Immunoglobulin G4-Related Cholangitis: A Variant of IgG4-Related Systemic Disease

Abstract

IgG4-related sclerosing cholangitis as part of IgG4 systemic-related diseases is commonly associated with autoimmune pancreatitis. Major clinical manifestations of IgG4-related sclerosing diseases are apparent in the organs in which tissue fibrosis with obstructive phlebitis is pathologically induced. IgG4-related sclerosing cholangitis is included within the heterogeneous group of ‘sclerosing cholangitis’. Sclerosing cholangitis may be associated with choledocholithiasis, infection or biliary malignancies. Sclerosing cholangitis of unknown etiology is called primary sclerosing cholangitis (PSC). Conservative therapy of PSC is usually unsuccessful, the disease involves extra- and/or intrahepatic biliary tree, and the end point of this disease is liver cirrhosis. Typically, PSC is identified at the age of 30 to 40 years, and the disease is frequently associated with inflammatory bowel diseases. On the other hand, IgG4-related sclerosing cholangitis is not associated with inflammatory bowel diseases. In patients with IgG4-related sclerosing cholangitis, a first symptom can be obstructive jaundice, whereas obstructive jaundice is rarely present in PSC. Clinically, patients with IgG4-related sclerosing cholangitis are older at diagnosis compared to patients with PSC. A typical diagnostic feature of IgG4-related sclerosing cholangitis is elevation of serum immunoglobulin G4. In patients with IgG4-related sclerosing cholangitis, response to steroid therapy is high; in patients with PSC corticosteroid therapy is unsuccessful. Histochemically abundant infiltration of IgG4-positive plasma cells is detected in the biliary duct wall. Histologically, we can identify dense lymphoplasmacytic infiltration of the bile duct wall, transmural fibrosis, lymphoplasmacytic infiltration and fibrosis in the periportal area of the liver – a typically obliterative phlebitis. The biliary epithelium is usually intact in contrast to PSC, where mucosal erosion is often present. Steroids are the first-choice therapy of IgG4-related sclerosing cholangitis. In the literature, cholangiocarcinoma in patients with IgG4- related sclerosing cholangitis was not described, whereas cholangiocarcinoma develops in up to 10–30% of patients with PSC.

Isolated Mass-Forming IgG4-Related Cholangitis as an Initial Clinical Presentation of Systemic IgG4-Related Disease

“…Solitary organ involvement without pancreatitis has also been reported [ 1 , 3 , 4 ]. IgG4-RD tends to present as diffuse lesion in the involved organs, especially in pancreas and biliary tract [ 13 ]. Localized mass-forming autoimmune pancreatitis had frequently been misdiagnosed as malignancy and had resulted in unnecessary surgical resections [ 6 , 7 ].…”

Hepatobiliary IgG4 Cholangiopathy

“…Typical histopathological findings include dense lymphoplasmacytic inflammation, transmural and storiform fibrosis, and obliterative phlebitis. 1,11 Peribiliary glands are encased in the fibroinflammatory process. Perineural extension of the inflammatory process is also commonly seen.…”

Cholangitis: Diagnosis, Treatment and Prognosis

“… 33 Presentation of obstructive jaundice, which is rarely seen in PSC, can assist in clinical differentiation of these two entities. 35 In addition to these, one can bring into mind that patients with PSC are generally younger that those with IAC. 33 …”