Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity

Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials.     

Comparison Between INSPIRE and Domjan method for measuring lumbar lateral flexion in patients of psoriatic arthritis (PsA) and correlation with radiographic damage

Clinical Rheumatology - Assessment of spinal lateral flexion (SLF) is important in spondyloarthritis (SpA). The INSPIRE method of measuring SLF requires one set of measurements, is faster,...     

Outcome of pregnancy in women with psoriatic arthritis compared to healthy controls

Clinical Rheumatology - The mean age at onset of psoriatic arthritis (PsA) ranges between the 4th–6th decades of life. However, little is known about fertility and pregnancy outcome in PsA...     

The SLICC inception cohort for atherosclerosis

The Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) is a group of rheumatologists and methodologists from 27 international centers who have a particular interest and expertise in systemic lupus erythematosus. Initially, its efforts focused on development and validation of disease activity and damage indices. In 2000, the SLICC Registry for Atherosclerosis was established to determine the incidence, prevalence, nature, and risk factors of atherosclerotic coronary artery disease in systemic lupus erythematosus. Risk factors for coronary artery disease at presentation to the cohort were reported, as well as their accumulation over the first few years. Development of the metabolic syndrome was also described. Among the first 1078 patients who entered the cohort, 61 vascular events have occurred in 47 patients who were older at diagnosis and more likely male and hypertensive than were the patients without vascular events. Additional studies using this cohort are ongoing.     

Manometric, sensorimotor, and neurophysiologic evaluation of anorectal function

With advances in diagnostic technology, it is now accepted that in the field of functional bowel disorders, symptom-based assessment is unsatisfactory as the sole means of directing therapy. A robust taxonomy based on underlying pathophysiology has been suggested, highlighting a crucial role for physiologic testing in clinical practice. A wide number of complementary investigations currently exist for the assessment of anorectal structure and function, some of which have a clinical impact in patients with functional disorders of evacuation and continence by markedly improving diagnostic yield and altering management. The techniques, limitations, measurements, and clinical use of manometric, sensorimotor, and neurophysiologic tests of anorectal function are presented.     

Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: A multinational,double‐blind,randomized, placebo‐controlled clinical trial

Objective

Current treatment options for psoriatic arthritis (PsA) are limited. Leflunomide, an oral pyrimidine synthesis inhibitor, is highly effective in the treatment of rheumatoid arthritis, and small studies have suggested similar efficacy in PsA. We undertook this double‐blind, randomized, placebo‐controlled trial to evaluate the efficacy and safety of leflunomide in patients with PsA and psoriasis.

Methods

One hundred ninety patients with active PsA and psoriasis (at least 3% skin involvement) were randomized to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. The primary efficacy end point was the proportion of patients classified as responders by the Psoriatic Arthritis Response Criteria (PsARC). Additional efficacy (joint and skin involvement), safety, and quality‐of‐life assessments were performed.

Results

At 24 weeks, 56 of 95 leflunomide‐treated patients (58.9%; 95% confidence interval [95% CI] 48.4–68.9) and 27 of 91 placebo‐treated patients (29.7% [95% CI 20.6–40.2]) were classified as responders by the PsARC (P < 0.0001). Significant differences in favor of leflunomide were also observed in the proportions of patients achieving modified American College of Rheumatology 20% improvement criteria, improvement in the designated psoriasis target lesion, and mean changes from baseline in Psoriasis Area and Severity Index scores and quality‐of‐life assessments. Diarrhea and alanine aminotransferase increases occurred at higher rates in the leflunomide group. No cases of serious liver toxicity were observed.

Conclusion

Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies.

     

Natural history of hypercholesterolemia in systemic lupus erythematosus.

OBJECTIVE: To determine the natural history of hypercholesterolemia in the first 3 years of disease in an inception cohort of patients with systemic lupus erythematosus (SLE) followed at a single center and to determine the influence of hypercholesterolemia on the subsequent development of coronary artery disease (CAD) related events. METHODS: We identified patients who were seen at the University of Toronto lupus clinic within 1 year of diagnosis from January 1, 1974, to December 31, 1987, and who were seen at least once a year in the first 3 years. Patients were divided into 3 groups: Normal cholesterol: serum total cholesterol (TC) < 5.2 mmol/l throughout the 3 year period of study. Sustained hypercholesterolemia: at least one measurement of TC of > 5.2 mmol/l in each of the first 3 years at the clinic. Variable hypercholesterolemia: TC > 5.2 mmol/l in no more than 2 of the first 3 years of followup. Patients were followed from inception until the present day. The primary outcome was the time of the first CAD related event (myocardial infarction, angina, or sudden unexplained death). RESULTS: One hundred thirty-four patients (118 women, 16 men) were studied: 33 (24.6%) had normal cholesterol, 54 (40.3%) had sustained hypercholesterolemia, and 47 (35.1%) had variable hypercholesterolemia. Using multiple logistic regression the best predictors of sustained hypercholesterolemia were cumulative dose of steroids, no antimalarial therapy, and age of onset of SLE > 35 years old. CAD related events occurred in 1 (3%) of the normal TC group, 3 (6.4%) of the variable group, and in 15 (27.8%) of the sustained group (p = 0.003), 79% of all CAD events occurred in the sustained group. The best predictors of CAD were sustained hypercholesterolemia, lung involvement, and age at onset of SLE > 35 years. CONCLUSION: Within 3 years of diagnosis, 75.4% of patients with SLE had elevated TC, which was sustained in 40.3% of all patients. Older age at onset as well as increased cumulative dose of steroids and no antimalarial therapy are significant predictors of this group. It is this group that experiences the majority of CAD related events. Aggressive lipid lowering therapy should be targeted at such patients.