Rheumatoid Arthritis: Job-Deslandre C

Florea A, Job-Deslandre C. · Service de Rhumatologie A, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris, France. · Presse Med. · Pubmed #18819772 No free full text.

Abstract: During pregnancy, oestrogen and progesterone levels are increased. Consequently the initial predominant immune cellular response (Th1 type) is decreased, whereas humoral response (Th2 type) is increased. Due to this switch, a lot of Th2 anti-inflammatory cytokines IL-4 and IL-10 are synthesized. During the last months of pregnancy Treg lymphocytes level is elevated leading to overexpression of IL-4 and IL-10. Due to these mechanisms, reduce disease activity of rheumatoid arthritis (RA) occurred. Impaired fertility has not been demonstrated in women with RA. However, some studies suggest that polyarthritis could induced a reduced weight at birth and more frequent pregnancy and delivery complications. Methotrexate and biotherapies have demonstrated no effect on fertility; however these drugs must be stopped before conception for a period equal to seven fold of the half live of the molecule. No teratogenic effect are known for sulfazalasine and hydroxychloroquine; these drugs could be used during pregnancy. It is also the same for ciclosporine, which used is quite unfrequent in RA. Methotrexate is teratogenic in animal models and is forbidden during pregnancy. For leflunomide which is metabolised in A771726, highly teratogenic, a washout period of 3,5 months is necessary. All commercially available TNFalpha inhibitors are classified by the food and Drug Administration as pregnancy risk category B: no adverse pregnancy adverse effects have been observed in animal studies, but there have been insufficient controlled human studies. The published experiences with TNFalpha inhibition in pregnancy is limited to some case reports and ongoing registry. More recently some cases of Vater syndromes (polymalformations) were possibly related to TNFalpha blocking agents. Such treatment must be avoided during pregnancy. Only few case reports are published concerning rituximab use during pregnancy. No data have been found for abatacept.

Job-Deslandre C. · Service de Rhumatologie A, Hopital Cochin, Paris. · Presse Med. · Pubmed #10745946 No free full text.

Abstract: EPIDEMIOLOGY: Juvenile spondylarthropathy accounts for about 20% of all cases of chronic juvenile idiopathic arthritis. The spondyloarthropathy concept includes chronic inflammatory rheumatic conditions involving the spine, peripheral joints, and tendon insertions. There is an HLA B27 linkage and the condition predominates in boys, mean age 11 years. CLINICAL PRESENTATION: The usual clinical signs are asymmetrical involvement of the joints of the lower limbs associated in 30 to 50% of the cases with enthesiopathy. The diagnosis is based on the B Amor criteria and ESSG. The clinical course follows an episodic pattern in 80% of the cases. TREATMENT: Nonsteroidal antiinflammatory drugs and local care are used. Sulfasalazine can be useful but its efficacy has not been proven. The functional prognosis is relatively good; spinal ankylosis is uncommon and hip involvement (destructive coxitis) occur in 30% of patients. About 80% of the patients have minor or no disability after a 10-year course.

Lequerré T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job-Deslandre C, Fautrel B, Le Loët X, Sibilia J, Anonymous00361, Anonymous00362. · Rheumatology Department, Rouen University Hospital & Inserm 905, 76031 Rouen, France. · Ann Rheum Dis. · Pubmed #17947302 No free full text.

Abstract: BACKGROUND: Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis (SoJIA) or adult-onset Still disease (AoSD). OBJECTIVES: To assess the efficacy and the safety of anakinra treatment in SoJIA and AoSD. METHODS: SoJIA and AoSD patients were treated with anakinra (1-2 mg/kg/day in children, 100 mg/day in adults); we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. RESULTS: A total of 35 patients were included, 20 with SoJIA and 15 with AoSD. Their mean age (range) at the onset of treatment was 12.4 (3-23) and 38.1 (22-62) years, respectively; disease duration was 7.0 (1-16) and 7.8 (2-27) years, respectively. Active arthritis was present in all cases but one. Of the 20 SoJIA patients, 5 achieved ACR 50% improvement in symptoms (ACR50) response criteria at 6 months. Steroid dose had been decreased by 15% to 78% in 10 cases. A total of 11 of the 15 AoSD patients achieved at least a 50% improvement for all disease markers (mean follow-up: 17.5 (11-27) months). Steroids had been stopped in two cases and the dose was decreased by 45% to 95% in 12 patients. Two patients stopped anakinra due to severe skin reaction, and two patients due to infection: one visceral leishmaniasis and one varicella. CONCLUSION: Anakinra was effective in most AoSD patients, but less than half SoJIA patients achieved a marked and sustained improvement.

Yocum DE, Allard S, Cohen SB, Emery P, Flipo RM, Goobar J, Jayawardena S, Job-Deslandre C, Jubb RW, Krüger K, Lopes Vaz A, Manger B, Mur E, Nygaard H, Weiner SM, Rainer F, Sack MR, Schiff MH, Schnitzer TJ, Trigg LB, Whatmough I, Schmidt AG. · Arizona Arthritis Center, University of Arizona, Tucson, Arizona, USA. · Rheumatology (Oxford). · Pubmed #10725065 links to  free full text

Abstract: OBJECTIVE: To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period. METHODS: In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals. RESULTS: Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups. CONCLUSION: These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.

Thelier N, Assous N, Job-Deslandre C, Meyer O, Bardin T, Orcel P, Lioté F, Dougados M, Kahan A, Allanore Y. · Department of Rheumatology A, Paris Descartes University, Paris, France. · J Rheumatol. · Pubmed #18634144 No free full text.

Abstract: OBJECTIVE: To analyze the pattern of osteoarticular lesions in patients with sarcoidosis hospitalized in 4 rheumatology departments. METHODS: We carried out a systematic retrospective analysis of cases with sarcoidosis admitted in the last 10 years, using hospital databases. Two distinct groups were defined from the outset: patients with Löfgren's syndrome (LS) or sarcoid rheumatism (SR). We assessed the following items: distribution of arthritis, chronicity, systemic manifestations, biochemical and immunological measures. RESULTS: We included 100 patients (75% women); 43% had LS and 57% SR. Osteoarticular symptoms revealed the disease in 85% of patients. The patients in the LS group were younger than those in the SR group (41 +/- 9 vs 48 +/- 13 yrs; p < 0.006) and were more likely to have oligoarthritis involving ankles (58% vs 32%; p = 0.04) and high C-reactive protein concentrations (63% vs 33%; p < 0.005). Patients with SR presented osteoarticular symptoms in the form of oligoarthritis (32%), polyarthritis (32%), bony erosion in 8/57 (14%), and osteitis in 9/57 (16%). Lung interstitial involvement was more frequent in the SR group than in the LS group (38% vs 18%; p = 0.03). Chronic polyarthritis was associated with the detection of rheumatoid factor (p = 0.004). Osteitis occurred in older patients (p = 0.02). CONCLUSION: SR was the most frequent manifestation leading to hospitalization; it was characterized by oligoarthritis and polyarthritis and associated with interstitial lung involvement. Osseous involvement occurred in a quarter of SR patients with similar frequency of erosions targeting the distal small bones and osteitis. These latter occurred at a later age.

Josselin L, Mahr A, Cohen P, Pagnoux C, Guaydier-Souquières G, Hayem G, Job-Deslandre C, Liferman F, Pourrat J, Guillevin L. · Department of Internal Medicine, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75679 Paris cedex 14, France. · Ann Rheum Dis. · Pubmed #18445626 No free full text.

Abstract: BACKGROUND: Results of uncontrolled studies have suggested that infliximab is efficacious against systemic necrotising vasculitides (SNV) refractory to conventional treatment. However, its safety and ability to induce and maintain remission over the long term remain unknown. OBJECTIVES: To report the use of infliximab to treat refractory SNV, focusing on patients' longer-term outcomes. METHODS: The medical charts of patients given adjunctive infliximab for refractory SNV >/=2 years before this evaluation were reviewed retrospectively. RESULTS: The 15 patients (median age 46 (range 20-69) years, median follow-up 35 (24-41) months) included 10 with Wegener's granulomatosis, 1 microscopic polyangiitis, 3 rheumatoid arthritis-associated and 1 cryoglobulinaemia-related vasculitides. Infliximab was taken for a median time of 8 (2-31) months; 2 patients are still being treated. By day 45, 11 patients had entered remission (Birmingham Vasculitis Activity Score (BVAS) = 0) and 4 others had responded (BVAS decrease >/=50%). Five patients achieved sustained remissions (>/=6 months, corticosteroids </=7.5 mg/day). Thirteen stopped infliximab because of loss of efficacy (n = 4), remission (n = 6) or non-compliance, chest tightness or side effect (1 each). Ten patients relapsed (median interval 13 months), 3 while still receiving infliximab; 2 were successfully re-treated with infliximab. CONCLUSION: These observations highlight infliximab as a potentially useful and safe salvage treatment for patients with refractory SNV.

Sornay-Soares C, Job-Deslandre C, Kahan A. · Rheumatology A Department, Cochin Teaching Hospital, Paris V University, Paris, France. · Joint Bone Spine. · Pubmed #15288854 No free full text.

Abstract: OBJECTIVE: To retrospectively evaluate the benefits of knee joint lavage with intraarticular glucocorticoid injection in patients who have juvenile idiopathic arthritis with knee involvement unresponsive to repeated intraarticular glucocorticoid injections. PATIENTS: Seventeen knees in 10 children (eight girls and two boys) were treated from 1997 to 2000. Mean age was 14 years 9 months and mean disease duration was 7.2 years. The diagnoses were juvenile oligoarthritis (n = 6, including two with extended disease), systemic arthritis (n = 2), juvenile spondyloarthropathy (n = 1), and juvenile dermatomyositis (n = 1). Repeated intraarticular triamcinolone hexacetonide injections had been performed in all the patients, the mean number of injections being 2.2 per patient within the last 30 months. Plain radiographs were normal in six of the eight patients. Mean erythrocyte sedimentation rate was 21.7 mm/h and mean C-reactive protein level was 20.6 mg/l. Joint fluid was obtained from 10 knees and had a mean cell count of 12?660 mm(-3). Second-line therapy was with methotrexate alone or combined with cyclosporine or azathioprine. Oral glucocorticoids and/or nonsteroidal antiinflammatory drugs were used for symptom relief. TREATMENT PROCEDURE: Lavage was performed under strict aseptic conditions with simple analgesia, on a day-hospital basis. After aspiration of the joint, lavage was performed with saline, and a delayed-action glucocorticoid was injected. The knee joint was immobilized in the extended position for 48 h. Efficacy criteria were presence of effusion, presence of pain, and presence of a systemic treatment-sparing effect. RESULTS: Freedom from effusion and pain was noted in all 17 knees after 1 month, in eight (47%) knees after 6 months, and in seven (41%) knees after 12 months. The patients with the longest lasting improvements had systemic polyarthritis. After joint lavage, second-line treatment was reduced in two patients and oral glucocorticoid therapy was stopped in two others. None of the variables studied (age, sex, disease duration, inflammatory syndrome, or joint fluid cytology) predicted a good response. No adverse effects were recorded. CONCLUSION: These preliminary results show that joint lavage with glucocorticoid injection is safe in children. The improvements were modest, but the patients had a history of arthritis refractory to multiple triamcinolone hexacetonide injections. Thus, joint lavage may have a place in the treatment pyramid just before synovectomy.

Chkirate B, Job-Deslandre C. · Service de pédiatrie IV, hôpital d'Enfants, centre hospitalier universitaire, lbn Sina, Rabat, Maroc. · Arch Pediatr. · Pubmed #11339131 No free full text.

Abstract: Fibroblastic rheumatism is a rare entity. Nineteen cases were reported in the literature, and among them, only one in a child. CASE REPORT: Cam. (born August 19, 1988) had an onset of disease in October 1996 with nodules on the MCP and PIP, elbows and tibia, with partial improvement after three months. In April 1997, she suffered from arthralgia and stiffness of both wrists, and then of the big toes. X-rays showed destructive and erosive lesions on both wrists and on the PIP of the second and third fingers and the big toes. Laboratory investigations disclosed normal values for ESR and CRP and negative results for ANA and RF. The diagnosis of fibroblastic rheumatism was based on the typical histologic pattern of a nodule. The treatment associated colchicin and rehabilitation. In August 1998, the wrists' stiffness began to improve, though the big toes remained totally stiff. The radiologic erosive lesions did not show progress. COMMENTS: The diagnosis of fibroblastic rheumatism is based on the histologic pattern of the nodules. The erosive evolution of the arthropathies is infrequent (8/15 cases in adults). Juvenile onset is very rare; only one case has been reported, in a 10-year-old boy. The mechanism of the disease remains unknown. As it is very rare, the therapeutic strategies are not well established. CONCLUSION: This disease should be considered among the causes of juvenile arthritis with erosion.

Guillaume S, Prieur AM, Coste J, Job-Deslandre C. · Université Paris V, France. · Arthritis Rheum. · Pubmed #10943877 links to  free full text

Abstract: OBJECTIVE: To describe the long-term outcome and determine predictors of severity among patients with oligoarticular-onset juvenile idiopathic arthritis (JIA). METHODS: In a longitudinal study, 207 patients with oligoarticular-onset JIA who were referred between 1988 and 1998 were evaluated. At disease onset, selected clinical and laboratory data were collected as independent variables. A polyarticular disease course, joint erosion, uveitis, and remission were assessed as dependent variables. Longitudinal analyses were performed with the Kaplan-Meier method, and multivariate analysis with the Cox model. RESULTS: After 6 years of followup, the probability of a polyarticular course of disease was 50%, joint erosion was 35%, uveitis was 30%, and remission was 23% in these patients. Joint erosion was strongly associated with a polyarticular course. A high erythrocyte sedimentation rate (ESR) as well as involvement of more than 1 joint or involvement of an upper limb at disease onset were predictors of disease extension. A high ESR was also a strong predictor of a destructive course, and a family history of psoriasis was predictive of uveitis occurrence. No predictive factor for remission could be identified. CONCLUSION: Oligoarticular-onset JIA is a severe disease with frequent complications. Factors predictive of severity in oligoarticular-onset JIA were identified. This could allow early identification of high-risk patient subgroups, warranting a more aggressive therapeutic approach.

Prieur AM, Job-Deslandre C. · Unité d'Immuno-Hématologie pédiatrique, Hôpital des Enfants-Malades, Université Paris V. · Presse Med. · Pubmed #10745944 No free full text.

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