Fungal Lesions of the Oral Mucosa Diagnosis and Management

Oral fungal infections are opportunistic and due to impaired host resistance. The increasing number of immunosuppressed individuals contributes to rising numbers of mycoses worldwide, and the ease of global migration has allowed the geographic range of endemic mycoses to expand. Deep fungal infections can clinically mimic other pathologic conditions including malignancy. This review highlights the pathogenesis, clinical features, diagnosis, and treatment recommendations of eight fungal infections that can be encountered in the dental setting.

Key points

  • Candidiasis is a superficial and most common fungal infection.

  • Most deep fungal infections are uncommon.

  • Immunosuppressed individuals with deep fungal infections experience more severe, often life-threatening disease, and early diagnosis and appropriate treatment are imperative.



Candidiasis is caused by the Candida species, a dimorphic group of fungi that can exist both in yeast and mold form. Candida species are found in soil, food, and the human body, and are accepted as members of the normal oral flora in an estimated 30% to 60% of healthy individuals. , Candida albicans is the most common species found in the oral cavity.

Disease-causing candidal overgrowth can be encountered with the use of broad-spectrum antibiotics and corticosteroids (including inhaled steroids), in denture wearers with poor oral hygiene, xerostomic patients, and immunocompromised individuals with human immunodeficiency virus (HIV), uncontrolled diabetes, individuals undergoing chemo- and/or radiotherapy and transplant patients. Children with undeveloped immune systems may be susceptible to candida overgrowth. Candidiasis may be localized or disseminated, depending on the state of the host’s immune system and mucosal barriers.

Clinical Features

Pseudomembranous candidiasis (“thrush”) is the most common form featuring white wipeable patches often revealing an erythematous mucosa ( Fig. 1 ). It commonly affects the dorsal tongue, buccal mucosa, palate, and oropharynx. The other forms of candidiasis mostly show erythematous lesions and include acute atrophic candidiasis, median rhomboid glossitis, chronic multifocal candidiasis, angular cheilitis, and denture stomatitis (chronic atrophic candidiasis). In acute atrophic candidiasis, the oral mucosa appears red and the tongue shows atrophic areas with loss of filiform papillae ( Fig. 2 ), necessitating the differentiation from other possible causes of atrophic glossitis such as vitamin/nutrient deficiencies. , Patients often present with a burning sensation of the oral mucosa.

Fig. 1
Pseudomembranous candidiasis.
( Courtesy of Donald M. Cohen, DMD, MS, MBA; Indraneel Bhattacharyya, DDS, MSD; and Nadim M. Islam, DDS, BDS, Gainesville, FL.)

Fig. 2
Atrophic candidiasis.
( Courtesy of Daniel Mandic, DDS, Jackson, MS; with permission .)

Median rhomboid glossitis appears as an erythematous patch on the midline of the posterior tongue dorsum characterized by loss of the filiform papillae ( Fig. 3 ). , This presentation is often asymptomatic and observed in individuals who smoke and/or use steroid inhalers. It may influence the development of another clinical presentation termed chronic multifocal candidiasis if contact with the palate leads to palatal involvement.

Fig. 3
Median rhomboid glossitis.
( Courtesy of Donald M. Cohen, DMD, MS, MBA; Indraneel Bhattacharyya, DDS, MSD; and Nadim M. Islam, DDS, BDS, Gainesville, FL; with permission .)

Angular cheilitis may occur as part of chronic multifocal candidiasis or alone, presenting as erythematous lesions with commissural fissuring and crusting ( Fig. 4 ). , Causes include reduced vertical dimension resulting in accentuated skin folds allowing collection of saliva in the area, thus providing a moist environment for Candida to thrive. Individuals who habitually lick their lips and bite the corners of their mouths can also develop such lesions. Angular cheilitis may be caused solely by C albicans or in combination with Staphylococcus aureus or by S aureus alone. , As in acute atrophic candidiasis, it is pertinent to exclude other factors for the development of these lesions such as vitamin and nutritional deficiencies. ,

Fig. 4
Angular cheilitis.
( Courtesy of Donald M. Cohen, DMD, MS, MBA; Indraneel Bhattacharyya, DDS, MSD; and Nadim M. Islam, DDS, BDS, Gainesville, FL; with permission .)

Use of dentures for prolonged periods of time combined with poor oral hygiene or ill-fitting prostheses may create an environment fostering candidal overgrowth. This is termed denture stomatitis, or chronic atrophic candidiasis , and presents as erythematous mucosa in the area covered by a removable prosthesis. ,

A less common presentation that is white, does not wipe off, and is often more localized is chronic hyperplastic candidiasis (candidal leukoplakia), usually occurring on the anterior buccal mucosa and lateral border of tongue. , According to some investigators, such lesions may represent leukoplakias suprainfected with candida organisms. Candida can induce epithelial hyperplasia and hyperkeratosis. Lesions of hyperplastic candidiasis can also present as speckled white and red areas (speckled leukoplakia). Chronic hyperplastic candidiasis may be associated with an increased risk for the development of oral dysplastic lesions and candida is often seen accompanying dysplastic and cancerous oral lesions.

Lastly, chronic mucocutaneous candidiasis is a rare form in which individuals develop persistent candida infections of not only the oral mucosa but other mucous membranes, skin, hair, and nails as part of a distinct immunologic disorder. Some patients may also have endocrine abnormalities, iron-deficiency anemia or autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) syndrome.


The classic clinical presentation of candidiasis is often diagnostic but can be confirmed by exfoliative cytology, culture, or mucosal biopsy. Culturing is considered the most sensitive method. However, culturing of clinical lesions unrelated to Candida can still identify the presence of Candida as this organism is often part of normal oral flora. Cytologic smears are beneficial, cost-effective, noninvasive diagnostic tools in certain clinical settings, especially in erythematous candidiasis. Microscopically, Candida organisms show 2 to 6 μm hyphae and yeasts (pseudohyphae), with special stains Grocott–Gomori methenamine silver (GMS) and periodic acid-Schiff (PAS) used to highlight yeast spores and hyphae. , Lesions of chronic hyperplastic candidiasis are expected to resolve after antifungal therapy.


Use of clotrimazole troches (10 mg, 5x daily for 7–14 days) or cream, or nystatin rinse (4–6 mL 4x daily for 7–14 days) can address mild candidiasis. Patients with angular cheilitis may benefit from the application of clotrimazole cream. Moderate to severe candidiasis can be treated with oral fluconazole (100–200 mg daily for 7–14 days). Itraconazole solution (200 mg once daily for up to 28 days) is used for candidiasis nonresponsive to fluconazole.

Rinsing with water or saline after the use of corticosteroid inhalers should decrease the incidence of candidal infection. , In addition to oral antifungal therapy, patients with candida-associated denture stomatitis should adopt improved hygiene practices of thoroughly disinfecting their dentures twice a day and removing them while sleeping. , Of benefit will be applying antifungal cream to the intaglio surface of the denture (1% Clotrimazole OTC cream, 2–4 x daily). Fabrication of new dentures may be necessary if prostheses are ill-fitting and above recommendations do not lead to improvement.



Histoplasmosis is an endemic fungal infection caused by Histoplasma capsulatum , a dimorphic fungus native to and localized within the geographic regions of the Ohio and Mississippi River valleys in the United States, as well as in Mexico and Central and South America. , Histoplasma capsulatum is naturally found in moist, warm, and nitrogen-rich soil, such as in areas containing bird or bat-disturbed soil. Inhalation of spores initiates lung infection. , After transforming from conidia, yeast cells are phagocytized in their primary host cell (the macrophage) where they reside and remain localized to the lungs or disseminate. Residing in macrophages is considered an important ability of H capsulatum to survive and spread throughout the body.

Clinical Features

When infection occurs, both the patient’s immune status and intensity of exposure to the fungal organisms determine symptoms and severity of the illness. , An exposed individual may be asymptomatic if exposure to the fungal organisms is low; however, if high, symptoms will likely develop. Patients may present with a self-limited form of acute pulmonary histoplasmosis characterized by flu-like symptoms such as fever, headache, myalgia, cough, and chest pain. Lung involvement presenting as calcified hilar lymph nodes or pulmonary infiltrates may be observed radiographically. Immunocompromised individuals who have acquired the organisms may develop reactivation of infection and expression of disease as pulmonary or extrapulmonary. A less common manifestation of disease seen in such patients is chronic histoplasmosis and closely resembles tuberculosis.

Dissemination of disease may occur during the first few weeks after acute infection. Oral lesions of histoplasmosis reportedly occur in 20% to 76% of patients with progressive disseminated histoplasmosis, although they may occur in all forms of infection. , These lesions present as indurated ulcers with rolled borders, similar in appearance to squamous cell carcinoma, or as nodules and granulomatous lesions of the tongue, palate, gingiva, and buccal mucosa ( Figs. 5–7 ). ,

Fig. 5
Histoplasmosis presenting as a granular and ulcerated lesion of the left palate in a middle-aged patient with liver and endocrine comorbidities.
( Courtesy of Stephen H. Roth, DDS, New York, NY; with permission .)

Fig. 6
( Courtesy of Donald M. Cohen, DMD, MS, MBA; Indraneel Bhattacharyya, DDS, MSD; and Nadim M. Islam, DDS, BDS, Gainesville, FL.)

Fig. 7
Histoplasmosis presenting as a nonhealing ulceration in the area of recently extracted tooth #1.
( Courtesy of Donald M. Cohen, DMD, MS, MBA; Indraneel Bhattacharyya, DDS, MSD; and Nadim M. Islam, DDS, BDS, Gainesville, FL; with permission .)


Diagnostic tools include microscopic examination, culture, and serology. When possible, histopathologic examination of tissue is recommended. Special stains GMS and PAS readily disclose H capsulatum characterized by small 2 to 4 μm, oval, narrow-based budding yeasts. Blood culture using the lysis-centrifugation method has improved sensitivity and can rapidly detect H capsulatum in disseminated disease or enzyme immunoassay (EIA) to detect Histoplasma antigen in serum and urine. , ,


Acute histoplasmosis is self-limiting with most cases resolving without therapy. For progressive disseminated histoplasmosis of mild-to-moderate severity, itraconazole (200 mg 3x/day) for 3 days and then twice daily for at least 12 months is recommended. For moderately severe to severe disseminated disease, liposomal Amphotericin B (3.0 mg/kg daily) is recommended for 1 to 2 weeks, followed by oral itraconazole (200 mg 3x/day) for 3 days and then 200 mg twice daily for a total of at least 12 months. For immunosuppressed patients who cannot be reversed or relapsed cases, lifelong therapy with itraconazole (200 mg daily) may be required. The level of itraconazole in the blood should be evaluated to ensure adequate drug exposure.

Mucormycosis (Zygomycosis)

Mucormycosis represents a group of mycoses causing morbidity and mortality due to relentless progressive invasion of affected tissues especially if driven by an underlying predisposing condition. The term zygomycosis that includes both mucormycosis and entomophthoramycosis (a tropical infection) has been used interchangeably with the term mucormycosis, especially in individuals with rhinocerebral disease.


Humans are constantly exposed to and acquire mucormycosis via direct skin/mucosa penetration or inhalation of fungal spores. Inhalation can lead to sinus, orbital, nasal, central nervous system (CNS) or pulmonary infections. Risk factors for the development of mucormycosis include: (1) diabetic ketoacidosis (causing most often rhinocerebral infection), leading to dissociation of iron from sequestering proteins and resulting in enhanced fungal survival and virulence, (2) solid-organ and hematopoietic stem cell transplantation, (3) defects in phagocytic function such as in patients with neutropenia or treated with high-dose glucocorticoids, (4) hemodialysis and chelation therapy leading to increased free iron delivered to the fungus, (5) penetrating trauma/burns and (6) use of intravenous catheters and moist dressings causing macerated skin. Rhino-orbital-cerebral mucormycosis has emerged as a suprainfection in patients with coronavirus disease-2019 (COVID-19), especially in India. It is unclear if the virus predisposes patients to the fungal infection or if the infection is a consequence of another underlying cause in patients with COVID-19, such as diabetes mellitus and use of corticosteroids.

Clinical Features

In the maxillofacial region, mucormycosis presents as a rhino-orbital-cerebral and cutaneous disease. Patients may initially present with nonspecific dull sinus pain, nasal stuffiness/congestion, pain affecting the eyes, blurry vision, and cutaneous cellulitis. Fever may occur in 50% of the patients. Nasal involvement can extend intraorally causing swelling of the maxillary alveolus and palate, leading to tissue ulceration and necrosis, occasionally with black coloration ( Fig. 8 ). If patients are not treated or treatment is delayed, extension of disease can involve the ethmoid sinus and the orbits causing proptosis with chemosis, diplopia, and loss of vision. Lesions can also involve the trigeminal/facial/orbital/optic nerves and cavernous sinus. Progression of disease varies, which may be related to the site of infection, species, and the patients’ immunocompetence. Although some patients deteriorate in days, it may take months to years for lethal progression if untreated.

Nov 25, 2023 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Fungal Lesions of the Oral Mucosa Diagnosis and Management

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