S3363 A Complicated Case of Recurrent Pancreatitis in a Patient With 2 CFTR Gene Mutations

Introduction: Recurrent pancreatitis is a multifactorial condition influenced by both environmental and genetic factors. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are a known contributor, with certain variants associated with recurrent pancreatitis. We present a case of a young, otherwise healthy man with recurrent necrotizing pancreatitis requiring extensive surgical intervention, who ultimately found to have cystic fibrosis (CF). Case Description/Methods: A 27-year-old man with no past medical history presented with epigastric pain radiating to his back, described as more intense but similar to 5 previous self-managed episodes. Imaging revealed necrotizing pancreatitis without gallstones or ductal dilation. He was admitted for conservative management and discharged. However, over the following year, he experienced 11 hospital admissions for acute-on-chronic pancreatitis or its complications, including 2 intensive care unit stays. One episode involved multiple pancreatic fluid collections with walled-off necrosis (WON) extending into the colon, requiring 3 exploratory laparotomies with debridement, necrosectomy, and partial colectomy with colostomy. Additional complications included an infected pancreatic fluid collection managed with retroperitoneal drain placement and WON managed by cystogastrostomy stent. He was on no medications and laboratory testing was negative for alcohol use with normal triglycerides and IgG4. With no clear etiology identified, genetic testing was pursued, revealing 2 CFTR mutations (1585-1G > A and 5T_TG12), both associated with an increased risk of chronic pancreatitis. He additionally underwent sweat chloride testing, which confirmed CF, and he was started on CFTR modulator therapy. Discussion: While an uncommon etiology of recurrent pancreatitis, growing evidence supports a significant role for genetic mutations in its pathogenesis. Individuals with 2 CFTR mutations have been shown to carry an approximately 40-fold increased risk of developing pancreatitis. As targeted therapies for these mutations become available, it is crucial for clinicians to consider genetic testing in appropriate clinical contexts. This case underscores the clinical relevance of CFTR mutations in pancreatic disease and highlights the expanding role of genetic evaluation in complex or idiopathic cases.