by Kristy Fleming, MD
A 30-year-old Guatemalan-born male presents to a tertiary-care hospital center complaining of nausea, fever, diarrhea, cough and new asymptomatic bumps on his forehead. The lesions had been present for the last few weeks and he was found to have numerous small erythematous papules scattered on his face, chest, back, arms and legs. His past medical history was significant for HIV infection and his most recent CD4 count was 153/µl. The patient was not currently on highly active anti-retroviral therapy. A peripheral blood smear was performed and found parasitized macrophages. What’s your diagnosis?Submit your answer and read the full explanation below. If you like this activity or have a suggestion, tell us about it in the comment box at the bottom of the page.
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Histoplasmosis, also known as Darling’s disease, is caused by the dimorphic fungus Histoplasma capsulatum var. capsulatum.1 H. capsulatum is found in the soil in hot humid environments. It is endemic in the southeastern and central United States and also occurs in the mid-Atlantic regions.
Bats, birds and fowl are known H. capsulatum reservoirs, often shedding the organism in their feces; therefore, caves, chicken coops and unoccupied buildings tend to be high-risk areas for contracting the infection.
Spore inhalation is the most common route of infection, but in rare cases direct cutaneous inoculation can occur. There has never been a reported case of person-to-person transmission.
Most infections are asymptomatic or cause limited lung disease, but in cases involving a large inoculum or an immunocompromised host, progressive disseminated histoplasmosis can occur.
Disseminated histoplasmosis may affect multiple organ systems, including the respiratory system, reticuloendothelial system, genitourinary tract, adrenal glands, gastrointestinal tract and skin.1,2 Mucocutaneous involvement with ulcerations and granulomas of the oronasopharynx occur in 20% of disseminated histoplasmosis, and skin involvement occurs in approximately 6%.2
Skin lesions are nonspecific and vary greatly in morphology. Reported lesion morphologies include: erythema nodosum, erythema multiforme, umbilicated papules or nodules, ulcerations, abscesses, furuncles and pyoderma.1,2 Purpura is the most common cutaneous manifestation in children and is a poor prognostic marker.2
Histoplasmin skin testing is available, but in endemic areas as much as 90% of the population can test positive.1 Therefore clinicians should perform skin biopsy and tissue culture to confirm histoplasmosis.
Histopathologic analysis will often demonstrate characteristic dermal collections of foamy histiocytes containing numerous intracellular budding yeasts with a clearing rim resembling a halo. Periodic Acid Schiff or Gomori methenamine silver stain will reveal clusters of spherical yeast in the papillary dermis, and either test is encouraged to confirm the diagnosis of disseminated histoplasmosis. Clinicians may also consider a Fite stain to rule out mycobacteria infection.
Clinicians may also perform a bone marrow biopsy or blood culture, but these tests require patients with an intact immune system, and plates may need to be incubated for as long as one month.1 Alternatively, urinary enzyme-linked immunosorbent assay is currently the best diagnostic test available for detecting disseminated disease.2
Patients with limited lung disease may not require therapy, but all immunocompromised or acutely ill patients will need systemic antifungal treatment. Intravenous amphotericin B titrated up to 1mg/kg/day is the treatment of choice.1,2
For patients with moderate disease, itraconazole 200 mg/day for nine months is generally adequate. Patients with HIV require life-long suppressive itraconazole at a dose of 200 mg/day.2
Kristy Fleming, MD, is a third year dermatology resident at Baylor College of medicine.
1. J Bolognia, JL Jorizzo, RP Rapini. Dermatology 2nd Ed. Elsevier; 2008:1153-1155.
2. James WD, Berger TG, Elston DM. Andrew’s Diseases of the Skin: Clinical Dermatology.10th ed. Pennsylvania: Saunders Elsevier; 2006: 316-317.