Metachronous Esophageal Ulcers after Immune-mediated Colitis Due to Immune Checkpoint Inhibitor Therapy: A Case Report and Literature Review

Abstract

Although cases of gastrointestinal toxicity of pembrolizumab have been reported, cases of acute immunemediated colitis accompanied with metachronous esophageal disorders (esophagitis and ulcer) are rare. We herein report a case of acute colitis and metachronous esophageal ulcers due to an immune-related adverse event following concomitant pembrolizumab chemotherapy for lung adenocarcinoma. To our knowledge, there have so far been no reports of cases in which both acute immune-mediated colitis and metachronous esophageal ulcers developed. We therefore report the details of this case along with a review of the pertinent literature.

Pembrolizumab-induced esophagitis dissecans superficialis in a patient with squamous cell lung carcinoma

“…Currently, ICIs are used for advanced cancers, and they often cause irAEs, including gastrointestinal mucositis. ICIs-induced esophagitis is thought to be rare and to our knowledge, 26 previous cases of esophagitis caused by ICIs have been published: 10 cases with nivolumab 2-11) , 4 with nivolumab and ipilimumab [12][13][14][15] , 9 with pembrolizumab 8, [16][17][18][19][20][21][22][23] , 1 with atezolizumab 24) , 1 with avelumab 25) , and 1 with durvalumab 26) . In many of these cases, besides discontinuation of the ICI, administration of corticosteroids was required.…”

Multiple White Plaques in the Esophagus: A Possible Case of Esophageal Mucosal Alteration Associated With Immune-Related Adverse Events of Immune Checkpoint Inhibitors

“…Because of this, the presence of multiple white plaques in the esophagus was considered a possible mucosal alteration associated with irAEs. Interestingly, esophageal involvement with irAEs is infrequently reported, but cases of multiple ulcers as typical features of esophageal lesions exist [9][10][11][12][13]. Other endoscopic features of esophageal manifestations of irAEs include distal esophagitis resembling Barrett's esophagus [14], thick mucoid secretions, diffuse mucosal congestion with edema, erythema, mucosal friability [15], and ulcers with desquamative esophagitis in the distal esophagus [16].…”

“…Infliximab and vedolizumab are also used for steroid-refractory colitis associated with ICIs [19]. Steroids have also been used for ICI-related esophageal lesions in previous reports [9][10][11][12]. Proton pump inhibitors or vonoprazan have been prescribed independently [13] or in combination with steroids [9,12] for the treatment of esophageal ulcers because acid reflux theoretically causes further deterioration of mucosal damage in the esophagus.…”

“…Steroids have also been used for ICI-related esophageal lesions in previous reports [9][10][11][12]. Proton pump inhibitors or vonoprazan have been prescribed independently [13] or in combination with steroids [9,12] for the treatment of esophageal ulcers because acid reflux theoretically causes further deterioration of mucosal damage in the esophagus. Appropriate management of esophageal white plaques such as those seen in the present cases, however, has not yet been determined, likely because these lesions do not appear to further deteriorate the patient's health.…”

Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors

“…Upper gastrointestinal tract conditions including oesophagitis, [131][132][133][134][135][136][137] oesophagitis dissecans superficialis, 138 oesophageal stenosis, 139 gastritis, [140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156] gastroparesis and enteric neuropathy, 157-160 enteritis (discussed above) and coeliac disease [161][162][163] have been reported in association with ICI use. Data are largely limited to case reports and small series, and oncology society guidelines do not detail algorithmic management.…”