Abstract

Rheumatoid arthritis (RA) may be complicated by vasculitis. Vasculitis usually affects small vessels of the skin causing nailfold infarcts, but may also affect larger vessels and cause severe damage to internal organs. In such cases, treatment with high doses of corticosteroids or other immunosuppressive drugs may be necessary. TNF-alpha blockade has been shown to be an effective and safe treatment for RA, but thus far no reports have addressed the effect of TNF-alpha blockade on extra-articular manifestations of RA, such as vasculitis. We report a patient with RA and nailfold infarcts which repeatedly disappeared for several weeks following monthly i.v. injections with an anti-TNF alpha receptor fusion protein. A 46 year old woman was diagnosed as having rheumatoid factor positive, erosive RA in 1982. Due to the uncontrollable disease she was included in 1994 in a study with Ro 45-2081, a fusion protein combining two p55 TNF receptors with the Fc component of an IgG human antibody (Roche, Basel, Switzerland, sTNFR:Fc). After a three months placebo controlled phase she was treated with 50 mg sTNFR:Fc every four weeks. Clinical response was impressive with swollen joint counts decreasing from 32 to 5 and C-reactive protein CRP levels declining from 95 at baseline to 20 after the first injection. Low disease activity was sustained for the following years. Besides sTNFR:Fc her medication consisted of oral prednisone 5 mg a day and occasionally paracetamol 500 mg. In the spring of 1999 she first noticed nailfold infarcts on the fingers of both hands. These lesions disappeared after every injection of sTNFR:Fc and reappeared three weeks thereafter when the clinical effects of sTNFR:Fc were decreasing. This effect on the digital vasculitis has been well documented during several cycles of sTNFR:Fc administration.

Highlights

  • The presence of autoantibodies directed to citrullinated antigens in serum is highly specific for rheumatoid arthritis (RA)

  • We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA)

  • Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, this did not reach statistical significance (P = 0,18)

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Summary

Introduction

The presence of autoantibodies directed to citrullinated antigens in serum is highly specific for RA. Anti-CCP concentrations (expressed in Units per mg total IgG) were on average 1.34 times higher in SF compared to serum (n = 20, P < 0.05) or 1.37 when only positive samples were included (n = 11, P < 0.05) Conclusion: Citrullinated antigens are present in the synovia of both RA and control patients with similar prevalence. At higher concentrations (>1ng/μl) of RNA-oligonucleotides unspecific hybridization-signals prevailed in tissues of all diseases (even in normal controls) The combination of both methods (in situ-hybridization and immunohistochemistry) identifies the single cells inside the synovial lining layer which contains the highly expressed RAB3 “Kreisler” (maf B) gene. Conclusions: These data demonstrates for the first time that statins (and fluvastatin) are able to inhibit an endothelial proadhesive and pro-inflammatory phenotype induced by different stimuli including anti-β2GPI antibodies or pro-inflammatory cytokines These findings suggest a potential usefulness for statins in the prevention of the APS pro-atherothrombotic state

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