IgG4-Related Hepatobiliary Diseases

IgG4-related disease is a recently described (2003) fibroinflammatory disease characterised by multiorgan involvement. It was first described in the context of autoimmune pancreatitis, although it was later found that many other sites can be affected: bile duct, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, meninges, aorta, breasts, prostate, thyroid, pericardium and skin. Many diseases once thought to be distinct are now included in the IgG4 disease spectrum: Mikulicz syndrome, Kuttner’s tumour, Riedel’s thyroiditis and others.

IgG4-related diseases are characterised by the simultaneous appearance of swelling in one or more organs, a chronic-recurrent course, and elevated levels of IgG4 (immunoglobulin G subclass 4) in blood tests.

Liver and biliary involvement are part of the syndrome and present with biliary stenosis and/or dilatative lesions and are therefore easily confused with forms of sclerosing cholangitis or tumours. However, the diagnosis is not straightforward and there is no single test that automatically leads to the diagnosis. The clinical manifestations of IgG4-related disease are related to the compressive effect of the fibrous mass on the affected organ and can vary widely.

Therefore, definitive diagnosis requires biopsy of the affected tissue and histological examination. Patients with biliary and/or hepatic involvement typically present with obstructive jaundice, weight loss and abdominal pain. In the case of concomitant autoimmune pancreatitis, there will be symptoms due to the inadequate function of the pancreas. Unfortunately, there are no specific symptoms and this requires a very accurate differential diagnosis to avoid unnecessary surgery if tumour-like disease is suspected.

Ultrasonography may suggest the presence of dilatation, stenosis or space-occupying lesions in the biliary tract, but a CT scan and/or MRI with biliary-specific study is always necessary. A more invasive procedure called ERCP may then be required to examine the bile duct and take biological samples, especially in cases where cholangioscopy is available.

IgG4-related disease is more common in men than in women and is more common after the age of 60. Rarely, paediatric cases have been described. There is often a history of allergy or atopy, possibly associated with increased eosinophils and serum IgE. More rarely, an association with other systemic or organ-specific autoimmune diseases (thyroiditis) has been described.

The first line of treatment is the administration of glucocorticoids (cortisone). In the event of non-response or relapse, other immunosuppressive drugs, such as methotrexate and azathioprine, or biological drugs, such as rituximab, may need to be introduced.