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*B-coefficients or odds ratio when appropriate, odds ratio are printed in italics Multivariable linear and logistic regression analyses were used, where appropriate, to estimate the independent association of clinical and radiological TBJ involvement as independent variables with patient and disease characteristics, hand functions and activities, psychosocial variables and health-related quality of life as dependent variables. Statistical analysis Implications for practice

To compare efficacy, toxicity, and the pharmacokinetics of the combination of sulphasalazine (SASP) and methotrexate (MTX) vs MTX alone in the treatment of SASP-resistant RA we conducted a controlled open clinical trial. Forty RA patients with active arthritis despite adequate SASP therapy, were allocated randomly to regimes of either SASP+MTX or MTX alone. The patients were evaluated openly by a single observer for 24 weeks. In the first 15 patients using the combination, pharmacokinetics of MTX without and with SASP were studied. Thirty-eight patients completed the trial. The mean decrease in the disease activity score in the group of patients receiving the combination was significantly greater than in the MTX group (-2.6 vs -1.3 respectively). The same pattern was seen concerning the other efficacy variables. There was no difference in the occurrence of toxicity. SASP had no influence on the pharmacokinetics of MTX. In conclusion in this open study the efficacy of the combination of MTX and SASP seems to be superior to MTX alone, the toxicity of both therapies was similar. This effect was not explained by the pharmacokinetics of MTX which were not altered by concomitant SASP administration.

To study the effect of folates on discontinuation of methotrexate (MTX) as single-drug antirheumatic treatment due to toxicity, to determine which type of adverse events are reduced, to study the effects on the efficacy of MTX, and to compare folic with folinic acid supplementation in a 48-week, randomized, double-blind, placebo-controlled trial.Patients with active RA (n = 434) were randomly assigned to receive MTX plus either placebo, folic acid (1 mg/day), or folinic acid (2.5 mg/week). The initial MTX dosage was 7.5 mg/week; dosage increases were allowed up to a maximum of 25 mg/week for insufficient responses. Folate dosages were doubled once the dosage of MTX reached 15 mg/week. The primary end point was MTX withdrawal because of adverse events. Secondary end points were the MTX dosage and parameters of efficacy and toxicity of MTX.Toxicity-related discontinuation of MTX occurred in 38% of the placebo group, 17% of the folic acid group, and 12% of the folinic acid group. These between-group differences were explained by a decreased incidence of elevated liver enzyme levels in the folate supplementation groups. No between-group differences were found in the frequency of other adverse events or in the duration of adverse events. Parameters of disease activity improved equally in all groups. Mean dosages of MTX at the end of the study were lower in the placebo group (14.5 mg/week) than in the folic and folinic acid groups (18.0 and 16.4 mg/week, respectively).Both folate supplementation regimens reduced the incidence of elevated liver enzyme levels during MTX therapy, and as a consequence, MTX was discontinued less frequently in these patients. Folates seem to have no effect on the incidence, severity, and duration of other adverse events, including gastrointestinal and mucosal side effects. Slightly higher dosages of MTX were prescribed to obtain similar improvement in disease activity in the folate supplementation groups.

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Objectives To explore the association between radiographic and clinical involvement of the thumb base joint with patient and disease characteristics and with pain and limitations in activities in hand osteoarthritis (OA). Methods Baseline data of 151 patients with hand OA participating in a randomized clinical trial on the effectiveness of a multidisciplinary treatment program was used. Clinical involvement of the thumb base joint was defined as tenderness at palpation in at least one thumb base joint whereas radiological involvement was defined as Kellgren and Lawrence score ≥ 2 in at least one thumb base joint. Multivariable linear and logistic regression analyses were used, where appropriate, to estimate the independent association of clinical and radiological thumb base joint involvement as independent variables with patient and disease characteristics, hand functions and activities, psychosocial variables and health-related quality of life as dependent variables. Results: In 38% (n=58) of the patients (mean age 59.2 years, 83% female) ≥ 1 thumb base joint was tender on palpation whereas in 69% (93 out of 135 patients) ≥ 1 thumb base joints had KL8.4)), number of co morbidities (B(CI): 0.5 (0.0;1.0)), limitations in hand activities (Australian Canadian Osteoarthritis Hand Index) (B(CI): 4.0 (1.7;6.3)), passive coping strategies and pain (subscale “bodily pain” of the short form health survey (SF-36)) (B(CI): -6.8 (-12.8; -0.8)). Radiological involvement of the thumb base joint was, adjusted for clinical involvement, associated with age (B (CI): 4.8 (1.9; 7.7)), number of hand joints with KL7.8)) and presence of erosions (yes/no) (odds ratio (CI): 4.1(1.9;9.2)). Conclusions In patients with established hand OA clinical involvement of the thumb base is associated with a higher clinical burden whereas radiological involvement of the thumb base joints is associated with older age and more structural abnormalities. Our results imply that clinical involvement of the thumb base joint rather than radiological involvement should be a starting point for symptomatic treatment. An aberrant pain behavior style might underlie the expression of OA-related symptoms. Disclosure of Interest None Declared

To establish the symptoms and clinical course of juvenile-onset mixed connective tissue disease, we studied 14 patients, classified according the criteria of Kasukawa et al. The patient records were studied retrospectively and all patients were examined in a 1-day follow-up program. Systemic lupus erythematosus and polymyositis/dermatomyositis-like symptoms disappeared in time, whereas scleroderma-like symptoms (such as in the Raynaud phenomenon) and joint abnormalities persisted. Extensive limitation of joint function was found in four patients. At the time of follow-up, no active renal disease was found. Thrombocytopenia was still present in one of the three patients who had had this feature. All patients had abnormalities of esophageal motility. Long-term corticosteroid treatment was associated with aseptic bone necrosis in three patients and growth retardation in one. We conclude that the Kasukawa criteria are easy to apply to children, and that juvenile-onset mixed connective tissue disease has many similarities to the adult form of the disease.

Objective. To evaluate correlations between changes in anti–U1 RNA antibody levels and disease activity in 9 patients with systemic lupus erythematosus (SLE) overlap syndrome who were prospectively followed up for at least 3 years. Methods. Anti–U1 RNA antibody levels were measured quantitatively, using a nitrocellulose filter binding assay. Disease activity was measured with a validated SLE activity index. Results. All 9 major disease exacerbations were associated with peaks in anti–U1 RNA antibody level. Conclusion. These results seem to indicate that measuring anti–U1 RNA antibody levels can be useful for monitoring disease activity.

In a three year prospective study disease activity variables and levels of antibody against the RNP-peptides 70K and A were measured in 18 patients with mixed connective tissue disease. Antibody measurement entailed use of cloned autoantigens in an enzyme linked immunosorbent assay (ELISA). Fluctuations in antibody levels against 70K and A were most commonly noted in patients who also had changes in disease activity, but these changes in serology and disease activity were synchronous in only a minority of the episodes. Even major disease flares were associated with changes in anti-A levels in only a few, and with changes in anti-70K levels in none of the episodes. The data indicate that measurements of anti-70K and anti-A levels are not useful in monitoring disease activity or response to treatment in mixed connective tissue disease, and suggest that these antibody specificities do not play a direct part in the pathogenesis of disease manifestations.

Using the immunoblotting technique, sera from 433 patients with rheumatic diseases were screened for the presence of antibodies against several nuclear and cytoplasmic antigens, such as RNP, Sm, Ro(SSA), La(SSB), CR-19 (centromeric antigen), Topo-1 (Scl-70), Jo-1, histone and 56 kD. At the same time clinical data from these patients were collected without prior knowledge of the immunoblotting results. Syndrome-specific autoantibodies were found for mixed connective tissue disease (antibodies against the RNP related 70 kD antigen), for CREST (anti-CR-19 antibodies), for diffuse scleroderma (anti-Topo-1 antibodies) and for polymyositis (anti-Jo-1 antibodies). Almost all specific autoantibodies were present exclusively in patients with a connective tissue disease. Controls were only in a few cases positive for antihistone and anti-56 kD antibodies. Associations of specific autoantibodies with clinical and laboratory features of the patients were mostly as expected. However, some unexpected associations were ...

Sera of 34 patients with progressive systemic sclerosis and of 11 patients with polymyositis/dermatomyositis (PM/DM) were analyzed by the immunoblotting technique for the presence of marker antibodies. The presence of anti-centromere, anti-Topoisomerase-I (anti-Topo-I) and anti-Jo-1 antibodies was found to be highly specific for the CREST syndrome, diffuse scleroderma and PM/DM, respectively, but only of limited sensitivity (78, 44 and 45%, respectively). Anti-Topo-I positive diffuse scleroderma patients had a more severe disease (digital pitting scars and renal insufficiency) than anti-Topo-I negative diffuse scleroderma patients. Anti-Jo-1 was associated with interstitial lung disease. Longitudinal studies showed a constant antibody pattern. Our results confirm the clinical usefulness of these marker antibodies.

Description des signes cliniques et biologiques (anticorps anti RNP, anti Sm, anti k70, anti nucleaires, anti DNA natif) a propos de 5 enfants de 4 a 7 ans avec un recul moyen de 3,8 ans. Sont aussi etudies la motricite œsophagienne et la fonction respiratoire

A quantitative immunoblotting assay (QIBA) for the determination of specific antibody titres in human autoimmune sera is described. In this assay, a total HeLa nuclear protein fraction, immobilized on nitrocellulose blot strips, was used as source of antigens and immunoreactive species of autoantibodies were quantitated by an enzyme linked second antibody procedure. Besides being more discriminative, QIBA appeared to be up to 500 times more sensitive than immunodiffusion or immunoelectrophoresis. In this study we used 21 sera from patients with SLE or MCTD for a quantitative analysis of their specific autoantibody content. Within this group, a very diverse spectrum of antibody populations was observed; anti-RNP sera appeared to contain, among others, high tired antibody versus 70K and 31K polypeptides while all (n = 6) anti-Sm sera recognized a 25kD protein doublet. In a follow-up study of two MCTD patients significant flares in specific antibody content could be observed.

A novel frequently occurring autoantibody specificity in serum from connective tissue disease patients is described. The autoantibodies as detected by immunoblotting are directed against a 56,000 Dalton (56K) antigen, that after biochemical fractionation predominantly is found in the cytoplasmic fraction of various cell types and tissues. Attempts to localize the antigen more precisely were unsuccessful primarily because these antibodies do not produce a positive immunofluorescence pattern. The antigen in its native form is not associated with DNA or one of the common cytoplasmic or nuclear RNAs in the cell. Immunoprecipitation studies also showed that the protein is not closely associated with other proteins in a multi-component complex. Anti-56K antibodies are found in about 8% of patients with connective tissue disease, most commonly in patients with Sjögren's syndrome (14%). It is not found in patients with mixed connective tissue disease, polymyositis/dermatomyositis or scleroderma and rarely (less than 1%) in healthy control subjects. The fact that 22% of the anti-56K sera also contain La/SS-B antibodies support the idea that this antibody specificity might be characteristic for a subclass of Sjögren's syndrome patients.

Specific nuclear proteins, separated according to their molecular weight (mol. wt) by polyacrylamide gel electrophoresis (PAGE) and subsequently transferred to nitrocellulose sheets, are able to bind antibodies in sera from patients suffering from different types of connective tissue diseases. Antibodies against a characteristic set of nuclear protein antigens are found in sera from patients with mixed connective tissue disease (MCTD). Screening of 21 MCTD sera revealed a typical immunoblot pattern with major protein antigens of mol. wt 70,000 (20/21) (not identical with the Scl-70 antigen characteristic for scleroderma), mol. wt 31,000 (17/21), two proteins around mol. wt 23,000 (15/21) and two around mol. wt 19,000 (10/21). The 70,000, 23,000 and 19,000 antigens appeared to be rather insoluble nuclear proteins (i.e. components of the nuclear matrix). On behalf of their structural character they were present in nuclei from several types of cells but only in low amounts detectable in salt extracts of thymus acetone powder. The presence of antibodies directed against the mol. wt 70,000 antigen correlated strongly with the diagnosis of MCTD. This 70,000 antigen is not identical with the RNP antigen, a soluble ribonuclease sensitive ribonucleoprotein, since antibodies against nuclear RNP can be separated from anti-nuclear matrix antibodies by affinity chromatography using immobilized thymus salt extract. The distinct character of soluble nuclear RNP and structural nuclear matrix antigens is further supported by the fact that from 14 other anti-RNP sera obtained from patients with systemic lupus erythematosus (SLE), only three contained antibodies against the mol. wt 70,000 protein. Since the immunoblot pattern obtained with MCTD sera mostly was clearly distinguishable from the patterns obtained with sera from patients with related connective tissue diseases our results suggest that the immunoblotting technique might be useful as a diagnostic tool and support the concept of MCTD as a distinct entity.

Using the immunoblotting technique, sera from 433 patients with rheumatic diseases were screened for the presence of antibodies against several nuclear and cytoplasmic antigens, such as RNP, Sm, Ro(SSA), La(SSB), CR-19 (centromeric antigen), Topo-1 (Scl-70), Jo-1, histone and 56 kD. At the same time clinical data from these patients were collected without prior knowledge of the immunoblotting results. Syndrome-specific autoantibodies were found for mixed connective tissue disease (antibodies against the RNP related 70 kD antigen), for CREST (anti-CR-19 antibodies), for diffuse scleroderma (anti-Topo-1 antibodies) and for polymyositis (anti-Jo-1 antibodies). Almost all specific autoantibodies were present exclusively in patients with a connective tissue disease. Controls were only in a few cases positive for antihistone and anti-56 kD antibodies. Associations of specific autoantibodies with clinical and laboratory features of the patients were mostly as expected. However, some unexpected associations were found, for example polymyositis and calcinosis with anti-Sm antibodies, sicca symptoms with anti-centromere antibodies and leucopenia with Ro(SSA) and La(SSB).

Several micro-organisms, especially viruses, have been associated with juvenile and adult onset Still's disease. In the present study a search for probable triggering viral infections in five consecutive patients with early, active adult onset Still's disease has been made. In one patient echovirus 7 was identified as a probable triggering agent. Evidence of infection with this virus was acquired by virus cultures and serological tests. In two patients the illness was probably initiated by a rubella reinfection. Both had initially high stable monospecific IgG antibody titres but no IgM antibodies to this virus. In the remaining two cases no particular triggering viral infection could be designated. Evidence of a viral infection was thus found in three of these five patients. Adult onset Still's disease may represent a reaction pattern to certain infections.