Histoplasmosis Following Systemic Immunomodulatory Therapy for Ocular Inflammation

Abstract

Histoplasmosis is a known complication of systemic immunosuppressive therapy, particularly among patients who are receiving tumor necrosis factor α inhibitors. There are limited data on the development of disseminated or pulmonary histoplasmosis among patients who are receiving systemic immunosuppressive medication for noninfectious ocular inflammation. Retrospective case series. We reviewed all patients with uveitis or scleritis who subsequently developed pulmonary or disseminated histoplasmosis at the Mayo Clinic in Rochester, Minnesota between September 1, 1994 and July 1, 2017, with a 3:1 age- and sex-matched control cohort who did not develop histoplasmosis. This was a single institutional study examining patients that developed histoplasmosis after the initiation of systemic immunomodulatory therapy (IMT). Patients had to develop either disseminated or pulmonary histoplasmosis while receiving systemic immunosuppressive therapy and have an ophthalmic examination at Mayo Clinic Rochester. The control group was comprised of patients who received systemic IMT for ocular inflammation but did not develop histoplasmosis. Nine cases of histoplasmosis were identified: 2 disseminated and 7 pulmonary. Both patients with disseminated histoplasmosis were taking tumor necrosis factor α inhibitors. Seven of the 9 patients received systemic antifungal medication, including both disseminated cases. Over a median follow-up of 4.4 years, none of the patients died, and there were no recurrences of histoplasmosis. When compared to the control cohort, there was no correlation between length of time on IMT and the risk of histoplasmosis. Ocular inflammation patients on systemic immunomodulatory therapy may develop pulmonary or disseminated histoplasmosis. Most cases require treatment with systemic antifungal medication, but it might not be necessary to stop systemic immunomodulatory medication for ocular inflammation. Ophthalmologists should be aware that patients receiving systemic immunomodulatory therapy have a higher risk of developing Histoplasma infections. Prompt diagnosis and treatment using the expertise of an infectious diseases specialist may ensure low mortality for these patients.