Histoplasmosis in Patients With Cell-Mediated Immunodeficiency: Human Immunodeficiency Virus Infection, Organ Transplantation, and Tumor Necrosis Factor-α Inhibition

Background. Histoplasmosis causes severe disease in patients with defects of cell-mediated immunity. It is not known whether outcomes vary related to the type of immunodeficiency or class of antifungal treatment. Methods. We reviewed cases of active histoplasmosis that occurred at Vanderbilt University Medical Center from July 1999 to June 2012 in patients with human immunodeficiency virus (HIV) infection, a history of transplantation, or tumor necrosis factor (TNF)-alpha inhibitor use. These groups were compared for differences in clinical presentation and outcomes. In addition, outcomes were related to the initial choice of treatment. Results. Ninety cases were identified (56 HIV, 23 transplant, 11 TNF-alpha inhibitor). Tumor necrosis factor-alpha patients had milder disease, shorter courses of therapy, and fewer relapses than HIV patients. Histoplasma antigenuria was highly prevalent in all groups (HIV 88%, transplant 95%, TNF-alpha 91%). Organ transplant recipients received amphotericin B formulation as initial therapy less often than other groups (22% vs 57% HIV vs 55% TNF-alpha; P = .006). Treatment failures only occurred in patients with severe disease. The failure rate was similar whether patients received initial amphotericin or triazole therapy. Ninety-day histoplasmosis-related mortality was 9% for all groups and did not vary significantly with choice of initial treatment. Conclusions. Histoplasmosis caused milder disease in patients receiving TNF-alpha inhibitors than patients with HIV or solid organ transplantation. Treatment failures and mortality only occurred in patients with severe disease and did not vary based on type of immunosuppression or choice of initial therapy.