Remittent non-destructive polysynovitis in P-ANCA-positive vasculitis patients with anti-CCP antibodies

Abstract

Patients with antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AASV) commonly suffer from arthralgias and, sometimes, polyarthritis during disease flares. Although rheumatoid factor (RF) can be detected in up to 37–50% of AASV patients, anti-cyclic citrullinated peptide (anti-CCP) antibodies are rare. Herein, we describe the clinical features of five P-ANCA–positive vasculitis patients, who had persistent and/or high anti-CCP levels and, more importantly, suffered from remittent non-destructive arthralgias and polysynovitis, independently of the vasculitis course and without evidence of RA. Two were initially thought to have RA rather than microscopic polyangiitis and, at AASV diagnosis, all had kidney involvement and three had alveolar hemorrhages. With a median follow-up of 30 months, one suffered vasculitis relapses, preceded by polysynovitis, and others had remittent arthralgias and polysynovitis, while their vasculitides remained in remission. None of these patients had radiological destructive arthritis. We discuss the challenge of diagnosing these patients positive for anti-CCP and ANCA, and with dominant articular manifestations. AASV patients with anti-CCP antibodies may experience relapsing polysynovitis and non-erosive polyarthritis prior to vasculitis flares, but also independently of the vasculitis course, which is uncommon in AASV, and might represent a small subgroup of AASV patients.

Introduction

Arthralgias are very common at diagnosis or disease flares in patients with microscopic polyangiitis (MPA) or Wegener's granulomatosis (WG), and may precede other more specific manifestations, like alveolar hemorrhage and/or rapidly-progressive glomerulonephritis. Polysynovitis or non-erosive polyarthritis is also common during flares, but to a lesser degree, in up to 30% of these patients [1].

Antineutrophil cytoplasm antibodies (ANCA) are the hallmarks of these two vasculitides, being detectable in 60–80% of MPA patients, usually with a perinuclear labeling pattern (P-ANCA) in indirect immunofluorescence (IIF) and generally directed against myeloperoxidase (MPO) in enzyme-linked immunosorbent assay (ELISA), and in 90% of patients with systemic WG, most often with an IIF cytoplasmic labeling pattern and directed against proteinase 3 in ELISA [2]. Several other auto-antibodies, like antinuclear (ANA) or anticardiolipin antibodies, and rheumatoid factor (RF) can also be detected in these ANCA-associated vasculitides (AASV), all of which are usually transiently present at diagnosis, at low titer and/or without clinical pathogenicity [1], [3]. The frequency and clinical significance of anti-cyclic citrullinated peptide (anti-CCP) antibodies have been studied less.

Herein, we describe the clinical features of five P-ANCA-positive vasculitis patients, who had persistent and/or high anti-CCP levels and, more importantly, suffered from remittent non-destructive arthralgias and polysynovitis, independently of the vasculitis course and with no evidence of RA.