Histoplasmosis in a Nonendemic Area: An Often Unrecognized Disease

Abstract

Background. In nonendemic regions, providers are often unfamiliar with the protean manifestations of histoplasmosis. Consequently, the disease may be overlooked, leading to delays in diagnosis. As pockets of previously unrecognized endemicity are identified and an increasing number of people migrate from high-prevalence areas, it becomes imperative to better characterize histoplasmosis in a traditionally nonendemic region. Methods. We performed a retrospective chart review of microbiologically or histopathologically-confirmed cases of histoplasmosis at Yale New Haven Hospital in Connecticut from 2005 to 2015. Active histoplasmosis was defined as symptomatic disease. Results. A total of 20 patients were identified. An incidental diagnosis was made in 8 patients after biopsy of asymptomatic pulmonary nodules, most commonly as part of malignancy screening (n = 4). Among 12 patients with active histoplasmosis, the mean age was 54 years, 10 were male, 6 were Hispanic, and 7 were immunosuppressed (HIV/ AIDS =5, HSCT = 1, SOT = 1). Eleven patients reported travel to endemic areas (Caribbean in 6). Constitutional symptoms were present in 6. Five patients were admitted to the ICU, and 2 developed ARDS. Disseminated histoplasmosis was diagnosed in 8 cases. The most common extrapulmonary sites were the oral mucosa (n = 3) and bone marrow (n = 3). Histopathology and culture were positive in 11 and 5 cases, respectively. Urine Histoplasma antigen was positive in 6 patients. Eight patients received amphotericin B. Median time to diagnosis from symptom onset and initial evaluation were 41 days (15-226 days) and 28 days (4-106), respectively. Median time to first Histoplasma antigen testing was 29 days (2-114 days). Extensive workup (35 imaging or invasive procedures) was performed in 9 patients while 6 were either discharged or died without diagnosis. Treatment success was achieved in 8 patients; 2 failed treatment and 2 died. Conclusion. The epidemiology of histoplasmosis may differ in nonendemic areas. In this Connecticut series, we noted an elevated prevalence of immunosuppression, particularly HIV/AIDS, and travel to the Caribbean. Failure to recognize the disease may contribute to delayed diagnosis, extensive testing and worse outcomes. Histoplasmosis should be considered in patients presenting with compatible signs and symptoms in a nonendemic area. (Figure Presented) .