IgG4-related gastrointestinal disease

Abstract

IgG4-related disease (IgG4-RD) is a chronic, immune-mediated, systemic fibroinflammatory disorder characterized by a dense IgG4-positive lymphoplasmacytic infiltrate, storiform fibrosis and, in many organs, obliterative phlebitis[1],[2]. Although the pancreas is its hallmark site as type 1 autoimmune pancreatitis, the disease may also involve the biliary tract, liver, gastrointestinal tract, mesentery and several extra-digestive organs[2],[4],[5]. Clinical heterogeneity and overlap with malignancies, infections and other autoimmune diseases make early recognition challenging[2],[8].

Diagnosis relies on the integration of clinical, serological, radiological and histopathological findings. Elevated serum IgG4 may support suspicion, but it lacks specificity and can be normal in a relevant proportion of patients[5],[8],[26]. Recent advances in immunopathogenesis have highlighted the role of clonal cytotoxic CD4+ T cells and circulating plasmablasts as key drivers of inflammatory activity and fibrosis[2],[10],[27]. In pancreatic disease, the HISORt criteria remain particularly useful in clinical practice, whereas the 2019 ACR/EULAR classification criteria have helped standardize patient inclusion in research settings[3],[13],[15].

Glucocorticoids remain the first-line therapy for remission induction, with high response rates[13],[23]. Rituximab has become established in refractory or relapsing disease and in selected high-risk patients, although uncertainty remains regarding the optimal maintenance strategy[24],[25],[30]. In this evolving therapeutic landscape, inebilizumab has emerged as one of the most relevant recent advances after positive phase 3 results, reinforcing the role of B-cell–targeted therapy in IgG4-RD. This review summarizes current evidence on epidemiology, pathogenesis, diagnosis, gastrointestinal manifestations, treatment and prognosis of IgG4-RD, with special emphasis on its relevance in Digestive Diseases.

Keywords: IgG4, autoimmune pancreatitis, IgG4-related sclerosing cholangitis, Fibrosis, Rituximab.