IgG4-related sclerosing cholangitis

Abstract

IgG4-sclerosing cholangitis (IgG4-SC) is the biliary manifestation of the systemic fibro-inflammatory condition IgG4-related disease. Most commonly it affects men in their seventh decade, but accurate estimates of incidence and prevalence are unknown, particularly in the Western world. The disease often manifests with obstructive jaundice. On imaging its appearance is frequently indistinguishable from primary sclerosing cholangitis or cholangiocarcinoma. Making this distinction is paramount to avoid patients undergoing unnecessary surgical resections for suspected cancer. Although serum IgG4 is raised in the majority of cases, this is not specific to the disease, and diagnosis is based on the combination of this finding together with imaging, histology, involvement of other organs, and responsiveness to steroid therapy. Histologically, disease lesions have a lymphoplasmacytic infiltration, abundant IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Steroids are highly effective at treating IgG4-SC, but half of patients relapse requiring further immunosuppressive therapy. Long term, patients are at risk of irreversible fibrosis, organ dysfunction, and malignancy. The immunological mechanisms of pathogenesis are not yet clear, although there is evidence that both B cells and T cells are involved. This review summarizes the current evidence of IgG4-SC epidemiology and its clinical, radiological, and histological features, treatment, natural history, and pathophysiology.