Frank Verhoeven

Utility of 18F-fluoro-dexoxyglucose positron emission tomography for the diagnosis of polymyalgia rheumatica: a controlled study

OBJECTIVES To compare (18)F-fluoro-dexoxyglucose PET/CT (FDG-PET/CT) findings in patients with polymyalgia rheumatica (PMR) and controls without rheumatologic disease. METHODS We retrospectively included 50 patients with a diagnosis of PMR as well as 53 patients with a neoplasm as a control group. All patients underwent FDG-PET/CT. Seventeen hotspots were analysed. We performed a semi-quantitative analysis of FDG uptake (4-point score from 0 to 3). The cut-offs for the number of sites with high activity and for FDG uptake score were assessed using receiver operating characteristics curves and odds ratios (ORs). RESULTS The two groups were comparable for the median patient age (69.3 years for PMR vs 68.1 for controls). Significant differences between the two groups were found for FDG uptake score (1.12 vs 0.34, P < 0.00001) and for the number of sites with significant uptake (score ⩾ 2): 6.36 sites vs 1.49 sites (P < 0.00001). The presence of three or more sites with significant uptake was correlated with the diagnosis of PMR with 74% sensitivity and 79% specificity (OR = 10.8). For the FDG uptake score, the cut-off was 0.53 (sensitivity 80%, specificity 77%, OR = 13.6). We found significant differences in all sites for FDG uptake score and the number of sites with significant uptake, particularly marked for shoulders, ischial tuberosities and interspinous bursitis (P < 0.00001 for FDG uptake score). CONCLUSION Our results suggest that the number of sites with significant FDG uptake and the uptake score could be relevant criteria for the diagnosis of PMR.

Physical activity in patients with rheumatoid arthritis.

INTRODUCTION Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease and is associated with an excess risk of cardiovascular disease. For the general population, the World Health Organization has issued detailed recommendations on the type of physical activity appropriate for decreasing the cardiovascular risk. The objective of this work is to review available data on the effects of physical activity in patients with RA. RESULTS RA is responsible for a marked decrease in physical activity. Physical activity significantly diminishes both the cardiovascular risk and the DAS 28. Vascular benefits from physical activity include improved endothelial function and slowing of the atherosclerotic process. Physical activity also has favorable effects on bone, slowing radiographic disease progression in small joints and increasing bone mineral density at the femoral neck, although these effects are not statistically significant. Finally, engaging in physical activity increases self-esteem, alleviates symptoms of depression, improves sleep quality, and decreases pain perception. Aerobic exercise is the most commonly advocated type of physical activity. Most interventions were of short duration (4 weeks) and involved aerobic activity (running or cycling) for 60minutes a day 5 days a week. Resistance training has been shown to decrease systemic inflammation and increase muscle strength. The main obstacles to physical activity in patients with RA are related to both the patients, who lack both motivation and knowledge, and the rheumatologists, who also lack knowledge and place insufficient emphasis on promoting physical activity. CONCLUSION Physical activity provides many benefits in patients with RA and should be widely performed. Promoting physical activity should be among the objectives of therapeutic patient education for RA.

Ultrasonographic Evaluation of the Anterior Chest Wall in Spondyloarthritis: A Prospective and Controlled Study

Objective. To determine the prevalence and type of ultrasonographic (US) lesions of the anterior chest wall (ACW) in cases of spondyloarthritis (SpA). Methods. This monocentric, prospective, and controlled study included patients consulting for SpA (Assessment of Spondyloarthritis International Society criteria) and control subjects. Clinical (pain and swelling) and US assessments (synovitis, joint effusion, erosion, ankylosis, margin narrowing, or Doppler signal) were performed on the sternoclavicular (SCJ) and the manubriosternal (MSJ) joints. The main characteristics of SpA were recorded [disease duration, biologic features, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), radiographic and extraarticular involvement]. Results. The study included 131 patients with SpA and 49 control subjects (same age and sex ratio). Clinical and US involvement of ACW were found in, respectively, 39% and 35.5% of SpA and in 12% and 14.3% of controls (p < 0.01). US highlighted erosions (34 vs 0), margin narrowing (12 vs 0), power Doppler activity (18 vs 2; p < 0.05), and ankylosis of the MSJ (24 vs 3). US involvement was associated with disease duration (14.9 vs 11.1 years; p = 0.04), age (45 vs 41 years; p = 0.004), radiographic change of sacroiliac joint (p = 0.05), and presence of inflammatory bowel disease (IBD; p = 0.03). No associations were found with HLA-B27, psoriasis, enthesitis, uveitis, or clinical involvement of ACW. Clinical involvement is associated with a higher BASDAI (47 vs 32; p = 0.0009) and ASDAS (2.9 vs 2.2; p = 0.006). Conclusion. US involvement of ACW is frequent in SpA (36.5%), mainly with erosion of SCJ and ankylosis of MSJ. It is associated with disease duration, radiographic sacroiliitis, and IBD.

Etanercept improves endothelial function via pleiotropic effects in rat adjuvant-induced arthritis

OBJECTIVES To determine the effect of etanercept on endothelial dysfunction and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. METHODS At the first signs of arthritis, etanercept (10 mg/kg/3 days, s.c.) or saline was administered for 3 weeks in AIA rats. Body weights and arthritis scores were monitored daily. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclo-oxygenase (COX-2), arginase, endothelium-derived hyperpolarizing factor and superoxide anions (O2 (-)°) production. Aortic expression of endothelial nitic oxide synthase (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22(phox) and p47(phox) was evaluated by western blotting analysis. Blood pressure, heart rate and blood levels of triglycerides, cholesterol and glucose were measured. RESULTS Etanercept significantly reduced arthritis score (P < 0.001). It improved Ach-induced relaxation (P < 0.05) as a result of increased NOS activity, decreased COX-2/arginase activities and decreased O2 (-)° production. These functional effects relied on increased eNOS expression and phosphorylation, and decreased COX-2, arginase-2 and p22(phox) expressions. No correlation was found between arthritis score and Ach-induced relaxation. The treatment did not change triglycerides, cholesterol and glucose levels, but significantly increased systolic blood pressure and heart rate (P < 0.05). CONCLUSION Our data demonstrated that efficient dosage of etanercept on inflammatory symptoms improved endothelial function in AIA. This beneficial effect on endothelial function is disconnected from its impact on CV risk factors and relates to pleiotropic effects of etanercept on endothelial pathways. These results suggest that etanercept could be a good choice for patients with rheumatoid arthritis at high risk of CV events.

Aortitis during etanercept therapy for ankylosing spondylitis: finding the culprit.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 9 mai 2012

Arthritis occurrence or reactivation under Vedolizumab treatment for inflammatory bowel disease. A four cases report

Joint Bone Spine - In Press.Proof corrected by the author Available online since lundi 20 mars 2017

Cryotherapy decreases synovial Doppler activity and pain in knee arthritis: A randomized-controlled trial

OBJECTIVE To measure and compare the effects of 2 local cryotherapy techniques on synovial power Doppler activity (primary outcome) and pain in non-septic knee arthritis without any concurrent treatment. METHODS 30 patients were randomized (ice: 30min, n=15 or cold CO2: 2min, n=15 both applied twice at 8h interval). Contralateral non-treated arthritic knees were used as paired controls (n=11 and n=10 respectively). The PDUS semi-quantitative score (0-3) and pain visual analogic scale were evaluated before/after each cold application, 2min, 2h, 24h after the first application. PDUS scores were checked in double-blind by 2 ultrasonographists. RESULTS The inter-class effect size of local cryotherapy on the power Doppler score remained significant the day after treatment in local cryotherapy-treated compared to contralateral non-treated knees (Global difference: -1 [95% confidence interval: -1.23; -0.77]; ice: -0.73 [-1.06; -0.4]; CO2: -0.7 [-1.18; -0.22]). Both techniques significantly and to the same extent reduced the power Doppler score and pain visual analogic scale at all evaluation times and globally throughout the 24 hour-study period. No dropout nor adverse event was reported. In multivariate analysis, the Power Doppler score decrease was associated with pain decrease, while pain decrease was associated with the female sex and ice technique. CONCLUSION Local ice and cold CO2 applied twice equally reduced synovial Power Doppler activity and pain over 24h in knee arthritis. These effects remained significant the day after treatment. ClinicalTrials.gov identifier: NCT02573298.

IL1 blockade in crystal-induced arthritis: Impact of disease duration and the inflammatory syndrome. Comments on the article by Couderc M. et al. “Efficacy of anakinra in articular chondrocalcinosis”

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 25 octobre 2012

Immunogenicity of TNF alpha inhibitors in rheumatology: many questions, enough answers?

Biologic therapeutic agents and particularly anti-tumor necrosis factor (TNF) agents have revolutionized the therapeutic management of many inflammatory disorders, and notably rheumatologic inflammatory diseases. Nevertheless, up to 30% of these patients do not develop a response, and more than 30% of the initial responders experience loss of response over time [1]. As these biodrugs are proteins, with high molecular weight, they are prone to generate antidrug antibodies (AdA). Presence of AdA has been shown to be associated with poorer response and more frequent injection reactions [2]. Occurrence of AdA was demonstrated with the different available TNF inhibitors, with different incidences [1–3], regardless of humanization of the sequence of the monoclonal antibodies. This has been developed in a recent review in this journal [4]. The questions of occurrence of AdA and outcomes associated with their presence were detailed in this narrative review [4]. This immunogenicity may appear early, mainly in the first months of exposition to anti-TNF agents, with variable frequencies, depending on the type of TNF inhibitor and the type of measurement assay. Many factors may be associated to and perhaps responsible for AdA development, and besides the type of TNF inhibitor, the underlying disease may play a role; for example rheumatoid arthritis with a high auto immune background may be more prone to develop such AdA, compared to spondyloarthritis, but this has not been confirmed to date. In the same way, the level of inflammation may also favor this event, immunization being more frequent in case of elevated C-reactive protein. The role of coprescription with a conventional synthetic disease modifying drug (csDMARD) needs to be taken into account. There is a body of evidence suggesting that use of concomitant csDMARD may be able to reduce occurrence of AdA [5], particularly in rheumatoid arthritis, but also in other conditions (Crohn’s disease, psoriatic arthritis, and perhaps spondyloarthritis). This may explain the better survival curves of therapeutic maintenance in patients with csDMARDs associated to the TNF blocker in some cohorts of patients with psoriatic arthritis or spondyloarthritis. The other body of causative factors is the rhythm of administration, that may lead to several and variable drug levels, and many arguments are in favor of an increased risk of development of AdA under low drug levels (trough levels). This may be a plea in favor of loading dose at initiation of treatment, and in fact this is the proposed regimen for some TNF inhibitors, namely infliximab and certolizumab.

Glucocorticoids Improve Endothelial Function in Rheumatoid Arthritis: A Study in Rats with Adjuvant‐induced Arthritis

To determine the effect of glucocorticoids (GCs) on endothelial dysfunction (ED) and on traditional cardiovascular (CV) risk factors in the adjuvant‐induced arthritis (AIA) rat model. At the first signs of AIA, a high dose (HD) [10 mg/kg/day, intraperitoneally (i.p.), GC‐HD] or low dose (LD) (1 mg/kg/day, i.p., GC‐LD) of prednisolone was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclooxygenase 2 (COX‐2), arginase, endothelium derived hyperpolarizing factor (EDHF) and superoxide anions ( O2– °) production. Aortic expression of endothelial NOS (eNOS), Ser1177‐phospho‐eNOS, COX‐2, arginase‐2, p22phox and p47phox was evaluated by Western blotting analysis. Arthritis scores, blood pressure, heart rate and blood levels of cytokines, triglycerides, cholesterol and glucose were measured. GC‐HD but not GC‐LD reduced arthritis score significantly and improved Ach‐induced relaxation (P < 0·05). The positive effect of GC‐HD resulted from increased NOS activity and EDHF production and decreased COX‐2/arginase activities and O2– ° production. These functional effects relied upon increased phospho‐eNOS expression and decreased COX‐2, arginase‐2 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression. Despite the lack of effect of GC‐LD on ED, it increased NOS and EDHF and down‐regulated O2– ° pathways but did not change arginase and COX‐2 pathways. GC‐HD increased triglycerides levels and blood pressure significantly (P < 0·05). Both doses of GCs decreased to the same extent as plasma interleukin (IL)‐1β and tumour necrosis factor (TNF)‐α levels (P < 0·05). Our data demonstrated that subchronic treatment with prednisolone improved endothelial function in AIA via pleiotropic effects on endothelial pathways. These effects occurred independently of the deleterious cardiometabolic effects and the impact of prednisolone on systemic inflammation.