Type 3 Autoimmune Pancreatitis: Clinical Features and Treatment Strategies for Immune Checkpoint Inhibitor-Associated Pancreatitis

Autoimmune pancreatitis (AIP) has traditionally been classified into two subtypes: type 1, associated with immunoglobulin G4-related disease and type 2, characterized by idiopathic duct-centric pancreatitis. The emergence of immune checkpoint inhibitors (ICIs) in cancer treatment has introduced a new entity, type 3 AIP, representing ICI-induced pancreatic autoimmunity. This review examines the pathophysiology, clinical features, diagnosis, treatment, and outcomes of type 3 AIP. The condition affects 0.6-4% of patients receiving ICI therapy, with higher incidence in combination therapy compared to monotherapy. Pathophysiologically, activated CD8+ T-cells appear to be the primary mediators of pancreatic injury. Two-thirds of patients are asymptomatic with only elevated pancreatic enzymes, while symptomatic cases typically present with epigastric pain radiating to the back. Diagnosis requires establishing temporal association with ICI therapy, elevated pancreatic enzymes, characteristic imaging findings, and exclusion of other etiologies. Management depends on disease severity, ranging from monitoring with continued ICI therapy in asymptomatic patients to temporary or permanent discontinuation in more severe cases. The efficacy of steroid therapy remains controversial, with limited evidence supporting its role in preventing long-term complications. Over 50% of patients develop pancreatic atrophy within 1 year, leading to potential endocrine and exocrine insufficiency requiring long-term pancreatic enzyme supplementation and diabetic management. As ICI use expands across oncology, greater awareness of type 3 AIP among clinicians and the development of evidence-based management protocols are essential to improve patient outcomes and quality of life.