Background: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder characterized by lymphoplasmacytic infiltration, tumefactive lesions, IgG4-positive plasma cells, and progressive fibrosis affecting multiple organs. Its heterogeneous presentation frequently overlaps with malignancy, infection, vasculitis, and other autoimmune disorders.

Objectives: This review summarizes contemporary evidence on the epidemiology, immunopathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of IgG4-RD.

Methods: A descriptive review of English-language literature published from January 2019 through June 2026 was conducted using PubMed/MEDLINE, Web of Science, and Google Scholar. Relevant original studies, observational studies, reviews, meta-analyses, consensus statements, guidelines, and classification criteria were considered and narratively synthesized.

Results: IgG4-RD involves complex interactions among B cells, plasmablasts, T-cell subsets, macrophages, cytokines, and fibroblasts, resulting in chronic inflammation and fibrosis. Commonly affected sites include the pancreas, biliary tract, salivary and lacrimal glands, kidneys, lungs, retroperitoneum, orbit, and vascular and nervous systems. Diagnosis requires integration of clinical findings, serology, imaging, and histopathology while excluding mimicking disorders. Serum IgG4 elevation is supportive but neither sensitive nor specific enough for diagnosis alone. Characteristic histopathology includes lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and increased IgG4-positive plasma cells. Glucocorticoids remain widely used for remission induction, while rituximab is increasingly important for relapsing, refractory, or steroid-dependent disease.

Conclusion: Early recognition of IgG4-RD is essential to prevent irreversible fibrosis and organ dysfunction. Improved understanding of its immunopathogenesis and expanding targeted therapies may enhance long-term disease control.