IgG4- related disease: an orphan disease with many faces

Abstract

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21st century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD.

Figure 1

A: IgG4- related disease with involvement of the orbits, ocular nerves and salivary glands. Contrast- enhanced T1 weighed magnetic resonance coronal imaging of the head showing massive thickening of the infraorbital nerve (red arrow). B: Histopathological examination of orbital muscle (upper panel) and parotid gland biopsies (lower panel) reveals dense lymphoplasmacellular infiltration and fibrosis (left pictures, HE staining) with dense infiltration of IgG4- producing plasma cells (right pictures, anti-IgG4, rabbit monoclonal, 1:1000 a.r., Abcam, Cambridge, UK).

Figure 2

Comprehensive diagnostic criteria for IgG4- related disease (modified after Umehara et al. [[22]]). *Histopathology suggestive of IgG4-RD, e.g. lymphoplasmacytic infiltration and fibrosis.