Abstract

IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory condition triggered by autoimmunity that can affect multiple organ systems, with the hepatobiliary tract and kidneys being two of the most commonly involved. Given that the clinical and imaging presentation of IgG4-RD is similar to that seen in cases of malignancy, infections, and other autoimmune conditions, diagnosis is difficult, especially in the setting of acute care when delayed diagnosis could result in the performance of unnecessary invasive tests and improper treatment. This paper reviews the recent advances in diagnosis and management of the disease, specifically classification, imaging, pathology, biomarkers, and treatment modalities for IgG4 related disease affecting the biliary tree and kidney. A structured review of the literature in PubMed/MEDLINE, Embase, and Cochrane Library was performed for the period up until November 2025, including mainly the literature from 2012 to 2025 and landmark earlier papers. IgG4-RD is shown to primarily involve men above 50 years of age, typically manifesting itself as IgG4-related sclerosing cholangitis in the hepatobiliary system and as tubulointerstitial nephritis in the kidneys; however, glomerulonephritis and inflammatory pseudotumors can occur. The diagnosis of IgG4-RD is achieved by using the combination of clinical findings with distinct radiologic findings, high levels of serologic parameters, and histopathological evidence of lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and the increased number of plasma cells positive for IgG4. Recently, circulating plasmablasts have been shown to be a better biomarker than serum IgG4 in certain patients. Induction therapy is based on glucocorticoids, while rituximab is used as an efficient steroid-sparing alternative in case of recurrences or refractoriness to corticosteroids. The importance of early diagnosis of IgG4-RD in order to differentiate this condition from malignancies and inflammatory diseases and achieve successful treatment cannot be underestimated.