Isolated immune-mediated enteritis in patients treated with immune checkpoint inhibitor therapy

Immune checkpoint inhibitors (ICIs) commonly cause colitis, but isolated immune-mediated enteritis (IMEN) is poorly characterized. This study describes the clinical features, diagnostic findings, and outcomes of IMEN.

We retrospectively identified adults with cancer who developed IMEN within one year of ICI initiation, confirmed as duodenitis, ileitis, or both.

Among 20,991 ICI-treated patients, 30 (0.143%) developed isolated IMEN. Median age was 69.5 years; 73.3% were male, and 80% white. The most common malignancies were gastrointestinal/hepatobiliary (26.7%) and melanoma (23.3%). Presenting symptoms included nausea (66.7%), diarrhea (53.3%), and vomiting (46.7%); 62.5% of patients with diarrhea had grade ≥2 severity. Disease involved duodenitis plus ileitis in 50%, isolated duodenitis in 30%, and isolated ileitis in 20%. Median fecal calprotectin levels were highest in duodenitis plus ileitis (1335.5 μg/g), followed by ileitis (319 μg/g) and duodenitis (78 μg/g). Endoscopy showed nonulcerative inflammation in 60% and ulceration in 20%. Hospitalization was longest in duodenitis plus ileitis (median 13.5 days). Corticosteroids were required in 66.7% of ileitis cases; additional immunosuppression was needed in 33.3% of ileitis and 66.7% of duodenitis plus ileitis. Isolated duodenitis improved with supportive therapy alone. Remission occurred in 63.3% overall. ICI therapy was resumed in 12.5%, exclusively in patients with isolated duodenitis. Complications included fistula formation (10%); all-cause mortality was 36.7%.

IMEN is a rare but clinically significant ICI-related toxicity. Fecal calprotectin correlates with ileitis severity and not duodenitis, and small-bowel endoscopy facilitates diagnosis and management.