[An unusual digestive complication under anti-PD-1 (pembrolizumab)]

Abstract

The most commonly reported pattern of anti-PD-1 induced colitis is an active colitis characterized by neutrophilic inflammation and prominent apoptosis. On the other hand, reports of collagenous colitis (which is a microscopic colitis) are exceptional. In this report, we describe an unusual case of anti-PD1-associated collagenous colitis in a 76-year-old man, treated with pembrolizumab for a stage IV cutaneous melanoma. Fourteen months after the start of pembrolizumab, the patient developed a grade 3 diarrhea (up to 9 stools per day) associated with profound hypokalemia. No bacterial, viral or parasitological infectious agents were found from stool analysis. The rectosigmoidoscopy showed colonic diffuse congestion with no ulceration. Systematic biopsies were performed during endoscopy. Histologically, the fragments analyzed revealed a moderately thickened subepithelial collagen layer (20-30μm thick) associated with a mild mixed inflammatory infiltrate within the lamina propria. There were no granuloma lesions, ulcerations or viral inclusion bodies. The patient was initially successfully treated with corticosteroids (prednisone) and temporary interruption of pembrolizumab. However, during corticosteroids tapering, a relapse was observed. The treatment was switched to budesonide, leading to a complete and definitive resolution of diarrhea. To date, budesonide has been stopped and pembrolizumab has not been restarted. Currently, there is a bone progression treated by radiotherapy alone. In case of a more important progression, a systemic treatment will be secondarily discussed.

Keywords: Anti-PD-1; Checkpoint inhibitors; Colite; Colite collagène; Colitis; Collagenous colitis; Inhibiteurs de point de contrôle.