Immune-checkpoint inhibitors (ICIs) are an essential therapeutic option for many types of cancers; their mechanism of action involves the activation of cytotoxic T cells through targeting PD-1, PD-L1 and CTLA4. Gastrointestinal adverse events due to ICI toxicity can occur, ranging from mild diarrhoea to severe colitis mimicking inflammatory bowel disease [1, 2]; pancreas, liver and small bowel involvement, although possible, are less frequent [1, 3]. We present the case of a ICI-related acute pancreatitis, asymptomatic hepatitis and a steroid-refractory small bowel ulcerative and atrophic enteropathy.

A 57 years-old woman with history of triple-negative breast cancer treated with 6 months of neoadjuvant paclitaxel, carboplatin, doxorubicin, cyclophosphamide and pembrolizumab, followed by mastectomy and adjuvant pembrolizumab was referred to our department for chronic severe diarrhoea and weight loss in the last 4 months. She suffered from ICI-related mild acute oedematous pancreatitis 3 months before, which led to pembrolizumab discontinuation.

Laboratory test showed normocytic anaemia (Hb 11.7 g/dL), asymptomatic elevation of liver enzymes (GGT 1085 U/L, total bilirubin 2.1 mg/dL, direct bilirubin 1.45 mg/dL) and high levels of faecal calprotectin (403 mg/kg) with negativity of coeliac serology, C. difficile serology, stool culture and stool parasites. 

Colonoscopy revealed a mosaic pattern in the ileum and normal findings in all the colon, with histological evidence of focal criptitis in the descending colon only. Gastroscopy showed a severe ulcerative duodenitis, with severe villous atrophy at the histopathological examination. Capsule endoscopy revealed multiple duodenal ulcerations and severe duodenal and ileal villous atrophy with only mild villous blunting in the jejunum.

Prednisone 1 mg/kg/day for 3 weeks was started, but without any improvement in symptoms or laboratory findings. Capsule endoscopy was repeated, showing healing of the duodenal ulcers but persistence of villous atrophy in the duodenum and ileum. Budesonide 9 mg daily and cholestyramine 4 g twice daily were added, but without any significant clinical improvement. The patient was therefore referred to a tertiary centre.

This case emphasises the necessity for clinicians to perform an exhaustive evaluation in patients undergoing ICIs therapy with clinical or endoscopic suspicion of gastrointestinal toxicity, in order to reduce diagnostic delay and the consequent risk of steroid inefficacy and related complications.