Rheumatoid Arthritis: France

Fautrel B, Pham T, Mouterde G, Le Loët X, Goupille P, Guillemin F, Ravaud P, Cantagrel A, Dougados M, Puéchal X, Sibilia J, Soubrier M, Mariette X, Combe B, Anonymous00061, Anonymous00062. · Pierre and Marie Curie University - Paris VI, UFR de Médecine, France. · Joint Bone Spine. · Pubmed #18037319 No free full text.

Abstract: OBJECTIVES: To update French Society for Rheumatology guidelines regarding the use of TNFalpha antagonists for treating patients with rheumatoid arthritis (RA). METHODS: Existing guidelines were updated using the AGREE instrument. Items that required updating were selected by a task force, the relevant literature was critically appraised, and new wording was suggested by a limited committee of experts then validated by the task force and subsequently by a panel of external reviewers. The three-topic structure of the recommendations (indication, initiation, and adjustment) and the final algorithm format were maintained. RESULTS: Of the 12 items, five were selected for updating; one pertained to the indication for treatment with TNFalpha antagonists, two to treatment initiation, and two to treatment adjustment. Of the four initially recommended criteria for determining that TNFalpha antagonist therapy is indicated, the first three were left unchanged (confirmed diagnosis of RA; active disease for more than 1month with objective evidence of inflammation or progressive structural damage, or dependency on glucocorticoid therapy, or progressive radiographic damage; and failure to respond adequately to methotrexate - or another agent when methotrexate is contraindicated - in the optimal tolerated dosage). The fourth and last criterion was modified as follows: co-morbidities should be evaluated in order to distinguish absolute contraindications from relative contraindications that require referral to a specialist. Of the four initial recommendations about TNFalpha antagonist initiation, the first and fourth were left unchanged (a workup should be performed prior to treatment initiation, and the patient should receive regular standardized follow-up); the second and third recommendations were modified as follows: there is no evidence that one TNFalpha antagonist is more effective than the others, and concomitant methotrexate therapy is generally advisable, regardless of the TNFalpha antagonist used. Of the four recommendations about treatment adjustment, the first two were modified as follows: the goal of treatment is to achieve the EULAR response criteria or better; and in non-responders, the dosage or dosing interval can be modified when infliximab is used, methotrexate should be added when the TNFalpha antagonist is used alone, and in all other situations the patient should be switched to a different TNFalpha antagonist. The other two recommendations about treatment adjustment were left unchanged (patients who fail to tolerate one TNFalpha antagonist can be switched to another TNFalpha antagonist if allowed by the nature of the adverse event; and when a remission is achieved, reduction or discontinuation of symptomatic drugs - most notably glucocorticoids - is appropriate, followed in the event of a prolonged remission by changes in the dosage and/or dosing interval of the TNFalpha antagonist or concomitant disease-modifying drug). CONCLUSION: These recommendations are designed to help practitioners optimize the use of TNFalpha antagonists in patients with RA seen in everyday practice. They do not constitute regulations.

Combe B, Landewe R, Lukas C, Bolosiu HD, Breedveld F, Dougados M, Emery P, Ferraccioli G, Hazes JM, Klareskog L, Machold K, Martin-Mola E, Nielsen H, Silman A, Smolen J, Yazici H. · Immuno-Rhumatologie, Lapeyronie Hosp, Montpellier, France. · Ann Rheum Dis. · Pubmed #16396980 No free full text.

Abstract: OBJECTIVE: To formulate EULAR recommendations for the management of early arthritis. METHODS: In accordance with EULAR's "standardised operating procedures", the task force pursued an evidence based approach and an approach based on expert opinion. A steering group comprised of 14 rheumatologists representing 10 European countries. The group defined the focus of the process, the target population, and formulated an operational definition of "management". Each participant was invited to propose issues of interest regarding the management of early arthritis or early rheumatoid arthritis. Fifteen issues for further research were selected by use of a modified Delphi technique. A systematic literature search was carried out. Evidence was categorised according to usual guidelines. A set of draft recommendations was proposed on the basis of the research questions and the results of the literature search.. The strength of the recommendations was based on the category of evidence and expert opinion. RESULTS: 15 research questions, covering the entire spectrum of "management of early arthritis", were formulated for further research; and 284 studies were identified and evaluated. Twelve recommendations for the management of early arthritis were selected and presented with short sentences. The selected statements included recognition of arthritis, referral, diagnosis, prognosis, classification, and treatment of early arthritis (information, education, non-pharmacological interventions, pharmacological treatments, and monitoring of the disease process). On the basis of expert opinion, 11 items were identified as being important for future research. CONCLUSIONS: 12 key recommendations for the management of early arthritis or early rheumatoid arthritis were developed, based on evidence in the literature and expert consensus.

Salmon-Ceron D, Anonymous00085, Anonymous00086. · Service de Médecine Interne, Hôpital Cochin, Paris. · Ann Med Interne (Paris). · Pubmed #12598827 No free full text.

Abstract: An unusually large number of cases of tuberculosis, often with miliary or widespread dissemination, has been reported in patients taking infliximab for rheumatoid arthritis or Crohn's disease. Recommendations have been issued in France regarding the definition of high-risk patients, the screening methods to be used in these patients, and possible prophylactic treatments. The present update is also intended to help physicians manage tuberculosis occurring before or during infliximab therapy.

Wautier JL, Schmid-Schönbein GW, Nash GB. · Institut National de la Transfusion Sanguine, Paris, France. · Clin Hemorheol Microcirc. · Pubmed #10517484 No free full text.

Abstract: The measurement of leukocyte rheology in vascular disease is a recent development with a wide range of new opportunities. The International Society of Clinical Hemorheology has asked an expert panel to propose guidelines for the investigation of leukocyte rheology in clinical situations. This article first discusses the mechanical, adhesive and related functional properties of leukocytes (especially neutrophils) which influence their circulation, and establishes the rationale for clinically-related measurements of parameters which describe them. It is concluded that quantitation of leukocyte adhesion molecules, and of their endothelial receptors may assist understanding of leukocyte behaviour in vascular disease, along with measurements of flow resistance of leukocytes, free radical production, degranulation and gene expression. For instance, vascular cell adhesion molecule (VCAM-1) is abnormally present on endothelial cells in atherosclerosis, diabetes mellitus and inflammatory conditions. Soluble forms of intercellular adhesion molecule (ICAM-1) or VCAM can be found elevated in the blood of patients with rheumatoid arthritis or infections disease. In the second part of the article, possible technical approaches are presented and possible avenues for leukocyte rheological investigations are discussed.

Roudier J. · INSERM UMR 639, Université de la Méditerranée,13005, Marseille, France. · Arthritis Res Ther. · Pubmed #16542468 links to  free full text

Abstract: The factors that trigger the development of extraarticular features of rheumatoid arthritis (RA) are still unknown. HLA-DR alleles such as HLA-DR4 and HLA-DR1 are associated with the risk to develop RA. A large scale study from Sweden and the Mayo Clinic suggests that HLA-DR4, but not HLA-DR1, is associated with the risk to develop extraarticular RA.

Guillevin L. · Service de Médecine Interne, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris René Descartes, Paris, France. · Rheumatology (Oxford). · Pubmed #19487226 No free full text.

Abstract: Vasculitis can occur either as a primary condition or secondary to CTDs, infection, medication or malignancy. This article reviews the clinical presentation and management of vascular disease associated with SLE and SS, as well as the primary necrotizing vasculitides. Although pulmonary arterial hypertension (PAH) has traditionally been considered a rare complication of SLE, estimates of its prevalence range from 0.5% to 14% and it has a significant impact on prognosis. In contrast to PAH associated with other CTDs, patients with SLE respond well to immunosuppressive agents (cyclophosphamide in conjunction with corticosteroids). Improvements or stabilization of PAH symptoms and quality of life have also been observed with the oral, dual endothelin receptor antagonist, bosentan. SS is associated with a range of cutaneous and systemic signs of vasculitis. Immunosuppressive agents are effective, but are associated with an increased risk of lymphoma. The necrotizing vasculitides include WG, Churg-Strauss syndrome and microscopic polyangiitis, and are characterized by autoantibodies to neutrophil cytoplasmic constituents. WG is one of the most common forms of vasculitis; patients usually present with signs of respiratory disease. All three necrotizing vasculitides respond to cyclophosphamide and corticosteroids, while the less toxic AZA and MTX are effective for maintenance therapy. Future therapeutic approaches may include rituximab, plasma exchanges, the TNF antagonist infliximab and haematopoietic stem cell transplantation.

Kieffer C, Cribier B, Lipsker D. · The Université Louis Pasteur, Hôpitaux Universitaires, Strasbourg, France. · Medicine (Baltimore). · Pubmed #19352297 No free full text.

Abstract: We conducted the current study to define within the spectrum of the neutrophilic dermatoses a group of patients with an urticarial rash clinically and a neutrophilic dermatosis histopathologically. We reviewed the literature on neutrophilic urticaria and we report here a series of patients with this unique presentation. We reviewed all cutaneous biopsies submitted to our department between 2000 and 2006 in which histopathologic evaluation was compatible with this entity. We then retrieved the patient medical records and obtained information about follow-up and associated diseases. This allowed us to identify 9 patients with an urticarial eruption that was characterized histopathologically by a perivascular and interstitial neutrophilic infiltrate with intense leukocytoclasia but without vasculitis and without dermal edema. Four patients also had small foci of necrobiotic collagen bundles. The eruption consisted of pale, flat or only slightly raised, nonpruritic macules, papules, or plaques. Elementary lesions resolved within 24 hours. Purpura, angioedema, and facial swelling were not seen, but dermographism was present in 1 patient. Six patients had fever, 7 had polyarthritis, and 6 had leukocytosis. Seven patients had associated systemic diseases: adult-onset Still disease (3 patients), systemic lupus erythematosus (3 patients), and Schnitzler syndrome (1 patient).A similar rash has been reported previously in the literature, mostly in patients with systemic inflammatory diseases, but the majority of patients reported under the undefined designation of "neutrophilic urticaria" did have a different clinicopathologic presentation. Thus, we suggest naming this eruption "neutrophilic urticarial dermatosis," to emphasize that this entity expands the broad group of cutaneous manifestations of neutrophilic aseptic disease. This entity bears important medical significance as it is strongly indicative of an associated systemic disease, mainly Schnitzler syndrome, adult-onset Still disease, lupus erythematosus, and the hereditary autoinflammatory fever syndromes.

Monteleone G, Pallone F, Macdonald TT. · Department of Internal Medicine, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy. · Cytokine Growth Factor Rev. · Pubmed #19261537 No free full text.

Abstract: Interleukin-21 (IL-21) is produced mostly by activated CD4+ T cells and controls the differentiation and functional activity of effector T helper cells, counteracts the suppressive effects of regulatory T cells, and stimulates non-immune cells to make inflammatory mediators. IL-21-driven tissue damage has been demonstrated in a number of organs, such as the gut, pancreas, and brain. Therefore new treatment modalities to neutralise IL-21 in vivo would be a valuable addition to the therapeutic armamentarium to combat immune-mediated inflammation. Here we describe the emerging role of IL-21 in the initiation and progress of the tissue-damaging inflammatory response in immune-mediated pathologies.

Cyteval C. · University of Montpellier I, Department of Radiology, Lapeyronie Hospital, Montpellier, France. · Semin Musculoskelet Radiol. · Pubmed #19235673 No free full text.

Abstract: Rheumatoid arthritis (RA) activity is closely correlated with inflammation. The synovial membrane is the principal site of inflammation in which the inflammatory process enhances capillary perfusion and permeability. Doppler ultrasonography (DUS), using the amount of color pixels in the region of interest, and dynamic magnetic resonance imaging (DE-MRI), using the early enhancement rate and relative enhancement of the synovium, are both able to detect this inflammation in the wrist and hand. Although these techniques are both capable of monitoring synovium inflammation modifications after RA treatment, DE-MRI may be better for quantifying inflammation changes. It yields additional information about joint inflammation and complements clinical and biological examination, the current reference standard. DUS could become an essential tool for RA joint monitoring in routine practice in view of its sensitivity in the detection of synovitis, feasibility in outpatient clinics, and low cost, whereas DE-MRI could become a valid imaging gold standard against which other measures should be compared, especially in clinical trials.

Combe B. · Immuno-Rhumatologie, Hopital Lapeyronie, CHU de Montpellier, Montpellier I University, Montpellier, France. · Best Pract Res Clin Rheumatol. · Pubmed #19233046 No free full text.

Abstract: Rheumatoid arthritis (RA) is a very heterogeneous disease, the outcome of which is difficult to predict. The vast majority of the patients will have disease progression with bone erosions and cartilage breakdown resulting in joint destruction, functional impairment, and increased mortality. The management of RA to prevent and control disease progression has changed considerably in the past few years. The treatment goal should now be to achieve clinical remission in order to prevent structural damage and long-term disability. A very early use of effective disease-modifying anti-rheumatic drugs (DMARDs) is a key point in patients at risk of developing persistent and erosive arthritis. Intensive treatment such as combination DMARDs plus steroids or mainly biological therapies can induce high rates of remission and control of radiological progression, and can provide better outcomes than DMARD monotherapy in early RA, and should be considered very early in at-risk patients. In addition, close monitoring of disease activity and radiographic progression is mandatory in order to adapt DMARD therapy and strategy if necessary.

Mouterde G, Carotti M, D'Agostino MA. · Service de rhumatologie, Hôpital Ambroise Paré, 92100 Boulogne-Billancourt, France. · J Radiol. · Pubmed #19212282 No free full text.

Abstract: Contrast-enhanced US (ultrasonography) can be used for the study of musculoskeletal diseases but this application still belongs to clinical research. Despite a theoretical value for the identification of microvascularity, the technical limitations of musculoskeletal US are challenging the use of contrast enhanced US. This can explain the slow development of this application and the reason why it remained limited to the assessment of Doppler signal intensity increase. However, the recent availability of real time contrast-enhanced US imaging and quantification data is very promising. The majority of published papers involves rheumatoid arthritis and demonstrates the value of this technique to improve diagnosis, stage the activity of the disease and follow the patients under therapy. These preliminary studies are extending to other disorders (inflammatory arthritides as well as degenerative disorders). Structures other than articular synovium are undergoing investigations (bone, enthesis). New applications are being developed such as contrast-enhanced US of muscular diseases. This new imaging technique appears to have great potentials for the assessment of musculoskeletal diseases.

Fromont A, De Seze J, Fleury MC, Maillefert JF, Moreau T. · Department of Neurology, University Hospital of Dijon, 21000 Dijon, France. · Cytokine. · Pubmed #19109035 No free full text.

Abstract: BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine involved in certain inflammatory diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn's disease. The anti-TNF-alpha treatments used for RA may be associated with inflammatory demyelinating events affecting the central nervous system and may possibly aggravate known MS. OBJECTIVE: We report here three new cases of inflammatory demyelinating events of the central nervous system following treatment with anti-TNF-alpha. RESULTS: The neurological symptoms appeared on average 5 months after initiation of the treatment. For all patients, the inflammatory process was confirmed by brain magnetic resonance imaging. The symptoms totally or partially regressed as soon as anti-TNF-alpha treatment was stopped except for one patient who developed clinically defined MS. CONCLUSIONS: Inflammatory demyelination of the central nervous system may be associated with the use of anti-TNF-alpha. Patients with rheumatoid arthritis treated with these treatments should benefit from a follow-up which includes brain MRI.

Underner M, Hadjadj S, Beauchant M, Bridoux F, Debiais F, Meurice JC. · Unité de Tabacologie, CHU de Poitiers, France. · Rev Mal Respir. · Pubmed #19107017 No free full text.

Abstract: INTRODUCTION: In addition to being a major cardiovascular risk factor, smoking promotes or worsens thyroid, digestive, renal and bone diseases. BACKGROUND: Smoking is positively associated with hyperthyroidism. It is associated with Graves' disease and it especially increases the risk of the development of severe exophthalmos. In contrast, smoking might exert a protective action for thyroid carcinoma. Smoking increases the severity of hepatic lesions in patients with chronic hepatitis C. Smoking accelerates the progression of primary biliary cirrhosis and increases the risk of hepatocellular carcinoma. Smoking increases risk of both hyperplastic and adenomatous polyps. While Crohn's disease is associated with smoking, ulcerative colitis is largely a disease of non smokers. Smoking increases risk of development of both renal cell carcinoma and chronic nephropathies, particularly in types 1 and 2 diabetes. Smoking is a risk factor for decreased bone density and is associated with a significantly increased risk of fracture. Smoking is related to the development of rheumatoid arthritis and may adversely influence its severity. CONCLUSIONS: Smoking might be considered a risk factor for the development of several thyroid, digestive, renal and bone diseases. Consequently, smoking prevention and cessation programs must be strongly encouraged among the patients concerned.

Lioté H. · Service de Pneumologie et réanimation respiratoire, Hôpital Tenon, Paris, France. · Rev Mal Respir. · Pubmed #19107015 No free full text.

Abstract: The occurrence of tuberculosis (TB) in patients treated with immunosuppressive drugs (ISD) is an old problem that has been highlighted by cases occurring in patients using anti-TNFalpha drugs. After a brief review of anti-tuberculosis immunity to highlight the immunosuppressant targets, we show how an epidemiological approach allows the control of risk in patients with drug-induced immunosuppression. The assessment and the control of this risk are usually complicated by underlying immunosuppressant disease, co-morbidities, associated drugs and local disease prevalence. Steroid therapy in systemic diseases and ISD protocols in graft rejection prevention illustrate this problem particularly well. The management strategy adopted to combat anti-TNF related tuberculosis in rheumatoid arthritis (RA) has allowed these biases to be avoided. The incidence of TB in RA has been recorded in some national databases (USA, Spain). A four fold increase was registered after the introduction of anti-TNF agents in 2001 which could be considered as the true risk of the drug. Several national health agencies proposed guidelines to screen and prevent TB risk in these patients. Their effectiveness was confirmed by the incidence of TB returning the level prior to the introduction of these agents. Recommendations could be improved by using interferon-gamma screening tests and a better benefit/risk prophylaxis. They should be observed and if possible extended to new and other ISD.

Jouzeau JY, Moulin D, Koufany M, Sebillaud S, Bianchi A, Netter P. · UMR CNRS-Nancy Université, France. · J Soc Biol. · Pubmed #19094928 No free full text.

Abstract: Peroxisome proliferators activated receptors (PPAR) are ligand-inducible nuclear transacting factors comprising three subtypes, PPARalpha, PPARbeta/delta and PPARgamma, which play a key role in lipids and glucose homeostasis. All PPAR subtypes have been identified in joint or inflammatory cells and their activation resulted in a transcriptional repression of pro-inflammatory cytokines (IL-1, TNFalpha), early inflammatory genes (NOS(2), COX-2, mPGES-1) or matrix metalloproteases (MMP-1, MMP-13), at least for the gamma subtype. PPAR full agonists were also shown to stimulate IL-1 receptor antagonist (IL-1Ra) production by cytokine-stimulated articular cells in a subtype-dependent manner. These anti-inflammatory and anti-catabolic properties were confirmed in animal models of joint diseases where PPAR agonists reduced synovial inflammation while preventing cartilage destruction or inflammatory bone loss, although many effects required much higher doses than needed to restore insulin sensitivity or to lower circulating lipid levels. However, these promising effects of PPAR full agonists were hampered by their ability to reduce the growth factor-dependent synthesis of extracellular matrix components or to induce chondrocyte apoptosis, by the possible contribution of immunosuppressive properties to their anti-arthritic effects, by the increased adipocyte differentiation secondary to prolonged stimulation of PPARgamma, and by a variable contribution of PPAR subtypes depending on the system. Clinical data are scarce in rheumatoid arthritis (RA) patients whereas thousands of patients worldwilde, treated with PPAR agonists for type 2 diabetes or dyslipidemia, are paradoxically prone to suffer from osteoarthritis (OA). Whereas high dosage of full agonists may expose RA patients to cardiovascular adverse effects, the proof of concept that PPAR agonists have therapeutical relevance to OA may benefit from an epidemiological follow-up of joint lesions in diabetic or hyperlipidemic patients treated for long periods of time with glitazones or fibrates. Additionally, cellular and animal studies are required to assess whether partial agonists of PPAR (SPPARMs) may preserve therapeutical properties with potentially less safety concern.

Toussirot E, Streit G, Wendling D. · Department of Rheumatology, University Hospital Jean Minjoz, Bd. Fleming, F-25030 Besancon Cedex, France. · Recent Pat Inflamm Allergy Drug Discov. · Pubmed #19075965 No free full text.

Abstract: TNFalpha plays a pivotal role not only in the inflammatory process but also in the normal response against pathogens and therefore, interfering with this cytokine may increase the risk of infection. TNFalpha antagonists are commonly used in daily clinical practice for the treatment of inflammatory rheumatic diseases including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis since the beginning of 2000. The spectrum of pathogens giving infectious disease in patients under anti-TNFalpha therapies ranges from common bacteria to more opportunistic organisms such as Mycobacterium tuberculosis. The infections which were described with TNFalpha inhibitors may have a benign course or may be a serious, life threatening disease, and may be localized or disseminated. These TNFalpha inhibitors related infections were described in the randomized clinical trials, and were then declared to post-marketing surveillance systems and special registries. Tuberculosis (TB) is the most frequent opportunistic infection which has been reported with TNFalpha antagonists and the highest risk appears to be associated with infliximab, and at a lesser extent with etanercept. Currently available data and recent patents on the risk of TB with adalimumab are not sufficient to conclude, but TB cases were also reported with this agent. The description of TB infections with TNFalpha inhibitors led to the establishment of new guidelines for screening patients at high risk of developing TB. These data highlight the importance of post-marketing surveillance and special registries for accurately evaluating the safety profile and particularly the infectious risk of this very effective class of drug in inflammatory rheumatic diseases.

Salliot C, van der Heijde D. · Paris Descartes University, Medicine Faculty, Rheumatology B Department, Cochin Hospital, Paris, France. · Ann Rheum Dis. · Pubmed #19060002 links to  free full text

Abstract: OBJECTIVE: To perform a systematic literature review of the long-term safety of methotrexate (MTX) monotherapy in rheumatoid arthritis (RA). METHODS: A search was performed in Medline, Cochrane and EMBASE. Adults with RA who had received MTX monotherapy for more than 2 years were studied. RESULTS: 88 published studies were included. Over 12 years of treatment, the termination rate of MTX due to toxicity was less than for sulfasalazine, gold, d-penicillamine and higher than for hydroxychloroquine (level of evidence 2a-2b). Long-term use of MTX does not appear to be a risk factor for serious infections, including herpes zoster (2b-4), and could provide a survival benefit by reducing cardiovascular mortality (2b). The prevalence of raised liver enzymes (more than twice the upper limit of normal) is close to 13% of patients; 3.7% of patients stopped MTX permanently owing to liver toxicity (2b). Data on the risk for liver fibrosis/cirrhosis are conflicting: a meta-analysis showed an incidence of fibrosis of 2.7% after 4 years of MTX (2a). However, two other studies on sequential liver biopsies did not show evidence for developing severe damage (2b). Insufficient data are available to fully assess the risk of lymphoma and malignancies, although there is no strong evidence of increased risk (2b-4). CONCLUSION: This systematic literature search on MTX monotherapy with relatively low-dose use during at least 2 years shows favourable long-term safety.

Vittecoq O, Lequerré T, Goëb V, Le Loët X, Abdesselam TA, Klemmer N. · Department of Rheumatology, Rouen University Hospital & Inserm U905, Rouen, France. · Best Pract Res Clin Rheumatol. · Pubmed #19028372 No free full text.

Abstract: Smoking has an impact on the development and outcome of rheumatoid arthritis (RA) and lupus. In RA, smoking is associated with the development of the anti-cyclic citrullinated peptide (CCP2)-positive subset. This risk is increased in heavy smokers carrying at least one copy of the HLA DRB1 shared epitope (SE) alleles. Whereas this interaction between smoking and SE relevant in northern Europe, discrepant results have been observed in other geographic locations, suggesting the involvement of other environmental stimuli and/or gene polymorphisms. There is no interaction between tobacco exposure and PTPN22 1858T for the development of anti-CCP-positive or anti-CCP-negative RA. A strong association exists between smoking and the occurrence of extra-articular manifestations (subcutaneous nodules and cardiovascular events), but smoking has no influence on radiographic outcome. In lupus, tobacco exposure has an impact on the production of anti-double-stranded Desoxyribonuclic (dsDNA) and possibly on the development of the disease, as well as on disease activity/severity. In both diseases, smoking might interfere with drug efficacy.

Toussirot E, Roudier J. · Department of Rheumatology, University Hospital Jean Minjoz, Besançon; and EA 3186 Agents Pathogènes et Inflammation, University of Franche Comté, Besançon, France. · Best Pract Res Clin Rheumatol. · Pubmed #19028369 No free full text.

Abstract: Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS) are complex disorders with a genetic background and the involvement of environmental factors, including viruses. The Epstein-Barr virus (EBV) is a plausible candidate for playing a role in the pathophysiology of these diseases. Both SLE and RA are characterized by high titers of anti-EBV antibodies and impaired T-cell responses to EBV antigens. Compared with normal subjects, elevated EBV load in peripheral blood has been observed in SLE and RA. EBV DNA or RNA has been evidenced in target organs of RA (synovium) or pSS (salivary glands). Finally, molecular mimicry has been demonstrated between EBV proteins and self antigens in these three conditions. In addition, SLE, RA, and pSS are associated with an increased risk of lymphoma with a potential role for EBV. The influence of new and emergent treatments of these autoimmune diseases (biological therapies) on EBV load and the course of latent EBV infection requires further studies.

Fautrel B. · Pierre & Marie Curie-Paris VI University/Paris Universitas, Department of Rheumatology, Pitié-Salpêtrière Hospital, 83 boulevard de l'Hôpital, 75651 Paris, Cedex 13, France. · Best Pract Res Clin Rheumatol. · Pubmed #19028363 No free full text.

Abstract: Adult-onset Still disease (AOSD) is an uncommon inflammatory condition of unknown origin typically characterized by four main (cardinal) symptoms: spiking fever > or =39 degrees C, arthralgia or arthritis, skin rash and hyperleucocytosis (> or =10,000 cells/mm3) with neutrophils > or =80%. As many other manifestations are possible, diagnosis is potentially challenging. Determination of the total and glycosylated ferritin levels, although not pathognomonic, can help in diagnosis. The disease evolution of AOSD can be monocyclic, polycyclic or chronic. In chronic disease, joint involvement is often predominant and erosions are noted in one-third of patients. No prognostic factors have been identified to date. Therapeutic strategies are from observational data. Corticosteroids are usually the first-line treatment. With inadequate response to corticosteroids, methotrexate appears the best choice to control disease activity and allow for tapering of steroid use. For refractory disease, biological therapy with agents blocking interleukin-1 (anakinra) and then those blocking interleukin-6 (tocilizumab) seem the most promising.

Boissier MC, Assier E, Biton J, Denys A, Falgarone G, Bessis N. · Inserm ERI18, Bobigny, France. · Joint Bone Spine. · Pubmed #19028128 No free full text.

Abstract: Modulation of the T-cell response depends chiefly on regulatory T cells (Treg), which express CD4 and CD25. Some Treg cells are present naturally, whereas others are induced in response to antigens. The immunomodulating effects of Treg cells are mediated by membrane molecules (e.g., CTLA4, GITR, and OX40) and cytokines. IL-35 seems to be a crucial mediator, although IL-10 and TGFbeta are also important. The role for Treg cells in rheumatoid arthritis (RA) has been established in both patients and animal models. Treg function is deficient in RA, whereas Treg counts vary. Treg counts increase in patients who are responding to TNFalpha antagonist therapy. Among current hypotheses, Treg expansion or transfer may hold promise for the treatment of RA.

Miossec P. · Department of Immunology and Rheumatology, Hospital Edouard Herriot, University of Lyon, 69437 Lyon, France. · Arthritis Res Ther. · Pubmed #19007422 links to  free full text

Abstract: This review focuses on the contributions made by interactions between dendritic cells (DCs) and T cells, and by local production of cytokines and chemokines to the pathogenesis of rheumatoid arthritis (RA) synovitis. DCs are efficient professional antigen-presenting cells, which are critical for the development of innate and adaptative immune responses through interactions with T cells. Cytokines from DCs play a key role in the switch inside effector T-cell pathways. Chemokines are important mediators of the immune response because they regulate leucocyte recruitment to tissue, and they play a key role in inflammatory diseases by acting on T-cell and DC migration. Furthermore, the recently discovered T-helper-17 proinflammatory cytokines, present in syno-vium samples, are associated with the migration, differentiation and maturation of inflammatory cells, and they facilitate a network of interactions between all components of the immune response. An understanding of such interactions is essential because it is the key to therapeutic application.

Mariette X. · Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, Le Kremlin Bicêtre, Institut Pour la Santé et la Recherche Médicale (INSERM) U 802, France. · Rheum Dis Clin North Am. · Pubmed #18984420 No free full text.

Abstract: B-cell hyperactivity has been recognized for a long time in Sjögren's syndrome. This B-cell activation is firstly polyclonal but can progress to monoclonal B-cell lymphoproliferation. This article addresses the therapeutic potential of B-cell modulation in Sjögren's syndrome.

El Ibrahimi A, Daoudi A, Boujraf S, Elmrini A, Boutayeb F. · Department of Orthopedic Surgery, University Hospital of Fez, Morocco. · Int J Infect Dis. · Pubmed #18980853 No free full text.

Abstract: Sternoclavicular septic arthritis is an unusual event in healthy patients. Cases have been reported in diabetes mellitus patients, intravenous drug abusers and patients affected by rheumatoid arthritis. We report a case of this unique infection that occurred in a patient who was not at risk of septic arthritis. Through this case and a review of the literature, we discuss the difficulty of diagnosing this disorder, and the consequences of delayed treatment in terms of life-threatening outcomes and therapeutic options.

Chapman KE, Coutinho AE, Gray M, Gilmour JS, Savill JS, Seckl JR. · Endocrinology Unit, Centre for Cardiovascular Sciences, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. · Mol Cell Endocrinol. · Pubmed #18973788 No free full text.

Abstract: Cortisone, a glucocorticoid hormone, was first used to treat rheumatoid arthritis in humans in the late 1940s, for which Hench, Reichstein and Kendall were awarded a Nobel Prize in 1950 and which led to the discovery of the anti-inflammatory effects of glucocorticoids. To be effective, the intrinsically inert cortisone must be converted to the active glucocorticoid, cortisol, by the intracellular action of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Whilst orally administered cortisone is rapidly converted to the active hormone, cortisol, by first pass metabolism in the liver, recent work has highlighted an anti-inflammatory role for 11beta-HSD1 within specific tissues, including in leukocytes. Here, we review recent evidence pertaining to the anti-inflammatory role of 11beta-HSD1 and describe how inhibition of 11beta-HSD1, as widely proposed for treatment of metabolic disease, may impact upon inflammation. Finally, the mechanisms that regulate 11beta-HSD1 transcription will be discussed.