S6235 Olmesartan Enteropathy Mimicking Amyloidosis in Setting of New Multiple Myeloma Diagnosis

Introduction: Olmesartan-induced enteropathy is a rare but serious condition associated with the angiotensin receptor blocker olmesartan. It presents with chronic diarrhea, weight loss, and villous atrophy resembling celiac disease—but without improvement on a gluten-free diet. Early recognition is crucial for diagnosis and management. Case Description/Methods: A 71-year-old man presented with chronic diarrhea, nausea, vomiting, ∼100-pound weight loss, and profound weakness. Medications included olmesartan 40 mg daily. Symptoms began in June 2024 and persisted despite cholecystectomy for choledocholithiasis in October 2024 and after 3-week gluten-free diet failed to improved symptoms after an esophagogastroduodenoscopy (EGD) with duodenal biopsies in February 2025 showed villous blunting, lymphoplasmacytic infiltration, and rare PAS-positive macrophages. A few days after completing gluten-free diet trial, he presented to our hospital. Labs revealed anemia, elevated creatinine, hypercalcemia, and a gamma gap of 5.7. Celiac serologies, infectious stool studies, and HIV were negative. Initial concern was amyloidosis. Further testing showed low immunoglobulin A/immunolglobulin M, elevated immunoglobulin G and an M-protein on SPEP/UPEP. Bone marrow biopsy revealed plasma cell dyscrasia; skeletal survey showed calvarial lucencies. Repeat EGD showed erythematous gastric mucosa and mucosal changes in the duodenum. Duodenal biopsies again revealed villous blunting, lymphoplasmacytic infiltration, and rare PAS-positive macrophages; stains for AFB, Congo red, and Helicobacter pylori were negative. Gastric biopsies showed chronic atrophic gastritis with pyloric metaplasia. Given the failed gluten-free diet and histological findings on biopsy, olmesartan-induced enteropathy was favored over amyloidosis. Olmesartan was discontinued, and budesonide 3 mg three times a day was initiated. He was discharged on nasoduodenal tube feeds. One month later, he had gained 20 pounds, reported resolution of symptoms, and had the tube removed. Budesonide taper and repeat EGD were planned. He was referred to hematology for newly diagnosed multiple myeloma. Discussion: This case underscores the diagnostic challenge of olmesartan-induced enteropathy, especially with overlapping concern for amyloidosis. Despite initial suspicion for amyloid, histologic findings and clinical response to olmesartan cessation supported drug-induced enteropathy. Clinicians should consider olmesartan-induced sprue-like enteropathy in patients with unexplained malabsorptive symptoms and celiac-like histology unresponsive to dietary modification.