MYCOTIC DISEASES AND PERIODONTIUM

Introduction Mycoses in healthy individuals are more common in endemic areas than elsewhere, and they are often asymptomatic and may spontaneously resolve.

Immunocompromised persons are at particular risk from these mycoses, and clinical manifestations of infection by these organisms often suggest impaired immune competence. Patients at greatest risk include those with leukemia, leukopenia, solid tumors, transplants, or HIV disease. Also at risk are premature infants.

Oral mycotic diseases can be broadly classified as

o o o o o o

ORAL CANDIDIASIS (MONILIASIS, THRUSH) NONCANDIDAL/SYSTEMIC ORAL FUNGAL DISEASES histoplasmosis, mucormycosis, cryptococcosis, blastomycosis, coccidioidomycosis, and aspergillosis,

ORAL CANDIDIASIS (MONILIASIS, THRUSH)

Definition: It is disease caused by infection with yeast like fungus Candida albicans. Other causative organisms: Candida albicans (yeast & mycelial forms); Candida stellatoidea; Candida tropicalis; Candida parapsillosis; Candida pseudotropicalis; Candida famata; Candida rugosa; Candida krusei and Candida guilliermondi.

About oral candidiasis, four major types are recognized: (1) pseudomembranous; (2) hyperplastic; (3) erythematous (atrophic) and (4) angular cheilitis.

Predisposing factors Altered local resistance Poor oral hygiene Xerostomia Recent antibiotic treatment Dental appliance Compromised immune system function Early infancy Genetic immune deficiency

AIDS Corticosteriod therapy Panchytopenia Generalized patient debilitation Anaemia, malnutrition, malabsorbtion Diabetes mellitus Advanced systemic disease

Clinical features In infants Age-in neonates, oral lesion starts between the 6th and 10th day after birth. Cause-infection is contracted from the maternal vaginal canal where candida albicans flourishes during the pregnancy. Appearance-the lesions in infants are described as soft white or bluish white, adherent patches on oral mucosa. Symptoms-they are painless and notices on careful examinations.

In adult Sites-common sites are roof of the mouth, retromalar area, mucobuccal fold and its common in females as compared to males. Symptoms-patient may complain of burning sensation, spicy food will cause discomfort, rapid onset of bad taste and there may be history of dryness of mouth. Signs-Inflammation, erythema and painful eroded areas, -typical, pearly white or bluish white plaque -multiple, curdy, loosely adherent patches on any part of mucosa -mucosa adjacent to it appears red and moderately swollen -white patches of it are easily wiped out with wet gauze which leaves a normal erythematous area or atrophic area -deeper invasion by the organisms leaves an ulcerative lesion

upon the removal of the patch

Histopathological features

Fragments of plaque material may smear on a microscopic slide, macerated with 20 percent potassium hydroxide and examined for hyphae.
Presence of yeast cells are examined for hyphae or mycelia in the superficial and deeper layer of involved epithellium. The submucosa may contain chronic inflammatory cell infiltrate.

Differential diagnosis Plaque form of lichen planus-lesions of thrush can wiped with the help of gauze. Leukoplakia-history of recent administration of antibiotics will favor diagnosis of canadidiasis

Gangrenous stomatitis-pseudomembrane dirty in color and not raised above surface

Chemical burns-superficial white burns appear thin and delicate.

Treatment Removal of causes

Replacement of denture or relining or applying suspensions below it while insertion in mouth

The denture must be cleaned throughly and regularly and should be left out of mouth at night in hypochlorite solution. Withdrawal or change of antibiotics use if feasible.

Topical treatment-topical treatments are preferred because they limit systemic absorption, but the effectiveness depends entirely on patient compliance. Amphotericin B (Fungizone Oral) Suspension 1 ml swish and swallow QID x 2 weeks

Clotrimazole (Mycelex troches) dissolved in mouth 5 times/day x 2 weeks, or until plaques clear. Swish, retain in mouth as long as possible, then swallow.
Recommeded therapy is for two weeks. Note that oral suspension has a high sugar content, which may precipitate caries or xerostomia.

Alternative therapy-Nystatin vaginal pastilles dissolved in mouth are very effective, or may use Nystatin oral suspension "swish and swallow", 4-6 ml.

Systemic treatment Nystatin 250 mg TDS for 2 week followed by 1 troche per day for third week Fluconazole 100 mg QD X 14 days.

Ketoconazole 200mg, 1 tablet QD for 2 weeks. Instruct patient to take with acidic liquids (orange juice), and not with food. Longterm therapy with ketoconazole is not recommended due to side effects (gynecomastia in males). Repeated short courses are preferable. Check drug interactions if patient is on protease inhibitors.
Itraconazole 100 mg (200 mg daily orally for 2 weeks) In refractory cases, check to ensure that the causal organism is not azole-resistant. If discovered to be of mycotic etiology, treat with Amphotericin B.

 In cases so severe as to interfere with adequate nutrition and hydration, patient may require hospitalization for hydration and nutritional support. In patients who wear partials or dentures, have them soak the prosthesis in chlorhexidine solution (such as PerioGard), then place one ml of amphotericin B suspension on the acrylic portion of the appliance before reinserting into the mouth. This will prevent reinfection by the appliance. Maintenance therapy for future suppression may be necessary. One Mycelex troche dissolved in the oral cavity three times a day has been mentioned to have some efficacy in this regard.

SYSTEMIC ORAL FUNGAL DISEASES

o histoplasmosis,
It is also called as Darlings disease. Etiology

o It is caused by Histoplasma capsulatum, a dimorphic fungus that grows in the yeast form in infected tissue.
o Infection results from inhalation of dust contaminated with dropping particularly from infected birds. Types o Acute primary histoplasmosis o Progressive disseminated histoplasmosis o Chronic cavitary histoplasmosis Oral lesions are common in the progressive disseminated form.

Age-it is commonly seen in children and elderly Sites-it is seen on buccal mucosa, gingiva, tongue, palate or lip. Symptoms-patient may complain of sore throat, painful chewing, hoarseness, difficulty in swallowing. Appearance-oral lesion are nodular, ulcerative or vegetative. If left untreated it will progress to form firm papule or nodules which ulcerate and slowly enlarge. Base and surface-ulcerated area covered by non specific gray membrane and is indurated.

Histopathlogical features The mucosal epithelium shows ulceration, in majority of the cases.

In nonulcerated areas, pseudoepithelliomatous hyperplasia is often seen.

The submucosa shows a dense infiltrate of granulocytes, lymphocytes, plasma cells and histocytes. Multinucleated giant cells and caessation necrosis are often seen.

Differential Diagnosis
o Tuberculosis-sputum examination, tuberculin test. o Blastomycosis-biopsy and culturing the organisms from tissue. o Mucormycosis-biopsy. o Cryptococcosis-organisms cultured on Sabourauds glucose agar.

Management o Ketoconazole-6 to 12 months (Adult Dose 200-400 mg/d PO, with food or soda Pediatric Dose 5-10 mg/kg/d PO)

o Severe form-Amphotericin B, IV. (Adult Dose 0.3-1.5 mg/kg/d IV Pediatric Dose 0.25-1.5 mg/kg/d IV)

o mucormycosis,

It is also called as phycomycosis.

Etiology and predisposing factors o It is caused by saprophyte fungus.

o More common in patients with decreased resistance, due to diseases like diabetes, tuberculosis, renal failure, leukaemia, cirrhosis and in severe burn cases. Types
o Superficial o Visceral-Rhinocerebral or rhinomaxillary form Site-ulcerations of palate, due to necrosis and invasion of palatal vessels. Ulcer may be seen on gingiva, lip, and alveolar bone. Appearance-it is large and deep, causing denudation of underlying bone.

Radiographic features
o Paranasal sinus may reveal mucoperiosteal thickening of the involved sinus. o With decrease progression, there is increased nodularity and soft tissue thickening, usually mimics a tumor on a radiographic examination

Histopathological features
oThe tissue involved by mucormycosis shows necrosis and chronic inflamatory infiltrate. o The vessels in the area may be thrombosed with organisms in the lumen.

o The organisms appears as large, nonseptate hyphae with branching at obtuse angle.
o Round and ovoid sporangia are also seen.

Differential Diagnosis o Squamous cell carcinoma-indurated, longer history, resistance to therapy, firm borders, older patient, biopsy. o Apthous ulcer-short duration, painful, heals in one to three weeks.

 Management
o Surgical debriment is the treatment choice. o Systemic amphotericin. (Adult Dose 0.3-1.5 mg/kg/d IV Pediatric Dose 0.25-1.5 mg/kg/d IV) o Control of predisposing factor such as diabetes. o Elimination of secondary infection and symptomatic relief.

o cryptococcosis,
It is also called as torulosis. Etiology and predisposing factors o It is a chronic fungal infection caused by Crptococcus neoformans and Crptococcus bacillispora. o infection occurs due to inhalation of air borne microorganisms. o it has increased incidence in immunosupressive patients

Age-there is slight predilection for middle aged males.

Location-lesion of hard palate, soft palate, gingiva, extraction socket, tongue and tonsillar pillar are common.

Appearance-they appear as simple nonspecific, single or multiple ulcers. They are nodular and granulomatous, which may ulcerate during the course of disease.

Histopathological features

o In tissue section it appears as a small organisms with a large clear halo, sometimes described as tissue microcyst
o The tissue reaction is generally granulomatous type; epitheliod cell proliferation is minimal. o Multinucleated giant cells as well as inflammatory cell infiltrate are common.

Diagnosis-the organisms can be cultured on sabourauds glucose agar.

Management

o Mild to moderate cases can be treated with ketoconazole for 6 to 12 weeks. (Adult Dose 200-400 mg/d PO, with food or sodaPediatric Dose 5-10 mg/kg/d PO)
o The severe form requires amphotericin-B, intravenously for up to 10 weeks

o blastomycosis,
It is caused by Blastomyces dermatitidis. Etiology and predisposing factor-organisms is a normal inhabitant of soil and that is the reason for it to be common in agricultural worker. It is transmitted through respiratory track. It may be primary or secondary to some infection elsewhere in the body. Types o Primary pulmonary blastomycosis. o Cutaneous blastomycosis o Disseminated or systemic blastomycosis

Age-it is more common in men than women and typically occurs in middle age
Symptoms and signs-oropharyngeal pain, accompanied by the enlargment of cervical lymph nodes, may be presenting sign of oral disease. Appearance o Nonspecific, painless verrucous ulcer with indurated borders often mistaken for squamous cell carcinoma. o Other lesions are hard nodules and appear as sessile projection, granulomatous appearing plaque.

Radiographic features
o Radiographs may show periostitis and subperiosteal new bone formation.

o Oteoblastic reaction is usually present in later stages of disease.

o Chest radiograph shows concomitant pulmonary involvement in most of the cases.

Histopathological features
o The inflammed connective tissue shows occasional giant cells, macrophages and the typical round organisms, often budding, when appear to have a doubly refractile capsule.

o Microabcesses are frequently found and if the lesion is not ulcerated overlying pseudoepitheliomatous hyperplaisa may be prominent.

Diagnosis

o The index of suspicion increases when chronic, painless, oral ulcer appears in an agricultural worker or when review of system reveals pulmonary symptom.
o Diagnosis is made on the basis of biopsy and on culturing the organisms from tissue. Differential Diagnosis o Squamous cell carcinoma-present for weeks, palpation shows induration, older patient o Tuberculosis-undermined flabby borders, usually painless, sputum examination, mantoux test o Histoplasmosis-biopsy o Cryptococcosis-organisms culture. Management-amphotericin-B, intravenously for up to 10 weeks

o coccidioidomycosis
It is also called valley fever, desert fever or coccidiodal granuloma. Etiology-the disease appear to be transmitted to man and animals by inhalation of dust contaminated by spores of the causative organisms, Coccidioides immitis. Types o Primary nondisseminated coccidiodomycosis. o Progressive disseminated coccidioidomycosis.

Age and sex-it is common in all age groups and predominately seen in males. Incubation period-symptoms occur usually 14 days after inhalation of fungus. Infection is common in summer months, especially after periods of dust storm. It is self limiting and runs its course within 10 to 14 days.

Apperance-the lesions of oral mucosa and skin are proliferative, granulomatous and ulcerated lesions that are nonspecific in their clinical appearance. Healing-these lesions tend to heal by hyalinazation and scar formation.

Histopathlogical features

o The tissue is similar to any specific granuloma.

o There is accumulation of large mononuclear cells, lymphocytes and plasma cells.

o Foci of coagulation necrosis are often found in the center of small granulomas and multinucleated giant cells are scattered throughout lesion. o The organisms is found within the cytoplasm of giant cells, as well as is lying free in the tissue.

Management o Amphotericin B has been found to be effective Chemotherapeutic agent for the disease. Long-term therapy is required for complete cure.

Conclusion

o Fungal infections have the potential for serious injury to the peridontium. o The oral lesions associated with these deep fungal infections are chronic, may mimic neoplasms, and progress to form solitary, chronic deep ulcers with the potential for local destruction and invasion and systemic dissemination.

References o Carranzas Clinical Periodontology(Newman, Takei and Carranza) o Textbook of Oral Medicine-Anil Govindrao Ghom oWeb pages -Oral Diseases And Condition-Dr. Minh Nguyen -Noncandidal Fungal Infetion of the Mouth-Crispian Scully