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

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Abstract

Background

The advent of tumor necrosis factor-α (TNF-α) inhibitor therapy has transformed inflammatory bowel disease 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 disease alone 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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Acknowledgments

None.

Funding

None directly. Statistics: This work was supported by the National Center for Advancing Translational Sciences [Grant Number UL1 TR002377]. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

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

    Claire L. Jansson-Knodell

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

    Claire L. Jansson-Knodell & Courtney E. Harris

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

    Edward V. Loftus Jr.

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

    Randall C. Walker, Mark J. Enzler & Abinash Virk

Authors
  1. Claire L. Jansson-Knodell
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  2. Courtney E. Harris
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  3. Edward V. Loftus Jr.
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  4. Randall C. Walker
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  5. Mark J. Enzler
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  6. Abinash Virk
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Contributions

CJK, CH, EL, RW, ME, and AV were involved in study conception and design. CJK and CH were involved in data acquisition. CH contributed to statistical analysis. CJK, CH, EL, RW, ME, and AV interpreted the data. CJK and CH contributed to drafting of the manuscript. EL, RW, ME, and AV contributed to manuscript revision. AV conducted study supervision and was the guarantor of the article.

Corresponding author

Correspondence to Abinash Virk.

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Conflict of interest

Abinash Virk: inventor for travel health and wellness, LLC. Edward V Loftus Jr.: consulting for AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Eli Lilly, Genentech, Gilead, Janssen, Pfizer, Takeda, UCB; and research support from AbbVie, Amgen, Celgene/Receptos, Genentech, Gilead, Janssen, Medimmune, Pfizer, Robarts Clinical Trials, Takeda, UCB. Other authors have no disclosures.

Ethical considerations

The study was approved by the Mayo Clinic Institutional Review Board (IRB 18-002325). Patients who declined authorization for review of medical records for research purposes were excluded. For this type of study, formal consent was not required due to its retrospective nature.

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Jansson-Knodell, C.L., Harris, C.E., Loftus, E.V. et al. Histoplasmosis in Inflammatory Bowel Disease with Tumor Necrosis Factor-Alpha Inhibitors: Safe to Continue Biologics?. Dig Dis Sci 66, 190–198 (2021). https://doi.org/10.1007/s10620-020-06181-x

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  • DOI: https://doi.org/10.1007/s10620-020-06181-x

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