PD‐1 inhibitor gastroenterocolitis: case series and appraisal of ‘immunomodulatory gastroenterocolitis’

Aims PD‐1 inhibitors facilitate immune response against certain tumour types, including melanoma. These drugs have led to prolonged survival but can also result in autoimmune‐type side effects, including gastrointestinal inflammation. The histopathological effects of this medication class have not been well studied. Methods and results We identified 37 gastrointestinal tract biopsies from 20 patients taking a PD‐1 or PD‐L1 inhibitor and evaluated clinicopathological findings. Diarrhoea was the most common symptom, and endoscopic findings ranged from mild erythema to erosion/ulceration. Common histological findings included lamina propria expansion, villous blunting (if applicable), intra‐epithelial neutrophils and increased crypt/gland apoptosis, although intra‐epithelial lymphocytes were rarely prominent. A few cases showed crypt rupture with resultant histiocytic/granulomatous response. Most patients responded to drug cessation and/or steroids, but follow‐up endoscopies were not performed. Conclusions PD‐1/PD‐L1 inhibitors can cause gastritis, enteritis and colitis, similar to other immunomodulatory antibodies (such as CTLA‐4 inhibitors and PI3Kδ inhibitors), but the histological findings vary somewhat among drug classes. Clinical history, lack of prominent intra‐epithelial lymphocytes and crypt rupture may help to distinguish PD‐1 inhibitor gastroenterocolitis from mimics, which include other medication effect, inflammatory bowel disease, graft‐versus‐host disease, cytomegalovirus infection and autoimmune enteropathy.