Objectives

To develop widely acceptable preliminary criteria of global flare for childhood-onset SLE (cSLE).

Methods

Pediatric rheumatologists (n=138) rated a total of 358 unique patient profiles (PP) with information about the cSLE flare descriptors (cSLE-FD) from two consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-dsDNA antibodies, disease activity index score, protein/creatinine (P/C) ratio, complement levels and ESR. Based on 2996 rater responses about the course of cSLE (baseline vs. follow-up) the accuracy (sensitivity, specificity, area under the receiver operating characteristic curve) of candidate flare criteria was assessed. An international consensus conference was held to rank these candidate flare criteria as per the ACR-recommendations for the development and validation of criteria sets.

Results

The highest ranked candidate criteria considered absolute changes (Δ) of the SLEDAI or BILAG, MD-global, P/C ratio, and ESR; Flare scores can be calculated [0.5 × ΔSLEDAI + 0.45 × ΔP/C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR], where values ≥ 1.04 are reflective of a flare. Similarly, BILAG-based flare scores [0.4 × ΔBILAG + 0.65 × ΔP/C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR] of ≥ 1.15 were diagnostic of a flare. Flare scores increase with flare severity.

Conclusions

Consensus has been reached on preliminary criteria for global flares in cSLE. Further validation studies are needed to confirm the usefulness of the cSLE flare criteria in research and for clinical care.

Background. Infliximab (INF) has been shown to be beneficial in treating refractory uveitis, however, no data exist on optimal dosing and the efficacy of higher dosing. Objectives. To compare the efficacy of low-dose (LD) (<10 mg/kg), moderate-dose (MD) (≥10–15 mg/kg), and high-dose (HD) INF (≥15–20 mg/kg) in the treatment of uveitis. Methods. Retrospective chart review children with uveitis diagnosed at Childrens Hospital Los Angeles and Millers Children's Hospital, CA, USA. Results. Of the 34 INF-treated children, 6 patients received LD, 19 received MD, and 9 received HD. Average disease duration prior to therapy was 10.6, 24.6, and 37.1 months each group, respectively. Topical steroids were discontinued after an average of 3 months, 9.5 months, and 10.2 months in the LD, MD, and HD groups, respectively. We found that 66% of patients receiving LD, 42% of MD, and 66% receiving HD INF failed therapy and required either dose escalation or alternate medication for disease control. Conclusions. INF is beneficial in the treatment of uveitis, and dose escalation up to 4 times above the approved dose is often necessary to achieve disease control in patients with uveitis. Doses < 10 mg/kg every 4 weeks may not be sufficient to control disease.

To our knowledge there have been no reports of scleroderma-like skin changes, not affecting the hand in prepubertal patients with Type I Diabetes Mellitus (T1DM). We report a prepubertal caucasian male with T1DM, and early morpheatype skin changes of the trunk and extremities, not involving the hand.

Objective

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disorder with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in SLE pathogenesis. STAT1 and STAT4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for SLE susceptibility.

Methods

Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 genes on chromosome 2 were genotyped using Illumina platform as a part of extensive association study in a large collection of 9923 lupus cases and controls from different racial groups. DNA from patients and controls was obtained from peripheral blood. Principal component analyses and population based case-control association analyses were performed and the p values, FDR q values and Odds ratios with 95% confidence intervals (95% CIs) were calculated.

Results

We observed strong genetic associations with SLE and multiple SNPs located within the STAT4 gene in different ethnicities (Fisher combined p= 7.02×10−25). In addition to strong confirmation of the association in the 3rd intronic region of this gene reported previously, we identified additional haplotypic association across STAT4 gene and in particular a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to the proximity to STAT4.

Conclusion

Our findings indicate that the STAT4 gene is likely to be a crucial component in SLE pathogenesis among multiple racial groups. The functional effects of this association, when revealed, might improve our understanding of the disease and provide new therapeutic targets.

Staphylococcus aureus, a common pulmonary pathogen in cystic fibrosis (CF), produces exotoxins that are extremely potent superantigens. A number of animal studies have shown that superantigens cause pulmonary inflammation, but the possible role of superantigens in CF has not been investigated. The present study assessed possible differences between control and CF B cells in presenting superantigens to T cells. Immortalized B-cell lines were used as superantigen-presenting cells to avoid environmental influences (e.g., infection or antibiotics) common to freshly isolated cells. The results show that CF B-cell lines presented a staphylococcal superantigen to the immortalized T-cell line (Jurkat) as effectively as did control B-cell lines as measured by interleukin-2 production. However, in contrast to the case for control B-cell lines, dexamethasone did not inhibit CF B-cell lines from presenting superantigen. The resistance of superantigen-presenting CF B cells to corticosteroids suggests that the pulmonary response to superantigens may be poorly regulated in CF, leading to an exaggerated inflammatory response to S. aureus.