Background and aims: An increased risk of acute pancreatitis (AP) has been reported in patients with inflammatory bowel disease (IBD), but data on its prevalence, etiology, and outcomes are limited. Materials and Methods: A two-step retrospective analysis spanning 10 years (2011–2020) was conducted across 34 European centers. The first step surveyed the prevalence of AP in patients with IBD, while the second gathered data on disease characteristics, etiology, and outcomes. Results: The survey found an expected AP prevalence of 1.13% (780/68,989), though only 0.58% (n = 398) met the inclusion criteria. The mean age was 33.6 ± 14.3; 52% were female, and 56.5% had Crohn’s disease (CD). AP was clinically mild in most cases (86.9%). Among 347 patients with available imaging, no alterations were observed in 81 (23.3%), whereas edematous AP was observed in 218 (62.8%). Drugs (mainly azathioprine) were the leading cause (55.3%), followed by biliary (14.8%) and autoimmune (7.8%) causes. In 13.5% of patients, AP was considered idiopathic. During a median follow-up of 67 months [IQR 34–96] from the index episode, recurrence was observed in 13% of patients, and 1.5% developed chronic pancreatitis. CD patients exhibited distinct risk profiles, including ileal involvement and smoking, whereas ulcerative colitis (UC) patients showed more frequent autoimmune and idiopathic etiologies. Conclusions: The PANDORA study established a 0.58% prevalence of AP in IBD patients, which was lower than expected. AP is usually mild both clinically and radiologically. An ileal location in CD and extensive colitis in UC are usually reported, and azathioprine seems to be the most common cause of AP in this setting, especially a few weeks after its introduction.

Background and Aims: Pancreatic hyperenzymemia in inflammatory bowel disease (IBD) is an under-recognized and challenging condition, as elevated pancreatic enzymes may arise from heterogeneous mechanisms and do not necessarily reflect true pancreatic disorder. This multicenter study aimed to characterize the clinical spectrum, diagnostic work-up, and outcomes of hyperenzymemia in IBD. Methods: This retrospective multicenter study was conducted within the PANDORA network, including 34 international IBD centers. For the present analysis, only centers providing patient-level data on pancreatic hyperenzymemia were considered. Collected variables included demographic, clinical, biochemical, imaging, and therapeutic data. Cases were categorized into three predefined phenotypes: chronic asymptomatic pancreatic hyperenzymemia (CAPH), reclassified acute pancreatitis not meeting Atlanta criteria (recAP), and autoimmune pancreatitis (AIP). Results: A total of 148 IBD patients with elevated pancreatic enzymes were included (CAPH 54.7%, RecAP 35.1%, AIP 10.1%). Ulcerative colitis (UC) accounted for 56.8% of cases and Crohn’s disease (CD) for 43.2%. Overall, 73.6% of patients were asymptomatic at the time of enzyme elevation. Marked hyperenzymemia (≥3× ULN) occurred in 22.3% of patients and was more frequent in RecAP than in CAPH or AIP (50.0%, 6.2%, and 13.3%, respectively). IBD was clinically active in 48.6% of patients, with higher rates in CD. Notably, the clinical meaning of hyperenzymemia differed across IBD phenotypes: in CD it was more often associated with active inflammation, whereas in UC it more frequently prompted advanced imaging and led to the identification of AIP. Imaging strategies differed significantly across phenotypes, and drug withdrawal was common in CAPH and RecAP but unnecessary in AIP. Only two rechallenges confirmed a drug-related mechanism. Conclusions: Pancreatic hyperenzymemia in IBD encompasses a spectrum of conditions with different implications. A phenotype-oriented diagnostic approach is essential to avoid misclassification and unnecessary treatment changes.