(See also Overview of Biliary Function Overview of Biliary Function The liver produces about 500 to 600 mL of bile each day. Bile is isosmotic with plasma and consists primarily of water and electrolytes but also organic compounds: bile salts, phospholipids... read more .)
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 Primary Sclerosing Cholangitis (PSC) Primary sclerosing cholangitis (PSC) is patchy inflammation, fibrosis, and strictures of the bile ducts that has no known cause. However, 80% of patients with PSC also have inflammatory bowel... read more (PSC). It is the hepatic manifestation of IgG4-related disease IgG4-Related Disease Immunoglobulin G4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder that often manifests with tumor-like masses and/or painless enlargement of multiple organs... read more , 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 Diagnosis of Pleural Effusion 
). 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 Tumors of the Gallbladder and Bile Ducts Gallbladder and bile duct tumors can cause extrahepatic biliary obstruction. Symptoms may be absent but often are constitutional or reflect biliary obstruction. Diagnosis is based on ultrasonography... read more 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
Corticosteroids (monotherapy with prednisone) are the mainstay of treatment of IgG4-related sclerosing cholangitis. The goal is to induce complete remission. Treatment with high doses leads to rapid biochemical and symptomatic improvement with decreasing serum IgG4 levels, often preventing the need for biliary stenting. Complete remission can be achieved with corticosteroid (prednisone) monotherapy; maintenance therapy is required in most patients; the rate of relapse approaches 50% (1 Treatment reference 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... read more ). In patients who fail corticosteroid therapy, rituximab is also an effective treatment.
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.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
prednisone |
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS |
rituximab |
RIABNI, Rituxan, RUXIENCE, truxima |
