, natural history, treat-
ment, and prevention. Ann Intern Med 1988;108:221-
237.
20. Miller CS. Viral infections in the immunocompetent
patient. Dermatol Clin 1996;14:225-241.
21. Rentier B, Piette J, Baudoux L, et al. Lessons to be
learned from varicella-zoster virus. Vet Microbiol 1996;
53:55-66.
22. Millar EP, Traulis MJ. Herpes zoster of the trigeminal
nerve: the dentist’s role in diagnosis and management.
J Can Dent Assoc 1994;60:450-453.
23. Schwartz O, Pindborg JJ, Svenningsen A. Tooth exfo-
liation and necrosis of the alveolar bone following
trigeminal herpes zoster in HIV-infected patient. Dan
Dent J 1989;93:623-627.
24. Melbye M, Grossman RJ, Goedert JJ, Eyster ME, Big-
gar RJ. Risk of AIDS after herpes zoster. Lancet 1987;
1(Mar 28):728-730.
25. Cannon, RD, Holmes AR, Mason AB, Monk BC. Oral
Candida: Clearance, colonization, or candidiasis? J
Dent Res 1995;74:1152-1161.
26. Scully C, El-Kabir M, Samaranayake L. Candidosis. In:
Millard HD, Mason EK, eds. Perspectives on 1993 Sec-
ond World Workshop on Oral Medicine. Ann Arbor: Uni-
versity of Michigan; 1995:27-50.
27. Holmstrup P, Johnson NW. Chemicals in diagnosis and
management of selected mucosal disorders affecting
the gingiva. In: Lang NP, Karring T, Lindhe J, eds. Pro-
ceedings of the 2nd European Workshop on Periodon-
tology. Berlin: Quintessence; 1997:366-379.
28. Slots J, Rams TE, Listgarten MA. Yeasts, enteric rods
and pseudomonads in the subgingival flora of severe
adult periodontitis. Oral Microbiol Immunol 1988;3:47-
52.
29. Grbic JT, Mitchell-Lewis DA, Fine JB, et al. The rela-
tionship of candidiasis to linear gingival erythema in
HIV-infected homosexual men and parenteral drug
users. J Periodontol 1995;66:30-37.
30. Holmstrup P, Westergaard J. Periodontal diseases in
HIV-infected patients. J Clin Periodontol 1994;21:270-
280.
31. Holmstrup P, Axell T. Classification and clinical mani-
festations of oral yeast infection. Acta Odontol Scand
1990;48:57-59.
32. Holmstrup P, Samaranayake LP. Acute and AIDS-
related oral candidoses. In: Samaranayake LP, Mac-
Farlane TW, eds. Oral Candidosis. London: Wright, But-
terworth & Co. Ltd.; 1990:133-155.
33. Rindum JL, Stenderup A, Holmstrup P. Identification
of Candida albicans types related to healthy and patho-
logical oral mucosa. J Oral Pathol Med 1994;23:406-
412.
34. Rajah V, Essa A. Histoplasmosis of the oral cavity, or-
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 27
Ann Periodontol
opharynx and larynx. J Laryngol Otol 1993;107:58-
61.
35. Anaissie E, Kantarjian H, Jones P, et al. Fusarium: a
newly recognized fungal pathogen in immunosup-
pressed patients. Cancer 1986;57:2141-2145.
36. Cobb CM, Shultz RE, Brewer JH, Dunlap CL. Chronic
pulmonary histoplasmosis with an oral lesion. Oral Surg
Oral Med Oral Pathol 1989;67:73-76.
37. Loh FC, Yeo JF, Tan WC, Kumarasinghe G. Histoplas-
mosis presenting as hyperplastic gingival lesion. J Oral
Pathol Med 1989;18:533-536.
38. Weed LA, Parkhill EM. The diagnosis of histoplasmo-
sis in ulcerative disease of the mouth and pharynx. Am
J Clin Pathol 1948;18:130-140.
39. Chinn H, Chernoff DN, Migliorati CA, Silverman S Jr.,
Green TL. Oral histoplasmosis in HIV-infected patients.
A report of two cases. Oral Surg Oral Med Oral Pathol
1995;79:710-714.
40. Boutros HH, Van Winckle RB, Evans GA, Wasan SM.
Oral histoplasmosis masquerading as an invasive car-
cinoma. J Oral Maxillofac Surg 1995;53:1110-1114.
41. Axell T, Rundquist L. Oral lichen planus-a demographic
study. Community Dent Oral Epidemiol 1987; 15:52-
56.
42. Andreasen JO. Oral lichen planus. 1. A clinical evalu-
ation of 115 cases. Oral Surg Oral Med Oral Pathol
1968;25:31-42.
43. Holmstrup P. The controversy of a premalignant poten-
tial of oral lichen planus is over. Oral Surg Oral Med Oral
Pathol 1992;73:704-706.
44. Holmstrup P, Thorn JJ, Rindum J, Pindborg JJ. Malig-
nant development of lichen planus-affected oral
mucosa. J Oral Pathol 1988;17:219-225.
45. Scully C, Beyli M, Ferreira MC, et al. Update on oral
lichen planus: etiopathogenesis and management. Crit
Rev Oral Biol Med 1998;9:86-122.
46. Scully C, Almeida OPD, Welbury R. Oral lichen planus
in childhood. Br J Dermatol 1994;130:131-133.
47. Thorn JJ, Holmstrup P, Rindum J, Pindborg JJ. Course
of various clinical forms of oral lichen planus. A
prospective follow-up study of 611 patients. J Oral
Pathol 1988;17:213-218.
48. Rees TD. Adjunctive therapy. Proceedings of the
World Workshop in Clinical Periodontics. Chicago:
The American Academy of Periodontology; 1989:X-
1/X-39.
49. Eversole LR, Dam J, Ficarra G, Hwang C-Y. Leukocyte
adhesion molecules in oral lichen planus: a T cell medi-
ated immunopathologic process. Oral Microbiol Immunol
1994;9:376-383.
50. Eversole R. Oral mucosal diseases. Review of the lit-
erature. In: Millard HD, Mason DK, eds. Perspectives
on 1993 Second World Workshop on Oral Medicine.
Ann Arbor: University of Michigan; 1995:105-162.
51. Buechner SA. T cell subsets and macrophages in lichen
planus. In situ identification using monoclonal anti-
bodies and histochemical techniques. Dermatologica
1984;169:325-329.
52. Walsh LJ, Savage NW, Ishii T, Seymour GJ. Immun-
opathogenesis of oral lichen planus. J Oral Pathol Med
1990;19:389-396.
53. Schiødt M, Holmstrup P, Dabelsteen E, Ullman S.
Deposits of immunoglobulins, complement, and fi-
brinogen in oral lupus erythematosus, lichen planus,
and leukoplakia. Oral Surg Oral Med Oral Pathol 1981;
51:603-608.
54. Kilpi AM, Rich AM, Radden BG, Reade PC. Direct
Holmstrup
immunofluorescence in the diagnosis of oral mucosal
disease. Int J Oral Maxillofac Surg 1988;17:6-10.
55. Holmstrup P, Dabelsteen E. Changes in carbohydrate
expression of lichen planus affected oral epithelial cell
membranes. J Invest Dermatol 1979;73:364-367.
56. Sugerman PB, Savage NW, Seymour GJ. Phenotype
and suppressor activity of T-lymphocyte clones ex-
tracted from lesions of oral lichen planus. Br J Derma-
tol 1994;131:319-324.
57. Camisa C, Allen CM, Bowen B, Olsen RG. Indirect
immunofluorescence of oral lichen planus. J Oral Pathol
1986;15:218-220.
58. Holmstrup P. Reactions of the oral mucosa related to
silver amalgam: A review. J Oral Pathol Med 1991;20:1-
7.
59. Fujii H, Ohashi M, Nagura H. Immunohistochemi-
cal analysis of oral lichen planus-like eruption in
graft-versus-host disease after allogeneic bone mar-
row transplantation. Am J Clin Pathol 1988;89:177-
186.
60. Carrozzo M, Gandolfo S, Carbone M, et al. Hepatitis C
virus infection in Italian patients with oral lichen planus:
a prospective case-control study. J Oral Pathol Med
1996;25:527-533.
61. Fortune F, Buchanan JAG. Oral lichen planus and
coeliac disease. Lancet 1993;341:1154-1155.
62. Bagán JV, Aguirre JM, del Olmo JA, et al. Oral lichen
planus and chronic liver disease: A clinical and mor-
phometric study of the oral lesions in relation to
transaminase elevation. Oral Surg Oral Med Oral Pathol
1994;78:337-342.
63. Gandolfo S, Carbone M, Carozzo M, Gallo V. Oral lichen
planus and hepatitis C virus (HCV) infection: is there
a relationship? A report of 10 cases. J Oral Pathol Med
1994;23:119-122.
64. Nagao Y, Sata M, Tanikawa K, Itoh K, Kameyama T.
Lichen planus and hepatitis C virus in the Northern
Kyushu region of Japan. Eur J Clin Invest 1995;25:910-
914.
65. Hodge L, Marsden, RA, Black MM, Bhogal B, Corbett
MF. Bullous pemphigoid: The frequency of mucosal
involvement and concurrent malignancy related to indi-
rect immunofluorescence findings. Br J Dermatol
1981;105:65-69.
66. Brooke RI. The oral lesions of bullous pemphigoid. J
Oral Med 1973;28:36-40.
67. Shklar G, McCarthy PL. Oral lesions of mucous mem-
brane pemphigoid. A study of 85 cases. Arch Oto-
laryngol 1971;93:354-364.
68. Gallagher G, Shklar G. Oral involvement in mucous
membrane pemphigoid. Clin Dermatol 1987;5:18-27.
69. Silverman S Jr, Gorsky M, Lozada-Nur F, Liu A. Oral
mucous membrane pemphigoid. A study of sixty-five
patients. Oral Surg Oral Med Oral Pathol 1986;61:233-
237.
70. Laskaris G, Sklavounou A, Stratigos J. Bullous pem-
phigoid, cicatricial pemphigoid and pemphigus vul-
garis. A comparative clinical survey of 278 cases. Oral
Surg Oral Med Oral Pathol 1982;54:656-662.
71. Dahl MGC, Cook LJ. Lesions induced by trauma in
pemphigoid. Br J Dermatol 1979;101:469-473.
72. Williams DM, Leonard JN, Wright P, et al. Benign
mucous membrane (cicatricial) pemphigoid revisited:
A clinical and immunological reappraisal. Br Dent J
1984;157:313-316.
73. Daniels TE, Quadra-White C. Direct immunofluores-
cence in oral mucosal disease: A diagnostic analysis
27
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 28
Non-Plaque-Induced Gingival Lesions
of 130 cases. Oral Surg Oral Med Oral Pathol 1981;
51:38-54.
74. Laskaris G, Nicolis G. Immunopathology of oral mucosa
in bullous pemphigoid. Oral Surg Oral Med Oral Pathol
1980;50:340-345.
75. Manton SM, Scully C. Mucous membrane pemphigoid-
an elusive diagnosis. Oral Surg Oral Med Oral Pathol
1988;66:37-40.
76. Ullman S. Immunofluorescence and diseases of the
skin. Acta Derm Venereol 1988;Suppl. 140:1-31.
77. Laskaris G, Angelopoulos A. Cicatricial pemphigoid:
Direct and indirect immunofluorescent studies. Oral
Surg Oral Med Oral Pathol 1981;51:48-54.
78. Scully C, Laskaris G. Mucocutaneous disorders. Peri-
odontol 2000 1998;18:81-94.
79. Domloge-Hultsch N, Anhalt GJ, Gammon WR, et al.
Antiepiligrin cicatricial pemphigoid. A subepithelial bul-
lous disorder. Arch Dermatol 1994;130:1521-1529.
80. Domloge-Hultsch N, Gammon WR, Briggaman RA, Gil
SG, Carter WG, Yancey KB. Epiligrin, the major human
keratinocyte integrin ligand, is a target in both an
acquired autoimmune and an inherited subepidermal
blistering skin disease. J Clin Invest 1992;90:1628-
1633.
81. Leonard JN, Haffenden GP, Ring NP, et al. Linear IgA
disease in adults. Br J Dermatol 1982;107:301-316.
82. Leonard JN, Wright P, Williams DM, et al. The rela-
tionship between linear IgA disease and benign mucous
membrane pemphigoid. Br J Dermatol 1984;110:307-
314.
83. Eversole LR. Immunopathology of oral mucosal ulcer-
ative, desquamative, and bullous diseases. Selective
review of the literature. Oral Surg Oral Med Oral Pathol
1994;77:555-571.
84. Barth JH, Venning VA. Pemphigus. Br J Hosp Med
1987;37:326-327, 330-331.
85. Pisanti S, Sharav Y, Kaufman E, Posner LN. Pemphi-
gus vulgaris: Incidence in Jews of different ethnic
groups, according to age, sex, and initial lesion. Oral
Surg Oral Med Oral Pathol 1974;38:382-387.
86. Sciubba JJ. Autoimmune aspects of pemphigus vul-
garis and mucosal pemphigoid. Adv Dent Res 1996;
10:52-56.
87. Zegarelli DJ, Zegarelli EV. Intraoral pemphigus vulgaris.
Oral Surg Oral Med Oral Pathol 1977;44:384-393.
88. Nishikawa T, Hashimoto T, Shimizu H, Ebihara T, Ama-
gai M. Pemphigus: from immunofluorescence to mol-
ecular biology. J Dermatol Sci 1996;12:1-9.
89. Coscia-Porrazzi L, Maiello FM, Ruocco V, Pisani M.
Cytodiagnosis of oral pemphigus vulgaris. Acta Cyto-
logica 1985;29:746-749.
90. Lamey P-J, Rees TD, Binnie WH, Wright JM, Rankin KV,
Simpson NB. Oral presentation of pemphigus vulgaris
and its response to systemic steroid therapy. Oral Surg
Oral Med Oral Pathol 1992;74:54-57.
91. Lever WF, Schaumburg-Lever G. Immunosuppressants
and prednisone in pemphigus vulgaris.-Therapeutic
results obtained in 63 patients between 1961 and 1975.
Arch Dermatol 1977;113:1236-1241.
92. Nousari HC, Anhalt GJ. Bullous skin diseases. Curr
Opinion Immunol 1995;7:844-852.
93. Lozada-Nur F, Gorsky M, Silverman S Jr. Oral ery-
thema multiforme: Clinical observations and treatment
of 95 patients. Oral Surg Oral Med Oral Pathol 1989;
67:36-40.
94. Assier H, Bastuji-Garin S, Revuz J, Roujeau J-C. Ery-
thema multiforme with mucous membrane involvement
28
Volume 4 • Number 1 • December 1999
and Stevens-Johnson syndrome are clinically different
disorders with distinct causes. Arch Dermatol 1995;
131:539-543.
95. Bystryn J-C. Erythema multiforme with mucous mem-
brane involvement and Stevens-Johnson syndrome are
clinically different disorders. Comment. Arch Derma-
tol 1996;132:711-712.
96. Huff JC, Weston WL, Tonnesen MG. Erythema multi-
forme: A critical review of characteristics, diagnostic
criteria, and causes. J Am Acad Dermatol 1983:8:763-
775.
97. Barrett AW, Scully CM, Eveson JW. Erythema multi-
forme involving gingiva. J Periodontol 1993;64:910-
913.
98. Fabbri P, Panconesi E. Erythema multiforme “minus
and maius” and drug intake. Clin Dermatol 1993;
11:479-489.
99. Reed RJ. Erythema multiforme. A clinical syndrome
and a histologic complex. Am J Dermatopathol 1985;
7:143-152.
100. Ruokonen H, Malmstrom M, Stubb S. Factors influ-
encing the recurrence of erythema multiforme. Proc
Finn Dent Soc 1988;84:167-174.
101. Lozada F, Silverman S Jr. Erythema multiforme. Clin-
ical characteristics and natural history in fifty patients.
Oral Surg Oral Med Oral Pathol 1978;46:628-636.
102. Nesbit SP, Gobetti JP. Multiple recurrence of oral ery-
thema multiforme after secondary herpes simplex:
Report of case and review of literature. J Am Dent
Assoc 1986;112:348-352.
103. Aurelian L, Kokuba H, Burnett JW. Understanding the
pathogenesis of HSV-associated erythema multiforme.
Dermatol 1998;197:219-222.
104. Stutman HR. Stevens-Johnson syndrome and Myco-
plasma pneumoniae: Evidence for cutaneous infection.
J Pediatr 1987;111:845-847.
105. McKellar GM, Reade PC. Erythema multiforme and
Mycoplasma pneumoniae infection. Report and dis-
cussion of a case presenting with stomatitis. Int J Oral
Maxillofac Surg 1986;15:342-348.
106. Gebel K, Hornstein OP. Drug-induced oral erythema
multiforme. Results of a long-term retrospective study.
Dermatologica 1984;168:35-40.
107. Kauppinen K, Stubb S. Drug eruptions: Causative
agents and clinical types. A series of in-patients during
a 10-year period. Acta Derm Venereol 1984;64:320-
324.
108. Condemi JJ. The autoimmune diseases. JAMA 1987;
258:2920-2929.
109. Schiødt M. Oral manifestations of lupus erythematosus.
Int J Oral Surg 1984;13:101-147.
110. Schiødt M. Oral discoid lupus erythematosus. II. Skin
lesions and systemic lupus erythematosus in sixty-six
patients with 6-year follow-up. Oral Surg Oral Med Oral
Pathol 1984;57:177-180.
111. Pisetsky DS. Systemic lupus erythematosus. Med Clin
N Am 1986;70:337-353.
112. Jonsson H, Nived O, Sturfelt G. The effect of age on
clinical and serological manifestations in unselected
patients with systemic lupus erythematosus. J Rheuma-
tol 1988;15:505-509.
113. Standefer JA Jr, Mattox DE. Head and neck manifes-
tations of collagen vascular diseases. Otolaryngol Clin
N Am 1986;19:181-210.
114. Schiødt M, Pindborg JJ. Oral discoid lupus erythe-
matosus. I. The validity of previous histopathologic
diagnostic criteria. Oral Surg Oral Med Oral Pathol
A04_IPC_AAP_Annals_553640 6/7/00 8:48 AM Page 29
Ann Periodontol
1984;57:46-51.
115. Reibel J, Schiødt M. Immunohistochemical studies on
colloid bodies (Civatte bodies) in oral lesions of discoid
lupus erythematosus. Scand J Dent Res 1986;94:536-
544.
116. Schrieber L, Maini RN. Circulating immune complexes
(CIC) in connective tissue diseases (CTD). Neth J Med
1984;27:327-339.
117. Lüders G. Exogenously induced diseases of the oral
mucosa. Z Hautkr 1987;62:603-612.
118. Amlot PL, Urbanek R, Youlten LJF, Kemeny M, Lessof
MH. Type I allergy to egg and milk proteins: Compar-
ison of skin prick tests with nasal, buccal and gastric
provocation tests. Int Arch Allergy Appl Immunol
1985;77:171-173.
119. Council on Dental Materials, Instruments and Equip-
ment: Workshop. Biocompatibility of metals in den-
tistry. J Am Dent Assoc 1984;109:469-471.
120. Zaun H. Contact allergies related to dental restorative
materials and dentures. Aktuel Dermatol 1977;3:89-
93.
121. Ovrutsky GD, Ulyanow AD. Allergy to chromium using
steel dental prosthesis. Stomatologia (Moscow) 1976;
55:60-61.
122. Bergman M, Bergman B, Söremark R. Tissue accu-
mulation of nickel released due to electrochemical cor-
rosion of non-precious dental casting alloys. J Oral
Rehabil 1980;7:325-330.
123. Fisher AA. Contact stomatitis. Derm Clin 1987;5:709-
711.
124. Skoglund A. Value of epicutaneous patch testing in
patients with oral mucosal lesions of lichenoid char-
acter. Scand J Dent Res 1994;102:216-222.
125. Skaare A, Kjaerheim V, Barkvoll P, Rølla G. Skin reac-
tions and irritation potential of four commercial tooth-
pastes. Acta Odontol Scand 1997;55:133-136.
126. Sainio E-L, Kanerva L. Contact allergens in toothpastes
and a review of their hypersensivity. Contact Dermati-
tis 1995;33:100-105.
127. Drake TE, Maibach HI. Allergic contact dermatitis and
stomatitis caused by a cinnamic aldehyde-flavored
toothpaste. Arch Dermatol 1976;112:202-203.
128. Duffin P, Cowan GC. An allergic reaction to toothpaste.
J Irish Dent Assoc 1985;32:11-12.
129. Kerr DA, McClatchey KD, Regezi JA. Allergic gin-
givostomatitis (due to gum chewing). J Periodontol
1971;42:709-712.
130. Liccardi G, D’Amato M, D’Amato G. Oral allergy syn-
drome after ingestion of salami in a subject with mono-
sentitization to mite allergens. J Allergy Clin Immunol
1996;98:850-852.
131. Yamamoto T, Kukuminato Y, Nui I, et al. Relationship
between birch pollen allergy and oral and pharyngeal
hypersensitivity to fruit. J Oto Rhino Laryngegol Soc
Japan 1995;98:1086-1091.
132. Antico A. Oral allergy syndrome induced by chestnut
(Castanea sativa). Ann Allergy Asthma Immunol 1996;
76:37-40.
133. Wütrich B. Oral allergy syndrome to apple after a
lover’s kiss. Allergy 1997;52:235-236.
134. Rossi RE, Monasterolo G, Operti D, Corsi M. Evalua-
tion of recombinant allergens Bet v 1 and Bet v 2 (pro-
filin) by Pharmacia CAP system in patients with pollen-
related allergy to birch and apple. Allergy 1996;
51:940-945.
135. Helbling A. Important cross-reactive allergens. Sch Med
Holmstrup
Wochenschr 1997;127:382-389.
136. Asero R, Massironi F, Velati C. Detection of prognos-
tic factors for oral allergy syndrome in patients with
birch pollen hypersensitivity. J Allergy Clin Immunol
1996; 97:611-616.
137. Serio FG, Siegel MA, Slade BE. Plasma cell gingivitis
of unusual origin. A case report. J Periodontol 1991;
62:390-393.
138. Hedin CA, Karpe B, Larsson Å. Plasma-cell gingivitis
in children and adults. A clinical and histological
description. Swed Dent J 1994;18:117-124.
139. Almqvist H, Luthman J. Gingival and mucosal reactions
after intensive chlorhexidine gel treatment with or with-
out oral hygiene measures. Scand J Dent Res 1988;
96:557-560.
140. Flötra L, Gjermo P, Rølla G, Wærhaug J. Side effects
of chlorhexidine mouth washes. Scand J Dent Res
1971;79:119-125.
141. Najjar TA. Harmful effects of “aspirin compounds.” Oral
Surg Oral Med Oral Pathol 1977;44:64-70.
142. Dello Russo NM, Temple HV. Cocaine effects on gin-
giva. J Am Dent Assoc 1982;104:13.
143. Muhler JC. Dentifrices and oral hygiene. In: Bernier JL,
Muhler JC, eds. Improving Dental Practice Through Pre-
ventive Measures. St. Louis: C.V. Mosby Co.;1970:133-
157.
144. Di Felice R, Lombardi T. Gingival and mandibular bone
necrosis caused by a paraformaldehyde-containing
paste. Endod Dent Traumatol 1998;14:196-198.
145. Gordon SC, Daley TD. Foreign body gingivitis. Identi-
fication of the foreign material by energy-dispersive x-
ray microanalysis. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1997;83:571-576.
146. Buchner A, Hansen LS. Amalgam pigmentation (amal-
gam tattoo) of the oral mucosa. Oral Surg Oral Med
Oral Pathol 1980;49:139-142.
147. Gordon SC, Daley TD. Foreign body gingivitis. Clini-
cal and microscopic features of 61 cases. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 1997;83:562-
570.
148. Gazi MI. Unusual pigmentation of the gingiva. Report
of two different types. Oral Surg Oral Med Oral Pathol
1986;62:646-649.
149. Smukler H, Landsberg J. The toothbrush and gingival
traumatic injury. J Periodontol 1984;55:713-719.
150. Axéll T, Koch G. Traumatic ulcerative gingival lesion.
J Clin Periodontol 1982;9:178-183.
151. Gillette WB, Van House RL. Ill effects of improper oral
hygiene procedures. J Am Dent Assoc 1980;101:476-
481.
152. Blasberg B, Jordan-Knox A, Conklin RJ. Gingival ulcer-
ation due to improper toothbrushing. J Can Dent Assoc
1981;47:462-464.
153. Pattison GL. Self-inflicted gingival injuries: Literature
review and case report. J Periodontol 1983;54:299-
304.
154. Colby RA, Kerr DA, Robinson HBG. Color Atlas of Oral
Pathology. Philadelphia: JB Lippincott Company; 1961:
96.
155. Laskaris G. Color Atlas of Oral Diseases. Stuttgart:
Georg Thieme Verlag; 1994:66.
Send reprint requests to: Dr. Palle Holmstrup, University of
Copenhagen, School of Dentistry, 20 Norre Alle, DK-2200
Copenhagen, N. Denmark. Fax: 45-35-326699; e-mail:
palle.holmstrup@odont.ku.dk
29