Can Immunoglobulin G4-related disease (IgG4-RD) cause intrahepatic strictures?

From the Guidelines

Yes, IgG4-related disease (IgG4-RD) can cause intrahepatic strictures, as evidenced by the characteristic patterns of involvement, including type 2a and type 2b, which involve intrahepatic stenosis with or without prestenotic dilatation and peripheral bile duct pruning, as described in the British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis 1. The disease process involves infiltration of IgG4-positive plasma cells and lymphocytes into the bile duct walls, leading to fibrosis, wall thickening, and subsequent narrowing of the bile ducts. These strictures can occur in both the extrahepatic and intrahepatic biliary tree, often creating a pattern that may resemble primary sclerosing cholangitis on imaging. Some key points to consider in the diagnosis and management of IgG4-RD include:

• Elevated serum IgG4 levels can support the diagnosis, but are not always present and cannot be relied on for making a definite diagnosis or distinguishing IgG4-SC from PSC 1
• Characteristic imaging findings, including intrahepatic stenosis and peripheral bile duct pruning, can be identified using non-invasive imaging techniques such as MRCP 1
• Histopathological confirmation is ideal, and can be obtained through endoscopic biopsy or visually directed cholangioscopic biopsies 1
• Treatment primarily involves corticosteroids, typically starting with prednisolone 30-40mg daily for 2-4 weeks followed by a gradual taper over several months, with steroid-sparing agents like rituximab, azathioprine, or mycophenolate mofetil may be needed for maintenance therapy or in steroid-resistant cases 1. It is also important to note that early recognition and treatment are crucial to prevent progression to irreversible fibrosis and biliary cirrhosis, and that patients with suspected IgG4-SC should be referred to specialists or centers with experience in the disease for further evaluation and management 1.

From the Research

IgG4-Related Disease and Intrahepatic Stricture

• IgG4-related disease (IgG4-RD) is a chronic-fibroinflammatory disorder that can affect various organs, including the liver 2.
• The disease is characterized by elevation of serum IgG4 concentrations and abundant infiltration of IgG4-expressing plasma cells, which are key diagnostic features 2, 3.
• IgG4-RD can cause intrahepatic stricture, as it can lead to sclerosing cholangitis, which is a common manifestation of the disease 3.
• IgG4-related sclerosing cholangitis (ISC) is a subtype of IgG4-RD that affects the bile ducts and can cause intrahepatic strictures 3.
• The diagnosis of IgG4-RD and ISC requires a multidisciplinary approach, including serology, histology, and imaging 4, 3.
• Treatment of IgG4-RD and ISC typically involves high-dose corticosteroids, which can lead to rapid and consistent induction of disease remission 4, 3, 5.
• B-cell depletion with rituximab is also a promising therapeutic approach for IgG4-RD and ISC 4, 3, 5.

Clinical Manifestations and Diagnosis

• IgG4-RD can present with various clinical manifestations, including major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, and retroperitoneal fibrosis 5.
• The diagnosis of IgG4-RD should be based on specific histopathological findings, typical laboratory and radiological aspects, and an appropriate clinical context 5.
• The main histopathological features of IgG4-RD are a dense, polyclonal, lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis 5.

Treatment and Management

• The first-line treatment of IgG4-RD is based on glucocorticoids, which are usually efficacious 5.
• B-cell depletion induced by rituximab has also been found to induce remission in steroid-resistant disease or has been used as a steroid-sparing agent for relapsing disease 5.
• Cardiovascular lesions frequently require procedural and/or surgical interventions, such as aortic aneurysm repair and valve replacement 6.
• While systemic corticosteroids are the mainstay of IgG4-RD treatment, biological and disease-modifying agents are becoming more widely used 6.