[Diagnostic imaging for atraumatic shoulder pain]. / Epaule douloureuse atraumatique: diagnostic radiologique.

Shoulder pain is a common cause of consultation in primary care medicine. A detailed history and a carefully carried out physical exam allow to orientate the diagnosis towards an intrinsic or extrinsic cause and to the differential diagnosis. Rotator cuff injury is the most frequent affection. Plain radiography will often be done in first intention since it identifies direct or indirect signs associated with certain pathologies. Ultrasonography is an excellent way of evaluating soft tissue injury and allows a diagnosis in most cases (rotator cuff injury, tendinopathy of the long head of the biceps, bursitis, effusion, calcifications). Other imaging studies may be carried out depending on the pathology suspected.

[Joint manifestations in connective tissue diseases]. / Manifestations ostéo-articulaires dans les connectivites.

Joint manifestations are common and often constitute the first symptoms or signs of a connective tissue disease, which should be carefully looked for, according to the clinic, in particular with ultrasound and the research of autoantibodies. Articular manifestations are often severe and must be treated accordingly. In lupus, one can distinguish non-deforming non-erosive arthropathy, Jaccoud's arthropathy (deforming non-erosive) and erosive arthropathy (rhupus). Ultrasound has recently shown that destructive forms are in fact more frequent than initially considered. In addition, lupus can be complicated by necrosis or fractures, which are characterized by mechanical pain. In other connective tissue diseases, similar forms of arthropathies and complications are found, with some distinctions.

European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis.

OBJECTIVES: To agree terminology and to develop recommendations for the diagnosis of calcium pyrophosphate deposition (CPPD). METHODS: The European League Against Rheumatism (EULAR) CPPD Task Force, comprising 15 experts from 10 countries, agreed the terms and recommendations for diagnosis of CPPD using a Delphi consensus approach. Evidence was systematically reviewed and presented in terms of sensitivity, specificity and positive likelihood ratio (LR) to support diagnosis; ORs were used for association. Strength of recommendation (SOR) was assessed by the EULAR visual analogue scale. RESULTS: It was agreed that 'CPPD' should be the umbrella term that includes acute calcium pyrophosphate (CPP) crystal arthritis, osteoarthritis (OA) with CPPD and chronic CPP crystal inflammatory arthritis. Chondrocalcinosis (CC) defines cartilage calcification, most commonly due to CPPD and detected by imaging or histological examination. A total of 11 key recommendations were generated on the topics of clinical features, synovial fluid (SF) examination, imaging, comorbidities and risk factors. Definitive diagnosis of CPPD relies on identification of SF CPP crystals. Rapid onset inflammatory symptoms and signs are suggestive but not definitive for acute CPP crystal arthritis. Radiographic CC is not highly sensitive or specific, whereas ultrasonography appears more useful (LR=24.2, 95% CI 3.51 to 168.01) for peripheral joints. Recognised risk factors for CPPD include ageing, OA and metabolic conditions such as primary hyperparathyroidism, haemochromatosis and hypomagnesaemia; familial forms are rare. SORs varied from 53 to 99 (maximum 100). CONCLUSION: New terms for CPPD were agreed and 11 key recommendations for diagnosis of CPPD were developed using research evidence and expert consensus.

EULAR recommendations for calcium pyrophosphate deposition. Part II: management.

OBJECTIVES: To develop evidence-based recommendations for management of calcium pyrophosphate deposition (CPPD). METHODS: A multidisciplinary guideline development group of 15 experts, representing 10 European countries, generated key propositions for management of CPPD using a Delphi consensus approach. For each recommendation research evidence was searched systematically. Whenever possible, the effect size and number needed to treat for efficacy and RR or OR for side effects were calculated for individual treatment modalities. Strength of recommendation was assessed by the European League Against Rheumatism visual analogue scale. RESULTS: Nine key recommendations were generated, including topics for general management, treatment of acute attacks, prophylaxis against recurrent acute attacks and management of chronic symptoms. It was recommended that optimal treatment requires both non-pharmacological and pharmacological treatments. For acute CPP crystal arthritis, cool packs, temporary rest and joint aspiration combined with steroid injection are often sufficient. For prophylaxis or chronic inflammatory arthritis with CPPD, oral non-steroidal anti-inflammatory drugs with gastroprotective treatment and/or low-dose colchicine 0.5-1.0 mg daily may be used. Other recommendations included parenteral or oral corticosteroid for acute CPP arthritis in those unresponsive or unsuited to other measures, and low-dose corticosteroid, methotrexate or hydroxychloroquine for chronic inflammatory arthritis with CPPD. Asymptomatic CPPD requires no treatment. Strength of recommendations varies from 79% to 95%. CONCLUSION: Nine key recommendations for management of CPP crystal associated arthritis were developed using both research evidence and expert consensus. Strength of recommendations was provided to assist the application of these recommendations.

Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc.

STUDY DESIGN: Case-control study. OBJECTIVE: To determine whether inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-8] are elevated in tissues intimately surrounding involved nerve roots of patients suffering from radiculopathy form herniated disc (HD). SUMMARY OF BACKGROUND DATA: Proinflammatory cytokines are postulated to play an important role in radiculopathy from HD. Although TNF-alpha has been found in human HD, it is not known whether TNF-alpha concentrations are increased in symptomatic patients. Epidural fat (EF) is another tissue in close contact with nerve roots. Histologic modifications of EF have been reported in patients with sciatica but concentrations of inflammatory cytokines have never been studied. METHODS: Twenty-three lumbar HD along with adjacent EF (EFHD) were harvested from patients with radicular syndrome. As controls, 14 intervertebral discs (IVDs) and 10 samples of EF (EFC) were obtained from patients without radicular syndrome undergoing spine surgery. Tissue explants were incubated ex vivo for 48 hours and the concentrations of cytokines were measured by elisa in the supernatants. Results were standardized according to tissue weight. RESULTS: All 4 cytokines were found at higher concentrations in EFHD compared with HD (P < 0.001). TNF-alpha was the only cytokine found in significantly higher levels in EFHD compared with EFC [median, interquartile range 6.6, (1.6-16.3) pg/mL per milligram of tissue vs. 2.3 (1.3-5.0), P < 0.05] and to subcutaneous fat [0.35 (0-2.28), P < 0.001]. No significant increase of either cytokines was found in HD compared with IVD. CONCLUSION: Higher concentrations of TNF-alpha were found in EF from patients with radiculopathy from HD compared with patients suffering from other type of back pain. These results support the role of TNF-alpha in the pathogenesis of radiculopathy from HD.

[Polymyalgia rheumatica and giant cell arteritis: recent data and current situation]. / Polymyalgia rheumatica et artérite giganto-cellttulaire: données actuellttes.

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are two frequently linked inflammatory diseases of the elderly. The diagnosis of GCA is based on temporal artery biopsy, but results must not delay steroid therapy because of the potential sudden ocular and neurologic ischemic complications. PET-scan and MRI angiography can be helpful in difficult cases. The diagnosis of PMR is essentially clinical, centred on subacute onset of morning aching and stiffness in the shoulder and hip girdles. The treatment of both entities is still based on glucocorticoids (10-20 mg/j of prednisone for PMR, and 40-60 for GCA). Methotrexate, though, now appears a sometimes-useful corticosteroid-sparing agent, both in PMR and GCA. There also appears to be a role for low dose aspirin to decrease ischemic events in GCA.

[Myositis: current data on the classification, diagnosis and treatment]. / Myosites: données actuelles sur la classification, le diagnostic et le traitement.

The classification of idiopathic inflammatory myopathies has been refined with the characterization of new antibodies and their clinicopathological associations. The most widely used classification (Troyanov) defines pure polymyositis (PM) and dermatomyositis (DM), myositis overlap (presence of extra-muscular-extra-cutaneous manifestations or auto-antibodies), myositis associated to cancers and sporadic inclusion body myositis IBM). Overlap myositis are generally more severe and chronic than pure forms, and almost always require immunosuppressants. IBM remains difficult to treat, but immunosuppressants or immunoglobulins may be proposed, especially at the beginning of evolution.

[Diagnosis and treatment of calcium pyrophosphate crystal-induced arthropathy]. / Diagnose und Therapie der Kalziumpyrophosphatkristall-induzierten Arthropathie.

Calcium pyrophosphate dihydrate deposition (CPPDD) disease is the term used to describe a group of common and potentially severe metabolic arthropathies. In these, CPPD crystals form and are deposited in the cartilage matrix (chondrocalcinosis) and induce inflammatory and/or destructive mechanisms. Most cases are idiopathic, but hyperparathyroidism, hemochromatosis, hypomagnesemia and hypophosphatemia can promote or cause chondrocalcinosis. Early disease (with onset before the age of 60 years) thus requires that the patient be examined for these metabolic conditions, particularly hemochromatosis. The prevalence of CPPDD disease in the general population increases with age, being 10-15% in the age group 65-75 years and more than 40% in the over-80s. Although frequently asymptomatic, chondrocalcinosis can involve severe acute attacks of inflammatory arthritis (pseudogout) and also various types of chronic arthropathy including pseudorheumatoid arthritis, pseudo-osteoarthritis, and pseudoneuropathic joint disease. CPPD crystals can also be deposited in the bursae, ligaments, and tendons and generate inflammation and/or ruptures. The diagnosis is based on synovial fluid analysis (positively birefringent CPPD crystals visualized by compensated polarized light microscopy) and X-rays (punctate and linear radiodense areas in fibrocartilage and hyaline cartilage). Treatment is primarily symptomatic, since there is no known drug that can prevent progression of the joint destruction). Nonsteroid anti-inflammatory drugs (NSAIDs) and intra-articular or systemic glucocorticoids (amounts must be only small if use is prolonged) are the most useful treatments. Colchicine can be effective in recurring pseudogout, and magnesium can be used prophylactically. In a small uncontrolled series methotrexate was effective and aroused interest; it can be used when other treatments fail.

[Advances in the management of gout]. / Approches thérapeutiques de la goutte en 2006.

Gout is the most frequent cause of man's inflammatory arthritis after forty years of age and its prevalence is increasing. Although the physiopathology of this condition is starting to be thoroughly recognized, therapeutic approaches have not fundamentally changed during the last decades. In the absence of renal or digestive contraindications, non steroidal inflammatory drugs are the treatment of choice for acute flares of gout arthritis. If an indication for urate-lowering therapy exists, a xanthine oxydase inhibitor or an uricosurical treatment remains the treatment of choice, depending on the patient's co-morbidity. Purine restrictive diet, weight loss in case of obesity and lower alcohol intake are highly necessary co-measures.

[Calcium pyrophosphate dihydrate crystal induced arthropathy]. / Arthropathies à cristaux de pyrophosphate de calcium.

CPPD deposition disease is a common and potentially severe arthropathy. Hyperparathyroidism, hemochromatosis and hypomagnesaemia can favour chondrocalcinosis and must be looked for in early disease (< or =60 years). Chondrocalcinosis can cause severe attacks of inflammatory arthritis (pseudogout) as well as various forms of chronic arthropathies including pseudo RA, pseudo OA and pseudo neuropathic joint disease. Diagnosis is based on synovial fluid analysis, (positively birefringent CPPD crystals) and X-rays (punctuated and linear radio densities in cartilage). NSAIDs and i.a. or systemic glucocorticoids are the most useful treatments. Colchicine can be effective in recurring pseudogout, and magnesium for attacks' prevention. Methotrexate proved effective in a small uncontrolled series, and can be used when other treatments fail.

The active metabolite of leflunomide, A77 1726, increases proliferation of human synovial fibroblasts in presence of IL-1beta and TNF-alpha.

OBJECTIVE AND DESIGN: Excessive synovial fibroblast (SF) proliferation is detrimental in rheumatoid arthritis. We therefore sought to determine the effects of A77 1726, the active metabolite of leflunomide, on SF proliferation. METHODS: Human SFs were used. Cell proliferation was investigated using MTS assay, by (3)H-thymidine incorporation and cell counts. RESULTS: Whereas A77 1726 alone had no effects, it significantly increased the mitogenic effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Cyclooxygenase inhibition might be at least partly involved, since indomethacin displayed similar effects, and since prostaglandin E2 inhibited SF proliferation. In contrast, the effect of A77 1726 did not appear to be mediated through depletion of the pyrimidine pool or inhibition of tyrosine kinases. CONCLUSION: A77 1726 displays proliferative effects in presence of IL-1beta and TNF-alpha. Further elucidation of involved mechanisms may prove useful for the utilization of leflunomide, the development of related compounds or elaboration of new therapeutic strategies.

Benefits of a programme taking advantage of patient-instructors to teach and assess musculoskeletal skills in medical students.

AIM: To evaluate a rheumatoid arthritis patient-instructor-based formation-assessment programme for its ability to improve and assess musculoskeletal knowledge and skills in third-year medical students. METHODS: (1) The quality of our musculoskeletal teaching was assessed before patient-instructor intervention through an open-questions test (pre-test) and performance record forms (PRFs) filled in by the patient-instructors. (2) The improvement afforded by patient-instructors was evaluated through a second (identical) open-questions test (post-test). (3) The resulting skills in the students were further assessed by an individual patient-instructors physical status record form (PSRF), filled in by the students. RESULTS: Pre-tests and post-tests showed an improvement in correct answers from a mean score of 39% to 47%. The history-taking questions that obtained <50% scores in the pre-test mostly dealt with the consequences of a chronic illness. Intervention of patient-instructors especially improved knowledge of the psychosocial aspects and side effects of drugs. With regard to physical examination, patient-instructors makedly improved the identification of assessment of signs of active and chronic inflammation. PRF analysis showed that 10 of 28 questions answered by <50% of the students were related to disease characteristics of rheumatoid arthritis, extra-articular signs, side effects of drugs and psychosocial aspects. Analysis of the PSRF indicated that the weakness of our students' physical examination abilities in particular is related to recognising the types of swelling and differentiating tenderness from pain on motion. CONCLUSION: This study proves the considerable benefits of the involvement of patient-instructors in the teaching and assessment of clinical skills in students.

Evidence for differential acquired drug resistance to anti-tumour necrosis factor agents in rheumatoid arthritis.

BACKGROUND: Acquired drug resistance or gradual drug failure has been described with most disease modifying antirheumatic drugs (DMARDs) and is also starting to be recognised with anti-tumour necrosis factor (anti-TNF) agents. OBJECTIVE: To study acquired drug resistance to anti-TNF agents in rheumatoid arthritis (RA). METHODS: Swiss health authorities requested continuous monitoring of patients receiving biological agents. Intensification of co-therapy with traditional DMARDs, gradual dose escalation, and drug discontinuation rates in all patients receiving infliximab, etanercept, or adalimumab, adjusting for potential confounders, were analysed. Intensification of DMARD co-therapy and time to discontinuation of the three anti-TNF agents were analysed using a proportional hazards models. Dose escalation and evolution of RA disease activity (DAS28) were analysed using a longitudinal regression model. RESULTS: 1198 patients contributing 1450 patient-years of anti-TNF treatment met the inclusion criteria. The rate of intensification of traditional DMARD co-therapy over time was significantly higher with infliximab (hazards ratio = 1.73 (99% confidence interval (CI) 1.19 to 2.51)) than with the two other agents. Infliximab also showed significant dose escalation over time, with an average dose increase of +12% (99% CI 8% to 16%) after 1 year, and +18% (99% CI 11% to 25%) after 2 years. No significant differences in discontinuation rates were seen between the three anti-TNF agents (ANOVA, p = 0.67). Evolution of disease activity over time indicated a lower therapeutic response to infliximab (DAS28, p<0.001) compared with etanercept, after 6 months' treatment. CONCLUSIONS: In this population, infliximab was associated with a higher risk of requiring intensification of DMARD co-therapy than the other anti-TNF agents and a significant dose escalation over time. Analysis of RA disease activity indicated a reduced therapeutic response to infliximab after the first 6 months of treatment, suggestive of acquired drug resistance.

[Treatment of rheumatoid arthritis in 2005: prompt, agressive and customized]. / Traitement de la polyarthrite rhumatoïde en 2005: prompt, énergique et ajusté.

Treatment of rheumatoid arthritis in 2005: prompt, aggressive and customized Rheumatoid arthritis can be extremely serious (joint destruction, functional loss, decrease in life expectancy). Fortunately, our therapeutic means have recently progressed enormously (better appreciation of efficacy and ways to use DMARDs combinations and new molecules such as leflunomide and anti-TNFs, understanding of the importance of early adequate and intensive treatments when necessary). Huge progresses have also been performed with regards to evaluation and follow-up strategies (disease activity score--DAS, health assessment questionnaire--HAQ), which allows us to adapt the treatment much better. The goal now can and must be quick and total remission of the disease in all patients thus avoiding as much as possible irreversible joint damages with accompanying morbidities.

Interferon beta stimulates interleukin 1 receptor antagonist production in human articular chondrocytes and synovial fibroblasts.

BACKGROUND: Interferon (IFN) beta displays anti-inflammatory and immunosuppressive activity and has been considered for the treatment of rheumatoid arthritis (RA). Information about the effects of this molecule on joint cells is scarce, however. OBJECTIVE: To investigate the effects of IFNbeta on the production of interleukin-1 receptor antagonist (IL1Ra) in human articular chondrocytes and synovial fibroblasts. METHODS: Chondrocytes and synovial fibroblasts were stimulated with IFNbeta alone or in combination with interleukin (IL) 1beta. IL1Ra concentrations in culture supernatants and cell lysates were determined by ELISA. Expression of mRNA encoding the secreted sIL1Ra or the intracellular icIL1Ra1 isoforms was quantified by real time reverse transcriptase-polymerase chain reaction. RESULTS: In chondrocytes, IFNbeta alone had no effect, but dose dependently enhanced the secretion of IL1Ra induced by IL1beta. Chondrocyte cell lysates contained undetectable or low levels of IL1Ra, even after stimulation with IL1beta and IFNbeta. Consistently, IL1beta and IFNbeta induced sIL1Ra mRNA expression in chondrocytes, while expression of icIL1Ra1 was not detectable. Human articular chondrocytes thus mainly produce secreted IL1Ra. In synovial fibroblasts, IFNbeta alone dose dependently increased IL1Ra secretion. In addition, IFNbeta enhanced the stimulatory effect of IL1beta on IL1Ra production. In synovial cell lysates, IFNbeta and IL1beta also increased IL1Ra levels. Consistently, IFNbeta and IL1beta induced the expression of both sIL1Ra and icIL1Ra1 mRNA in synovial fibroblasts. CONCLUSION: IFNbeta increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis.

Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors.

OBJECTIVES: To examine the value of anti-cyclic citrullinated peptide (anti-CCP) antibodies, anti-keratin antibodies (AKA) and immunoglobulin M rheumatoid factors (IgM RF) in discriminating between rheumatoid arthritis (RA) and other rheumatic diseases, and to determine whether the clinical manifestations or severity of erosions in RA are associated with anti-CCP positivity. METHODS: In a cross-sectional study, we determined the concentrations or titres of these three markers in 179 RA patients and 50 controls. Erosions were quantified using the Larsen score in 129 patients. RESULTS: Sensitivity was highest for IgM RF (75%), followed by anti-CCP antibodies (68%) and AKA (46%). Specificity was highest for anti-CCP antibodies (96%), followed by AKA (94%) and IgM RF (74%). A correlation with clinical manifestations and severity of erosions was observed mainly for IgM RF positivity. CONCLUSIONS: With their excellent specificity, anti-CCP antibodies can be useful in establishing the diagnosis of RA, but IgM RF is a better predictor of disease severity.

Intravenous gammaglobulins in refractory polymyositis: lower dose for maintenance treatment is effective.

OBJECTIVES: To test lower dose immunoglobulins as a maintenance treatment in a patient with refractory polymyositis. METHODS: In a patient with longstanding refractory polymyositis, intravenous (IV) immunoglobulin treatment was introduced at a standard dose (2 g/kg monthly). After a few treatment courses, doses were reduced to 0.8 g/kg monthly, allowing perfusion over one single day. RESULTS: Although response to the standard dose was only partial, reduction of subsequent doses did not alter the evolution. On the contrary, the evolution was marked by further improvement, which has been sustained over the following year. CONCLUSION: Lower dose IV immunoglobulins as a maintenance treatment were used with excellent results in a case of refractory polymyositis allowing considerable reduction in treatment costs. Further trials should be undertaken to evaluate this interesting alternative.

Il-4 and IL-13, but not IL-10, protect human synoviocytes from apoptosis.

Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the ability of IL-4 and other Th2 cytokines to protect human synovial cells from apoptosis. Human synoviocytes or synovial explants were pretreated with IL-4, IL-10, and IL-13 before exposure to NO donor sodium-nitro-prusside (SNP). Apoptosis was evaluated by microscopy, annexin V-FITC, 3-(4,5-dimethylthiazol-2-gl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl-2H: tetrazolium inner salt (MTS) test, pulse field gel electrophoresis, and a method proposed in this study based on (32)P Klenow end labeling of high m.w. DNA. Pretreatment by IL-4 or IL-13, but not IL-10, protected human synoviocytes from apoptosis induced by SNP. Even at doses as high as 2 mM SNP, up to 86% and 56% protection was achieved, after IL-4 and IL-13 treatment, respectively. Cell survival was dependent on IL concentration. IL-4 and IL-13 also had antiapoptotic effects on SNP-treated human synovial explants. Effects of IL-4 and IL-13 varied in the presence of phosphatidylinositol-3 kinase and protein kinase C inhibitors, implying the involvement of these pathways in antiapoptotic signaling. Antiapoptotic effects were dramatically inhibited by LY294002, and partially by the protein kinase C inhibitor Gö 6976, while insulin-like growth factor increased synoviocyte survival. The possibility that IL-4 and IL-13 may enhance synovial expansion in vivo by their antiapoptotic effects is discussed.

Association of rheumatoid factors and anti-filaggrin antibodies with severity of erosions in rheumatoid arthritis.

OBJECTIVES: To evaluate and to compare the association of two types of autoantibodies-rheumatoid factors (RF) and anti-filaggrin antibodies (AFA)-with clinical severity and joint damage progression in rheumatoid arthritis (RA) patients. METHODS: In a cross-sectional study, we determined RF and AFA titres in 199 RA patients and 65 controls. Erosions apparent on X-rays were quantified using the Larsen score in 143 patients, and the distribution of these scores was studied according to disease duration in patients who were positive and negative for RF and AFA. RESULTS: RF were detected in 72% and AFA in 47% of RA patients. AFA were highly specific for RA (100%). RF positivity was correlated with the presence of subcutaneous nodules, sicca syndrome and the severity of erosions for a given disease duration. AFA positivity was correlated only with the presence of the HLA-DRB1 shared epitope. CONCLUSIONS: Since no significant correlation was observed between joint damage progression and AFA positivity, the determination of AFA does not appear to be useful in assessing the prognosis of RA. However, AFA, which appear early in RA, could be helpful for the diagnosis of RA in patients who do not fulfil four American College of Rheumatology criteria.