TNFalpha inhibition in psoriatic arthritis: cause for hope.
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Biomedical subjects
Publications and source records attributed to B Fournié.
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OBJECTIVE: Synovial angiogenesis is at the epicenter of rheumatoid pannus development and is largely dependent on vascular endothelial growth factor (VEGF). We sought to determine whether the VEGF level in rheumatoid synovial tissue is a marker for disease severity. PATIENTS AND METHODS: Twelve patients with rheumatoid arthritis (RA) underwent a clinical and radiological evaluation at the time of a synovial biopsy done during joint surgery required by RA progression (T1) and, on average, 10 years later (T2). Immunohistochemistry was used to detect and quantitate VEGF in the synovial biopsy taken at T1. RESULTS: VEGF labeling was seen on endothelial cells and macrophages in all 12 synovial biopsies. The amount of endothelial-cell VEGF labeling (assessed semi-quantitatively) was significantly correlated with Larsen score progression during the 10-year follow-up. The amounts of endothelial cell or macrophage VEGF labeling was not correlated with the joint count, radiological stage of the biopsied joint or progression of this stage, Larsen scores at T1 or T2, presence of rheumatoid factor, or presence of extra-articular manifestations. CONCLUSION: Our results suggest that the amount of VEGF in the rheumatoid synovium may be a marker for joint destruction in patients with RA.
OBJECTIVE: To develop a standardisable enzyme linked immunosorbent assay (ELISA), using human filaggrin, for detection of antifilaggrin autoantibodies in rheumatoid arthritis (RA). To compare the diagnostic performance of the ELISA with those of reference tests: "antikeratin antibodies" ("AKA"), and antibodies to human epidermis filaggrin detected by immunoblotting (AhFA-IB). METHODS: Two ELISAs were developed using either affinity purified neutral-acidic human epidermis filaggrin (AhFA-ELISA-pur) or a recombinant human filaggrin deiminated in vitro (AhFA-ELISA-rec) as immunosorbent. Antifilaggrin autoantibodies were assayed in 714 serum samples from patients with well characterised rheumatic diseases, including 241 RA and 473 other rheumatic diseases, using the two ELISAs. "AKA" and AhFA-IB tests were carried out in the same series of patients. The diagnostic performance of the four tests was compared and their relationships analysed. RESULTS: The titres of "AKA", AhFA-IB, and the AhFA-ELISAs correlated strongly with each other. The diagnostic sensitivity of the AhFA-ELISA-rec, which was better than that of AhFA-ELISA-pur, was 0.52 for a specificity of 0.95. This performance was similar to those of "AKA" or AhFA-IB. However, combining AhFA-ELISA-rec with AhFA-IB led to a diagnostic sensitivity of 0.55 for a specificity of 0.99. CONCLUSION: A simple and easily standardisable ELISA for detection of antifilaggrin autoantibodies was developed and validated on a large series of patients using a citrullinated recombinant human filaggrin. The diagnostic performance of the test was similar to that of the "AKA" and AhFA-IB. Nevertheless, combining the AhFA-ELISA-rec with one of the other tests clearly enhanced the performance.
PURPOSE: To evaluate the contribution of principal imaging techniques in diagnosis and treatment in adhesive capsulitis of the shoulder. MATERIALS AND METHODS: In 20 patients presenting adhesive capsulitis of shoulder since mean of 6,7 months, the following examinations were performed: radiographies, angioscintigraphy, MRI as well as an opaque arthrography and a bursography associated with corticosteroid injection. Patients were followed during one year. RESULTS: The opaque arthrography was to affirm the adhesive capsulitis for the inclusion of the patients. Radiographies (patchy demineralization) and scintigraphy (hyperfixation) were often pathological. In MRI, T1 fat-saturated sequences after contrast injection almost always showed enhancement of the articular capsula, the synovia, the miscellaneous bone or the sub-acromial bursa. The latter was often modified and retracted at bursography. In 19 of 20 cases, a functional improvement was observed after the opacifications. CONCLUSION: Therapeutic effect of both arthrography and bursography is almost proved. Post contrast MRI confirms presence of vascular troubles in all the shoulder structures even at this advanced stage.
OBJECTIVE: To evaluate the efficacy and safety of Harpagophytum in the treatment of hip and knee osteoarthritis comparatively with the slow-acting drug for osteoarthritis, diacerhein. PATIENTS AND METHODS: A multicenter, randomized, double-blind, parallel-group study was conducted in 122 patients with hip and/or knee osteoarthritis. Treatment duration was four months and the primary evaluation criterion was the pain score on a visual analog scale. Harpagophytum 2,610 mg per day was compared with diacerhein 100 mg per day. RESULTS: After four months, considerable improvements in osteoarthritis symptoms were seen in both groups, with no significant differences for pain, functional disability, or the Lequesne score. However, use of analgesic (acetaminophen-caffeine) and nonsteroidal anti-inflammatory (diclofenac) medications was significantly reduced in the Harpagophytum group, which also had a significantly lower rate of adverse events. CONCLUSION: In this study, Harpagophytum was at least as effective as a reference drug (diacerhein) in the treatment of knee or hip osteoarthritis and reduced the need for analgesic and nonsteroidal anti-inflammatory therapy.
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The presence of rheumatoid factors (RF) in the serum of rheumatoid arthritis (RA) patients is commonly evidenced by agglutination tests: the Waaler-Rose assay, based on the use of human red blood cells (RBCs) coated with rabbit anti-RBC antibodies, and the latex test, which uses latex particles coated with denatured human immunoglobulin G (IgG). The aim of the present study was to characterize the RF able to agglutinate human RBCs coated with macaque antihuman RBC IgG antibodies secreted from macaque-mouse heterohybridomas (two from rhesus monkey and one from crab-eating macaque). Human RBCs coated with macaque monoclonal antibodies (MacMoAbs) were used for agglutination tests and these were carried out in parallel with standard tests (Waaler-Rose and latex agglutination tests) on sera from 82 RA patients, 86 patients with other forms of inflammatory chronic arthritis and 47 healthy human subjects. MacMoAb-coated RBCs identified RF in the sera of 66% patients with RA. By contrast, the frequency of positive sera in other inflammatory diseases was 5% and all 47 healthy controls were negative. Antimacaque IgG antibodies were found to be more specific for RF than standard tests, in the sera of patients with RA.
UNLABELLED: Psoriatic arthritis probably owes to its radioclinical presentation its position as the most controversial and poorly understood of all major chronic inflammatory joint diseases. Differentiating psoriatic arthritis from ankylosing spondylitis and rheumatoid arthritis remains difficult. OBJECTIVE: To conduct a statistical analysis aimed at identifying clinical, radiological, and laboratory criteria for classifying psoriatic arthritis. PATIENTS AND METHODS: 260 patients were studied retrospectively, including 100 cases with psoriatic arthritis and 160 controls with ankylosing spondylitis meeting Amor's criteria (n = 80) or with rheumatoid arthritis meeting American College of Rheumatology criteria (n = 80). Mean disease duration was five years. Thirty-nine variables were recorded for each patient. Multiple logistic regression and discriminant analysis were used to select the classification criteria. RESULTS: Each of the two statistical methods selected the same nine criteria. After assigning a weighting coefficient to each of these criteria, sensitivity and specificity were better with the multiple logistic regression model (95% and 98%, respectively) than with the discriminant analysis model. CONCLUSION: Our classification criteria require further evaluation in multicenter prospective studies.
UNLABELLED: This article reports our experience with a five-day back school program focusing on active exercises, safe lifting, and occupational therapy. PATIENTS AND METHODS: The medical charts of 144 back school patients were reviewed retrospectively. Age, gender, type of low back pain, radiological findings, impact on work and psychological well-being, surgical history, and history of prior back school experience were recorded on the first and last back school session days (D1 and D5), after six months (M6), and after 12 months (M12). Efficacy was evaluated based on the number of days off work, Schöber's index, a visual analog scale pain score, and scores evaluating the active exercise, safe lifting, and occupational therapy techniques taught during the back school course. RESULTS: All evaluation scores were significantly better on D5 than on D1. This effect was sustained over time. The pain score fell by 50% between D1 and D5 (32.6 +/- 23.1 versus 16.3 +/- 18.5) and remained low at M6 and M12 (18.1 +/- 19.5 and 14.8 +/- 19.3) The number of days off work fell dramatically from baseline to M6 (51.2 +/- 63.8 vs 9.8 +/- 38.8) and remained low at M12. Forty-four patients were lost-to-follow-up between D5 and M6. CONCLUSION: Back school interventions are helpful in preventing recurrences of low back pain. Our promising data deserve to be confirmed in a larger study involving quality of life assessments, determination of the number of physician visits for low back pain during the M0-M6 and M6-M12 periods, and a comprehensive evaluation after 18 months.
OBJECTIVE: To investigate whether serial anticardiolipin determination contributes to the clinical management of patients with systemic lupus erythematosus (SLE) with no previous sign of the antiphospholipid syndrome (APS). METHODS: In 90 patients with SLE with no previous clinical manifestations of the APS, repeated clinical evaluations were performed, and serial blood samples (obtained over a 30 month period, range 13-53 mo) were screened for antiphospholipid antibodies (aPL). Anticardiolipin antibodies (aCL) were detected using an ELISA and considered positive if the result was >25 GPL on 2 separate occasions. Patients were not required to be on a specific treatment regimen during the study. RESULTS: Thirty-four patients (37%) had at least one positive ELISA and 11 (11/90, 12%) 2 positive ELISA for IgG aCL during the study. Lupus anticoagulant (LAC) was found in 16 patients, and a false positive VDRL in 5. At study completion, the total number of clinical or laboratory events associated with APS was 30. In univariate analysis, aCL was significantly associated only with LAC (p<0.012). Presence of aCL also correlated with hemoglobin level, anti-DNA antibody, leukocyte count, and the SLE Disease Activity Index (SLEDAI). LAC and aCL were significantly associated with each other (OR 5.17; 95% CI 1.5-17.7), but LAC had a better positive predictive value than aCL for arterial thrombosis and neurological events. CONCLUSION: Among our patients with SLE without previous clinical manifestations of APS, positive aCL did not predict the occurrence of APS within the next 3 years, but was statistically related to the clinical disease activity (SLEDAI).
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We report three cases of frozen shoulder (including one with bilateral involvement) in human immunodeficiency virus (HIV)-positive patients under triple antiretroviral therapy. In each case, the diagnosis was confirmed by arthrography, and the classic causes of frozen shoulder were ruled out. We suggest that protease inhibitor therapy may have contributed to the development of frozen shoulder in these patients. Long-term follow-up of the increasing numbers of patients under triple antiretroviral therapy will confirm or refute this hypothesis.
Synovial cysts are far less common at the hip than at the knee and usually occur in patients whose hip cavity communicates with the iliopsoas bursa. We report 12 cases of enlargement of the iliopsoas bursa, nine men and three women, with a mean age of 48 years. The six patients with septic bursitis had severe symptoms similar to those seen in septic arthritis of the hip. Chronic pain with or without a palpable inguinal swelling was the main symptom in the six remaining patients, some of whom had compression of neighboring structures making the diagnosis more difficult. Ultrasonography is the best first-line investigation in patients with an inguinal swelling. Computed arthrotomography with examination of the synovial fluid or magnetic resonance imaging should be performed as a confirmatory diagnostic test. Our series provides evidence of the efficacy of appropriate antimicrobial therapy in septic cases and of corticosteroid injections into the bursa or hip cavity in nonseptic cases.
OBJECTIVE: We previously reported that so-called antikeratin antibodies (AKA) and antiperinuclear factor (APF) recognize epitope(s) present on human epidermal filaggrin. In the present study, we developed a new diagnostic test for rheumatoid arthritis (RA) based on detection of antifilaggrin autoantibodies (AFA) by immunoblotting. METHODS: We tested 670 serum samples, including 190 RA. AFA titers were estimated by immunoblotting on filaggrin enriched human epidermis extracts, and AKA titers by indirect immunofluorescence (IIF) on rat esophagus epithelium. Diagnostic values of the tests were compared. RESULTS: Each test resulted in diagnosis of more than 40% of RA samples, with a specificity of 0.99. Although the tests were strongly correlated, their association allowed the diagnosis of more than 60% of RA samples, with the same specificity. CONCLUSION: Immunoblot detection of AFA, a simple and standardizable test, may be an alternative or complement to conventional IIF detection of AKA.
Hypertrophic osteoarthropathy is characterized by digital clubbing, arthropathy and periostosis of long tubular bones. Currarino's disease is an extremely rare variant of primary hypertrophic osteoarthropathy in which there is delayed closure of the fontanelles and an absence of skin involvement. Most reported cases have been in blacks. We report a case in a Caucasian adolescent.
OBJECTIVE: To demonstrate the therapeutic value of subacromial bursography (with a steroid injection) in adhesive capsulitis of the shoulder inadequately improved by arthrographic glenohumeral distension with steroid injection. METHOD: Twenty cases of adhesive capsulitis documented by glenohumeral arthrography were studied prospectively. A steroid was injected during distension arthrography, which was followed by physical therapy. Subacromial bursography without steroid injection was done routinely for diagnostic purposes. Constant's simplified score and range of motion were determined in each patient at baseline and after one, three, six and 12 months. Patients who were inadequately improved after one to three months underwent repeat subacromial bursography with steroid injection, followed by physical therapy. RESULTS: Of the 20 patients, 13 were noticeably improved 1.7 months on average after the distension arthrography. Of the remaining seven patients, six were improved 0.7 months on average after the bursography with steroid injection. CONCLUSION: Glenohumeral distension arthrography with steroid injection followed by physical therapy is effective in expediting the spontaneously favorable outcome of adhesive capsulitis and also allows to confirm the diagnosis. However, the subacromial bursa is almost consistently involved. Subacromial bursography with steroid injection can be useful in cases that fail to respond to conventional therapy.
A prospective study of anterior chest wall involvement was conducted in 50 ankylosing spondylitis patients and 50 psoriatic arthritis patients in the absence of palmoplantar pustulosis. All patients underwent a physical examination, tomograms, and a radionuclide bone scan. Magnetic resonance imaging with gadolinium was done in some cases. Half the patients in both groups had anterior chest wall involvement. Enthesitis was the mechanism of the lesions. The manubriosternal symphysis and sternocostoclavicular joints were the most common sites of involvement, although other entheses in the region were affected in some patients.
A new case of insufficiency fracture in a patient with tabes dorsalis is reported. Whereas the osteoarthropathies and bone lesions due to tabes dorsalis are well known, only one other case responsible for bone loss has been reported in the medical literature.