S3216 Ozempic-Induced Pancreatitis Leading to Recurrent Flares, Evolving Pseudocysts, and Superinfection: A Multidisciplinary Management Challenge

Introduction: Pancreatic pseudocysts commonly develop after acute pancreatitis but may become symptomatic or infected, warranting intervention. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide, have been associated with rare cases of drug-induced pancreatitis. We present a complex case of recurrent pancreatitis in a patient with pancreatic cystic lesions, including suspected pseudocysts, evolving into superinfection requiring necrosectomy and drainage. Case Description/Methods: A 55-year-old woman with a history of type 2 diabetes, hypothyroidism, gastroesophageal reflux disease, and Guillain-Barré syndrome presented with severe epigastric pain. Labs revealed lipase 2623 U/L. Computed tomography abdomen showed peripancreatic fat stranding and a 3.8 cm hypodense lesion in the pancreatic body. Prior magnetic resonance cholangiopancreatography (MRCP) had shown multiple stable 2–3 cm pancreatic cysts. She had a known history of semaglutide-induced pancreatitis with suspected pseudocyst and mildly elevated CA 19-9. Previous endoscopic ultrasound (EUS) revealed a 2.7 cm cyst in the pancreatic body without ductal communication; FNA was deferred. Following initial improvement, she was readmitted with worsening abdominal pain. Repeat imaging showed interval necrosis in the pancreatic neck and tail with evolving low-density peripancreatic collections. Magnetic resonance imaging confirmed enlargement of a pancreatic tail pseudocyst to 4.2 cm with surrounding fat necrosis. She was later readmitted for pneumonia and sepsis. Computed tomography abdomen revealed further pseudocyst enlargement and mild diverticulitis. Blood cultures grew Streptococcus constellatus, raising concern for infected pseudocyst. She had no peritoneal signs. Multidisciplinary consultation involving Infectious Disease, Gastroenterology, Surgery, and Interventional Radiology was obtained. She underwent esophagogastroduodenoscopy/EUS-guided drainage with cyst debridement and stent placement. Necrosectomy was not required. She improved with antibiotics and pancreatic enzyme replacement therapy. Discussion: This case illustrates the potential for GLP-1 agonist–associated pancreatitis to evolve into chronic, recurrent pancreatitis with pseudocyst formation and superinfection. Diagnostic imaging including magnetic resonance imaging and EUS is critical for characterizing cystic lesions and guiding management. Superinfection, suggested by positive cultures and clinical deterioration, mandates timely multidisciplinary intervention. Endoscopic drainage followed by surgical washout was successful in this case. Long-term surveillance remains essential, given the underlying cystic lesions and prior incomplete follow-up.