IgG4- related disease: an orphan disease with many faces.

Herwig Pieringer,Adelheid Wöhrer,Petra Reis,Jochen Zwerina,Bastian Oppl,Ilse Parzer

doi:10.1186/s13023-014-0110-z

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.

Highlights

Immunoglobulin G4- related disease (IgG4-RD) is a systemic fibro-inflammatory disorder of unknown origin
As IgG4-RD may affect virtually every organ, this disease is of interest for internal medicine physicians and for other specialties such as ear nose & throat, dermatology, ophthalmology, and neurology
Case vignette In January 2012, a 61 year- old female presented to a rheumatology unit with a long- standing history of recurrent inflammatory lesions of unknown origin since 1989, which had been previously diagnosed as pseudolymphoma and Sjögren’s syndrome (SS)

Summary

Introduction

Immunoglobulin G4- related disease (IgG4-RD) is a systemic fibro-inflammatory disorder of unknown origin. A distinct disease entity comprising patients presenting with inflammatory and/or fibrosing single or multiple organ lesions in conjunction with elevated serum IgG4 levels and tissue IgG4 production became clear. If patients are diagnosed with type 1 AIP and have in addition characteristic manifestations on imaging in combination with elevated IgG4 levels, a diagnosis of IgG4 related cholangitis is usually straightforward. Other diseases that need to be distinguished from IgG4-related sialadenitis and dacryoadenitis are lymphomas, sialolithiasis and carcinomas The latter may be surrounded by an inflammatory infiltrate containing IgG4 positive plasma cells complicating the exact diagnosis [69]. A variety of glomerular lesions, mainly different forms of glomerulonephritis, may be present in such patients All this has raised the suspicion that immune complexes are involved in the pathogenesis of IgG4-related tubulointerstitial nephritis [15]. This has led to the hypothesis that short lived plasma cells producing IgG4 are involved in the disease [84,120]

Conclusions and future perspectives

Mikulicz J

21. Deshpande V

Findings

98. Cornell LD