S6195 From Tumor Immunity to Autoimmunity: A Case of Celiac Disease Following ICI Therapy

Introduction: Immune checkpoint inhibitors (ICIs) are antineoplastic agents used in the treatment of various malignancies. They enhance the CD8+ T-cell response and activate the inflammatory cascade, enabling the immune system to more effectively target tumor cells. Pembrolizumab, an anti-PD-1 ICI, is associated with a wide array of adverse effects, much like other chemotherapies. We present a case of a patient who developed severe, persistent watery diarrhea shortly after initiating pembrolizumab therapy. This case highlights the importance of considering ICI-induced celiac disease in the differential diagnosis of similar presentations. Case Description/Methods: A 71-year-old woman presented with a 3-month history of severe watery diarrhea and dehydration following her second dose of adjuvant pembrolizumab after a left nephrectomy for renal cell carcinoma. She denied hematochezia, melena, nausea, vomiting, or abdominal pain. Her past medical history included gastroesophageal reflux disease, hypothyroidism, anxiety, and diverticulosis. Her medications included levothyroxine, fluoxetine, gabapentin, and pilocarpine. She had undergone cholecystectomy 1 year prior. She quit smoking 45 years ago, rarely used alcohol, and denied illicit drug use. Stool studies revealed brown stool, negative for calprotectin but positive for Campylobacter. Treatment for the infection did not alleviate her symptoms, and she continued to experience watery diarrhea up to 10 times per day. Follow-up blood work revealed positive anti-tissue transglutaminase (tTG) and anti-endomysial antibodies, as well as elevated lactoferrin levels, prompting endoscopic evaluation. Colonoscopy was unremarkable, but duodenal biopsies demonstrated increased intraepithelial lymphocytes with marked villous atrophy—findings consistent with Marsh grade 3b celiac disease. The patient was started on a gluten-free diet and reported significant symptom improvement at her 3-month follow-up while continuing pembrolizumab therapy. Discussion: Celiac disease has an increasing global prevalence, but its nonspecific symptoms can pose diagnostic challenges. Although rarely associated with ICIs, a recent review identified only 8 reported cases of ICI-induced celiac disease, with just 2 attributed to pembrolizumab. This case underscores the need to include celiac disease in the differential diagnosis of persistent diarrhea in patients receiving ICI therapy. Early recognition and treatment may significantly improve patient outcomes and quality of life.