Histoplasmosis refers to an infection caused by histoplasma capsulatum, a dimorphic fungus. We report a rare case of cutaneous histoplasmosis in an immunocompromised patient. The diagnosis was made by the cytopathologic examination of skin scraping smear, which showed numerous intracellular and extracellular periodic acid-schiff positive rounded yeast cells. The patient showed dramatic response with itraconazole and amphotericin B. We opine that skin scrape cytology can be useful in establishing the diagnosis of the disease, specially when the other facilities are not readily available.
Keywords: Cutaneous histoplasmosis, skin scrape cytology, immunodeficiency state
Histoplasmosis is a granulomatous fungal disease caused by Histoplasma capsulatum, a dimorphic fungus. On account of its varied clinical presentation, and perhaps due to lack of anticipation and awareness, it has been rarely reported. In 1959, Panja and Sen first reported histoplasmosis from India.  We are reporting a rare case of primary cutaneous histoplasmosis mimicking molluscum contagiosum in an immunocompromised patient.
A 38 years old male patient presented to the out-patient-department with numerous tender papular eruptions over the face, neck, chest and back sparing the oral cavity. The lesions were of sudden onset and gradually progressive with an umbilication, ulceration and crusting [Figure 1]. On clinical examination, neither hepatosplenomegaly nor lymphadenopathy was found. Examination of other systems revealed no significant abnormality.
On investigation, complete blood count was within normal range. Liver and renal function tests were within normal limit. The Venereal Disease Research Laboratory (VDRL) test was non-reactive. Screening ELISA for Human Immunodeficiency virus (HIV) was reactive for HIV type 1 with subsequent western blot confirmation. Peripheral CD4-lymphocyte count was 148/cumm, well below the lowest normal limit of 200/cumm. Serum lactate dehydrogenase enzyme level was 410 I.U./L. Chest X-ray did not show any abnormality [Figure 2].
Skin scraping from the lesions was performed with a proper precaution to exclude molluscum contagiosum. The lesion was first cleaned with a gauze piece soaked in 70% ethanol. Scrape smears were obtained from the lesion by means of a scalpel blade. Slides were stained by both Leishman-Giemsa and Periodic-Acid Schiff method. Smears showed inflammatory cells comprising mainly of histiocytes containing numerous intracellular small, ovoid cysts surrounded by a clear space [Figure 3]a. The organism showed an intense staining on Periodic-Acid Schiff method, and a diagnosis of cutaneous histoplasmosis was offered [Figure 3]b. Bone marrow aspiration was performed to exclude systemic involvement and it was unremarkable. Facility for fungal culture was not available in our set-up and hence could not be performed.
The patient was put on an antiretroviral therapy along with intravenous Amphotericin B at the dose of 5 mg/kg/day for 2 weeks, followed by maintenance on an oral Itraconazole. The lesions began to heal by 3 rd day, and the patient was discharged on completion of intravenous Amphotericin B therapy to attend the O.P.D. on follow-up.
Histoplasmosis, caused by capsulatum var capsulatum found in America and the tropics, reveals smaller yeast forms (size 3-4 microns) of the organisms embedded in histiocytes. Histoplasmosis by another strain, capsulatum var duboisii in Africa, shows a giant cell granuloma containing yeast cells of 10-15 microns in diameter. , The causative organisms are stained by the usual fungal stains such the PAS reaction and methenamine silver. In our case, we found aggregates of histiocytes containing intensely PAS positive smaller yeast forms in our cytological preparations, indicating an American and tropical form of the fungus. Fungal culture remains the gold standard diagnostic test for histoplasmosis, but may be negative in less severe cases. Cultures are positive in about 75% of the cases of progressive disseminated histoplasmosis and chronic pulmonary histoplasmosis. Cultures are typically negative in other forms of histoplasmosis.
In HIV- infected individuals, the risk factors for the development of histoplasmosis are CD 4 count <200 cells per microliter and history of exposure to excreta of bats and birds. CD 4 count in our patient was 148 per microliter. In these patients, it usually manifest as disseminated infection, and serum LDH level (> 600 I.U./L) is elevated in most of the cases of disseminated histoplasmosis.  Though in our case it was 410 I.U./L, suggesting localized form of the disease.
Nanda and co-workers reported a case of primary cutaneous histoplasmosis in an immunocompetent patient from a non-endemic area diagnosed by the skin biopsy. Our patient also had only cutaneous manifestations of the disease without any systemic involvement. 
Bhagwat et al described two unusual cases of histoplasmosis in HIV – infected individuals. One of the patients had cutaneous histoplasmosis, and another case presented with painful ulcers over the tongue. 
Arun Shirali and others published a case report of cutaneous and conjunctival involvement by histoplasmosis in an immunocompromised patient with disseminated disease, diagnosed by the skin and conjunctival biopsy and demonstration of the organism in bone marrow aspirate. 
In our case, we did not perform the skin biopsy because our provisional diagnosis was molluscum contagiosum, and we did a skin scraping with an intention of rapid diagnosis. Cutaneous lesions occur in only 6% patients with disseminated histoplasmosis, but may rarely be the presenting sign. In addition, there may be a number of non-specific cutaneous manifestations associated with histoplasmosis including erythema nodosum and erythema multiforme. 
In the present scenario of HIV emergence, a high index of suspicion has to be maintained for diagnosing opportunistic infection like histoplasmosis. In our opinion, cytology is the office procedure of choice in arriving at a specific diagnosis in most of the cases, which may allow for the rapid institution of life saving therapy.
Prof. Shikha Das, Head of the Department, Department of Pathology.
Source of Support: None, Conflict of Interest: None