Rheumatoid Arthritis: Saraux A

Fautrel B, Flipo RM, Saraux A. · Service de Rhumatologie, Groupe Hospitalier Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75651 Paris Cedex 13, France. · Rheumatology (Oxford). · Pubmed #18794185 No free full text.

Abstract: OBJECTIVES: Several anti-TNF-alpha prescription guidelines in RA have been published, among which those issued by the British (BSR) and French (SFR) Societies for Rheumatology in 2005 are the most comprehensive. Objectives of the PRISME II survey were to assess and compare eligibility for anti-TNF-alpha therapy of RA patients consulting their usual rheumatologist according to (i) the SFR and BSR guidelines and (ii) the rheumatologist's opinion. METHODS: PRISME II was a postal, cross-sectional, observational survey proposed to all office-based rheumatologists practising in France in 2005. Rheumatologists were to include three consecutive consulting anti-TNF-alpha-naïve RA patients. Disease activity was assessed using the disease activity score 28 (DAS28). Structural damage progression was estimated based on the reading by the usual rheumatologist. The factors determining eligibility in the rheumatologists' opinion were identified by a logistic regression analysis. RESULTS: Four hundred and thirty-four rheumatologists included 1132 patients. Ongoing RA structural progression was reported for 41% of the patients. According to the SFR and BSR criteria, 64 patients (7.0%) and 10 patients (0.9%), respectively, were eligible for anti-TNF-alpha therapy, while 10% were deemed eligible according to the rheumatologists' opinion. Determinants of eligibility according to the rheumatologists were: high disease activity (DAS28 >5.1), ongoing structural progression and elevated daily corticosteroid intake. These three determinants feature in the SFR guideline. CONCLUSIONS: The proportion of RA patients eligible for anti-TNF-alpha therapy varies greatly according to the BSR or SFR guidelines. In France, there is a remarkable convergence between rheumatologists' opinion and SFR guideline regarding the main factors to consider for initiation of an anti-TNF-alpha therapy.

Pers JO, Saraux A, Pierre R, Youinou P. · Department of Dentistry, Brest University Medical and Dental School, Brest, France. · J Periodontol. · Pubmed #18771364 No free full text.

Abstract: BACKGROUND: Because periodontitis presents many similarities with rheumatoid arthritis (RA) with regard to tumor necrosis factor-alpha (TNF-alpha)-induced bone resorption, the benefits of TNF-alpha blockade in RA prompted us to determine its efficacy in treating coexisting periodontitis. METHODS: Periodontal status was evaluated in 40 subjects with RA who were divided into two groups: Group I contained 20 subjects who had received infliximab every 6 weeks for > or =22 months at the time of periodontal evaluation. The 20 subjects in group II were evaluated before their first infusion with infliximab. Nine subjects in group II had periodontitis. These subjects were reevaluated after they received nine infusions of infliximab. RESULTS: Infliximab tended to aggravate gingival inflammation as indicated by differences in the modified gingival and papillary bleeding indices between subjects in groups I and II with coexisting periodontitis before and after treatment. Methotrexate had no effect on periodontal status. Although the plaque index revealed that bacterial infection persisted, the probing depth was equal in groups I and II and equivalent before and after treatment in subjects with periodontitis, whereas attachment loss was decreased after infliximab treatment. CONCLUSIONS: Inflammation and destruction constitute two interrelated yet separate components of periodontitis in patients with RA. Therefore, TNF-alpha blockade could be beneficial in the treatment of periodontitis.

Davaine AC, Saraux A, Prigent S, Kupfer-Bessaguet I, Roswag D, Plantin P, Schoenlaub P, Talarmin F, Zagnoli A, Misery L. · Department of Dermatology, University Hospital, Brest, France. · J Eur Acad Dermatol Venereol. · Pubmed #18713230 No free full text.

Abstract: BACKGROUND: Anti-tumour necrosis factors (anti-TNF) are more and more used, but the rate of skin adverse events is not known. OBJECTIVE: The aim was to assess the number of skin infections and other dermatoses in patients treated with anti-TNFalpha. PATIENTS AND METHODS: One hundred eighty-seven patients suffering from rheumatoid arthritis or ankylosing spondylitis underwent a dermatological exam. Patients with anti-TNF were compared with those without this treatment in a prospective transversal study. RESULTS: Among them, 59 patients were treated with anti-TNFalpha and steroids were prescribed in 100 cases. There was no difference in the prevalence of skin infections or eczema or tumours. Skin drug reactions were observed in six patients. Infections by dermatophytes appear very frequent, approaching 70% in both groups. CONCLUSIONS: This study shows that skin infections (or other skin diseases) are not more frequent in these patients. No differences were observed in infections (bacterial fungal, parasital or viral), tumours, psoriasis or the manifestations of atopic dermatitis. Nonetheless, a long-term survey might be interesting, especially about skin tumours.

Morvan J, Coste J, Roux CH, Euller-Ziegler L, Saraux A, Guillemin F. · School of Public Health, Nancy University, Nancy, France. · Ann Epidemiol. · Pubmed #18374278 No free full text.

Abstract: BACKGROUND: Two-phase surveys often are used to estimate prevalence, in particular when the disease is rare or the case ascertainment procedure difficult and/or costly. However, few authors of such surveys take into account the sensitivity error associated with the use of a screening procedure in the first phase and its imprecision in correcting the prevalence estimate and confidence interval. METHODS: Two examples of two-phase surveys of rheumatic diseases (hip and knee osteoarthritis, rheumatoid arthritis and spondyloarthropathies) are used to present methodological approaches to obtain corrected prevalence estimates. Two methods for assessing the accuracy of the screening procedure are described--two-phase pilot and case-control designs--that are best suited for frequent and rare diseases, respectively, and naive and corrected estimates of prevalence compared. RESULTS: When the sensitivity error is not taken into account, prevalence is underestimated, as is, especially, the width of its confidence interval. In our examples, the corrected confidence interval width increased up to 50% as compared with naïve one. CONCLUSIONS: The screening procedure accuracy should be thoroughly assessed in two-phase prevalence surveys and prevalence estimates and their confidence intervals corrected accordingly.

Pers JO, Daridon C, Bendaoud B, Devauchelle V, Berthou C, Saraux A, Youinou P. · Department of Immunopathology, Brest University Medical School, Brest, France. · Clin Rev Allergy Immunol. · Pubmed #18270858 No free full text.

Abstract: Although T-lymphocytes have long been regarded as the prime effector of autoimmune diseases, numerous studies have since highlighted a key role for B-lymphocytes. For example, disturbances in the distribution of circulating B-cell subsets were reported in primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). Consequently, this was the rationale to treat such patients for B-cell depletion with anti-CD20 monoclonal antibody (rituximab). The aim of this review is to describe and analyze the B-cell subset distribution at baseline and after rituximab therapy in patients with SLE, rheumatoid arthritis, and pSS. Finally, we will compare factors that may interfere with anti-CD20-mediated B-cell depletion in these autoimmune diseases.

Binard A, Alassane S, Devauchelle-Pensec V, Berthelot JM, Jousse-Joulin S, Chalés G, Le Henaff C, Thorel JB, Hoang S, Youinou P, Saraux A. · Unit of Rheumatology and the Laboratory of Immunology, la Cavale Blanche Hospital, Brest Teaching Hospitals, Brest, France. · J Rheumatol. · Pubmed #17985408 No free full text.

Abstract: OBJECTIVE: To evaluate clinical, laboratory, and radiological features and outcomes in patients with monoarthritis (MA), identified in a cohort of patients with early arthritis. METHODS: A cohort of 270 patients with undiagnosed arthritis of less than 1 year's duration was divided into 3 groups: single episode of MA (MA, n = 27), MA with a history of patient-reported arthritis (MA + past, n = 23), and oligo- or polyarthritis (OA/PA, n = 220). At 6-month intervals, all patients underwent a standardized examination, radiographs, and standard laboratory tests including rheumatoid factors (RF), antiperinuclear factor (APF), antikeratin antibody (AKA), anticyclic citrullinated peptide antibody (anti-CCP), antinuclear antibodies, and HLA-AB-DR typing. After a median followup of 30 months, the diagnosis was evaluated by a hospital-based rheumatologist. RESULTS: Age and sex did not differ across the 3 groups. Knee involvement was more common in the MA group than in the MA + past group (p < 0.03), whereas hand and metatarsophalangeal involvement was less common (p < 0.03 and p < 0.0001, respectively). RF and anti-CCP were less often positive in the MA group than in the MA + past group (p < 0.02 and p < 0.001, respectively) and the OA/PA group (p < 0.02 and p < 0.03). No patient in the MA group received a diagnosis of rheumatoid arthritis (RA). RA was less common and disease modifying antirheumatic drugs were prescribed less often in the MA group than in the other 2 groups (p < 0.0001 for both comparisons). CONCLUSION: The MA group was clearly different from the other groups, with a favorable outcome and no risk of progression to RA.

Combe B, Benessiano J, Berenbaum F, Cantagrel A, Daurès JP, Dougados M, Fardellone P, Fautrel B, Flipo RM, Goupille P, Guillemin F, Le Loet X, Logeart I, Mariette X, Meyer O, Ravaud P, Rincheval N, Saraux A, Schaeverbeke T, Sibilia J. · University Hospital, Montpellier, France. · Joint Bone Spine. · Pubmed #17905631 No free full text.

Abstract: OBJECTIVES: The French Society of Rheumatology initiated a large national multicenter, longitudinal and prospective cohort, the so-called "ESPOIR cohort study" in order to set up databases to allow various investigations on diagnosis, prognostic markers, epidemiology, pathogenesis and medico-economic factors in the field of early arthritis and rheumatoid arthritis. METHODS: Patients were recruited if they had undifferentiated arthritis or rheumatoid arthritis, of less than 6 months disease duration and if they were DMARD and steroids naïve. Patients have then to be followed every 6 months during the first 2 years then every year during at least 10 years. Clinical, biological, radiographic and medico-economic databases have been constituted to fit in the different objectives of the project and more than 20 scientific studies have already been accepted by the scientific committee. RESULTS: 813 patients were included (76.75% were female). The mean age was 48.07+/-12.55 years. The mean delay from the onset of symptoms to referral to the rheumatologist was 74.8+/-76.6 days. Baseline swollen and tender joint counts were 7.19+/-5.37 and 8.43+/-7.01; DAS28 score was 5.11+/-1.31. CRP was abnormal in 38.9% of the patients; 44.2%, 45.8% and 38.8% had respectively IgM rheumatoid factor (RF), IgA RF and anti-CCP antibodies. HLA DRB1*01 or 04 genes were found in 56.7% of them. Finally, 22% of these patients had erosions on hand or feet at baseline.

Guennoc X, Samjee I, Jousse-Joulin S, Devauchelle V, Roudaut A, Saraux A. · Rheumatology Department, Brest Teaching Hospital, CHU de Brest, 29609 Brest, France. · Joint Bone Spine. · Pubmed #17574895 No free full text.

Abstract: OBJECTIVE: To evaluate the quality of patient information about fluoroscopy-guided rheumatologic procedures, and to look for an impact on the patient's experience of the procedure. METHODS: One hundred and nineteen patients completed questionnaires before and after undergoing fluoroscopy-guided interventions. We looked for associations between the information supplied by the rheumatologist who recommended the procedure and pain, anxiety, awareness of potential complications, and the match between patient expectations and actual experience. RESULTS: 62.8% of patients reported receiving information about the procedure. Only 20.5% reported receiving specific information about potential adverse events, although 80.9% felt this information would have been useful. Most patients (74.8%) would have liked to receive additional information. Only 10.1% patients were given written information. Mean (+/-SD) anticipated pain severity as assessed in the waiting room before the procedure on a 0-10 scale was 4.5+/-2.4 in women and 4.2+/-2.3) in men. Actual pain severity during the procedure as assessed on the same scale was 2.7+/-2.6 in women and 2.2+/-1.6 in men. The level of information about the procedure did not influence anticipated or actual pain severity. Anxiety was reported by 59.8% patients and was more common in women (P<0.001), in patients given written information (P=0.05), and in patients undergoing their first intervention (P=0.05). Information was perceived as alleviating anxiety by 69.9% patients, and 77.3% of patients felt they would experience less anxiety if they had the procedure a second time. Only 21.2% patients were able to name a potential adverse event, and this proportion was not influenced by receiving written information. A mismatch between expectations about the procedure or its duration and actual experience was reported by 17 (17/69, 24.6%) and 34 (34/98, 34.7%) patients, respectively, with no significant differences across study subgroups. CONCLUSION: Information about interventional rheumatology procedures is required for ethical principles and legislation. Patients increasingly expect detailed information, which may increase the likelihood that the procedure unfolds smoothly. Our results indicate a need for optimizing patient information. Standardized written material deserves to be evaluated as a means of better meeting the informational needs of patients.

Pers JO, Devauchelle V, Daridon C, Bendaoud B, Le Berre R, Bordron A, Hutin P, Renaudineau Y, Dueymes M, Loisel S, Berthou C, Saraux A, Youinou P. · Brest University Medical School, Brest, France. · Arthritis Rheum. · Pubmed #17469105 links to  free full text

Abstract: OBJECTIVE: Treatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs) of patients with primary Sjögren's syndrome (SS). The purpose of this study was to track the repopulation of B cell subsets in PB as well as their subsequent homing into SGs in patients with primary SS treated with rituximab. METHODS: A series of 4-color flow cytometry experiments delineated B cell subsets in 15 patients with primary SS. All were tested on days 8 and 15 of treatment. Nine of the patients were followed up monthly for 10 months, and the remaining 6 patients were followed up monthly for 24 months. Enzyme-linked immunosorbent assays were developed to measure serum levels of BAFF and rituximab. SGs were biopsied at the start of the study and 4 months after treatment in 15 patients, 12 months after treatment in 3 patients, and 24 months after treatment in 2 patients. RESULTS: Baseline serum levels of BAFF correlated inversely (r = -0.92, P < 5 x 10(-4)) with the duration of B cell depletion: the higher the BAFF levels, the shorter the duration of B cell depletion. Four B cell subsets repopulated the PB: plasmablasts (CD19+, CD5-,IgD-,CD38++), transitional type 1 (T1) B cells (CD19+,CD5+,IgD+,CD38++), mature Bm2 cells (CD19+,CD5+/-,IgD+,CD38+/-), and memory B cells (CD19+,CD5-,IgD-,CD38-). Increased numbers of Bm2 cells and decreased memory B cells reappeared with time. Sequential SG biopsies revealed that B cells were absent in these glands for 12 months: they were detected 24 months after rituximab treatment. Memory and T1 B cells were the first B cells identified locally. CONCLUSION: The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.

Daridon C, Devauchelle V, Hutin P, Le Berre R, Martins-Carvalho C, Bendaoud B, Dueymes M, Saraux A, Youinou P, Pers JO. · Laboratory of Immunology, Brest University Medical School Hospital, Brest, France. · Arthritis Rheum. · Pubmed #17393395 links to  free full text

Abstract: OBJECTIVE: To identify the cells that produce BAFF in the salivary glands of patients with primary Sjögren's syndrome (SS), and to analyze BAFF receptor expression by local T and B lymphocytes. METHODS: We used 3 methods to identify the source of BAFF: in situ hybridization of the transcripts for BAFF combined with staining of membrane markers, regular and real-time reverse transcription-polymerase chain reaction (RT-PCR) of cultured epithelial cells, and RT-PCR of sorted single-cell T and B lymphocytes eluted from salivary glands. Cells expressing TACI, BCMA, and B lymphocyte stimulator receptor 3 (BR-3) were disclosed by combining each specific staining of the receptors with each specific staining of the cells. The function of BAFF generated by epithelial cells on B lymphocytes was determined in short-term cocultures. RESULTS: Transcripts for BAFF were seen in epithelial cells and infiltrating T lymphocytes and, for the first time, were detected in local B cells. It is interesting that BR-3 was present on these B cells but not on T cells. In contrast, TACI and, to a lesser degree, BCMA were observed on transitional B lymphocytes, whereas T lymphocytes were devoid of receptors for BAFF. Furthermore, this cytokine was shown to be functional, in that epithelial cell-bound BAFF extended the survival of normal B cells, but cell-free BAFF released in the supernatants did not. CONCLUSION: These experiments establish that in primary SS, BAFF is produced not only by epithelial cells and T cells but also by B cells. The expression of receptors for BAFF would thus allow these receptors to participate in an autocrine pattern of self-stimulation.

Meyer O, de Bandt M, Berthelot JM, Cantagrel A, Combe B, Fautrel B, Flipo RM, Lioté F, Maillefert JF, Saraux A, Wendling D, Guillemin F, Le Loët X, Anonymous00174. · Department of Rheumatology, AP-HP, Bichat Paris 7 University Hospital, CHU Bichat, 46 rue Henri Huchard, 75018 Paris, France. · Joint Bone Spine. · Pubmed #17194614 No free full text.

Abstract: BACKGROUND: The objective was to develop a clinical practice format for choosing a second-line disease-modifying anti-rheumatic drug (DMARD) after a 6-month course of a first-line DMARD in patients with early RA. METHODS: A panel of 34 experts selected treatment option from various scenarios using the Thurstone pairwise method. The experts had to choose between two proposed DMARDs without proposing other options. The scenarios were obtained using the three items: DAS28, rheumatoid factor status and radiographic structural damage. A sample of 240 among 480 scenarios for each expert was taken at random. Responses given by at least 20% of the experts were considered pertinent. RESULTS: Recommendations for choosing a second DMARD for early RA after failure of a 6-month course of a first-line DMARD were established according to 4 parameters: type of first-line DMARD, activity, RF status and radiographic joint damage. The results of this study suggest that in patients with early RA who fail a 6-month course of first-line DMARD therapy, the best options may be addition of corticosteroid when disease activity is moderate to high and switching to a biologic agent when further radiographic joint damage occurs, particularly in patients with positive tests for RF. CONCLUSION: Although our scenarios did not include step-up (add instead of substitute) strategies, except for corticosteroids, we feel that the format presented here can optimise the management of patients with early RA seen in clinical practice.

Roux CH, Saraux A, Le Bihan E, Fardellone P, Guggenbuhl P, Fautrel B, Masson C, Chary-Valckenaere I, Cantagrel A, Juvin R, Flipo RM, Euller-Ziegler L, Coste J, Guillemin F. · Department of Rheumatology, University Hospital, Nice, France. · J Rheumatol. · Pubmed #17117490 No free full text.

Abstract: OBJECTIVE: To determine geographical variation in the prevalence of rheumatoid arthritis (RA) and spondyloarthropathies (SpA) in France. METHODS: The survey sample was drawn from 7 areas of France. Households were randomly selected using the national telephone directory, and an individual within each household was randomly chosen by the next-birthday method. All cases of suspected RA and SpA were confirmed by the patient's rheumatologist or by clinical examination. Standardized estimates of prevalence were compared between regions and groups of regions. RESULTS: In total 15,219 anonymous telephone numbers were selected. An average response rate of 64% led to a total of 9395 respondents included in the study. The highest regional rates of RA were observed in the south (range 0.59-0.66%), and the lowest in the north (range 0.14-0.24%), with a national rate of 0.31% (95% CI 0.18-0.48%). Regional heterogeneity was observed for SpA, with the highest rates in Bretagne (0.47%) and the Sud-Est (0.53%) and a national rate of 0.30% (95% CI 0.17-0.46%). CONCLUSION: This study is the largest of its kind conducted in France. It shows inter-regional variations, mainly in RA, with a higher prevalence in the south of the country. The many potential reasons for the heterogeneity observed, including genetic and environmental factors, warrant further research.

Devauchelle V, Essabbani A, De Pinieux G, Germain S, Tourneur L, Mistou S, Margottin-Goguet F, Anract P, Migaud H, Le Nen D, Lequerré T, Saraux A, Dougados M, Breban M, Fournier C, Chiocchia G. · Institut Cochin, Département d'Immunologie, 27 rue du Faubourg Saint-Jacques, 75674 Paris Cedex 14, France. · J Immunol. · Pubmed #17056579 links to  free full text

Abstract: We previously compared by microarray analysis gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) tissues. Among the set of genes identified as a molecular signature of RA, clusterin (clu) was one of the most differentially expressed. In the present study we sought to assess the expression and the role of CLU (mRNA and protein) in the affected joints and in cultured fibroblast-like synoviocytes (FLS) and to determine its functional role. Quantitative RT-PCR, Northern blot, in situ hybridization, immunohistochemistry, and Western blot were used to specify and quantify the expression of CLU in ex vivo synovial tissue. In synovial tissue, the protein was predominantly expressed by synoviocytes and it was detected in synovial fluids. Both full-length and spliced isoform CLU mRNA levels of expression were lower in RA tissues compared with OA and healthy synovium. In synovium and in cultured FLS, the overexpression of CLU concerned all protein isoforms in OA whereas in RA, the intracellular forms of the protein were barely detectable. Transgenic overexpression of CLU in RA FLS promoted apoptosis within 24 h. We observed that CLU knockdown with small interfering RNA promoted IL-6 and IL-8 production. CLU interacted with phosphorylated IkappaBalpha. Differential expression of CLU by OA and RA FLS appeared to be an intrinsic property of the cells. Expression of intracellular isoforms of CLU is differentially regulated between OA and RA. We propose that in RA joints, high levels of extracellular CLU and low expression of intracellular CLU may enhance NF-kappaB activation and survival of the synoviocytes.

Daridon C, Pers JO, Devauchelle V, Martins-Carvalho C, Hutin P, Pennec YL, Saraux A, Youinou P. · Laboratory of Immunology, Brest University Medical School Hospital, BP824, F-29609 Brest, France. · Arthritis Rheum. · Pubmed #16802367 links to  free full text

Abstract: OBJECTIVE: To identify B cell subpopulations participating in the lymphocyte infiltrate of salivary glands from patients with primary Sjögren's syndrome. A special emphasis was placed on those B lymphocytes included in the ectopic germinal centers (GCs). METHODS: The presence of B cells in salivary glands and their polyclonality were ascertained by phenotyping and reverse transcription-polymerase chain reaction in salivary gland samples from 18 patients. Their phenotype was thoroughly analyzed using a number of double-staining combinations. The results obtained in tissue sections were confirmed by fluorescence-activated cell sorting analysis of B cells eluted from salivary glands, and these findings were compared with those in tonsils. RESULTS: Memory-type B cells were defined as CD20+, CD27+ and were seen in all specimens, whereas GCs were found in only 7 specimens. Furthermore, B cells found in these GCs lacked certain characteristics of centroblasts and centrocytes. Instead, they fulfilled the criteria for transitional type II (TII) B cells and resembled marginal-zone B cells. BAFF (the assistance of which is required for proper transformation of transitional TI B cells into transitional TII B cells) accumulated adjacent to transitional and marginal-zone-like B lymphocytes. Further evidence for the involvement of BAFF came from the expression of its receptors on infiltrating B cells. CONCLUSION: These transitional TII and marginal-zone-like B cells are probably instrumental in the local production of autoantibodies and possibly influential in the ensuing destruction of epithelial cells.

Saraux A, Devauchelle-Pensec V, Engerran L, Flipo RM. · Department of Rheumatology, La Cavale Blanche Teaching Hospital, Brest, France. · J Rheumatol. · Pubmed #16783865 No free full text.

Abstract: OBJECTIVE: To evaluate the proportion of patients with rheumatoid arthritis (RA) visiting office-based rheumatologists for persistently active RA despite past or current methotrexate (MTX) treatment, and to describe the management of these patients in France in 2003. METHODS: All French rheumatologists were invited to participate in a cross-sectional postal survey. During a predetermined week, they were to include the first 2 patients seen for RA with a history of past or current MTX treatment. Adequacy of current treatment was assessed based on the 28-joint Disease Activity Score 28 (DAS28) and on current MTX and corticosteroid regimens. RESULTS: Of the 1800 French rheumatologists, 492 returned 838 assessable patient questionnaires. Mean patient age was 58 years and mean time since RA diagnosis was 10 years; 77% of patients were currently taking MTX, and 51% a corticosteroid. High dosages were noted for MTX (> 15 mg/week) in 20% of patients and for corticosteroid therapy (> 10 mg/day) in 5%. Nevertheless, 41% of patients had active RA (DAS28 score 3.2 to 5.1) and 7% had very active RA (DAS28 score > 5.1). The treatment was left unchanged in 78% of patients, and biological therapy was contemplated in only 16% of patients. CONCLUSION: Although half of MTX-treated patients with RA visiting office-based rheumatologists had active or very active disease, a change in treatment was rarely considered.

Devauchelle-Pensec V, Berthelot JM, Jousse S, Samjee I, Josseaume T, Colin D, Chalés G, Thorel JB, Hoang S, Martin A, Youinou P, Le Goff P, Saraux A. · Unit of Rheumatology, Cavale Blanche Hospital, CHU Brest, Brest, France. · J Rheumatol. · Pubmed #16783864 No free full text.

Abstract: OBJECTIVE: To evaluate the ability of baseline hand radiographs to predict the diagnosis 2 years later in a cohort of patients with early arthritis. METHODS: A total of 258 patients with arthritis onset within the previous year were evaluated. At baseline, all patients underwent a standardized evaluation including laboratory tests and radiographs. Hand radiographs were read by a blinded observer who used a standardized procedure for detecting features of crystal deposition diseases and rheumatoid arthritis (RA). After 30 +/- 11.3 months, the final diagnosis was established by a panel of rheumatologists. All radiographs were evaluated. RESULTS: Significant associations were found between radiographic features and a clinical diagnosis of RA, calcium pyrophosphate dihydrate (CPPD) arthritis, and hydroxyapatite arthritis. No radiographic abnormalities suggesting psoriatic arthritis or gout were seen. The sensitivities of hand radiographs for diagnosing CPPD or hydroxyapatite arthritis ranged from 80% to 100%. Baseline hand radiographs suggested the final diagnosis in 31/258 patients, including 21 (22.5%) of the 93 patients with RA, 10 of the 11 (91%) patients with CPPD or hydroxyapatite deposition disease, and none of the patients with other disorders. Sensitivity was 29%, specificity 86.5%, positive predictive value 61%, and negative predictive value 63%. CONCLUSION: In our cohort of patients with recent arthritis, the overall performance of hand radiographs in predicting a diagnosis 2 years later was modest. However, they had an excellent diagnostic value for calcium deposition diseases.

Saraux A, Fautrel B, Maillefert JF, Flipo RM, Kaye O, Lafforgue P, Gourves K, Guillemin F, Anonymous00195. · Rheumatology Units of the Brest, Dijon, Paris La Pitiè, Lille, and Marseille La Timone Teaching Hospitals, France. · J Rheumatol. · Pubmed #16583465 No free full text.

Abstract: OBJECTIVE: To conduct a practice survey of laboratory and imaging studies used by French rheumatologists to identify the cause of recent-onset arthritis. METHODS: We selected a random sample of 210 rheumatologists, who were asked to recruit all patients with recent-onset arthritis (at least one joint involved, for less than one year) during a 2 week period, and to record laboratory and imaging studies performed. Results were analyzed in the overall group, in diagnostic subgroups, and in clinical presentation subgroups. RESULTS: The 119 rheumatologists who participated recruited 104 patients. Investigations done in 50% to 75% of patients were blood cell counts; erythrocyte sedimentation rate; serum assays of C-reactive protein, rheumatoid factors, antinuclear antibodies; and hand radiographs. Investigations in 50% to 74% of patients were serum ASAT/ALAT, creatinine, and uric acid; and foot radiographs. Finally, 25% to 49% of patients were tested for proteinuria; antikeratin antibodies; hepatitis B, hepatitis C, and Lyme serologies; creatine phosphokinase; blood iron; HLA-B27; and radiographs of chest and pelvis. No differences were found between investigations in patients with suspected rheumatoid arthritis and/or undifferentiated arthritis and those in other patients. In contrast, suspected diagnoses and presence of extraarticular manifestations classically associated with specific diseases modified the selection of investigations. CONCLUSION: Although considerable variability occurred, our study suggests that a limited panel of laboratory and imaging studies is performed in at least 25% of patients with recent-onset arthritis, regardless of clues suggesting a specific diagnosis.

d'Arbonneau F, Pers JO, Devauchelle V, Pennec Y, Saraux A, Youinou P. · Immunology Laboratory, Brest University Medical School, F-29609 Brest, France. · Arthritis Rheum. · Pubmed #16385503 links to  free full text

Abstract: OBJECTIVE: To determine the effect of excessive production of BAFF on the distribution and function of B cell subsets in patients with primary Sjögren's syndrome (SS). METHODS: The phenotype of B lymphocytes was analyzed by flow cytometry. Differences in the expression level of membrane IgD and CD38 were used to identify B lymphocyte subsets evolving from naive Bm1 through memory Bm5 cells. Based on our finding of a low expression of CD45RA, we sorted Bm2/Bm2' cells to determine the time course of translocation of the CD19 molecule and the B cell receptor into lipid rafts, by confocal microscopy. Serum levels of BAFF were measured by an enzyme-linked immunosorbent assay developed in-house. RESULTS: "Circulating" Bm2/Bm2' cells were expanded in patients with primary SS compared with rheumatic disease controls and with normal controls. In addition, these B cell subsets were functionally abnormal. Prolonged residency of the B cell receptor in lipid rafts in these cells was associated with elevated CD19 expression in B cells, most notably, Bm2 and Bm2' cells, obtained from the patients with primary SS. BAFF levels were higher in the patients than in the normal controls and correlated with the percentage of Bm2/Bm2' cells and their expression of CD19 in primary SS patients. These correlations were confirmed by placing sorted Bm1 or Bm2 cells from normal controls in culture in the presence or absence of BAFF. CONCLUSION: Bm2/Bm2' cells express more CD19 molecules in primary SS patients than in normal controls. BAFF might participate in this elevated expression of CD19. These patients might be suitable candidates for treatment with BAFF antagonists.

Pers JO, d'Arbonneau F, Devauchelle-Pensec V, Saraux A, Pennec YL, Youinou P. · Brest University Medical School, France. · Arthritis Rheum. · Pubmed #16052575 links to  free full text

Abstract: OBJECTIVE: To correlate the periodontal status of 15 patients with primary Sjögren's syndrome (SS) with their salivary levels of BAFF. METHODS: The periodontal status of 15 patients who fulfilled the criteria for primary SS was compared with that of 15 controls with xerostomia who did not fulfill the criteria for primary SS but had similar symptoms of dry mouth. The level of BAFF was measured in paired samples of saliva and serum using in-house enzyme-linked immunosorbent assays. Periodontitis was assessed by the plaque index, the modified gingival index, the papillary bleeding index, and the periodontal pocket depth. RESULTS: Notwithstanding the better oral hygiene practices of the patients with primary SS compared with those of the xerostomia controls and the subsequent reduction of their plaque index scores, complications of periodontitis, such as bleeding, gingival hypertrophy, and periodontal pockets, were not improved. This failure to ameliorate the complications of periodontitis in patients with primary SS was associated with high levels of BAFF in their saliva compared with the levels in xerostomia controls (7.4 +/- 2.1 versus 1.0 +/- 0.4 ng/ml [P < 0.002]). The levels of BAFF in saliva did not correlate with the levels in sera but did correlate with the periodontal pocket depth (P < 0.002). CONCLUSION: These findings are similar to the bone resorption observed in patients with rheumatoid arthritis. They suggest that the known effect of B cells in periodontitis would be partly mediated by salivary BAFF in patients with primary SS.

Croquefer S, Renaudineau Y, Jousse S, Gueguen P, Ansart S, Saraux A, Youinou P. · Laboratory of Immunology, Brest University Medical School Hospital, BP824, F29609 Brest, France. · Ann N Y Acad Sci. · Pubmed #16014531 No free full text.

Abstract: In murine systemic lupus erythematosus (SLE) models, nephritogenic anti-dsDNA IgG has been shown to cross-react with a kidney antigen, alpha-actinin, and to be critical in renal pathogenesis. In humans, studies of anti-alpha-actinin antibodies (Abs) are scarce, and these antibodies remain to be evaluated. We have thus far tested sera from patients with SLE (n = 103), rheumatoid arthritis (RA, n = 93), and primary Sjögren syndrome (pSS, n = 34), and from healthy subjects (n = 160), for the presence of anti-alpha-actinin and anti-DNA Abs. The latter were tested using several methods [IIF on Crithidia luciliae (Crit) and ELISA using dsDNA]. Anti-alpha-actinin Abs were confirmed by Western blot. Sera from 23 of 103 SLE patients, 3 of 93 RA patients, 1 of 33 pSS patients, and 1 of 160 controls scored positive for anti-alpha-actinin Abs. In SLE, the positivity was significantly associated with anti-dsDNA reactivity (22 of 23): 19 of 23 sera were alpha-actinin-positive/dsDNA-positive and 13 were alpha-actinin-positive/Crit-positive. Few cases were alpha-actinin-positive/dsDNA-negative: 1 SLE, 3 RA, and 1 control. Furthermore, anti-alpha-actinin Abs have been detected at high level before or at the early stage of lupus nephritis when compared with active and inactive SLE without kidney manifestations.

Pers JO, Daridon C, Devauchelle V, Jousse S, Saraux A, Jamin C, Youinou P. · Department of Immunology, Brest University Medical School Hospital, BP824, F29609, Brest, France. · Ann N Y Acad Sci. · Pubmed #16014518 No free full text.

Abstract: The B-cell activity factor (BAFF) acts as a positive regulator of B-cell function. To gain further insight into the understanding of B-cell hyperactivity in autoimmune diseases, the serum level of BAFF was determined in 43 systemic lupus erythematosus (SLE) patients, 58 primary Sjögren's syndrome (pSS) patients, 28 rheumatoid arthritis (RA) patients, and 68 normal control subjects using an in-house sandwich ELISA. A commercial kit was used to detect soluble CD23 (sCD23) reflecting B-cell activation. In-house assays for the detection of autoantibodies also were used. We found an increased level of BAFF in SLE, pSS, and RA sera compared with normal subjects (respectively, 10.6 +/- 8.5, 15.8 +/- 12.9, 9.7 +/- 1.5 ng/mL vs. 4.6 +/- 2.9 ng/mL, P < .001). sCD23 released on B-cell activation also was found to be elevated in SLE, pSS, and RA compared with normal sera. However, no correlation was found between the circulating BAFF and the level of sCD23. By contrast, we observed that high levels of BAFF were associated with the presence of autoantibodies (anti-double-stranded DNA antibodies in SLE, anti-SSA antibodies in pSS, and rheumatoid factors in RA). Our data suggest that BAFF is influential in driving antibody production rather than activation of the B lymphocytes in autoimmune diseases.

Le Loët X, Berthelot JM, Cantagrel A, Combe B, De Bandt M, Fautrel B, Flipo RM, Lioté F, Maillefert JF, Meyer O, Saraux A, Wendling D, Guillemin F. · Department of Rheumatology, Rouen University Hospital, France. · Ann Rheum Dis. · Pubmed #15994280 links to  free full text

Abstract: OBJECTIVE: To elaborate a clinical practice decision tree for the choice of the first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid arthritis of less than six months' duration. METHODS: Four steps were employed: (1) review of published reports on DMARD efficacy against rheumatoid arthritis; (2) inventory of the information available to guide DMARD choice; (3) selection of the most pertinent information by 12 experts using a Delphi method; and (4) choice of DMARDs in 12 clinical situations defined by items selected in step 3 (28 joint disease activity score (DAS 28): < or =3.2; >3.2 and < or =5.1; >5.1; rheumatoid factor status (positive/negative); structural damage (with/without)-that is, 3 x 2 x 2). Thus, multiplied by all the possible treatment pairs, 180 scenarios were obtained and presented to 36 experts, who ranked treatment choices according to the Thurstone pairwise method. RESULTS: Among the 77 items identified, 41 were selected as pertinent to guide the DMARD choice. They were reorganised into five domains: rheumatoid arthritis activity, factors predictive of structural damage; patient characteristics; DMARD characteristics; physician characteristics. In the majority of situations, the two top ranking DMARD choices were methotrexate and leflunomide. Etanercept was an alternative for these agents when high disease activity was associated with poor structural prognosis and rheumatoid factor positivity. CONCLUSIONS: Starting with simple scenarios and using the pairwise method, a clinical decision tree could be devised for the choice of the first DMARD to treat very early rheumatoid arthritis.

Saraux A, Guillemin F, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E, Cantagrel A, Chary-Valckenaere I, Euller-Ziegler L, Flipo RM, Juvin R, Behier JM, Fautrel B, Masson C, Coste J. · Rheumatology Unit, University Hospital, Brest-Cedex, France. · Ann Rheum Dis. · Pubmed #15817661 links to  free full text

Abstract: OBJECTIVE: To estimate the prevalence of spondyloarthropathies (SpAs) in France in a multiregional representative sample in the year 2001. METHODS: A two stage random sample was constituted in seven areas from the national telephone directory and the next birthday method in each household. Interviewers were patient-members of self help groups trained to administer telephone surveys using a validated questionnaire for detecting inflammatory joint disease. Quality of data collection was controlled periodically. SpA was confirmed by the patient's rheumatologist or by clinical examination. Prevalence estimates after probability sampling correction were standardised for age and sex (1999 national census). RESULTS: Among the 15 219 anonymous telephone numbers selected, 3.6% were places of work or secondary residences and were excluded. The phone interview participation rate ranged across regions from 55.1 to 69.9%. 3554 men and 5841 women were included in the study. Twenty nine cases of SpA were confirmed. All but one fulfilled ESSG criteria. Mean age was 47 years (range 21-78). The overall prevalence standardised for age and sex was 0.30% (95% confidence interval (CI) 0.17 to 0.46). Prevalence was similar in women (0.29% (95% CI 0.14 to 0.49)) and men (0.31 % (95% CI 0.12 to 0.60)). Geographical analysis by department clustering found no significant differences. The prevalence of SpA was as high as that of rheumatoid arthritis. CONCLUSION: Prevalence of SpA in France was 0.30% in 2001, with no difference between women and men. Ankylosing spondylitis and psoriatic arthritis were the most common SpA subsets.

Guillemin F, Saraux A, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E, Cantagrel A, Chary-Valckenaere I, Euller-Ziegler L, Flipo RM, Juvin R, Behier JM, Fautrel B, Masson C, Coste J. · EA 3444 School of Public Health, Faculty of Medicine, University of Nancy, Nancy, France. · Ann Rheum Dis. · Pubmed #15800010 links to  free full text

Abstract: BACKGROUND: Prevalence estimates of rheumatoid arthritis (RA) vary across Europe. Recent estimates in southern European countries showed a lower prevalence than in northern countries. OBJECTIVES: To estimate the prevalence of RA in France in a multiregional representative sample in the year 2001. METHODS: A two stage random sample was constituted in seven areas (20 counties) from the national telephone directory of households and by the next birthday method in each household. Patient-interviewers, member of self help groups, were trained to administer telephone surveys using a validated questionnaire for case detection of inflammatory rheumatism, and conducted the survey under quality control. All suspected cases of RA were confirmed by their rheumatologist or by clinical examination. Prevalence estimates after probability sampling correction were standardised for age and sex (national census 1999). RESULTS: An average response rate of 64.7% (two stages combined) led to a total of 9395 respondents. Standardised prevalence was 0.31% (95% confidence interval 0.18 to 0.48) for RA, 0.51% in women and 0.09% in men, with a higher age-specific prevalence in the 65-74 year age band. A geographical analysis of county clustering showed significant variation across the country. CONCLUSION: This national multiregional cooperative study demonstrates the usefulness of working in association with patients of self help groups. It showed a similar prevalence of RA to that of the spondyloarthropathies estimated concomitantly during the survey. It provides a reliable basis for definition of population targets for healthcare delivery and drug treatments.

Ollivier Y, Saraux A, Le Goff P. · Unit of Rheumatology, Hôpital de la Cavale Blanche, CHU Brest, BP 814, F 29609 Brest-Cedex, France. · Clin Exp Rheumatol. · Pubmed #15638052 No free full text.

Abstract: OBJECTIVE: To evaluate the influence of lifestyle factors on the prevalence of rheumatoid arthritis (RA) by comparing Roman Catholic nuns and the general female population. METHOD: RA prevalence in the general population was evaluated using a standardized telephone survey in 1857 homes taken at random. Individuals who reported an inflammatory joint disease were contacted by a rheumatologist of our unit, missing data were collected from the general practitioner or rheumatologist with the patient's permission, and if necessary a physical examination was done by a rheumatologist. The 9 largest Roman Catholic nun communities in Brittany were screened using the same standardized questionnaire administered face-to-face; nuns who reported an inflammatory joint disease were interviewed and examined by rheumatologists. In both populations, RA was diagnosed when (1) the rheumatologist of our unit who interviewed the patient considered the RA classification criteria positive and (2) the rheumatologist who examined the patient gave a diagnosis of RA independently from RA classification criteria. RESULTS: Data were available for 1706 adult females in the general population and 721 nuns. Of the 20 nuns who reported RA or polyarthritis, 11 received a diagnosis of RA (prevalence 1.52%). The prevalences adjustedfor the French population after 40 years were 1.66% (95% confidence interval, 0.84-2.44) and 1.33 (0.27-2.40) among the nuns and the general female population, respectively. CONCLUSION: Although our nun population was too small for definite conclusions, we found no evidence of a difference in RA prevalence among nuns and the general female population in Brittany.