IgG4-related autoimmune pancreatitis: a journey

IgG4-RD is an immune-mediated fibroinflammatory disease characterized by tumefactive lesions, a characteristic histopathological pattern, and, in many (but not all) patients, elevated serum IgG4 concentrations and dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells. Autoimmune pancreatitis (AIP), particularly type 1, is the pancreatic manifestation of this systemic disorder. The conceptualization of IgG4-RD has evolved dramatically over the past century, from isolated case reports of swollen glands to recognition as a unified multiorgan disease. This review traces the historical milestones in the understanding of IgG4-RD and AIP, from Mikulicz's 1892 description of symmetric glandular swelling, the description of autoimmune pancreatitis to contemporary targeted B-cell therapies. The diagnostic evolution from early histopathological observations to the 2011 international consensus criteria are explained, as are the therapeutic advances from corticosteroids to CD19-targeted biological agents demonstrated in the MITIGATE and INDIGO trials. Finally, emerging biomarkers, imaging modalities such as FAPI-PET, and the ongoing debate regarding cancer risk in IgG4-RD are discussed. This historical perspective underscores the rapid translation of pathological insights into clinical practice, offering a framework for future research directions in this fascinating disease entity.