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Clinical Infection & Immunity

Case Report

Volume 2, Number 2-3, September 2017, pages 43-45

Primary Cutaneous Histoplasmosis With Disseminated Tuberculosis as an Initial Presentation of AIDS

Histoplasmosis is an opportunistic fungal infection caused by the fungus Histoplasma capsulatum frequently associated with acquired immunodeficiency syndrome (AIDS) and other immunocompromised patients. Disseminated histoplasmosis is the most common form associated with AIDS [1, 2]. Cutaneous lesions in histoplasmosis can be divided as primary or secondary lesions. Primary cutaneous infection of the skin is rare and usually cutaneous involvement is the manifestation of systemic disease. Cutaneous involvement is reported in nearly 10% of human immunodeficiency virus (HIV)-associated histoplasmosis cases [2]. Histoplasmosis has been increasingly reported from India in the past few years and most of the cases are found to be associated with HIV infection [1-5]. Cutaneous involvement is not the manifestation commonly found in the reports from India. Besides, concomitant tuberculosis (TB) and histoplasmosis infection has been a rare presenting feature in AIDS [6]. Here we report an HIV-infected patient presenting with primary cutaneous histoplasmosis and disseminated TB, which to the best of our knowledge is a unique case.

A 37-year-old previously healthy male patient presented to the Rheumatology Department in Command Hospital Lucknow for complaints of significant weight loss, chronic cough and ulcerative lesions on the face of 3 months duration. Clinical evaluation revealed a cachexic individual with pallor. On cutaneous examination, there were multiple discrete papulonodular lesions on the right cheek (Fig. 1a). Few of the lesions showed ulcerations with a hemorrhagic base. Rest of the general and systemic examination was unremarkable. A differential diagnosis of molluscum contagiosum, cutaneous cryptococcosis, cutaneous histoplasmosis, and cutaneous military TB was considered.

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Figure 1. (a) Ulcerative papular lesions of histoplasmosis on the face (at presentation). (b) Significant healing of lesions after 6 weeks of treatment.

Initial investigations revealed hemoglobin of 9 g/dL with normal leucocyte and platelet counts. All biochemical and metabolic parameters were within normal limits. Chest roentogram and CECT showed military mottling suggestive of TB or fungal infection. Sputum smear analysis revealed acid-fast bacillus (AFB) which confirmed TB. Serologies for venereal disease research laboratory test and Australia antigen were negative. ELISA test for HIV-1 was reactive. He had very low CD4 counts (14/µL) and a high viral load. Skin biopsy from the lesions revealed irregular acanthosis of lining epithelium with focal areas of ulceration. Underlying dermis was edematous with dense aggregates of neutrophils, lymphocytes and histiocytes. Numerous giant cells containing capsulated yeasts of histoplasma were seen with positive staining of yeasts with periodic acid-Schiff (PAS) and Grocotts silver methenamine stain (Fig. 2).

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Figure 2. Capsulated yeasts of histoplasma (× 400) (a) showing positive staining with PAS (b) and Grocotts silver methenamine stain (c).

He was diagnosed to have AIDS with cutaneous histoplasmosis and military TB. He was started on highly active antiretroviral therapy (tenofovir 300 mg OD, emtricitabine 200 mg OD, and efavirenz 600 mg OD), anti-tubercular therapy (ATT) and anti-fungals (Inj liposomal amphotericin for 2 weeks followed by itraconazole 200 mg BD). He was also provided prophylaxis for Mycobacterium avium-intracellulare and Pneumocystis jiroveci infection. He showed a good initial response to management, but subsequently his condition deteriorated with sudden development of marked pancytopenia (Hb: 4.0 g%. TLC: 1,100/mm³, platelets: 7,000 lac/mm³). Bone marrow studies showed evidence of necrotizing granulomas with positive staining for AFB confirming disseminated bone TB. Trimethoprim/sulfamethoxazole was discontinued due to possible bone marrow suppression associated with this medication. He was also administered blood component replacement therapy (granulocyte colony stimulating factor, platelet and red blood cell transfusions) with a good hematological recovery. The cutaneous lesions gradually healed well (Fig. 1b). He also attained adequate clinical and radiological resolution with ATT. His immunological response to anti-retroviral therapy (ART) was excellent as his CD4 counts improved to 314/µL with 4 weeks of ART.

Histoplasmosis is an opportunistic fungal infection caused by the dimorphic fungus Histoplasma capsulatum that can affect both immunocompromised and immunocompetent individuals [1, 2]. It may occur in three forms: 1) primary acute pulmonary form; 2) chronic pulmonary; and 3) disseminated form. Disseminated form presenting with molluscum-like skin lesions is a characteristic feature of cutaneous histoplasmosis and is an AIDS defining illness especially with a CD4 count < 75 cells/µL [1]. Incidence is reported to be 2-5% in AIDS patients and < 0.05% in non-HIV patients [7]. Skin lesions may occur with all the three forms of histoplasmosis or, rarely, as primary cutaneous histoplasmosis. Cutaneous lesions occur in up to 17% of patients with disseminated histoplasmosis [8, 9] and more importantly, primary cutaneous histoplasmosis like in our case is very rare, and can present with nodules, ulcers, abscesses or molluscum contagiosum-like lesions [10]. Other diseases can produce cutaneous lesions in HIV patients in this clinical setting and should be included in the differential diagnosis. Drug eruptions, HIV-associated prurigo, scabies, psoriasis, and other bacterial, viral, and fungal diseases are some of the disorders that can mimic cutaneous histoplasmosis [11]. Therefore, a high index of suspicion and the isolation of the fungus in tissues is essential for the correct diagnosis.

Histoplasmosis in any form closely simulates TB clinically [12], and sometimes also in histological sections [13]. Special techniques such as the Gomori’s methenamine silver method or PAS reaction are required to demonstrate the yeast forms in tissue sections [13], as was done successfully in our case.

The various drugs employed in treatment of histoplasmosis are amphotericin, ketoconazole, itraconazole and terbinafine, of which itraconazole is the drug of choice, except in severe systemic involvement, where amphotericin is preferred [14]. Singhi et al treated a case of disseminated primary cutaneous histoplasmosis in an immunocompetent female with itraconazole showing excellent results [15]. An expert group recommended itraconazole 200 mg three times daily for 3 days followed by 200 mg twice daily for 12 months for immunocompromised hosts with pulmonary histoplasmosis or with the progressive or disseminated disease [16]. Our patient who had a severely immunocompromised status, was aggressively managed with liposomal amphotericin for 14 days followed by oral itraconazole for a highly probable disseminated histoplasmosis infection. Subsequently, positive AFB staining from bone marrow and sputum smear confirmed that we are dealing with an extremely rare case of AIDS with isolated primary cutaneous histoplasmosis and concomitant disseminated TB. Such a unique initial presentation of AIDS, to the best of our knowledge, has never been reported in the literature.

Source of Support

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Conflicts of Interest

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