IgG4-related sclerosing cholangitis (IgG4-SC) is a rare cholangiopathy that causes symptoms similar to those of primary sclerosing cholangitis. IgG4-SC can manifest with cholangitis and pancreatitis. Diagnosis requires an abnormal cholangiogram, elevated serum IgG4 levels, and histologic analysis. Treatment with corticosteroids leads to dramatic and lasting remission.
(See also Overview of Biliary Function.)
IgG4-related sclerosing cholangitis (IgG4-SC) is a biliary stricturing disease caused by an IgG4-predominant subepithelial lymphoplasmacytic infiltration of intrahepatic and extrahepatic bile ducts.
IgG4-SC is clinically distinct from primary sclerosing cholangitis (PSC). It is the hepatic manifestation of IgG4-related disease, a family of immune-mediated fibro-inflammatory conditions. IgG4-SC is rare, affecting predominantly men in the 6th and 7th decades of life. More than 70% of patients with IgG4-SC also have autoimmune pancreatitis (AIP) (1). A form of IgG4-SC independent of AIP is less common.
General reference
1. Umehara H, Okazaki K, Masaki Y, et al: A novel clinical entity, IgG4-related disease (IgG4RD): General concept and details. Mod Rheumatol 22(1):1-14, 2012. doi: 10.1007/s10165-011-0508-6
Symptoms and Signs of IgG4-SC
Presentation may be similar to that of primary sclerosing cholangitis or cholangiocarcinoma with symptoms that include jaundice, weight loss, and abdominal pain.
Diagnosis of IgG4-SC
Cholangiogram
IgG4 levels
Histology tests
IgG4-SC should be considered particularly in patients with pancreatitis plus cholangiopathy. Accurate differentiation of IgG4-SC from other forms of sclerosing cholangitis is critical because IgG4-SC requires different treatment and confers favorable outcomes. Diagnosis requires an atypical cholangiogram, elevated IgG4 levels (in most, but not all, patients) and representative histological features, including a diffuse lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells of both intra- and extra-hepatic bile duct walls, storiform (“cartwheel”) fibrosis, and preserved bile duct epithelial layer. Particularly in older patients, IgG4-SC can be misdiagnosed as hepatobiliary malignancy.
Treatment of IgG4-SC
Corticosteroids
Treatment reference
1. Sandanayake NS, Church NI, Chapman MH, et al: Presentation and management of post-treatment relapse in autoimmune pancreatitis/immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol 7(10):1089-1096. doi: 10.1016/j.cgh.2009.03.021
Key Points
IgG-SC is a unique cholangiopathy, distinct from PSC.
Suspect IgG-SC particularly in patients with both pancreatitis and cholangiopathy.
Diagnosis requires an abnormal cholangiogram, elevated serum IgG4 levels, and histologic analysis.
Treatment with corticosteroids leads to dramatic and lasting remission.
