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

• Published in: Digestive diseases and sciences 2021, Vol.66 (1), p.190-198
• Main Authors: Jansson-Knodell, Claire L., Harris, Courtney E., Loftus, Edward V., Walker, Randall C., Enzler, Mark J., Virk, Abinash
• Format: Article
• Language: English
• Subjects: Adalimumab; Adalimumab - pharmacology; Adalimumab - therapeutic use; Adult; Aged; Antigens; Biochemistry; Biological Products - pharmacology; Biological Products - therapeutic use; Cohort Studies; Comorbidity; Crohn's disease; Diseases; Drug therapy; Female; Follow-Up Studies; Fungal infections; Gastroenterology; Health aspects; Hepatology; Histoplasmosis; Histoplasmosis - blood; Histoplasmosis - diagnostic imaging; Histoplasmosis - drug therapy; Humans; Immunotherapy; Inflammatory bowel disease; Inflammatory Bowel Diseases - blood; Inflammatory Bowel Diseases - diagnostic imaging; Inflammatory Bowel Diseases - drug therapy; Infliximab - pharmacology; Infliximab - therapeutic use; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Middle Aged; Monoclonal antibodies; Necrosis; Oncology; Original Article; Retrospective Studies; TNF inhibitors; Transplant Surgery; Tumor necrosis factor; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor necrosis factor-TNF; Ulcerative colitis; Young Adult
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-020-06181-x

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   0.05). 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.