Histoplasmosis in Inflammatory Bowel Disease Patients on Tumor Necrosis Factor-a Medications

Abstract

Introduction: The advent of tumor necrosis factor (TNF)-a antagonist therapy has transformed the management of inflammatory bowel disease (IBD); however, these medications carry a boxed warning from the Food and Drug Administration (FDA) for risk of serious infection. We aimed to study the invasive fungal infection, histoplasmosis, in the setting of TNF-a blocker therapy. Methods: We performed a retrospective review of patients with IBD receiving TNF-a therapy who developed disseminated or pulmonary histoplasmosis during the time period January 2001 - May 2018. Patients with indications for TNF-a drugs other than ulcerative colitis or Crohn's disease were excluded. The medical records of patients were reviewed for demographics, medications, symptoms, diagnosis, treatment, and outcomes including mortality. IBD was diagnosed by biopsy, radiographic, or endoscopic evidence of disease. Results: We identified 49 patients (age range 19-74; average 42 years) with a confirmed diagnosis of histoplasmosis while receiving TNF-a inhibitors. Infliximab and adalimumab were the most commonly used. A majority of patients had Crohn's disease. The diagnosis of histoplasmosis was confirmed by multiple modalities with serology being the most frequently obtained. The most common lab finding besides anemia was elevated alkaline phosphatase. For antifungal treatment, amphotericin was given in 17 cases as the initial agent. Itraconazole, the drug of choice for histoplasmosis, was given in all 49 patients. Treatment duration ranged from 3-15 months. Treatment location was split evenly between inpatient (49%) and outpatient (51%) locations with 6 patients (12%) requiring ICU-level care. Average length of stay was 15.4 days (range 2-56 days). TNF-a therapy was continued in 7 patients concurrently with azole therapy and 17 patients resumed TNF-a medication after completing treatment for histoplasmosis. There was 1 histoplasmosis recurrence. Median follow-up was 3.2 years. A total of 3 deaths occurred (6%). Conclusion: Disease outcomes were mostly favorable. Many patients were young with few or no comorbidities and were able to resume biologic therapy; however, those treated inpatient had an extended length of stay > 2 weeks on average indicative of the severity of histoplasmosis. Recurrence after resumption of anti-TNF-a therapy was low. Practitioners should be vigilant for disseminated fungal infections in this patient population.671 Figure 1 No Caption available.