Ultrasound prevalence of wrist, hand, ankle and foot synovitis and tenosynovitis in systemic sclerosis, and relationship with disease features and hand disability.

INTRODUCTION: In systemic sclerosis, few studies have shown that hand and wrist ultrasound is more sensitive than clinical examination in the detection of synovitis and tenosynovitis. Even fewer studies have investigated ankle and foot involvement with ultrasound. Our objectives were to investigate ultrasound prevalence of wrist, hand, ankle and foot synovitis and tenosynovitis in patients with systemic sclerosis classified with ACR/EULAR 2013 criteria, and to study their relationship with disease features and hand disability. METHODS: Consecutive patients with systemic sclerosis, classified with ACR/EULAR 2013 criteria, were included in a monocentric cross-sectional study. They underwent standardized musculoskeletal clinical examination and hand, wrist, ankle and foot ultrasound. Clinical, biological and imaging data were also collected. RESULTS: Fifty-five patients were included. Ultrasound was more sensitive than clinical examination to detect at least one synovitis (respectively 52% versus 25%, P=0.025) and at least one tenosynovitis (respectively 16% versus 4%, P=0.009); 18% of patients had ankle tenosynovitis and 29% had ankle and/or foot synovitis, mostly located at metatarsophalangeal joints (25.5%). Having at least one ultrasound hand synovitis was associated with higher Cochin hand functional disability scale (mean 25±3 versus 12±2, P=0.003) and diffuse cutaneous subset (P=0.038). CONCLUSION: Our study shows that ultrasound is more sensitive than clinical examination to detect synovitis and tenosynovitis in systemic sclerosis. The foot involvement is less frequent than hand involvement, mainly localized at metatarsophalangeal joint. Finally, having at least one synovitis of the hand is associated with diffuse cutaneous subset and higher hand disability.

Efficacy of triple association methotrexate, sulfasalazine and hydroxychloroquine in early treatment of rheumatoid arthritis with insufficient response to methotrexate: Meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the efficacy of the triple synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) combination methotrexate, sulfasalazine and hydroxychloroquine versus a biologic DMARD (bDMARD) in the treatment of early rheumatoid arthritis. METHODS: A systematic literature search was performed using the PubMed and Cochrane databases, and abstracts presented at rheumatology scientific meetings until December 2013. Randomized controlled trials comparing the efficacy and the safety of biologic DMARD with the triple combination were included. Outcome measures were Van der Heijde modified Sharp score (SHS), remission rate, ACR criteria response, adverse events. RESULTS: A total of 1225 abstracts were screened. We extracted data from 5 trials including patients (515 in the triple combination group and 710 in the bDMARD group). We showed higher ACR70 response (OR=1.79, 95% CI [1.17, 2.72]) in patients treated with bDMARDs, whereas radiological progression was not different from patient with triple combination (OR=1.10, 95% CI [-0.04, 0.28]). At year 2, ACR70 response and remission rate, the results were similar in both groups with respectively OR=1.44 (95% CI [0.86, 2.43]) and SMD=0.45 (95% CI [0.17, 0.72]). The proportion of serious adverse events was similar in both groups OR=1.02 (95% CI [0.68, 1.52], P=0.92, I2=0%). Gastro-intestinal adverse events were higher in the triple combination group (OR=1.75, 95% CI [0.73, 4.21], P=0.21, I2=75%). Infectious adverse events were more frequent in the bDMARD group (OR=0.50, 95% CI [0.35, 0.70], P<0.0001, I2=36%). CONCLUSION: Biological treatment seems to be more efficient than triple combination in terms of radiological progression in RA with inadequate response to methotrexate.

Risk of postoperative infections and the discontinuation of TNF inhibitors in patients with rheumatoid arthritis: A meta-analysis.

OBJECTIVE: To determine whether continuation of tumor necrosis factor inhibitors (TNFi) before surgery increases the risk of surgical site infection (SSI) in rheumatoid arthritis (RA) patients. METHODS: A systematic review of the literature was conducted from January 2000 to May first 2014, using the databases of PubMed, Cochrane review, Embase, and manual research of abstracts presented in scientific congresses. Most included studies were retrospective. We compared the risk of SSI in the case of discontinuation of TNFi versus continuing TNFi treatment before a surgery. RESULTS: Six studies, with a total of 2743 patients (1360 in the group continuing TNFi agent and 1383 in the group discontinuing TNFi) were included. There was a decreased risk of SSI in patients stopping TNFi (relative risk [RR]=0.62 [95% confidence interval [CI] 0.43-0.89], P=0.99, I2=0%). Concerning overall complications, there was also a decreased risk in patients discontinuing TNFi treatment (RR=0.60 [95% CI 0.42-0.87], P=0.26, I2=25%). CONCLUSION: This meta-analysis showed an increased risk of SSI in patients under TNF inhibitor, and a decreased risk of SSI in case of interruption of treatment during the perioperative time.

Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies.

Growth arrest and DNA damage-inducible gene 34 (GADD34) is an inducible cofactor of protein phosphatase 1, which has an important role in the unfolded protein response. GADD34 has been shown to be necessary for type I interferon and proinflammatory cytokine production in response to viral infection in murine models. We investigate the expression of GADD34 in rheumatoid arthritis (RA), in which proinflammatory cytokines have an important pathogenic role. The objective of this study was to evaluate the potential of GADD34 expression as a biomarker in RA patients. We report a case-control study on GADD34 gene expression in peripheral blood mononuclear cells of patients (n = 75) with RA and age- and sex-matched healthy controls (n = 25). The study was approved by the relevant local ethics committees. GADD34 gene expression level in peripheral blood mononuclear cells was measured by quantitative PCR and analyzed with Mann-Whitney test. The relation between GADD34 gene overexpression and clinical or biological characteristics was analyzed with univariate and multivariate analysis. GADD34 gene expression was significantly higher in RA patients compared with healthy controls (p ≤ 0.001). Interestingly, GADD34 overexpression in PBMC of patients was related to the presence of circulating anti-citrullinated protein antibodies (p = 0.030). Data of this study strengthen the evidence of an unfolded protein response during the course of RA and provide an insight of the potential interest in GADD34 as a relevant marker for RA.