A cross-sectional study on the prevalence of metabolic syndrome in psoriasis compared to psoriatic arthritis.

BACKGROUND: Increasing epidemiological evidence suggests associations between psoriasis, psoriatic arthritis (PsA) and metabolic disease. Elucidating the complex relationship between these comorbidities may have important management implications. OBJECTIVE: The aim of this study was to examine the difference in prevalence of metabolic disease burden between patients with psoriasis who lack arthritic manifestations (PsO) and PsA patients. METHODS: We performed a cross-sectional study in 123 patients with PsO and PsA. Metabolic syndrome was defined using the new criteria developed by the International Diabetes Foundation (IDF) in 2004. Therefore, clinical examination and standard survey were performed and fasting blood samples were collected. RESULTS: One hundred and four patients were analysed, of which 49 were PsO and 55 were PsA patients. We found that prevalence of the metabolic syndrome according to the IDF criteria was significantly higher in the PsO (44.9%) compared with the PsA group (25.5%) (P = 0.037). Looking closer at the individual components of the metabolic syndrome, this difference can mainly be attributed to the significantly higher prevalence of abdominal obesity in PsO (83.7%) vs. PsA (65.5%) (P = 0.034). For other individual components of the metabolic syndrome such as triglycerides, high-density lipoproteins, hypertension and plasma glucose, we could not show statistically significant differences between the groups. CONCLUSION: Metabolic syndrome is more prevalent in patients with PsO than in PsA patients, mainly determined by the higher prevalence of abdominal obesity in PsO compared with PsA group.

[Early referral of first line patients suspected of axial spondyloarthritis: the Belgian results of the RADAR study]. / Renvoi précoce au spécialiste de patients avec une suspicion de spondyloarthropathie axiale en première ligne: les résultats belges de l'étude RADAR.

Currently, there is a 5 to 7 years gap between the first symptoms and the diagnosis of ankylosing spondylitis. A better patient referral might reduce this gap and accelerate the adequate treatment implementation. The study objective was to compare 2 referral strategies used in first line. In Belgium, 208 referral physicians assigned to 16 rheumatology centres were randomized to refer chronic back pain patients (with onset <45 years) using 1 of the 2 referral strategies: Strategy 1 :1 of 3 criteria (inflammatory back pain, HLA-B27, sacroiliitis on imaging); or Strategy 2: 2 of6 criteria (IBP inflammatory back pain, HLA-B27, sacroiliitis, family history, good response to NSAIDs, extra-articular manifestations). Among the 141 referred patients with strategy 1 and 2, 26.0 and 36.9% respectively were diagnosed with Axial Spondylarthritis (SpA). Inflammatory back pain, sacroiliitis and good respond to NSAIDs were the most frequently used criteria (92.9 %, 36.2 % and 33.3% respectively). This study emphasizes the high prevalence of undiagnosed axial SpA in patients with chronic back pain and stressed the necessity to increase awareness of the disease.

Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic intestinal mucosal phenotype.

BACKGROUND: Vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) are major regulators of pathological angiogenesis, which is a prominent feature of both Crohn's disease (CD) and peripheral synovitis in spondyloarthritis. OBJECTIVE: To investigate the presence of VEGF-A and PlGF in the gut of spondyloarthritis patients and to link this finding with subclinical gut inflammation in these patients. METHODS: Intestinal biopsies from healthy controls, CD patients, spondyloarthritis patients with or without subclinical gut inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A, PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed. RESULTS: Spondyloarthritis patients with subclinical gut inflammation had markedly increased intestinal VEGF-A expression (p<0.001), mucosal vascularisation (p<0.001) and VCAM-1 expression (p<0.01) compared with healthy controls and RA patients, which, unlike in CD patients, was also seen when the gut inflammation was in a quiescent state. PlGF expression was highly increased in the subclinically inflamed gut of spondyloarthritis (p<0.01 compared with healthy controls), but not at all in CD. CONCLUSION: A pro-angiogenic intestinal phenotype is observed in spondyloarthritis patients with quiescent chronic gut inflammation. This favours an environment for enhanced trafficking of immune cells in this subpopulation.

Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine.

AIM: To study the relationship between disease activity, radiographic damage and physical function in patients with ankylosing spondylitis (AS) PATIENTS AND METHODS: Baseline and 2-year data of the Outcome in Ankylosing Spondylitis International Study (OASIS)(217 patients) were used. Physical function was expressed by the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI); disease activity by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and by erythrocyte sedimentation rate and C-reactive protein; and structural damage by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Syndesmophyte- and non-syndesmophyte sum cores, and numbers of affected (bridged) vertebral units were derived from the mSASSS. Univariate correlations were calculated on baseline values using the Spearman rank correlation. Multivariate associations were investigated by generalised estimating equations (GEE) on baseline and 2-year data. RESULTS: mSASSS correlated moderately well with BASFI (Spearman's r = 0.45) and DFI (r = 0.38). BASDAI correlated well with BASFI (r = 0.66) and DFI (r = 0.59). Correlation coefficients for mSASSS versus BASFI and DFI decreased by increasing levels of BASDAI, being zero at the highest quintile of BASDAI. GEE showed that both BASDAI and mSASSS independently and significantly helped to explain either BASFI or DFI. Results were similar for syndesmophyte sum score, non-syndesmophyte sum score, number of affected VUs or number of VUs with bridging. The lumbar part of the mSASSS contributed similarly to the cervical part in explaining BASFI/DFI. CONCLUSION: Physical function impairment in AS is independently caused by patient-reported disease activity and the level of structural damage of the lumbar and cervical spine. Syndesmophytes and other radiographic abnormalities contribute to physical function impairment.

ASAS/EULAR recommendations for the management of ankylosing spondylitis: the patient version.

BACKGROUND: The ASAS/EULAR (Assessment of SpondyloArthritis International Society/European League Against Rheumatism) recommendations for the management of ankylosing spondylitis (AS) have been developed by rheumatologists for a target population of health professionals. OBJECTIVE: To extend the cooperation between ASAS and EULAR by translating the recommendations into a language that can be easily understood by patients in order to further disseminate and evaluate the recommendations. METHODS: In cooperation with patient organisations 18 patients with AS (17 European, one Canadian) were invited to attend a meeting in February 2008. As a starting point the original publication and a version created by Canadian patients with AS were used. To improve the understanding of potential problems, data on the evaluation of a recent German translation were presented. After intensive discussions the wording was adjusted and a vote was held on the new wording of the recommendations aiming for >80% agreement on each sentence. Finally, patients were asked to indicate their level of agreement with the content of the recommendations. RESULTS: Ten recommendations were successfully translated into a patient-understandable version. The original text was changed in most cases. In all but one case (recommendation No 4) there was broad agreement with the proposed translation. The overall agreement with the content of the recommendations was high: 8.7 (0.6). CONCLUSION: For the first time, EULAR recommendations were successfully converted into a patient-understandable language version by a large international group of patients in collaboration with rheumatologists. The evaluation showed broad agreement. Translations into different languages and further dissemination in individual countries will be performed.

New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS).

OBJECTIVE: Inflammatory back pain (IBP) is an important clinical symptom in patients with axial spondyloarthritis (SpA), and relevant for classification and diagnosis. In the present report, a new approach for the development of IBP classification criteria is discussed. METHODS: Rheumatologists (n = 13) who are experts in SpA took part in a 2-day international workshop to investigate 20 patients with back pain and possible SpA. Each expert documented the presence/absence of clinical parameters typical for IBP, and judged whether IBP was considered present or absent based on the received information. This expert judgement was used as the dependent variable in a logistic regression analysis in order to identify those individual IBP parameters that contributed best to a diagnosis of IBP. The new set of IBP criteria was validated in a separate cohort of patients (n = 648). RESULTS: Five parameters best explained IBP according to the experts. These were: (1) improvement with exercise (odds ratio (OR) 23.1); (2) pain at night (OR 20.4); (3) insidious onset (OR 12.7); (4) age at onset <40 years (OR 9.9); and (5) no improvement with rest (OR 7.7). If at least four out of these five parameters were fulfilled, the criteria had a sensitivity of 77.0% and specificity of 91.7% in the patients participating in the workshop, and 79.6% and 72.4%, respectively, in the validation cohort. CONCLUSION: This new approach with real patients defines a set of IBP definition criteria using overall expert judgement on IBP as the gold standard. The IBP experts' criteria are robust, easy to apply and have good face validity.

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection.

OBJECTIVE: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). METHODS: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (> or =3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. RESULTS: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having "non-radiographic" axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature ("imaging arm") or the presence of HLA-B27 plus at least two SpA features ("clinical arm"). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). CONCLUSION: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. TRIAL REGISTRATION NUMBER: NCT00328068.

Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal.

OBJECTIVE: Non-radiographic axial spondyloarthritis (SpA) is characterised by a lack of definitive radiographic sacroiliitis and is considered an early stage of ankylosing spondylitis. The objective of this study was to develop candidate classification criteria for axial SpA that include patients with but also without radiographic sacroiliitis. METHODS: Seventy-one patients with possible axial SpA, most of whom were lacking definite radiographic sacroiliitis, were reviewed as "paper patients" by 20 experts from the Assessment of SpondyloArthritis international Society (ASAS). Unequivocally classifiable patients were identified based on the aggregate expert opinion in conjunction with the expert-reported level of certainty of their judgement. Draft criteria for axial SpA were formulated and tested using classifiable patients. RESULTS: Active sacroiliitis on magnetic resonance imaging (MRI) (odds ratio 45, 95% CI 5.3 to 383; p<0.001) was strongly associated with the classification of axial SpA. The knowledge of MRI findings led to a change in the classification of 21.1% of patients. According to the first set of candidate criteria (sensitivity 97.1%; specificity 94.7%) a patient with chronic back pain is classified as axial SpA in the presence of sacroiliitis by MRI or x rays in conjunction with one SpA feature or, if sacroilitiis is absent, in the presence of at least three SpA features. In a second set of candidate criteria, inflammatory back pain is obligatory in the clinical arm (sensitivity 86.1%; specificity 94.7%). CONCLUSION: The ASAS group has developed candidate criteria for the classification of axial SpA that include patients without radiographic sacroiliitis. The candidate criteria need to be validated in an independent international study.

Extra-articular manifestations.

Rheumatoid arthritis and spondyloarthritis, a concept which includes diseases like ankylosing spondylitis, psoriatic arthritis, and arthritis/spondylitis associated with inflammatory bowel disease, are both chronic inflammatory rheumatologic conditions. This article focuses on extra-articular manifestations, defined as diseases and symptoms not directly related to the locomotor system. The different manifestations are addressed per body system. Diagnostic and prognostic implications of these manifestations in daily practice are discussed.

Sensitivity and specificity of criteria for spondyloarthritis in children with late onset pauciarticular juvenile chronic arthritis as well as their characteristics.

OBJECTIVE: To evaluate the sensitivity and specificity of criteria designed for spondyloarthritis in a university hospital treated population of children with late onset pauciarticular juvenile chronic arthritis and a control population. METHODS: Four sets of criteria especially designed for juvenile patients: Garmisch-Partenkirchen juvenile spondylitis criteria (= Garmisch), SEA (=seronegative enthesopathy and arthritis) syndrome, Enthesitis Related Arthritis (ERA), Atypical spondyloarthritis for children and two sets of criteria for patients without age specification (European spondyloarthropathy Study Group - ESSG and Amor) were evaluated in a cross-sectional way in a group of 43 consecutive patients with late onset pauciarticular juvenile chronic arthritis (LOPA) seen over a six-month period in the outpatient clinic. These criteria were analysed in 69 patients with other forms of juvenile chronic arthritis as well. The sensitivity and specificity were calculated for each set, as well as positive predictive value and likelihood ratio. The characteristics described in the different sets of criteria were separately evaluated in the LOPA patients and the other patients. RESULTS: For sensitivity, the Garmisch criteria scored the highest value (97.7%). However, sensitivity was significantly lower in two of the juvenile sets (SEA syndrome and Atypical spondyloarthritis), respectively 44.2% and 51.2%, as opposed to the other criteria (>85%; p<0.01 by Mc Nemar test). Specificity and positive predictive value (PPV) was the highest for the SEA syndrome criteria (98.5%, vs. 95.0%) followed by the ERA (95.6 % vs. 92.1 %) and the Garmisch criteria (94.2% vs. 91.3%). The positive likelihood ratio (LR+) was >10 in SEA (30.5), ERA (18.7) and Garmisch (16.8). The negative likelihood ratio (LR-) was <0.1 only in the Garmisch criteria (0.02). CONCLUSION: Sensitivity, specificity, PPV, LR+ and LR- for the Garmisch-Partenkirchen criteria suggest that they classify almost the same population as defined by LOPA. The SEA syndrome criteria, which were not designed to be classification criteria, being very specific, cannot be used in this patient population to classify a sufficient number of patients. The sensitivity and specificity for the ESSG criteria being similar in these children as in adults suggest they have similar characteristics. The Garmisch-Partenkirchen criteria and/or LOPA definition are major candidates for future research in identifying spondyloarthritis in juvenile patients.

Classification models for disease: the effect of associations between markers on calculating the risk for disease by likelihood ratio products.

OBJECTIVES: The risk for disease or a bad prognosis can be calculated by means of prediction or classification models that take into account multiple variables. Different methods exist to construct such models. Some of those methods, including the likelihood ratio (LR) product method neglect dependency between variables. We aimed to evaluate the effect of neglecting dependency between variables in prediction or classification models. PATIENTS AND METHODS: Population I consisted of 1003 consecutive patients with a new diagnostic problem for which RA was included in the differential diagnosis and final diagnoses (RA or non-RA) were established after 1 year. The baseline variables included in the model are rheumatoid factor, anti-citrullinated protein/peptide antibodies and the HLA-shared epitope. Population II consisted of 847 patients with definite ankylosing spondylitis (AS). Six variables (psoriasis, inflammatory bowel disease, uveitis, HLA-B27 status and latest available CRP) were evaluated. Here, specificities of the features were derived from literature and different scenarios of association between variables in controls and diseased are estimated. RESULTS: When two features are similarly associated in cases and controls, risks for disease will be overestimated by neglecting dependency between variables. In the presented datasets, this resulted in a up to 12% overestimation of the risk. CONCLUSIONS: We showed how the height of over- or underestimation of risks can be evaluated when dependencies between two variables are neglected. This is important to evaluate the predictive value of combinations of features in cases where no data are available on associations in controls.

Evidence-based recommendations for the management of ankylosing spondylitis: systematic literature search of the 3E Initiative in Rheumatology involving a broad panel of experts and practising rheumatologists.

OBJECTIVE: Recommendations and/or guidelines represent a popular way of integrating evidence-based medicine into clinical practice. The 3E Initiatives is a multi-national effort to develop recommendations for the management of rheumatic diseases, which involves a large number of experts combined with practising rheumatologists addressing specific questions relevant to clinical practice. METHODS: Ten countries participated in three rounds of discussions and votes concerning the management of AS. A set of nine questions was formulated in the domains of diagnosis, monitoring and treatment, after a Delphi procedure. A literature search in MedLine was conducted. Predefined outcome parameters for the domains of diagnosis, monitoring and treatment were assessed. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements by each national group, following which the final international recommendations were formulated. RESULTS: A total of 2699 papers were found and 467 were selected for analysis. Twelve key recommendations were developed: three in the domain of diagnosis addressing general diagnostic considerations, early AS diagnosis and general practitioners' referral recommendations; three concerning monitoring of AS disease activity, severity and prognosis; six concerning pharmacological treatment (except biologics): non-steroidal anti-inflammatory drugs/COX-II inhibitors, bisphosphonates and treatment of enthesitis. The compiled agreement among experts ranged from 72% to 93%. CONCLUSION: Recommendations for the management of AS were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement. Involvement of a larger and more representative group of rheumatologists may improve their dissemination and implementation in daily clinical practice.

Healthcare consumption and direct costs of rheumatoid arthritis in Belgium.

The aim of this study was to compare the socioeconomic consequences of early and late rheumatoid arthritis in Belgium and to assess the patient out-of-pocket contributions. This multicentre longitudinal study in Belgium evaluated patients with rheumatoid arthritis. Early disease was defined as diagnosis since less than 1 year. At baseline sociodemographic and disease characteristics were assessed and during the following year patients recorded all healthcare- and non-healthcare-related direct costs and out-of-pocket contributions. The study included 48 patients with early and 85 patients with late rheumatoid arthritis. Mean disease duration was 0.5 vs 12.5 years in patients with early and late rheumatoid arthritis, respectively. The disease activity score (DAS28) was comparable between both groups (4.1 vs 4.5, p = 0.14), but physical function (Health Assessment Questionnaire, HAQ) was more impaired in patients with long-standing disease (1.0 vs 1.7, p < 0.001). Work disability had increased from 2% in patients with early to 18% in patients with late disease. The annual societal direct costs per patient were 3055 Euros (median: 1518 Euros) opposed to 9946 Euros (median: 4017 Euros) for early and late rheumatoid arthritis, respectively. The higher direct cost for patients with long-standing disease was seen for all categories, but especially for physiotherapy and need for devices and adaptations. Patients with early as well as late disease contribute out of pocket about one-third to the direct healthcare costs. Within each group, HAQ was a strong determinant of costs. In Belgium, patients with long-standing rheumatoid arthritis are nine times more likely to be work disabled than patients with less than 1 year disease duration and have a threefold increase in costs. Differences in healthcare consumption between patients could be mainly explained by differences in physical function (HAQ).

Chemical agents and enzymes used for the extraction of gut lymphocytes influence flow cytometric detection of T cell surface markers.

Chemical agents (DTT, EDTA) and enzymes (collagenase, DNAse) are often used for the generation of a single cell suspension from tissue samples. In this study, flow cytometry was used to examine the effect of chemical agents and enzymes on the expression of cell membrane markers of T lymphocytes from tonsils and peripheral blood. Expression of CD4, CD8, CD25, CD38, L-selectin, CD44, alphaEbeta7 and alpha4beta7 were studied. Incubation of lymphocytes with DTT and EDTA resulted in a decrease of CD38, alphaEbeta7 and alpha4beta7 expression. Incubation with collagenase A and DNAse resulted in a decrease of CD25, L-selectin, alphaEbeta7 and alpha4beta7. The results of this study indicate that a careful interpretation is necessary for phenotypic descriptions of lymphocyte populations obtained by enzymatic isolation techniques.

Review article: bone and joint diseases in inflammatory bowel disease.

The intestinal and articular systems are closely linked in inflammatory bowel disease. Clinical and immunological studies support an important aetio-pathogenetic link between intestinal and articular inflammation. There is increasing evidence for a negative link between bone mass density and intestinal inflammation. This paper will focus on the prevalence, aetio-pathogenesis and treatment of arthritis (peripheral, sacroiliitis and spondylitis) and osteoporosis in inflammatory bowel disease.

Focal up-regulation of E-cadherin-catenin complex in inflamed bowel mucosa but reduced expression in ulcer-associated cell lineage.

The E-cadherin-catenin complex is important for the maintenance of epithelial architecture. We studied its expression in Crohn disease, ulcerative colitis, acute ileitis, and controls. Immunohistochemical stainings for E-cadherin, alpha-catenin, beta-catenin and gamma-catenin were performed. E-cadherin messenger RNA (mRNA) was detected using riboprobes. In active inflammation, there was up-regulation of the complex. In particular, epithelium adjacent to ulcers showed increased expression of protein and mRNA, but in ulcer-associated cell lineage, the intensity of staining was weak to negative. In focal inflammation, up-regulation was found in affected areas. Reparative epithelium growing over denuded areas showed weaker expression. Since structural or functional perturbation in any of the molecules of the E-cadherin-catenin complex results in loss of intercellular adhesion, the preexistent epithelium may benefit from up-regulation to try to maintain its normal architecture under inflammatory conditions. Reduced expression in reparative epithelium and ulcer-associated cell lineage could facilitate the motility of these cells.

Bowel inflammation and the spondyloarthropathies.

The concept of spondyloarthropathies gathers together a group of chronic diseases in which not only the locomotor system is involved but also other organs, especially the gastrointestinal tract. In humans, ileocolonoscopic studies demonstrated the presence of inflammatory gut lesions in all the diseases in the spondyloarthropathy group; their presence varied in the different diseases between 20% and 70%. The inflammation could be related to specific disease features in the spondyloarthropathies. Further research supports the hypothesis of subclinical inflammatory bowel disease in some patients with spondyloarthropathy, in which the locomotor inflammation was the only clinical manifestation. The link between gut inflammation and arthropathy has also been demonstrated in animal models, notably the human leukocyte antigen B27 transgenic rats. The temporal relationship between activity and severity of colonic involvement and flares of peripheral arthritis directs treatment of choice. For all forms of enterogenic arthropathies, nonsteroidal anti-inflammatory drugs remain the acute treatment form. Caution is in order, however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation.

Goldsalts, levamisole and D-penicillamine as first choice slow-acting antirheumatic drugs in rheumatoid arthritis--a long-term follow-up study.

In the present study, 345 rheumatoid arthritis patients were treated using goldsalts, D-Penicillamine or levamisole as the slow-acting antirheumatic drug of first choice. Goldsalts were given to 182 patients, levamisole to 139 and D-Penicillamine to 24. At the time of the present evaluation, 83 patients were still on goldsalts (44.6%), 63 on levamisole (45.2%) and 11 on D-Penicillamine (45.9%). Adverse reactions required interruption of treatment in 64 patients on goldsalts (35.2%), in 44 on levamisole (31.7%) and in 5 on D-Penicillamine (20.8%). Inefficacy was responsible for withdrawal of 33 patients receiving goldsalts (18.1%), 30 receiving levamisole (21.6%) and 8 receiving D-Penicillamine (33.3%). The duration of treatment was 4.6 years for goldsalts, 3.6 years for levamisole and 3.6 years for D-Penicillamine. In the present analysis none of the compounds was found to have a definite advantage over the others. The rather favourable treatment continuation rates in this study can be attributed to the fact that the slow-acting antirheumatic drugs were given at an early stage of the disease, preferably before the occurrence of radiological lesions.