Repetitive episodes of ischemia and reperfusion (I/R) are a cardinal feature of the pathogenesis of systemic sclerosis (SSc), which precedes tissue fibrosis. The complement system is a key mediator ...of tissue damage after I/R, primarily by activation of the lectin pathway. This study investigated whether serum levels and polymorphisms of mannose-binding lectin (MBL) and ficolin-2 (FCN2), two pattern recognition receptors of the lectin pathway, are associated with the predisposition to and clinical features of SSc.
A case-control study was undertaken involving 90 patients with SSc from a single SSc outpatient clinic and 90 age- and sex-matched blood donors. MBL and FCN2 levels and polymorphisms were measured in both groups, and in cases correlated with clinical data.
MBL levels and genotypes were equally distributed in cases and controls while there were some significant differences in FCN2 polymorphisms. Median MBL levels were higher in SSc cases with diffuse disease compared with controls (2.6 versus 1.0 μg/ml, P <0.001).
Overall, predisposition to SSc was not influenced by the lectin pathway of complement in our matched case-control study. However, our preliminary data suggest that MBL, and to a lesser extent FCN2, may modulate disease manifestations of SSc, particularly in diffuse cutaneous disease.
Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with increased risk of cardiovascular disease (CVD). Treatment for CVD may involve pharmacological agents ...that antagonise beta adrenergic receptors. These receptors may play an important role in immunology, and the effects of beta-blockers (BB) in RA is unknown. The aim of this study was to investigate the association between BB use and remission in patients with RA initiating tocilizumab +/− conventional synthetic (cs-) DMARD therapy. Methods: Data was pooled from five randomised trials investigating tocilizumab and/or csDMARD treatment in RA (primarily methotrexate). The association between BB use and remission according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) was assessed by Cox proportional hazard analysis. Sensitivity analysis in patients with pre-existing CVD and an exploratory analysis of the impact of other CVD drugs were conducted. Results: Data were available from 5502 participants, 594 (10.8%) of whom were using systemic BB. BB use was associated with less frequent SDAI remission in the total adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.57–0.87, p = 0.001 and CVD cohort adjusted HR 0.72 (0.57–0.90, p = 0.005). The association was consistent between trials (interaction p = 0.44) and treatment arms (interaction p = 0.06). No significant association between remission and β1-receptor selectivity was identified ( p = 0.16), and the association was independent from other cardiovascular drug use. Similar associations between BB use and CDAI remission were observed. Conclusion: In a large, pooled cohort of RA patients initiating csDMARDs and/or tocilizumab, BB use was independently associated with less frequent remission.
Background
We aimed to evaluate the construct validity of the Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) in Australian systemic sclerosis (SSc) patients.
Methods
SSc ...patients, identified through the Australian Scleroderma Cohort Study database, completed two quality-of-life instruments concurrently, the PROMIS-29 and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). The construct validity of the PROMIS-29 was assessed by the correlations between the PROMIS-29 and the SF-36 and Health Assessment Questionnaire Disability Index (HAQ-DI). Cronbach's alpha was used to test the internal reliability of all instruments in Australian SSc patients and non-parametric correlation, including Spearman's correlation, was used to test the construct validity of PROMIS-29 against the SF-36 and HAQ-DI.
Results
A total of 477 completed questionnaires were returned, equating to a response rate of 59.6%. The mean (±SD) age of respondents at the time of the survey was 64.1 (±11.1) years. They were predominantly female (87.4%), with limited disease subtype (lcSSc) (77.8%) and long disease duration from onset of first non-Raynaud's phenomenon symptom at the time of survey (10.9 ± 11.1 years). For the correlation analysis between the PROMIS-29 and the legacy instruments, all Spearman correlation coefficients were in the logical direction and highly significant suggesting that the PROMIS-29 is a good alternative to other validated measures of disease burden.
Conclusions
Our study indicates that the PROMIS-29 questionnaire is a valid instrument for measuring health-related quality of life in Australian females with lcSSc of long duration.
Objective
To simultaneously image bone and synovium in the individual joints characteristically involved in early rheumatoid arthritis (RA).
Methods
Forty patients with early, untreated RA underwent ...gadolinium‐enhanced magnetic resonance imaging (MRI) of the second through fifth metacarpophalangeal joints of the dominant hand at presentation, 3 months, and 12 months. In the first phase (0–3 months), patients were randomized to receive either methotrexate alone (MTX) or MTX and intraarticular corticosteroids (MTX + IAST) into all joints with clinically active RA. The MTX‐alone group received no further corticosteroids until the second phase (3–12 months), when both groups received standard therapy.
Results
In the first phase, MTX + IAST reduced synovitis scores more than MTX alone. There were significantly fewer joints with new erosions on MRI in the former group compared with the latter. During the second phase, the synovitis scores were equivalent and a similar number of joints in each group showed new erosions on MRI. In both phases, there was a close correlation between the degree of synovitis and the number of new erosions, with the area under the curve for MRI synovitis the only significant predictor of bone damage progression. In individual joints, there was a threshold effect on new bone damage related to the level of synovitis; no erosions occurred in joints without synovitis.
Conclusion
In early RA, synovitis appears to be the primary abnormality, and bone damage occurs in proportion to the level of synovitis but not in its absence. In the treatment of patients with RA, outcome measures and therapies should focus on synovitis.
Objective
Inflammatory arthritis of the hands is a frequent clinical presentation with a variable outcome. Patients not satisfying the classification criteria for recognized arthritides are described ...as having undifferentiated inflammatory arthritis, for which there are no accepted therapeutic algorithms. This study assessed the clinical outcome of patients with undifferentiated arthritis of the hands after use of a treatment algorithm, and evaluated the prognostic features in these patients.
Methods
One hundred consecutive patients with undifferentiated arthritis of the hands were assessed following use of a pragmatic treatment algorithm that was based on clinical presentation and response to treatment. The following standard step‐up treatment protocol was used: 1) nonsteroidal antiinflammatory drugs (NSAIDs), 2) a single dose of corticosteroid administered by either intramuscular or intraarticular injection, and 3) disease‐modifying antirheumatic drugs (DMARDs). Patients with specific rheumatologic diagnoses were excluded. The primary outcome was persistence of synovitis at 12 months.
Results
Seventy‐eight percent of patients received NSAIDs, 72% received corticosteroids, and 30% received DMARD therapy. Among patients who had synovitis at 12 months, the prevalence of rheumatoid factor (RF) seropositivity, swollen joints, and synovitis at baseline was greater than in those without persistent synovitis. Logistic regression analysis showed baseline investigations to be poor predictors of subsequent DMARD use, with the best predictor being persistence of synovitis at 12 weeks. Rheumatoid arthritis (RA) developed in 14 patients. Logistic regression analysis showed that significant predictors of RA were RF seropositivity and the painful joint count at baseline. No patient who experienced resolution of synovitis by 12 weeks had persistent synovitis that subsequently required DMARD therapy. Only 13% of patients entered remission. Early resolution of synovitis was associated with an excellent prognosis.
Conclusion
Undifferentiated arthritis of the hands is not a benign condition, with 30% of patients receiving DMARD therapy by 12 months and low remission rates. Results of the clinical assessment at 12 weeks is the single best predictor of future therapy. This study provides background data for use in determining future therapeutic interventions.
Objective
To determine the factors that predict clinical outcome at 6 months for patients with mild, early inflammatory arthritis.
Methods
Sixty‐three patients with mild, untreated, early arthritis ...were given a single dose of corticosteroids at presentation. Administration was intramuscular if disease was polyarticular (n = 53) or intraarticular if patients had <5 synovitic joints (n = 10). The primary outcome measure was clinical disease remission or persistence of arthritis at 6 months following injection.
Results
At 6 months following injection, 49 of the 63 patients (78%) had persistent inflammatory joint disease. The other 14 (22%) had clinical disease remission. Regression analysis showed that only disease duration was significantly associated with persistent arthritis (P < 0.05). The other significant factor (by chi‐square test) was the presence of the shared epitope (SE). Of the patients fulfilling the American College of Rheumatology (ACR) criteria at presentation (51% of the total), 53% with disease duration of ≤12 weeks at presentation had persistent disease 6 months later, compared with 94% of those who presented with disease duration of >12 weeks.
Conclusion
The strongest predictor of persistent disease was a disease duration of >12 weeks. Rheumatoid factor and SE were also predictors to a lesser extent. Patients who both fulfilled the ACR classification criteria for rheumatoid arthritis (RA) and had a short disease duration included some with an excellent prognosis. Therefore, 12 weeks may be a more appropriate disease duration to use for the RA classification criteria. Administering a bolus of corticosteroids may be a useful diagnostic/therapeutic approach.
Objective
To determine the outcome and the factors that predict the persistence of synovitis following intraarticular corticosteroid injections in patients with recent‐onset oligoarthritis.
Methods
...Fifty‐one patients with ≤5 joints with synovitis (disease duration ≤12 months) were treated with intraarticular injections of methylprednisolone into all joints with clinical synovitis. Predictors of outcome were sought, with the primary end point a complete response (no synovitis on clinical examination) at 12 weeks.
Results
Patient's and physician's assessments of disease activity, the swollen joint count, and function (by Health Assessment Questionnaire) were all significantly improved at 12 weeks (P < 0.001). Twenty‐nine patients (57%) were judged to have had a complete response at 2 weeks. The best predictor of response at 12 and 26 weeks was the presence or absence of synovitis at 2 weeks (P = 0.002 and P = 0.004, respectively). At 52 weeks of followup, nearly 50% of the patients still had evidence of synovitis.
Conclusion
Intraarticular corticosteroids are an effective treatment for early oligoarthritis, but there is still a high level of long‐term morbidity. Failure to respond by 2 weeks indicates a high likelihood of persistent disease, and this is relevant when producing management guidelines and selecting patients for studies focusing on early intervention.
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