Histoplasma capsulatum Caused a Localized Tongue Ulcer in a Non-HIV Patient—A Case From Nonendemic Country

A 56-year-old male, smoker (25 cigarettes per day) for 30 years, was referred to the Oral Medicine Clinic, University Dental Hospital with nonhealing, gradually enlarging ulcer on tongue for 4 months.

He complained of a painful ulcer over the left side of his tongue which was associated with odynophagia. He didn’t have chronic cough, fever, malaise, loss of appetite or loss of weight, and systemic symptoms suggestive of inherited or acquired immunodeficiency including HIV.

His past medical history was marked by diabetes mellitus and chronic obstructive pulmonary disease, and he was on oral hypoglycemic drugs.

He denied past orofacial surgeries, trauma, high-risk sexual behavior, or long-term immunosuppressive drugs. This nonalcoholic patient had no history of traveling abroad.

He was averagely built, afebrile male. Oral examination revealed a solitary, 2 × 4 × 1 cm size, tender, irregular ulcer on the left posterior tongue with indurations (Figure 1). The pain intensity was at 10 in the visual analog scale. There was no regional lymphadenopathy or hepatosplenomegaly. Rest of the general and systemic examinations were normal.

Figure 1.

The photo shows the solitary, irregular ulcer on the left posterior tongue with indurations.

Histopathology of first 2 biopsies of the lesion showed chronic granulomatous inflammation. However, they were negative for Ziehl-Neelsen staining. The patient tested normal for renal and hepatic biochemical tests, chest radiography, and colonoscopy. He had neutrophil leukocytosis and Erythrocyte Sedimentation Rate (ESR) was 22 mm per first hour. He was negative for HIV, Venereal Disease Research Laboratory test (VDRL), and Mantoux tests.

He was treated with anti-inflammatory drugs and cellulose-based covering agent for 6 weeks and subsequently started with oral prednisolone. There was an initial response, but he left against medical advice after 5 days of treatment.

He readmitted 3 months later along with expanded ulcer with few areas of necrosis and it was biopsied again. Mycological evaluation revealed yeast cells in the direct smear, and white cottony growth was observed on the agar (26°C) after 14 days. The tease mount of the growth revealed hyaline, septate fungal filaments, and macroconidia (Figure 2). After 7 days of incubation on blood–brain–heart infusion agar at 37°C, yeast-like growth was observed, and the isolate was confirmed as Histoplasma capsulatum.

Figure 2.

The tease mount of the growth reveals hyaline, septate fungal filaments, and macroconidia with tubercles and small, round microconidia (×40).

The histology report revealed mixed inflammatory infiltrate containing macrophages, neutrophils, and plasma cells. Small circular organisms positive for Periodic acid–Schiff (PAS) and Grocott gomori suggestive of histoplasmosis were seen both within and outside of macrophages (Figure 3).

Figure 3.

Gomori methenamine silver stain section of the biopsy of the ulcer shows small oval yeasts cells suggestive of Histoplasma capsulatum (×40).

He was initially started with oral itraconazole, yet converted to intravenous amphotericin B after 7 days while he was monitoring in the intensive care unit. Under treatment, his physical condition was aggravated with uncontrolled diabetes mellitus which was complicated by a secondary bacterial infection. Evidence of bacterial pneumonia was observed clinically, microbiologically, and radiologically. Intravenous antibiotics were started to cover up the pathogen. Unfortunately, the patient remained frail and died due to sepsis after 1 month from starting treatments.

Histoplasmosis is a systemic fungal infection caused by H capsulatum, a dimorphic fungus. ^1,2 All together, 3 varieties of H capsulatum have been recognized, in which H capsulatum var. capsulatum and H capsulatum var duboisii are human pathogens and H capsulatum var. farciminosum is an equine pathogen. ¹

Histoplasmosis is endemic in certain regions of the world, with a rising incidence in some Asian countries. ^3,4 However, it is a rare disease condition in Sri Lanka and only very few cases have been reported. ^{5 –7}

The disease has wide range of clinical presentations, ranging from asymptomatic infection, chronic pulmonary infections, to disseminated infections. ⁸ Around 30% to 50% of patients with disseminated histoplasmosis present with oral lesions. ^8,2,9 They usually have clinical manifestations of dissemination such as fever, weight loss, mucocutaneous lesions, lymphadenopathy, hepatosplenomegaly, and features of adrenal insufficiency. ^2,8,10 A localized oral lesion without dissemination is an uncommon presentation. ^2,11,12 Since oral lesions could be the primary manifestation of the dissemination, evaluation of the patient for the dissemination and possible immunocompromised condition is important. ¹³

These mucosal lesions appear in almost every part of the oral mucosa, yet the commonest sites are tongue, palate, and buccal mucosa. ^12,14 These lesions could be nodular, ulcerative, verrucous, or plaque-like. ¹¹ Oral histoplasmosis mimics other oral ulcerative lesions such as chronic traumatic ulcers, squamous cell carcinoma, lymphomas, Crohn disease, ulcerative necrotic gingivitis or stomatitis, tuberculosis, and necrotizing sialometaplasia. ² Consequently, in the absence of proper awareness, the clinicians may misdiagnose the condition. ^10,15

Amphotericin B and certain azoles are effective against H capsulatum. ¹⁰ Itraconazole and fluconazole have been effective in treating head and neck histoplasmosis with 85% to 100% and 86% of cases, respectively. ⁹ The refractory cases to initial azole treatment should be converted into amphotericin B. ⁹