Fibromyalgie et autres douleurs neuropathiques : l'amitriptyline n'est pas la panacée

Les douleurs neuropathiques ou associées à la fibromyalgie sont difficiles à traiter et limitent la qualité de vie des personnes atteintes. La pratique actuelle tend à combiner des thérapies physiques et/ou cognitives avec des interventions pharmacologiques. L'amitriptyline est un antidépresseur tricyclique couramment utilisé pour traiter la fibromyalgie ou les douleurs neuropathiques, bien que son indication première ne soit pas le traitement de ces affections. Cette revue systématique mise à jour a évalué l'efficacité analgésique de l'amitriptyline dans le traitement des douleurs précitées ainsi que les effets indésirables associés

Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation

INTRODUCTION: Spontaneous resorption of disc herniation (DH) after sciatica is well documented. The matrix metalloproteinases (MMP)-1 and MMP-3 are enzymes potentially involved in this process. Glucocorticoid injections are commonly used for treatment, and other anti-inflammatory molecules like tumor necrosis factor (TNF) inhibitors are under clinical investigation. However, little is known about the effect of these molecules on DH resorption. METHODS: DH tissue was harvested from patients undergoing surgery for sciatica. Samples were thoroughly washed. Diced explants were cultured ex-vivo in 1) 0.5 ml Dulbecco's modified Eagle's medium (DMEM) 10% fetal calf serum (FCS), (controls), 2) recombinant interleukin 1 receptor antagonist (IL-1Ra), (100 ng/ml), 3) dexamethasone (10E-5 M), or 4) TNF inhibitor monoclonal antibody (10 microg/ml). Supernatants were harvested at 48 hours and frozen. Immunocapture activity assays determined total MMP activity, active MMP levels and pro-MMP levels. RESULTS: Fourteen DH tissue samples were analysed. Levels of all forms of MMP-3 were higher than the respective levels of MMP-1(P < 0.01). In particular, the median (interquartile range [IQR]) total MMP-3 level was 0.97 (0.47 - 2.19) ng/mg of tissue compared to 0.024 (0.01 - 0.07) ng/mg of total MMP-1 level (P < 0.01). Incubation with IL-1Ra, dexamethasone, or TNF inhibitors significantly decreased levels of all forms of MMP-3 (P < 0.05). Dexamethasone significantly decreased the ratio of active MMP-3 to total MMP-3 activity. A significant inhibitory effect of dexamethasone was observed only on active MMP-1, while IL-1 and TNF inhibitor had no significant effect on any form. CONCLUSIONS: MMP-3 appears to play a greater role than MMP-1 in DH resorption. Dexamethasone, IL-1-Ra and TNF inhibitor decreased active MMP-3, indicating that the clinical use of these drugs may affect the resorption of DH under certain conditions

A 64-Year-Old Woman with Chest Pain, Limb Weakness, and Endometrial Cancer

Necrotizing autoimmune myopathy (NAM) is a rare subgroup of idiopathic inflammatory myopathies (IIM). This pathology usually affects proximal limb muscles and in some cases the myocardium. Patients usually display proximal limb weakness. Muscular biopsy is required to confirm the diagnosis. We report the case of a 64-year-old woman with an atypical first presentation of NAM, manifested by chest pain in the context of metastatic endometrial cancer. The diagnosis of NAM was however made when she returned a second time with proximal limb weakness. A treatment with prednisone was then initiated, to which rituximab was rapidly associated, beside a specific chemotherapy

The active metabolite of leflunomide, A77 1726, increases the production of IL-1 receptor antagonist in human synovial fibroblasts and articular chondrocytes

Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis. In this study, we investigated the effect of A77 1726 – the active metabolite of leflunomide – on the production of IL-1 receptor antagonist (IL-1Ra) by human synovial fibroblasts and articular chondrocytes. Cells were incubated with A77 1726 alone or in combination with proinflammatory cytokines. IL-1Ra production was determined by ELISA. A77 1726 alone had no effect, but in the presence of IL-1β or tumour necrosis factor-α it markedly enhanced the secretion of IL-1Ra in synovial fibroblasts and chondrocytes. The effect of A77 1726 was greatest at 100 μmol/l. In synovial fibroblasts and de-differentiated chondrocytes, A77 1726 also increased IL-1β-induced IL-1Ra production in cell lysates. Freshly isolated chondrocytes contained no significant amounts of intracellular IL-1Ra. A77 1726 is a known inhibitor of pyrimidine synthesis and cyclo-oxygenase (COX)-2 activity. Addition of exogenous uridine did not significantly modify the effect of A77 1726 on IL-1Ra production, suggesting that it was not mediated by inhibition of pyrimidine synthesis. Indomethacin increased IL-1β-induced IL-1Ra secretion in synovial fibroblasts and de-differentiated chondrocytes, suggesting that inhibition of COX-2 may indeed enhance IL-1β-induced IL-1Ra production. However, the stimulatory effect of indomethacin was consistently less effective than that of A77 1726. A77 1726 increases IL-1Ra production by synovial fibroblasts and chondrocytes in the presence of proinflammatory cytokines, and thus it may possess chondroprotective effects. The effect of A77 1726 may be partially mediated by inhibition of COX-2, but other mechanisms likely concur to stimulate IL-1Ra production

Online Training on Skin Cancer Diagnosis in Rheumatologists: Results from a Nationwide Randomized Web-Based Survey

International audiencePatients with inflammatory rheumatisms, such as rheumatoid arthritis, are more prone to develop skin cancers than the general population, with an additional increased incidence when receiving TNF blockers. There is therefore a need that physicians treating patients affected with inflammatory rheumatisms with TNF blockers recognize malignant skin lesions, requiring an urgent referral to the dermatologist and a potential withdrawal or modification of the immunomodulatory treatment. We aimed to demonstrate that an online training dedicated to skin tumors increase the abilities of rheumatologists to discriminate skin cancers from benign skin tumors. A nationwide randomized web-based survey involving 141 French rheumatologists was conducted. The baseline evaluation included short cases with skin lesion pictures and multiple choice questions assessing basic knowledge on skin cancers. For each case, rheumatologists had to indicate the nature of skin lesion (benign; premalignant/ malignant), their level of confidence in this diagnosis (10-points Likert scale), and the precise dermatological diagnosis among 5 propositions. Different scores were established. After randomization, only one group had access to the online formation consisting in 4 elearning modules on skin tumors, of 15 minutes each (online training group). After reevaluation, the trained and the non-trained group (control group) were compared. The primary end-point was the number of adequate diagnoses of the nature of the skin lesions. The mean number of adequate diagnosis for the benign versus premalignant/malignant nature of the lesions was higher in the online training group (13.4 vs. 11.2 points; p value <0.0001). While the other knowledge scores were also significantly higher, no statistical difference was observed on the level of self-confidence between the 2 groups. In conclusion, the online formation was effective to improve the rheumatologists' ability to diagnose skin cancer

:5; Personal non-commercial use only

ABSTRACT. The detection and characterization of a large array of autoantibodies, including at least 8 different antisynthetase, anti-SRP, -200/10

Personal non-commercial use only

ABSTRACT. The detection and characterization of a large array of autoantibodies, including at least 8 different antisynthetase, anti-SRP, -200/10

Anakinra is a possible alternative in the treatment and prevention of acute attacks of pseudogout in end-stage renal failure

We describe the case of a 71-year-old man with recurrent pseudogout attacks affecting multiple joints. He had end-stage renal failure that contra-indicated the use of non-steroidal anti-inflammatory drugs and was resistant to therapy with glucocorticoids. Based on the recent findings that interleukin (IL)-1beta is involved in crystal-induced inflammation, the patient received anakinra, a specific IL-1 inhibitor, in order to treat an acute attack of pseudogout. In addition, anakinra was administered as preventive therapy 3days per week after each hemodialysis session. Under this treatment, he did not present any severe episode of arthritis after a follow-up of 8 months. This observation suggests that anakinra is efficacious and safe for the prevention of crystal-induced arthritis in patients with severe renal failure