Diagnosis of IgG4-related sclerosing cholangitis

Abstract

IgG4-related sclerosing cholangitis (IgG4-SC) is often associated with autoimmune pancreatitis. However, the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis suggests cholangiocarcinoma (CC). IgG4-SC responds well to steroid therapy, whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention. Since IgG4-SC was first described, it has become a third distinct clinical entity of sclerosing cholangitis. The aim of this review was to introduce the diagnostic methods for IgG4-SC. IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical, serological, morphological, and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis. When intrapancreatic stenosis is detected, pancreatic cancer or CC should be ruled out. If multiple intrahepatic stenoses are evident, PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. Associated inflammatory bowel disease is suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, CC should be discriminated by ultrasonography, intraductal ultrasonography, bile duct biopsy, and a higher cutoff serum IgG4 level of 182 mg/dL.

Keywords: IgG4; IgG4-related sclerosing cholangitis; Primary sclerosing cholangitis; Sclerosing cholangitis.

Figure 1

Cholangiographic classification of IgG4-related sclerosing cholangitis and differential diagnosis. Stenosis is located only in the lower part of the common bile duct in type 1; stenosis is diffusely distributed in the intra-and extra-hepatic bile ducts in type 2. Type 2 is further subdivided into two. Extended narrowing of the intrahepatic bile ducts with prestenotic dilation is widely distributed in type 2a. Narrowing of the intrahepatic bile ducts without prestenotic dilation and reduced bile duct branches are widely distributed in type 2b; stenosis is detected in both the hilar hepatic lesions and the lower part of the common bile ducts in type 3; strictures of the bile duct are detected only in the hilar hepatic lesions in type 4. IDUS: Intraductal ultrasonography; EUS-FNA: Endoscopic ultrasound-guided fine needle aspiration; IBD: Inflammatory bowel disease.

Figure 2

Schematic illustration of comparison of cholangiographic (primary sclerosing cholangitis vs IgG4-related sclerosing cholangitis) findings[28]. The schematic comparison of cholangiographic findings between IgG4-related sclerosing cholangitis (SC) and primary sclerosing cholangitis (PSC). IgG4-related SC displays segmental and long strictures and stricture of the lower common bile duct, whereas PSC displays band-like strictures (1-2 mm), beaded appearance (short and annular stricture alternating with normal or minimally dilated segments), pruned-tree appearance (diminished arbolization of intrahepatic duct and pruning), and diverticulum-like outpouching (outpouchings resembling diverticula, often protruding between adjacent strictures). 1: Band-like stricture; 2: Beaded appearance; 3: Pruned-tree appearance; 4: Dverticulum-like outpouching; 5: Segmental stricture; 6: Long stricture with prestenotic dilation; 7: Stricture of lower common bile duct.

Figure 3

Cholangiogram displaying stenosis in the intrahepatic ducts (A-1) and hilar hepatic lesions (B-1); intraductal ultrasonography revealing bile duct wall thickening in areas with stenosis (1) and without (2).

Figure 4

Algorithm for management of IgG4-related sclerosing cholangitis (cited from [22]). CC: Cholangiocarcinoma; PSC: Primary sclerosing cholangitis; IgG4-SC: IgG4-related sclerosing cholangitis; IDUS: Intraductal ultrasonography; EUS-FNA: Endoscopic ultrasound-guided fine needle aspiration; IBD: Inflammatory bowel disease; UDCA: Ursodeoxycholic acid.