Histoplasmosis in Inflammatory Bowel Disease with Tumor Necrosis Factor-Alpha Inhibitors: Safe to Continue Biologics?

Jansson-Knodell CL1,2, Harris CE2, Loftus EV Jr3, Walker RC4, Enzler MJ4, Virk A5. Dig Dis Sci. 2020 Mar 7. doi: 10.1007/s10620-020-06181-x. [Epub ahead of print]


Author information

1 Division of Gastroenterology and Hepatology, Indiana University, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.

2 Department of Internal Medicine, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.

3 Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.

4 Division of Infectious Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.

5 Division of Infectious Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA. virka@mayo.edu.


BACKGROUND: The advent of tumor necrosis factor-α (TNF-α) inhibitor therapy has transformed inflammatory boweldisease management; however, these medications carry a boxed warning for risk of serious infections, including invasive fungal infections.

AIMS: We aimed to study the clinical features, severity, and outcomes of histoplasmosis in patients on TNF-α inhibitors for IBD.

METHODS: We performed a retrospective review of IBD patients receiving TNF-α inhibitors who developed histoplasmosis from January 1, 2001, to May 31, 2018. Patients with drug indications other than ulcerative colitis or Crohn's disease were excluded. IBD was diagnosed histologically, radiographically, or endoscopically.

RESULTS: We identified 49 patients (median age 44 years; range 19-76) with histoplasmosis on TNF-α inhibitors. Patients with disseminated disease had a median urine antigen of 10.76 ng/mL compared with pulmonary diseasealone 0.375 ng/mL (p < 0.001). Charlson Comorbidity Index and urine antigen levels showed a trend toward predicting disease severity (p > 0.05). Median length of stay was 9.5 days. Itraconazole was used for maintenance in all patients. Median follow-up was 4.7 years. Total treatment duration ranged from 3 to 15 months. TNF-α inhibitor therapy was continued in nine and resumed in ten patients after completing antifungals. Three deaths occurred (6%).

CONCLUSIONS: Histoplasmosis outcomes were mostly favorable. Many patients were young with few comorbidities; however, those with more comorbidities experienced more severe histoplasmosis. Compared to prior studies, many of these patients resumed or continued biologic therapy. There were no histoplasmosis recurrences after resuming TNF-α inhibitor therapy. Vigilance for disseminated fungal infections in this patient population is essential.

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