Gastrointestinal and Extra-Intestinal Manifestations of IgG4–Related Disease

Abstract

IgG4-related disease (IgG4-RD) is a chronic relapsing multi-organ fibro-inflammatory syndrome of presumed autoimmune etiology. It is characterized by increased serum levels of IgG4 and tissue infiltration by IgG4 cells. Increased titers of autoantibodies against a spectrum of self-antigens and response to steroids have led to its characterization as an autoimmune disease. However, the pathognomonic antigens probably differ among manifestations, and different antigens or autoantibodies produce similar immune reactions in different organs. Little is known about the pathogenic effects, if any, of serum IgG4 or IgG4 plasma cells in tissues. Despite several animal models of the disease, none truly recapitulates human IgG4-RD. Histologic analyses of tissues from patients with IgG4-RD reveal a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells, storiform fibrosis, and obliterative phlebitis, although these features vary among organs. Typical presentation and imaging findings include mass-forming synchronous or metachronous lesions in almost any organ, but most commonly in the pancreas, bile duct, retroperitoneum, kidneys, lungs, salivary and lacrimal glands, orbit, and lymph nodes. In all organs, inflammation can be reduced by corticosteroids and drugs that deplete B cells, such as rituximab. Patients with IgG4-RD have relapses that respond to primary therapy. Intense fibrosis accompanies the inflammatory response, leading to permanent organ damage and insufficiency. Death from IgG4-RD is rare. IgG4-RD is a multi-organ disease with predominant pancreatico-biliary involvement. Despite its relapsing-remitting course, patients have an excellent prognosis.

Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor

“…However, the cut-off points vary depending on organ system. Some studies have suggested that IgG4 + /IgG + plasma cell ratio > 0.4 is a marker of IgG4-RD in the presence of classic histopathological features and with a compatible clinical features [1,17].…”

Immunoglobulin G4 (IgG4)-related disease of the stomach – a challenging differential diagnosis in suspected gastric cancer

“…Recently, Wallace et al analyzed 765 patients and could identify 4 different phenotypes of IgG4-RD (pancreato-hepato-biliary disease, retroperitoneal fibrosis and/or aortitis, head and necklimited disease, and classic Mikulicz syndrome with systemic involvement) [28]. Abdominal IgG4-RD mostly affects the pancreas, the bile ducts, and the retroperitoneum and represents the first 2 phenotype groups [1,28]. In contrast, gastric IgG4-RD is rare.…”

“…IgG4-RD mostly affects the pancreas, bile ducts, salivary and lacrimal glands, kidneys, retroperitoneum, mediastinum, and lung. Virtually any organ can be involved, and multiorgan involvement is common [1]. An infiltration of IgG4-positive plasma cells in the gastric tissue of patients with autoimmune pancreatitis (AIP) has been reported [2].…”

Liver Masses

“…IgG4-related sclerosing cholangitis is a rare disease and has a high degree of clinical and radiologic resemblance to cholangiocellular carcinoma. 1 It is important to differentiate it from malignant diseases, because IgG4-related sclerosing cholangitis can respond to steroid treatment with a better prognosis. The diagnosis of IgG4-related cholangitis usually needs serum IgG4 measurement as well as histologic analysis.…”

“…A ratio of IgG4/IgG cells of >40% is helpful to discriminate it from other disorders. 1 However, to establish the diagnosis, another histologic feature, such as storiform fibrosis, lymphoplasmacytic infiltration, or obliterative phlebitis, is necessary.…”