Persistent Skin-colored Papules Over Face in an Immunocompromised Patient.

A 46-year-old man presented with multiple skin-colored bumpy eruptions over his face with duration of 1 month, the lesions were asymptomatic and slowly increased in number and size. The patient had a history of occasional fever, weight loss, generalized weakness, and lethargy for the last 4 months. He was a driver by occupation and had multiple sexual partners in the past. No other family members had similar disease, and there was no history of any drug intake before onset of the lesions. On cutaneous examination, there were a few skin-colored, pea-sized papules over his face. Most of the papules had smooth surface, but some of them had central umbilication [Figure 1], rest of the skin and oral mucosa were normal. There was no significant lymphadenopathy. Biopsy was taken from one of the intact papules maintaining universal precautions and routine hematoxylin and eosin (H and E) staining was done.

Figure 1

Skin-colored papules over face with some showing central umbilication

Histopathological examination of the skin biopsy specimen with H and E stain showed diffuse macrophage infiltration of the entire dermis in low power view [Figure 2]. On high power view, round to oval bodies surrounded by clear space were seen within the cytoplasm of the macrophages [Figure 3]. Routine hemogram, urine analysis, serum biochemistry panel, chest X-ray, bone marrow examination, sputum examination, and abdominal ultrasound revealed no significant abnormalities. His CD4 count was 346.

Figure 2

Diffuse macrophage infiltration of the entire dermis (H and E, ×100)

Figure 3

Round to oval bodies surrounded by a clear space within the cytoplasm of the macrophages

Question

What is the diagnosis??

Answer

Primary cutaneous histoplasmosis

Discussion

Histoplasmosis is caused by dimorphic fungi histoplasma, an intercellular obligate parasite. There are two species of histoplasma causing the disease, Histoplasma capsulatum mainly found in America and tropics and Histoplasma duboisii found in Africa. H. capsulatum exists as a saprophyte in nature and is found in soil, thorns, and bird droppings.[1] The spores are infectious to man. It is rare infection and usually occurs in immunocompromised individuals, more so in HIV infected persons and usually with a CD4 counts < 200 cells/μl. H. capsulatum is considered endemic in certain Indian states such as West Bengal, where a study showed a prevalence of skin positivity of 9.4% to histoplasmin antigen.[2]

The major clinical presentations of histoplasmosis are pulmonary (acute or chronic), progressive disseminated histoplasmosis, and primary cutaneous histoplasmosis.[3] The infection remains restricted to lungs in 99% cases and disseminates to involve other organs such as, liver, spleen, bone marrow, and lymph nodes in only 1% cases. Sometimes skin and mucous membrane is also affected. Disseminated disease generally affects patients at extremes of age or immunosuppressed ones.[4] The cutaneous manifestation of histoplasmosis is varied. Umbilicated or nonumbilicated papules, nodules, plaques, pustules, ulcers, wart like lesions, and even erythema nodosum like lesions may occur. The mucosa may also get involved, and there may be gingival ulcers, plaques, and nodules. In disseminated disease, other common findings such as hepatomegaly and splenomegaly are present. Due to its varied clinical presentation, a high index suspicion is needed for diagnosing the disease followed by biopsy and culture.

Our case presented with a few skin colored, pea sized papules over his face. Most of the papules had smooth surface, but some of them had central umbilication. Biopsy was performed from an intact papule.

Fungal culture is considered the “gold standard” in the diagnosis of cutaneous histoplasmosis (primary or secondary). Sabouraud agar media at 30°C is used as culture media, which show hyphae with either tuberculate macroconidia or microconidia. Owing to lack of good microbiological laboratory facilities, we could not perform a culture in our case. Histopathological examination of the biopsy tissue yields much rapid results. The histologic picture from cutaneous lesions shows abundant parasitized histiocytes in the dermis (round to oval spores surrounded by a halo), as in our case, or extracellular pattern of free organisms in the dermis, perivascular infiltrate, and nuclear fragments[56] Special stains periodic acid schiff (PAS), Gomori methenamine silver helps to differentiate histoplasmosis from other intercellular organisms such as leishmaniasis, rhinoscleroma, granuloma inguinal, and Chagas disease as later etiologies will not take PAS stain. Due to unavailability, we were not able to perform special stains but clinically above mentioned entities can be ruled out as in our case.

Antibody detection tests such as complement fixation, DNA probes, and radioimmunoassay and detection of polysaccharide antigen in serum, urine, or broncho alveolar lavage are other successful methods for diagnosis but are expensive.

Diagnosis of primary cutaneous histoplasmosis is based on histopathological examination and absence of any signs or symptoms of pulmonary or systemic disease after thorough examination.[78]

In immunocompetent host, most acute forms of histoplasmosis are self limiting but in immunocompromised host and disseminated disease, systemic antifungal is needed. Among systemic drugs, lipid formulations of amphotericin B, itraconazole, posaconazole, voriconazole, and fluconazole are used. Duration of treatment varies from 6–12 weeks to 1 year according to severity of disease. Concomitant use of antiretroviral therapy improves the treatment outcome in HIV positive patients.

Primary cutaneous histoplasmosis in immunocompromised individuals is a rare entity, and it may occur when CD4 count is usually < 200, but in our case, the CD4 count is more than 300 which is quite significant. In addition, there are only a few sporadic case reports from India, which prompted us to report the current case.[910]

Declaration of patient consent

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Conflicts of interest

There are no conflicts of interest.