Objective. Systemic juvenile idiopathic arthritis (JIA) is frequently associated with the development of macrophage activation syndrome. This study was undertaken to better understand the relationship between systemic JIA and macrophage activation syndrome.Methods. Gene expression profiles were examined in 17 patients with untreated new-onset systemic JIA, 5 of whom showed evidence of subclinical macrophage activation syndrome (of whom 2 eventually developed overt macrophage activation syndrome). Peripheral blood mononuclear cells (PBMCs) were separated on Ficoll gradients, and purified RNA was analyzed using Affymetrix GeneChip expression arrays. A fraction of the PBMCs were used for flow cytometry to define the cellular composition of the samples.Results. Two hundred twenty-five differentially expressed genes (P < 0.05) that distinguished patients with systemic JIA from healthy controls (n ‫؍‬ 30) were identified. Clustering analysis indicated that expression patterns correlated with serum ferritin levels. Three main clusters distinguished systemic JIA patients with highly elevated ferritin levels (including those with subclinical macrophage activation syndrome) from those with normal or only moderately elevated ferritin levels. The first cluster comprised genes involved in the synthesis of hemoglobins and structural proteins of erythrocytes. This transcriptional profile was consistent with immature nucleated red blood cells, likely reflective of high red blood cell turnover. Also included were transcripts indicating immature granulocytes. The second cluster was enriched for genes involved in cell cycle regulation. The third cluster was enriched for genes involved in innate immune responses, including those involved in the negative regulation of Toll-like receptor/ interleukin-1 receptor-triggered inflammatory cascades and markers of the alternative pathway of macrophage differentiation. Additional differentially expressed genes of interest were those involved in the cytolytic pathway, including SH2D1A and Rab27a. Conclusion. These data indicate that gene expression profiling can be a useful tool for identifying early macrophage activation syndrome in patients with systemic JIA.At onset, systemic juvenile idiopathic arthritis (JIA), which constitutes ϳ10% of all cases of JIA, is distinguished from other forms of JIA by the prominence of extraarticular features, such as spiking fevers,

Intense exercise therapy is effective in initially treating childhood CRPS and is associated with low rate of long-term symptoms or dysfunction.

ABSTRACT. Objectives. To determine initial intravenous gammaglobulin (IVIG) treatment failures in Kawasaki disease (KD) and to report the outcome of retreatment and our use of pulse intravenous (IV) methylprednisolone and cyclophosphamide in patients with persistent KD.Study Design. Retrospective analysis of the treatment and response of children with KD over 3 years.Results. Fifty (77%) of 65 patients completely responded to a single treatment with IVIG (2 g/kg). Fifteen patients (23%) required retreatment; 10 patients fully responded but 5 had persistent disease (3 developed coronary aneurysms and 4 developed coronary artery thrombosis). Four of these 5 patients with persistent disease were treated with pulse IV methylprednisolone and 2 were also treated with IV cyclophosphamide. There was no progression of coronary aneurysms and no deaths. No initial patient characteristics predicted IVIG treatment failure or the development of coronary aneurysms.Conclusion. Nearly 23% of patients with KD may require retreatment and 8% may develop coronary aneurysm. Additional antiinflammatory therapy, such as IV methylprednisolone and IV cyclophosphamide, may be helpful in treating persistent KD. Pediatrics 2000;105(6). URL: http://www.pediatrics.org/cgi/content/full/105/6/ e78; corticosteroids, vasculitis, Kawasaki disease, heart disease, gammaglobulin therapy, cyclophosphamide.

The MITAX, MYOACT and MDI tools, which are now undergoing validity testing, should enhance the consistency, comprehensiveness and reliability of disease activity and damage assessment in patients with myositis.

Objective. Macrophage activation syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic macrophages. Levels of soluble interleukin-2 receptor ␣ (sIL-2R␣) and soluble CD163 (sCD163) may reflect the degree of activation and expansion of T cells and macrophages, respectively. This study was undertaken to assess the value of serum sIL-2R␣ and sCD163 in diagnosing acute macrophage activation syndrome complicating systemic juvenile idiopathic arthritis (JIA).Methods. Enzyme-linked immunosorbent assay was used to assess sIL-2R␣ and sCD163 levels in sera from 7 patients with acute macrophage activation syndrome complicating systemic JIA and 16 patients with untreated new-onset systemic JIA. The results were correlated with clinical features of established macrophage activation syndrome, including ferritin levels.Results. The median level of sIL-2R␣ in the patients with macrophage activation syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P ‫؍‬ 0.003). Similarly, the median level of sCD163 in patients with macrophage activation syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P ‫؍‬ 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2R␣ or sCD163 were comparable with those in patients with acute macrophage activation syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P ‫؍‬ 0.11), lower platelet counts, and significantly higher ferritin levels (P ‫؍‬ 0.02). Two of these 5 patients developed overt macrophage activation syndrome several months later.Conclusion. Levels of sIL-2R␣ and sCD163 are promising diagnostic markers for macrophage activation syndrome. They may also help identify patients with subclinical macrophage activation syndrome.In pediatric rheumatology the term "macrophage activation syndrome" refers to a set of symptoms caused by excessive activation and proliferation of T cells and well-differentiated macrophages (1,2). Such activation leads to a potentially fatal overwhelming inflammatory reaction. The pathognomonic feature of macrophage activation syndrome, the presence of numerous, welldifferentiated macrophages (histiocytes) actively phago-

Objective. To identify differences in peripheral blood gene expression between patients with different subclasses of juvenile idiopathic arthritis (JIA) and healthy controls in a multicenter study of patients with recent-onset JIA prior to treatment with diseasemodifying antirheumatic drugs (DMARDs) or biologic agents. Results. A total of 9,501 differentially expressed probe sets were identified among the JIA subtypes and controls (by analysis of variance; false discovery rate 5%). Specifically, 193, 1,036, 873, and 7,595 probe sets were different in PBMCs from the controls compared with those from the ERA, persistent oligoarthritis, RF-negative polyarthritis, and systemic JIA patients, respectively. In patients with persistent oligoarthritis, RF-negative polyarthritis, and systemic JIA subtypes, up-regulation of genes associated with interleukin-10 (IL-10) signaling was prominent. A hemoglobin cluster was identified that was underexpressed in ERA patients but overexpressed in systemic JIA patients. The influence of JAK/STAT, ERK/MAPK, IL-2, and B cell receptor signaling pathways was evident in patients with persistent oligoarthritis. In systemic JIA, up-regulation of innate immune pathways, including IL-6, Toll-like receptor/IL-1 receptor, and peroxisome proliferatoractivated receptor signaling, were noted, along with down-regulation of gene networks related to natural killer cells and T cells. Complement and coagulation pathways were up-regulated in systemic JIA, with a subset of these genes being differentially expressed in other subtypes as well. Methods

Objective Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. Methods A total of 221 participants with pediatric SLE (ages 10–21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n = 113) or placebo (n = 108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. Results Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P = 0.24). The atorvastatin group achieved lower hsCRP (P = 0.04), total cholesterol (P < 0.001), and low-density lipoprotein (P < 0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023–0.0144 mm/year; P < 0.05). Serious adverse events and critical safety measures did not differ between groups. Conclusion Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.

Objective. To evaluate risk factors for subclinical atherosclerosis in a population of patients with pediatric systemic lupus erythematosus (SLE).Methods. In a prospective multicenter study, a cohort of 221 patients underwent baseline measurements of carotid intima-media thickness (CIMT) as part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE disease measures, medications, and traditional risk factors for atherosclerosis were assessed. A standardized protocol was used to assess the thickness of the bilateral common carotid arteries and the mean maximal IMT of 12 segments. Univariable analysis identified potential associations with CIMT, which were examined in multivariable linear regression modeling.ClinicalTrials.gov identifier: NCT00065806.