IgG4-Related Cholangiopathy and Its Mimickers: A Current Review and Report Highlighting the Importance of Early Diagnosis

Abstract

Immunoglobulin (Ig) G4 (IgG4) related disease is a recently described clinical entity that can involve multiple organs. It is an autoimmune disorder characterized by a dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. A key distinguishing factor is its dramatic response to steroid therapy. It is crucial to differentiate IgG4-related cholangiopathy from its mimickers such as primary biliary cholangitis (PBC), secondary biliary cholangitis (SBC), primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC) and cholangiocarcinoma, as treatment modalities and outcomes of IgG4-related cholangiopathy differ significantly from these disorders. A 72 year-old man presented as a transfer with obstructive jaundice and was found to have elevated total bilirubin (5 mg/dL), alkaline phosphatase (315 mg/dL) and liver enzymes (AST of 77 mg/dL and ALT of 45 mg/dL). MRI of the abdomen revealed contrast filling the biliary tree and ERCP showed a stricture extending from the bifurcation of the hepatic duct into the right hepatic duct. He also had sausage-like strictures of the intra hepatic ducts, which were concerning for cholangiocarcinoma. Percutaneous transhepatic cholangiogram revealed a hepatic duct bifurcation stricture that involved the right intra hepatic duct. The differential diagnosis included cholangiocarcinoma, primary biliary cholangitis (PBC), secondary biliary cholangitis (SBC), PSC, inflammatory myofibroblastic tumor, and IgG4-related cholangiopathy. Due to concerns for hilar cholangiocarcinoma by cholangiography, the patient underwent right hepatectomy and left hepaticojejunostomy. Shown are gross images of the right lobe of the liver (Figures 1A and 1B), with an arrow indicating the intra-hepatic bile duct and arrowhead indicating the hilar mass (Figure 1B). On microscopy, there was periductal fibrosis (arrow), edema (arrowhead) and a rich lymphoplasmacytic inflammatory infiltrate (black arrow) (Figure 1C). A portal vein was found to be obscured by inflammatory cells (Figure 1D). There were areas of inflammatory cell encroachment upon portal veins. Obliterative phlebitis, or occlusion of portal veins by inflammatory cell infiltrates were evident. There was storiform fibrosis with notable eosinophils. This particular case demonstrated bile duct involvement and morphologically greater than 40% of plasma cell infiltrates were positive for IgG4. The patient subsuquently improved with oral steroid therapy.FigureTable: Table. Potential treatment regimens for IgG4-related disease