Immune checkpoint inhibitor‐induced diarrhea: Clinicopathological study of 11 patients

Abstract

We reviewed the records of patients with immune checkpoint inhibitor (ICI)-induced diarrhea during 2015 to 2019. ICI included nivolumab and ipilimumab. There were 11 patients with ICIinduced diarrhea aged 46-81 years (median, 63 years). On colonoscopy, four patients appeared normal, whereas loss of vascularity, erythema, granularity, erosions or ulcerations apparently mimicking ulcerative colitis were found in seven patients. Those seven patients had acute inflammation, cryptitis, crypt abscess and apoptosis, suggestive of ICI-induced colitis. Five of the seven patients were treated with prednisolone, two of whom were resistant to prednisolone and required infliximab. In contrast, none of the four patients without ICI-induced colitis required further treatment. Our observations suggest that diversity exists in the clinical, endoscopic and histological severity of patients with ICIinduced diarrhea. Colonoscopy together with biopsy is inevitable for the diagnosis of ICI-induced colitis, which requires intensive treatment.

Identification of characteristic subepithelial surface granulomatosis in immune‐related adverse event‐associated enterocolitis

“…In this study, we investigated histopathological findings in irAE‐related colitis. The histological patterns of UC‐like and GVHD‐like pattern colitis have also been reported in some previous studies, although the differential mechanisms and clinicopathological importance of these patterns were unclear 4‐6 . We identified SSG as a novel feature that was specific to colon tissue after ICI administration.…”

“…The histological patterns of UC-like and GVHD-like pattern colitis have also been reported in some previous studies, although the differential mechanisms and clinicopathological importance of these patterns were unclear. [4][5][6] We identified SSG as a novel feature that was specific to colon tissue after ICI administration. PD-1/programmed death-ligand 1 (PD-L1) inhibition sometimes complicates granuloma formation disorders, including sarcoid reaction and exacerbation of tuberculosis.…”

Remission of ulcerative colitis flare-up induced by nivolumab

“…Furthermore, when ICIs cause enterocolitis in a UC patient, there is difficulty in strictly differentiating between UC exacerbation and ICI-induced colitis, because the latter often causes endoscopic and histological findings similar to those of UC [6,7]. In the present case, in addition to the findings of UC, histological analysis showed increased crypt apoptosis which is unusual for IBD, while being typical of ICI-induced colitis [24,25]. Furthermore, mucosal remission was maintained despite the diarrhoea associated with axitinib.…”

Successful Treatment of an Immune-Mediated Colitis Induced by Checkpoint Inhibitor Therapy in a Patient with Advanced Melanoma

“…Dual checkpoint inhibition induced by combination therapy with nivolumab and ipilimumab improves response rates in patients with metastatic melanoma compared to monotherapy. However, a higher rate of toxicity, including immune-related colitis, seems to be present under this regimen showing itself as ICI-induced diarrhea [5, 10]. Diagnostic colonoscopy and multiple colonic biopsies are necessary for the diagnosis of ICI-induced colitis, as a diversity of clinical, endoscopic and histological manifestations have been observed in patients with ICI-induced diarrhea [10].…”

“…However, a higher rate of toxicity, including immune-related colitis, seems to be present under this regimen showing itself as ICI-induced diarrhea [5, 10]. Diagnostic colonoscopy and multiple colonic biopsies are necessary for the diagnosis of ICI-induced colitis, as a diversity of clinical, endoscopic and histological manifestations have been observed in patients with ICI-induced diarrhea [10]. In our case, erythema, erosions and ulcerations mimicking IBD were described during colonoscopy and histological examination revealed acute inflammatory infiltration of the mucosa with cryptitis and apoptosis.…”