S4367 A Rare Case of Immune Checkpoint Inhibitor Esophagitis Due to Pembrolizumab

Introduction: Immune-mediated esophagitis and ulcerative mucositis represent rare adverse effects of pembrolizumab therapy. We describe a case of grade 3/4 pembrolizumab-induced esophagitis and mucositis in a patient receiving treatment for stage IIA breast adenocarcinoma. Case Description/Methods: A 72-year-old woman with triple-negative, poorly differentiated stage IIA breast adenocarcinoma achieved complete response to neoadjuvant therapy (doxorubicin, cyclophosphamide, and pembrolizumab). During adjuvant pembrolizumab treatment, she developed severe odynophagia. Physical examination revealed posterior oropharyngeal erythema and lingual mucositis. Her symptoms proved refractory to empiric therapies including azithromycin, nystatin, fluconazole, micafungin, and saline gargles. Initial infectious workup was negative, but neck computed tomography demonstrated mucosal enhancement of the epiglottis and aryepiglottic folds suggestive of mucositis. Flexible laryngoscopy confirmed ulcerative mucositis with concomitant laryngopharyngitis. Pembrolizumab was discontinued, and she was initiated on prednisone 1 mg/kg, achieving significant pain improvement within 1 week. However, symptom recurrence occurred during steroid taper after 5 weeks. Subsequent esophagogastroduodenoscopy revealed diffuse gastric hyperemia, edema, and antral ulcers, with cultures positive for Candida albicans (HSV and CMV negative). Treatment with fluconazole and pantoprazole was initiated. Repeat endoscopy demonstrated persistent pharyngo-esophagitis with mid-esophageal ulceration, confirming chronic active immune-mediated esophagitis. Escalation to prednisone 1.5 mg/kg daily with continued proton pump inhibitors therapy ultimately resulted in complete symptom resolution. Discussion: Pembrolizumab, a PD-1 inhibitor monoclonal antibody, boosts antitumor immunity by blocking PD-1/PD-L1/2 interactions. This immune activation, though effective, can cause immune-related adverse events (irAEs) across organ systems. Gastrointestinal irAEs more often affect the lower tract (e.g., colitis), especially with CTLA-4 inhibitors, but PD-1/PD-L1 therapies show distinct upper GI patterns. These usually appear later (3–6 months post-treatment) and primarily involve the stomach. Only about 25 cases of ICI-related esophagitis are reported. Management includes acid suppression (proton pump inhibitors, H2 blockers), mucosal protectants (sucralfate), and corticosteroids for moderate to severe cases. This case highlights the need for clinician awareness of rare upper gastrointestinal irAEs, given their delayed onset, significant morbidity and complex treatment.