ABSTRACT

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is defined as a multi-organ systemic disorder with typical pathological findings affecting a wide range of organ systems and elevated IgG4 levels. The disease unifies a large number of clinical diagnoses previously considered as being confined to single organ systems. In recent years under the leadership of Japanese researchers a new nomenclature as "IgG4-related disease" was endorsed uniting the different organ involvements and diagnostic criteria have been defined. Typical histopathologic manifestations are lymphoplasmacytic infiltrate composed of IgG4+ plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The pathophysiology of the disease still remains controversial, including the natural history of the disease, the pathogenic role of IgG4, and its use as a biomarker. Although elevated autoreactive IgG4 antibodies are observed, there is no evidence that they are directly pathogenic. Glucocorticoids constitute the primary treatment option and the response is generally good. Treatment with steroids often decreases serum levels of IgG4 and tissue levels of IgG4+ plasma cells. In cases either refractory to steroids or resistant to dose reduction of steroids immunosuppressive therapy such as azathioprine or mycophenolate mophetil may be considered. In patients with recurrent or refractory disease, rituximab or bortezomib treatment is also recommended.