IgG4-related sclerosing disease

Abstract

Based on histological and immunohistochemical examination of various organs of patients with autoimmune pancreatitis (AIP), a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prostate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AIP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4-related sclerosing diseases. This disease includes AIP, sclerosing cholangitis, cholecystitis, sialadenitis, retroperitoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AIP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunostaining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.

Figure 1

Schematic illustration showing the relationship between IgG4-related sclerosing disease, AIP, IgG4-related sclerosing cholangitis, IgG4-related sclerosing sialadenitis, IgG4-related retroperitoneal fibrosis, and IgG4-related pseudotumors.

Figure 2

AIP. (A) Diffuse hypoechoic enlargement of the pancreas on ultrasonography; (B) Dense infiltration of IgG4-positive plasma cells in the pancreas.

Figure 3

IgG4-related sclerosing cholangitis. (A) Stenosis of the intrahepatic bile duct, similar to that in PSC; (B) Dense infiltration of IgG4-positive plasma cells in the bile duct wall.

Figure 4

IgG4-related sclerosing sialadenitis. (A) Bilateral swelling of submandibular glands (Gallium scintigraphy); (B) Dense infiltration of IgG4-positive plasma cells in the salivary gland.