ReviewAntineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome
Introduction
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides include granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis), eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) and microscopic polyangiitis (MPA) [1]. ANCA are present in the majority of cases during initial presentation, targeting either proteinase-3 (PR3) or myeloperoxidase (MPO) [1]. Although AAV are mainly characterized by manifestations related to necrotizing small-vessel vasculitis, some of them may be related to granulomatous inflammation, particularly in GPA and EGPA [2]. Atypical manifestations may also occur, such as orbital mass or pachymeningitis leading to organ- or life-threatening complications, and they are often characterized by poor response to conventional therapies [3], [4]. Because of their location, histological samples are rarely available, but when biopsies are feasible, histological examination can reveal findings suggestive of vasculitis and/or granulomatous inflammation, and also some fibrosis and/or lymphoplasmacytic infiltration [5].
IgG4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by inflammatory pseudotumors and histologically by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis [6]. Since its first identification in 2003, the spectrum of manifestations associated with IgG4-RD has become clearer [7]. Hence, different inflammatory diseases previously considered as idiopathic have been retrospectively included in the spectrum of IgG4-RD, such as a part of retroperitoneal fibrosis and inflammatory aortic aneurysms, Mikulicz's disease, Riedel thyroiditis, orbital inflammatory pseudotumors, tubulointerstitial nephritis, eosinophilic angiocentric fibrosis, or pachymeningitis [8], [9], [10]. Although quite rarely, IgG4-RD was found to be associated with medium or small-vessel vasculitides, in which histological description of vasculitis was associated with lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells [11], [12]. Furthermore, IgG4-positive plasma cell infiltrates and high serum IgG4 levels have been described in various conditions, such as EGPA and other eosinophilic disorders, Rosai-Dorfman disease or multicentric Castleman's disease [13], [14].
To puzzle out this potential overlap syndrome, we conducted a European multicenter observational study including patients presenting with both AAV and IgG4-RD.
Section snippets
Patients
We performed a European multicenter survey on behalf of the French Vasculitis Study Group (FVSG) among specialized vasculitis centers in Europe (mainly including departments of Internal Medicine, Rheumatology and Nephrology from Austria, Belgium, Italy and France), in order to identify patients who met AAV and IgG4-RD criteria; the two diseases could be present simultaneously or metachronously during the patients' medical history. AAV was defined by the American College of Rheumatology 1990
Patient characteristics
Eighteen patients were included, with an age ranging from 32 to 84 years (median 55.5 years), and a male/female ratio of 2.6. AAV and IgG4-RD were mainly diagnosed concomitantly in 13/18 (72%) patients, AAV preceded IgG4-RD in 3/18 (17%), and IgG4-RD was diagnosed before AAV in 2/18 (11%).
Discussion
We conducted a European multicenter study to investigate the potential overlap between AAV and IgG4-RD. We identified some patients presenting with clinical and/or histological evidence of both diseases, consistent with overlap syndrome given current classification criteria and raising the question of pathophysiological similarities and potential therapeutic strategies that could target both conditions.
In the present study, we observed that AAV and IgG4-RD overlap syndrome concerned mainly GPA
Funding support
None.
Disclosure statement
Authors have not conflicts of interest.
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