Rheumatoid Arthritis: Berthelot JM

Berthelot JM, Blanchais A, Marhadour T, le Goff B, Maugars Y, Saraux A. · No affiliation provided · Joint Bone Spine. · Pubmed #19211288 No free full text.

This publication has no abstract.

Berthelot JM, Maugars Y. · Rheumatology Department, Nantes Teaching Hospital, 44093 Nantes cedex 01, France. · Joint Bone Spine. · Pubmed #15474387 No free full text.

Abstract: Although uncontrolled clones of autoreactive T cells play a central role in the pathogenesis of autoimmunity, another mechanism potentially involved in many autoimmune diseases is deficiency of suppressor T cells, most notably those belonging to the antiidiopeptide TH3/Tr1 TCD4+CD25+(high) subset. Failure of suppressor mechanisms may be in part primary, due to defective positive selection of suppressor T cells in the thymus, and in part acquired, secondary to chronic infections promoted by deficiencies in innate immunity. Renewed interest in suppressor TCD4+ cells has generated plausible explanations for many events including paradoxical induction of autoimmune disorders by immunosuppressive agents or thymectomy. Insights into the physiology of these regulatory T-cell clones might suggest new treatment options, although many currently used drugs (including anti-TNF alpha agents) enhance the activity of several suppressor T-cell clones. Investigation of these suppressor clones in rheumatoid arthritis is still in its infancy and faces obstacles such as the need for identifying key clones in each individual patient and the presence of T-cell repertoire contraction. This last phenomenon exists at disease onset and may stem from early thymus dysfunction, which may also lead to a reduction in suppressor TCD4+ cell counts. Thus, although restoring deficient suppressor clones may provide a full recovery in animals, the high prevalence of T-cell repertoire contraction in humans with rheumatoid arthritis may severely limit the beneficial effects of this therapeutic approach.

Berthelot JM. · Rheumatology Unit, Nantes University Hospital, Nantes, France. · Reumatismo. · Pubmed #12649695 links to  free full text

Abstract: The concept of psoriatic arthritis (PsA) is not yet universally accepted. Indeed, few of the features said to be characteristic for PsA are pathognomonic, and a same patient can be classified as RA, SpA or PsA depending on the physician seen. The heterogeneity of PsA, the lack of significant differences in early-arthritis with and without psoriasis, and a pathogenesis somewhat different in PsA and psoriasis, also argue against the originality of PsA. Nevertheless, although PsA is possibly "just" a syndrome depending on the combination of numerous co-factors (perhaps shared with SpA and/or RA), its more achieved forms deserve to be segregated from other SpA and RA. Indeed, PsA best bridges the gap with SAPHO syndromes. Moreover, the profile of synovial cytokines seems somewhat different in PsA as compared to RA and SpA, and a special pattern of vascularisation has been confirmed by several teams which could account for the demonstrated link between trauma and some PsA onsets. Both the greater familial risk for PsA than for RA or psoriasis alone and the excessive paternal transmission of PsA strongly suggest a genetic background, although so far only MICA-A9 (expressed on gut epithelial cells) seems to be associated with susceptibility to PsA independently from psoriasis. To make further genetics studies informative, a careful selection of unequivocal cases of PsA is needed, which requires criteria selecting patients at the "top of the mountain" of PsA. One can expect that the sets of criteria proposed by McGonagle or Fournié could satisfy this wish.

Berthelot JM, Bataille R, Maugars Y, Prost A. · Rheumatology Department, Nantes Teaching Hospital, France. · Rev Rhum Engl Ed. · Pubmed #10526382 No free full text.

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Berthelot JM, Huguet D, Gouin F, Letenneur J, Bertrand-Vasseur A, Moreau A, Lemaitre R, Maugars Y, Prost A. · Rheumatology Department, Nantes Teaching Hospital, France. · Rev Rhum Engl Ed. · Pubmed #10418067 No free full text.

Abstract: We report a case of recurrent multiple bursitis (19 episodes at nine sites) requiring seven surgical procedures in a European women with a 38-year history of severe, nodular, destructive seropositive rheumatoid arthritis unresponsive to second-line drugs. The episodes of bursitis were not correlated with activity of the joint disease. Some cysts migrated over a considerable distance. At least two cysts contained chylous fluid. The histologic study of one cyst demonstrated a cholesterol crystal granuloma. Potential relationships linking cholesterol crystals, chylous cysts, and migrating multiple bursitis are discussed. The relevant literature is reviewed.

Berthelot JM, Saraux A, Maugars Y, Prost A, Le Goff P. · Rheumatology Department, Brest Teaching Hospital, France. · Rev Rhum Engl Ed. · Pubmed #10339779 No free full text.

This publication has no abstract.

Devauchelle Pensec V, Saraux A, Berthelot JM, Alapetite S, Jousse S, Chales G, Thorel JB, Hoang S, Nouy-Trolle I, Martin A, Chiocchia G, Youinou P, Le Goff P. · Unit of Rheumatology and the Laboratory of Immunology, Hôpital de la Cavale Blanche, CHU Brest, Brest, France. · J Rheumatol. · Pubmed #14705220 No free full text.

Abstract: OBJECTIVE: In a cohort of patients with early arthritis, to evaluate how well foot radiographs at study inclusion predicted a diagnosis of rheumatoid arthritis (RA) 2 years later. METHODS: A cohort of patients with arthritis of less than one year duration was evaluated in a multicenter study and followed for 30 +/- 11 months. An observer blinded to patient data read all 149 hand and foot radiographs done at study inclusion, using item 7 of the 1987 American College of Rheumatology (ACR) criteria for RA and Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for the 1987 ACR item 7 was 0.52 for bony decalcification and 0.87 for erosions. Intra and interobserver correlation coefficients for Sharp's scores ranged from 0.90 to 0.98. Erosions at the feet were significantly associated with RA. The item 7 erosion component at the feet was more specific than the full item 7 (97.5% vs 94%; p = 0.01). Sharp's erosion score at the feet was not better than the erosion component of item 7 (sensitivity 18%; specificity 97.5%). Combined use of radiographs of the hands and feet improved the diagnostic performance of the item 7 erosion component; (sensitivity and specificity of item 7 erosions at the hands combined with the feet were 32.5% and 94.5%, respectively). CONCLUSION: The "erosion" criterion at the feet had the best diagnostic performance and was significantly associated with a diagnosis of RA. Combining hand and foot radiographs improved diagnostic performance.

Fautrel B, Guillemin F, Meyer O, de Bandt M, Berthelot JM, Flipo RM, Lioté F, Maillefert JF, Wendling D, Saraux A, Combe B, Le Loët X, Anonymous00044, Anonymous00045, Anonymous00046. · Department of Rheumatology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Arthritis Rheum. · Pubmed #19333993 No free full text.

Abstract: OBJECTIVE: To survey rheumatologists' preferences for the choice of a second-line disease-modifying antirheumatic drug (DMARD) after inadequate response with methotrexate (MTX) therapy in rheumatoid arthritis (RA). METHODS: Thirty-six rheumatologists stated their preferences for RA treatment after inadequate response with MTX therapy (optimal dose at least 6 months). From the initial scenario, we derived 54 vignettes varying by rheumatoid factor or anti-cyclic citrullinated peptide antibody presence, swollen joint count, Disease Activity Score in 28 joints, and structural damage. Respondents stated their preference among 5 therapeutic options: MTX continuation, switch to another conventional DMARD, addition of another conventional DMARD, addition of anakinra, or addition of a tumor necrosis factor (TNF) blocker. Presentation by pairs yielded 10 combinations of strategies for each variant, totaling 540 vignettes; participants evaluated a random sample of 180 vignettes. Determinants of each top-ranked option were analyzed by logistic regression. The compilation of these data served to define a therapeutic algorithm. RESULTS: The responses of 33 rheumatologists were analyzable. Therapeutic preferences corresponded to the top-ranked options. For patients with mild or moderately active RA, either a switch or step-up strategy to another conventional DMARD was top ranked. TNF blockers were preferred for RA patients with high disease activity or progressive structural damage. On the basis of these preferences, we developed a simple decision tree for use in daily clinical practice. CONCLUSION: Our simple, easy-to-use decision tree developed from rheumatologists' preferences for therapy after failure of MTX therapy in RA treatment may guide rheumatologists in daily practice to choose a second-line DMARD.

Berthelot JM, De Bandt M, Goupille P, Solau-Gervais E, Lioté F, Goeb V, Azaïs I, Martin A, Pallot-Prades B, Maugars Y, Mariette X, Anonymous00064. · Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, 44093, Nantes Cedex 01, France. · Joint Bone Spine. · Pubmed #19059799 No free full text.

Abstract: OBJECTIVE: To report on the outcome of 15 cases of pregnancies in women treated with anti-TNF drugs during conception or pregnancy METHODS: French rheumatologists connecting to the web-site of CRI site: http://www.cri-net.com were asked to fill in a structured questionnaire reporting the outcome of pregnancy in women still treated by a TNF blocker at the time of conception. RESULTS: Spondylarthropathies (n=8), rheumatoid arthritis (n=4), juvenile idiopathic arthritis (n=2), and psoriatic arthritis (n=1) were treated by infliximab (n=3), adalimumab (n=2), or etanercept (n=10). Miscarriages occurred twice, and elective termination was preferred once. Anti-TNF had been administered during the first, second and third trimester of pregnancy in 12, three and two cases. The 12 babies were in good condition, without apparent malformation or symptoms of neonatal illnesses. CONCLUSION: The number of reported cases exceeds 300, but only 29 women were treated during their whole pregnancy. The rate of congenital malformations observed so far might appear reassuring compared to the general population for women exposed only during conception. Conversely, there are too few reports of exposure during pregnancy to allow any conclusion about the safety of TNF blockers, and additional long term follow-up of children would be welcome in order to rule out minor forms of VACTERL association that might have been overlooked at birth.

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.

Morel J, Deschamps V, Toussirot E, Pertuiset E, Sordet C, Kieffer P, Berthelot JM, Champagne H, Mariette X, Combe B. · Department of Immuno-Rheumatology, Montpellier I University and Lapeyronie Teaching Hospital, 34295 Montpellier, Cedex 5 France. · Ann Rheum Dis. · Pubmed #17604284 No free full text.

Abstract: OBJECTIVE: To date, only a few series of patients with paraneoplastic arthritis have been published. The charts of patients with cancer-associated arthritis were collected in order to describe characteristics of this rheumatism. METHODS: A questionnaire was created for this study and validated by experts based on specific criteria of inclusion and exclusion. Histology of neoplasia was included. RESULTS: In all, 16 males and 10 females with a mean (range) age of 57.5 years (28-85) were recruited from 17 nationwide centres in France. Patients presented with symmetric polyarthritis involving wrists and hands (85%) and extra-articular symptoms were frequent (84%). There was no specific biologic or radiographic feature. The mean (range) delay between the diagnosis of rheumatism and neoplasia was 3.6 months (0-21.2). Tumours were usually diagnosed after articular symptoms occurred (88.5%). Twenty patients had a solid cancer, and six a haematological malignancy. Adenocarcinoma of the lungs was the most frequent type of solid cancer (60%). Tumours were diagnosed at an early stage, which may explain the good median survival of 1.21 years (range 0.64-present) with a mean follow-up of 1.9 years (range 0.16-10). The percentage of articular symptoms resolution was significantly higher in patients with solid tumours, as compared to patients with haemopathy (p = 0.007). In cases of tumour relapse, rheumatic symptoms did not recur for 75% of patients. CONCLUSIONS: Underlying neoplasia should be considered in male patients with new onset polyarthritis, smokers, and particularly in patients chronically ill. Additional investigations should then be performed to diagnose cancer at an early stage.

Berthelot JM, Varin S, Cormier G, Tortellier L, Guillot P, Glemarec J, Maugars Y. · Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, Nantes Cedex 01, France. <> · Joint Bone Spine. · Pubmed #17337351 No free full text.

Abstract: OBJECTIVE: To assess the clinical results at 6 months of etanercept 25 mg once weekly (half-dose), and etanercept 25 mg twice weekly (full-dose), in patients with rheumatoid arthritis or spondylarthropathy. METHODS: Case records of all patients treated by etanercept for at least 6 months in the same rheumatology unit were retrospectively studied, to assess the mean values of DAS-28 and BASDAI, just before (J0), and after 6 months (M6) of treatment, in patients with rheumatoid arthritis or spondylarthropathy treated with etanercept 25 mg given either once or twice weekly. RESULTS: 112 patients had been treated for at least 6 months (44 at half-dose, and 68 at full-dose). Values of DAS-28 or BASDAI both at J0 and M6 were available in 92 patients. DAS-28 dramatically improved both in the half-dose group (from 5.2+/-0.8 to 3.5+/-0.8) and in the full-dose group (from 5.5+/-1.0 to 4.1+/-1.0). BASDAI also strikingly improved both in the half-dose group (from 60+/-13 to 25+/-18), and in the full-dose group (from 58+/-15 to 37+/-23). CONCLUSION: Although this was not a double-blind, prospective, randomised study, the strong improvement noticed in the half-dose group suggests that etanercept 25 mg once a week can induce major clinical and biological relief in some patients with RA or spondylarthropathy.

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.

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.

Ornetti P, Solau E, Gaudin P, Sibilia J, Berthelot JM, Puechal X, Tavernier C, Maillefert JF, Anonymous00229. · No affiliation provided · Ann Rheum Dis. · Pubmed #16100349 links to  free full text

This publication has no abstract.

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.

Berthelot JM. · Department of Rheumatology, CHU Nantes, 44093, Nantes Cedex 01, France. · Med Hypotheses. · Pubmed #15142643 No free full text.

Abstract: The lack of some suppressor T cells (including TCD4+CD25+(high) positively selected first in thymic medulla) specific to a restricted set of autoantigens may be the common link between all patterns of rheumatoid arthritis. In other words, instead of a 'peak' of TCD4+ effector T cells common to all patients with rheumatoid arthritis (which has so far never been demonstrated), a 'hole' in TCD4+CD25+(high) responses towards a limited set of autoantigens responsible for the normal maintenance of tolerance within the joints may be shared by many patients with rheumatoid arthritis. The hallmark of this disorder is the involvement of tissues subjected to friction stress bathed in a lubricating fluid (rheumatoid nodules and bursae, tendinous sheaths, pleura, pericardium, sclera, and joints covered by hyaline cartilage). Consequently, autoantigens shared by all forementioned places may be better candidates than autoantigens restricted to the hyaline cartilage (like collagen II). Tenosynovitis, bursitis and rheumatoid nodules can herald rheumatoid arthritis, and rheumatoid pericarditis is very frequent at the histological level. Lubricin and superficial zone protein (SZP), which are closely related products of the megacaryocyte stimulating factor (MSF) gene, are among the best candidate autoantigens for such a positive selection of suppressor T cells. Lubricin is responsible for most of the lubricating properties of synovial fluid, and SZP (expressed by the superficial articular chondrocytes from diarthrodial cartilages and lining cells of synovial villi) also shares lubricating and cytoprotective properties. Moreover, the expression of lubricin is very probable in pericardium and pleura, and can be induced by friction stress. Although this mucinous glycoprotein may already share close similarities at the antigenic levels with mucins previously demonstrated in Hassall's corpuscles of the thymus, evidence for the ectopic expression of lubricin/SZP within normal human thymus may further support this hypothesis. The prenatal positive selection within the thymus of a functional pool of TCD4+CD25+(high) clones specific for most peripheral tissues is critical (at least in mice) for the quality of tolerance for the rest of the organism's lifespan. Therefore, a poor expression of lubricin/SZP early in life within the human thymus may also favour a lack of suppressor T cells specific to tissues bathed with synovial fluid, i.e. the onset of rheumatoid arthritis later on in life. As studies of human thymus long before the onset of rheumatoid arthritis are hampered for obvious reasons, studies of murine thymus could be a first step. In as much as the human counterpart of lubricin is expressed in the thymic medulla of mice, the generation of knocked-out mice for its expression within the thymus could be one of the best models to test the above hypothesis. The stimulation of TCD4+CD25+(high) clones specific for immunodominant epitopes from the joints/synovial fluid (belonging perhaps to lubricin or SZP) could help restore a normal balance between effector T cells and suppressor T cells in rheumatoid arthritis patients.

Saraux A, Berthelot JM, Devauchelle V, Bendaoud B, Chalès G, Le Henaff C, Thorel JB, Hoang S, Jousse S, Baron D, Le Goff P, Youinou P. · Unit of Rheumatology and the Laboratory of Immunology, Hôpital de la Cavale Blanche, CHU Brest, BP 824, F-29609 Brest-Cedex, France. · J Rheumatol. · Pubmed #14719190 No free full text.

Abstract: OBJECTIVE: To compare the diagnostic values of antiperinuclear factor (APF), antikeratin antibody (AKA), and anti-cyclic citrullinated peptides (anti-CCP) to discriminate between patients with and without rheumatoid arthritis (RA) and to determine the diagnostic value of anti-CCP used alone or with other tests. METHODS: Two hundred and seventy patients with early arthritis underwent standardized investigations in 1995-1997. The clinical utility of APF, AKA, and anti-CCP in first-visit sera was evaluated using receiver-operating characteristic curves. Combinations of anti-CCP with other laboratory tests were assessed by multiple logistic regression. RESULTS: Anti-CCP, APF, and AKA were not perfectly correlated with one another. Anti-CCP with 53 UI as the cutoff was 47% sensitive and 93% specific, versus 52% and 79%, and 47% and 94%, for APF and AKA, respectively. Multiple logistic regression selected anti-CCP, AKA, IgM-rheumatoid factor (RF) ELISA, and the latex test. CONCLUSION: Rheumatologists can routinely use 2 or 3 tests for diagnosing RA (latex and/or IgM RF ELISA, and either AKA or anti-CCP ELISA) and can add a third or fourth test when the diagnosis remains in doubt.

Berthelot JM, Saulquin X, Coste-Burel M, Peyrat MA, Echasserieau K, Bonneville M, Houssaint E. · Rheumatology Unit, CHU Nantes, Nantes, France. · J Rheumatol. · Pubmed #12913921 No free full text.

Abstract: OBJECTIVE: To assess in a longitudinal 15 month followup study the CD8 T cell response to immunodominant Epstein-Barr virus (EBV) antigens of 17 patients with rheumatoid arthritis (RA); and to seek an association between these responses and both clinical activity/severity of RA and a qualitative PCR for EBV in peripheral blood. METHODS: At each patient's visit every 3 months: (1) RA activity was assessed for Disease Activity Score (DAS-28); (2) a qualitative PCR for EBV was performed; (3) CD8 T cell response to EBV epitopes was screened in peripheral blood, using an autopresentation assay of 13 EBV peptides previously identified as immunodominant targets in RA synovia. Activation of anti-EBV CD8 T cells was evaluated by measuring the release of tumor necrosis factor-a. RESULTS: The semiquantitative CD8 T cell response to EBV roughly paralleled RA clinical activity in only 4/17 patients. No clear association could be found between positive PCR for EBV (performed at least once in 10/17 patients) and RA activity/severity or fatigue. Reactivity was not qualitatively broader in samples where PCR for EBV proved positive, and most often focused on one or 2 EBV antigens. However, these antigens differed between patients, as did the magnitude of CD8 T cell response to immunodominant antigens at different timepoints for the same patient. CONCLUSION: The CD8 T cell response to EBV paralleled clinical activity in only 4/17 patients. Our pilot study does not support the hypothesis that this CD8 response contributes to RA activity/flares, although the quantitative variations in the pattern of this reactivity over time confirmed that control of EBV manifestations was difficult in most patients with RA.

Berthelot JM, Bernelot-Moens HJ, Klarlund M, McGonagle D, Calin A, Schumacher HR, Combe B, De Bandt M, Drosos AA, Flipo RM, Harris BJ, Kaarela K, Le Goff P, Meyer O, Punzi L, Zerbini CA, Saraux A, Anonymous00207. · Department of Rheumatology, Nantes University Medical School, CHU Nantes, France. · Clin Exp Rheumatol. · Pubmed #12051392 No free full text.

Abstract: OBJECTIVES: To determine areas of agreement and disagreement among experts in the interpretation of the published criteria for RA (ACR) and spondylarthropathies ( ESSG). METHODS: Thirty-two experts (16 from France and 16 from 10 other countries) replied anonymously to a mailed questionnaire. RESULTS: Tenosynovitis and 'sausage-like' painless swelling of the toes were considered as criteria for RA by 18 and 14 experts, respectively. The definition of symmetry differed widely among experts (symmetry of only one group of joints was sufficient for 13). Twenty-five experts considered erosions of other joints than the wrists and fingers as a criterion for RA, 17 thought that fulfilment of criteria could be achieved cumulatively, and 19 would appreciate clarifications of the current criteria. Among possible clarifications for RA, it was frequently recommended that morning stiffness and nodules be eliminated and that new marker antibodies, X-rays of the feet, and exclusion criteria be added. Twenty-three of the 29 experts who gave an opinion (79%) agreed with the notion of SP in the absence of axial signs and sacroiliitis, 26/31 (84%) indicated that a patient can have both RA and SP, and 19/30 (63%) thought that RA and SP could be regarded as syndromes more than diseases. Only 5/32 experts relied more on the criteria than on their clinical judgement in diagnosing RA. CONCLUSIONS: There would seem to be a needfor the optimisation of RA and ESSG criteria, particularly within the context of early arthritis.

Laborie Y, Berthelot JM, Alliaume C, Baron J, Caumon JP, Desmas V, Rossard A, Maugars Y, Prost A. · Rheumatology Department, Hôtel-Dieu, CHU Nantes, France. · Joint Bone Spine. · Pubmed #12027310 No free full text.

Abstract: OBJECTIVE: To determine the very long-term clinical and functional outcomes in rheumatoid arthritis (RA) patients followed by office-based or hospital-based physicians. PATIENTS AND METHODS: A questionnaire including items on clinical outcomes (active disease, remission, burn-out) and the Health Assessment Questionnaire (HAQ) was mailed to 122 patients with RA of at least 15 years' duration; 61 were followed by office-based physicians and 61 by hospital-based physicians. In the 88 (72%) respondents, mean age was 63 +/- 13 years and mean disease duration was 20.1 +/- 8.7 years. RESULTS; None of the patients experienced burn-out of their disease, and only six (7%) met Pinals' remission criteria. However, 23 (26%) reported a current subjective remission with a mean duration of 8.5 +/- 5.9 months. Although the mean pain score in the 88 patients was 4.1 +/- 2.3, only 50 (56%) patients reported a physician visit during the last 6 months. HAQ scores varied widely, the mean being 1.11 +/- 0.84. Forty (46%) patients had a history of arthroplasty (knee or hip in 29 (33%)). Of the 34 nonrespondents, seven had died (at a mean age of 74 years), and in four of these seven the cause of death was infection or immobility-related complications; in the 27 survivors, disease activity was considered minimal by the physicians or patients, 11 (41%) patients believed they were in remission, and mean time since the last physician visit was 3.9 years. Conclusion. Although burn-out within 20 years of RA onset seems exceedingly rare, clinical activity is milder than in early RA; over one-fourth of our patients believed they were in remission and over one half had not seen a physician during the last 6 months. Functional outcomes varied widely across patients but were acceptable overall, a result that is partly ascribable to the favorable effects of surgery. No differences in functional outcomes were found between patients followed by office-based physicians and those followed by hospital-based physicians.

Saraux A, Berthelot JM, Chalès G, Le Henaff C, Mary JY, Thorel JB, Hoang S, Dueymes M, Allain J, Devauchelle V, Baron D, Le Goff P, Youinou P. · Rheumatology Unit, Hôpital de la Cavale Blanche, Brest, France. · Arthritis Rheum. · Pubmed #11954009 No free full text.

Abstract: OBJECTIVE: To determine which laboratory test or tests at presentation best predicted a diagnosis of rheumatoid arthritis (RA) 2 years later. METHODS: Two hundred seventy patients with early arthritis seen in 7 hospitals underwent comprehensive evaluations at 6-month intervals for 2 years, when the diagnosis of RA was assessed by 5 rheumatologists. The sensitivity and specificity of each test at the first visit for discriminating between RA (38%, n = 98) and non-RA patients were determined. Optimal cutoffs for continuous tests were derived from receiver operating characteristic curves. Sensitivity and specificity of test combinations selected by multiple logistic regression were determined. RESULTS: IgM rheumatoid factor (RF) by enzyme-linked immunosorbent assay, IgG-antikeratin antibody (AKA), and latex test had the strongest associations with RA. These 3 tests formed the most powerful combination for distinguishing RA from non-RA. CONCLUSION: IgM-RF, IgG-AKA, and the latex test are the best laboratory tests for discriminating between patients with and without RA. Combining these tests slightly improves diagnostic value.

Saraux A, Berthelot JM, Chalès G, Le HC, Thorel J, Hoang S, Martin A, Allain J, Nouy-Trolle I, Devauchelle V, Youinou P, Le GP. · Rheumatology department of Brest, hĵpital de la Cavale-Blanche, France. · Joint Bone Spine. · Pubmed #11858354 No free full text.

Abstract: OBJECTIVE: The management of recent-onset rheumatoid arthritis (RA) is not well standardized. We conducted a survey of drugs prescribed to RA patients in Brittany at presentation and during the first 1 to 3 years of follow-up. METHODS: A cohort of 270 patients with recent-onset inflammatory joint disease was recruited between 1995 and 1997. The evaluation at presentation included a medical history, a thorough physical examination, and a standard battery of investigations. Follow-up at 6-month intervals was offered. At the last visit, between June and December 1999, a panel of five rheumatologists established that 98 patients had RA. RESULTS: At presentation, hydroxychloroquine and injectable gold were the most widely used second-line drugs, and only two patients were offered a combination of second-line drugs. At the last visit, the most commonly used drugs were methotrexate, injectable gold, and hydroxychloroquine (23, 23, and 21 patients, respectively); only three patients were on more than one second-line drug and 38 (38/98, 39%) patients were on glucocorticoid therapy. CONCLUSION: Rheumatologists in Brittany prefer monotherapy with hydroxychloroquine or injectable gold as the initial treatment. Later, they rely mainly on methotrexate, injectable gold, and hydroxychloroquine, often in combination with glucocorticoid therapy.

Devauchelle Pensec V, Saraux A, Berthelot JM, Alapetite S, Chalès G, Le Henaff C, Thorel JB, Hoang S, Nouy-Trolle I, Martin A, Baron D, Youinou P, Le Goff P. · Unit of Rheumatology and the Laboratory of Immunology, Hôpital de la Cavale Blanche, Brest, France. · J Rheumatol. · Pubmed #11764204 No free full text.

Abstract: OBJECTIVE: To evaluate the ability of hand radiographs collected at study inclusion to predict a diagnosis of rheumatoid arthritis (RA) 2 years later, in a cohort of patients with early arthritis. METHODS: We evaluated 270 patients with arthritis of less than one year duration. At the first visit, all patients underwent a standardized evaluation including laboratory tests and radiographs. Followup was 30+/-11.3 mo. The hand radiographs were read by observers blinded to patient data who looked for item 7 of the 1987 ACR criteria for RA and used Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for ACR item 7 was < 0.65 for bony decalcification and > 0.8 for erosions. Intra and interobserver correlation coefficients for Sharp score ranged from 0.90 to 0.95. The "erosion" component of ACR item 7 was more specific than the full item 7 (96% versus 87.5%; p = 0.02). Sharp erosion score was not better than the erosion component of item 7 (sensitivity 17%; specificity 96%). CONCLUSION: Regardless of the criterion used, hand radiographs were of limited value to predict which patients would be considered as having RA 2 years later. Diagnostic performance was similar for the "erosions" component of the 1987 ACR item 7 and for Sharp erosion score. The full 1987 ACR item 7 (erosions or bony decalcification) performed less well.

Saraux A, Berthelot JM, Chalès G, Le Henaff C, Thorel JB, Hoang S, Valls I, Devauchelle V, Martin A, Baron D, Pennec Y, Botton E, Mary JY, Le Goff P, Youinou P. · Rheumatology Unit, la Cavale Blanche Hospital, Brest Teaching Hospital, France. · Arthritis Rheum. · Pubmed #11710704 No free full text.

Abstract: OBJECTIVE: To determine how well the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 classification criteria for rheumatoid arthritis (RA), when used at study inclusion in a cohort of 270 patients with early (<1 year) arthritis, predicted a diagnosis of RA 2 years later and how well they classified these patients at the end of the 2 years. METHODS: Patients were evaluated during 1995-1997 at 7 hospitals in the Brittany region of France. Patients were evaluated at 6-month intervals until November 1999. The diagnosis made by a panel of 5 rheumatologists (P5R) after the last visit was used as the "gold standard." The ACR 1987 criteria for RA were applied prospectively, without taking into account the initial diagnosis. RESULTS: At the last visit (mean +/- SD followup 29.1 +/- 11.8 months; median 30 months), the P5R diagnosed RA in 98 patients. At the last visit, classification by the ACR criteria was satisfactory, and the combination of an office-based rheumatologist's (OBR's) diagnosis of RA and fulfillment of the ACR criteria was sensitive (87%; 85 of 98 RA patients had both) and highly specific (99%; 170 of 172 non-RA patients did not have both). Application of the criteria at the first visit was of limited value for predicting a diagnosis of RA 2 years later. CONCLUSION: After a 2-year followup, the ACR 1987 classification criteria used in combination with an OBR's diagnosis were effective in distinguishing patients with and without RA. The criteria were not useful for predicting RA in patients with arthritis onset within the previous year. Some patients who met the criteria at baseline and after 2 years did not have RA, suggesting that incorporating exclusion criteria may improve the performance of the ACR criteria when used without taking into account the diagnosis by a rheumatologist, particularly in early arthritis.