Since 1987, the US Centers for Disease Control and Prevention has considered disseminated histoplasmosis an acquired immunodeficiency syndrome (AIDS)–defining illness. Cutaneous manifestations of disseminated disease are diverse and often present as a nondescript rash with systemic complaints. Diagnosis is best established by histopathologic examination with appropriate stains for fungal organisms. Skin lesions often resolve within weeks of initiating treatment. We detail a case of cutaneous histoplasmosis and review its epidemiology, common presentations, diagnosis, and treatment options.
Infection with Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, usually results from inhalation of its spores, which live in soil, bird droppings, and bat guano. H capsulatum is found in a variety of locations throughout the world. In the United States, the Ohio and Mississippi River valleys are endemic regions.1 The fungus also is prevalent throughout Puerto Rico.2 Infection can result in pulmonary disease of varying length and severity. Many cases of infection are asymptomatic. Other manifestations of histoplasmosis include disseminated infection resulting in systemic disease. The cutaneous manifestations of histoplasmosis most often occur secondary to disseminated disease, though rare cases of primary skin infection resulting from direct inoculation have been reported.
CASE REPORT
A 32-year-old Hispanic man, seropositive for the human immunodeficiency virus (HIV) with a recent absolute CD4 cell count of 23/µL and a viral load of 350x103/µL, was admitted to the hospital with a 2-week history of a pruritic erythematous papular rash, fever, 8-pound weight loss, dysphagia, lethargy, and confusion. The patient started lamivudine and nevirapine 2 weeks earlier, after which he developed the rash and then his other symptoms. He was not taking any other medications.
The patient’s medical history was significant for HIV diagnosed 2 years prior, oral thrush, human papillomavirus anal warts, and a positive rapid plasma reagin test that resulted in treatment with intramuscular penicillin. The patient had a history of multiple sexual partners and intravenous drug use, which he stopped approximately 2 months prior to admission. The patient was born in Los Angeles, California, and was living in Brooklyn, New York, at the time of admission. He had traveled to Puerto Rico several years prior. He did not have any pets and denied any medication allergies.
Physical examination revealed distinct, well-circumscribed papules 2 to 4 mm in diameter on his face (Figure 1), trunk, extremities, palms, and soles. Oral examination was significant for petechiae on soft and hard palates without any white plaques. No lymphadenopathy was noted. Verrucous plaques were noted around the anus.
A chest x-ray demonstrated an opacity in the base of the right lung that the radiologist interpreted to be of indeterminate significance. The patient’s laboratory values were notable for a pancytopenia with a hemoglobin level of 7.7 g/dL (reference range, 13.5–17.5 g/dL), a hematocrit level of 22.5% (reference range, 39%–49%), a white blood cell count of 3300/µL (reference range, 4500–1100/µL), and a platelet count of 61x103/µL (reference range, 150–450x103/µL). His serum sodium level was 125 mEq/L (reference range, 135–145 mEq/L), his serum chloride level was 93 mEq/L (reference range, 60–100 mEq/L), and his blood urea nitrogen level was elevated at 22 mg/dL (reference range, 7–18 mg/dL). His serum creatinine and other electrolyte levels were all within reference range. The patient had a total calcium level of 6.3 mg/dL (reference range, 8.4–10.2 mg/dL) that was corrected to 8.3 mg/dL secondary to an albumin level of 1.5 g/dL (reference range, 3.5–5.5 g/dL). His total protein level was 5.6 g/dL (reference range, 6.0–8.0 g/dL). His liver function tests were notable for an aspartate aminotransferase level of 111 U/L, an alanine aminotransferase level of 53 U/L, and an alkaline phosphatase level of 458 U/L (reference ranges, 7–40 U/L, 7–40 U/L, and 38–126 U/L, respectively). The patient’s total and conjugated bilirubin levels were normal, but his lactate dehydrogenase level was elevated at 398 U/L (reference range, 90–190 U/L). Initial differential diagnoses included a drug hypersensitivity reaction, secondary syphilis, bacillary angiomatosis, a deep fungal infection, and miliary tuberculosis.
Sections of a skin biopsy stained with hematoxylin and eosin demonstrated perivascular, perifollicular, perineuronal, and intraneuronal infiltrate of parasitized histiocytes containing round to oval organisms 2 to 3 µg in diameter, suggestive of H capsulatum (Figure 2). Free organisms were present in the dermis and arrector pili muscles. Positive periodic acid–Schiff and Gomori methenamine silver stains showed oval fungal forms as well. Results of a urine H capsulatum antigen test also were positive. A diagnosis of disseminated histoplasmosis was made, and the patient was treated with intravenous amphotericin B 1 mg/kg daily over 3 weeks. His symptoms, including the rash, began to resolve, and the patient was discharged with a therapeutic regimen of oral itraconazole 200 mg twice daily.