Objective Ultraviolet (UV) radiation is considered to be an important environmental factor in the clinical course of children with juvenile dermatomyositis (DM). We aimed to evaluate the association between UV radiation and severe disease outcomes in juvenile DM. Methods This is a cross-sectional study of patients with juvenile DM enrolled in the US multicenter Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry from 2010 to 2015. The mean UV index (UVI) in the calendar month prior to symptom onset in each subject's zip code was calculated from daily satellite solar noon measurements. Multivariable logistic regression was used to model the relationship between the mean UVI and calcinosis as well as other outcomes of severe disease. Covariates included sex, race, age, time to diagnosis, disease duration, and latitude. Results In a multivariable model, there was no association between the mean UVI and calcinosis. African American race was associated with a 3-fold greater odds of calcinosis. However, there was a significant statistical interaction between race and mean UVI. Accounting for this interaction, the odds of calcinosis markedly decreased in African American subjects and steadily increased in non-African American subjects over a range of increasing the mean UVI. Higher mean UVI was associated with decreased odds of using biologics or nonmethotrexate disease-modifying antirheumatic drugs and skin ulceration. Conclusion We described a novel association between UV radiation, calcinosis, and race in a large cohort of patients with juvenile DM. This study furthers our knowledge of the role of UV radiation in the clinical course of juvenile DM and highlights the complex interplay between genes and environment in the clinical phenotypes and development of calcinosis in children with juvenile DM.

Lupus nephritis (LN) affects many patients with juvenile systemic lupus erythematosus (SLE) and is a significant cause of disease morbidity. Membranous plus proliferative LN (M + PLN) may represent a more difficult to treat subtype of juvenile LN, compared to isolated proliferative LN (PLN). In this retrospective observational study, we utilized data from the Childhood Arthritis and Rheumatism Research Alliance (CARRA) registry to compare response rates for pediatric M + PLN versus PLN. Response was assessed at the most recent CARRA registry visit gathered ≥6 months after diagnostic kidney biopsy. Estimated glomerular filtration rate (GFR) less than 90 ml/min/1.73 m(2), indicating renal insufficiency, was found in 16.1% of patients with M + PLN and 6.1% of patients with PLN (P = 0.071). We found no significant difference in achievement of response in either hematuria or proteinuria between PLN and M + PLN groups or between subgroups determined by presence of class III vs. class IV proliferative disease. Exposure rates to mycophenolate, cyclophosphamide, and rituximab were similar between groups. Future studies will be necessary to correlate pediatric LN renal histology data with treatment response as well as other disease outcome measures.

Children with systemic lupus erythematosus (SLE) have a high prevalence of antiphospholipid (aPL) antibodies and are at increased risk for aPL-related thrombosis. We investigated the association between annexin A5 anticoagulant activity and antibodies to the domain I portion of β2-glycoprotein I (anti-DI antibodies), and propose a potential mechanism for the pathogenesis of aPL-related thrombosis. Using samples from 183 children with SLE collected during the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we examined resistance to the anticoagulant effects of annexin A5, using the annexin A5 resistance (A5R) assay, and evaluated for anti-DI IgG antibodies. Children with SLE had higher frequency of anti-D1 antibodies ( p = 0.014) and significantly reduced A5R compared to pediatric controls: mean A5R = 172 ± 30% versus 242 ± 32% ( p < 0.0001). Children with SLE and positive anti-DI antibodies had significantly lower mean A5R levels compared to those with negative anti-DI antibodies: mean A5R = 155 ± 24% versus 177 ± 30% ( p < 0.0001). In multivariate analysis, anti-DI antibodies ( p = 0.013) and lupus anticoagulant (LA) ( p = 0.036) were both independently associated with reduced A5R. Children with SLE have significantly reduced annexin A5 anticoagulant activity that is associated with the presence of LA and anti-DI antibodies.

Children with juvenile idiopathic arthritis (JIA) often exhibit growth impairments. Treatment with adalimumab (ADA) has been shown to be safe and effective in JIA patients (pts) when dosed every other week (eow) for up to 3 years [1], but the effect of ADA on growth is not known.

Early diagnosis of macrophage activations syndrome (MAS) in systemic juvenile idiopathic arthritis (sjia) may be challenging because it may mimic the clinical features of the underlying disease or be confused with an infectious complication. However, the diagnostic value of the guidelines for hemophagocytic lymphohistiocytosis (HLH) or sjia-associated MAS has seldom been examined.

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.

Methods Patients with polyarticular course JIA (N=171) were enrolled in a phase 3, randomized-withdrawal, doubleblind (DB), stratified, parallel-group study, which consisted of a 16-wk open-label (OL) lead-in, a 32-wk DB phase, and an up to 5 year OL extension phase that included BSA dosing prior to a switch to fixed dose (FD). Patients on ADA (24 mg/m; max dose, 40 mg) were evaluated based on ACR pediatric response criteria for improvement (ACR Pedi 30/50/70/90) and monitored for adverse events (AEs).

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Address: 1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA, 2Albert Einstein College of Medicine, Bronx, NY, USA, 3Children's Hospital and Reginal Medical Center, Seattle, WA, USA, 4Duke University Medical Center, Durham, NC, USA, 5Childrens Hospital of Los Angeles, Los Angeles, CA, USA, 6Ohio State University and Children's Hospital, Columbus, OH, USA, 7Schneider Children's Hospital, New Hyde Park, NY, USA and 8Amgen, Thousand Oaks, CA, USA * Corresponding author

Objective To evaluate the impact of duration of untreated symptoms in children with juvenile dermatomyositis (JDM) on clinical and laboratory status at diagnosis.Study design We examined physical and laboratory data from the first physician visit for 166 untreated children with JDM. Disease activity scores (DASs) assessed skin and muscle involvement. Height and weight were compared with the National Health and Nutrition Examination Survey III dataset. Duration of untreated illness was designated as the time from first sign of rash or weakness to diagnostic visit.Results Boys and girls with untreated JDM were shorter and lighter than national norms (P > .0005 for both), and nonwhite children were weaker than white children (P > .0005). Older children had more dysphagia, (P = .017) and arthritis (P > .001). Duration of untreated JDM was negatively associated with DAS weakness (P > .0005), unrelated to DAS skin, and positively associated with pathological calcifications (P = .006). With untreated disease >= 4.7 months, serum levels of 4 muscle enzymes (aldolase, lactic dehydrogenase, creatine kinase, serum glutamic-oxaloacetic transaminase/aspartate aminotransferase) tended toward normal (P > .01 for each).Conclusions Duration of untreated symptoms is an important variable and should be included in decisions concerning both diagnostic criteria and intensity of therapy for children with JDM.

OBJECTIVE Previous studies showed that etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA. METHODS Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of > or = 30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by > or = 30%.) RESULTS Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for > or = 4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to < or = 5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for > or = 4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit. CONCLUSION Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for > or = 4 years.

Objective. To obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM).Methods. Parents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis.Results. Children for which both a parent interview and physician medical records at diagnosis were available (n = 286) were included. Diagnoses were as follows: definite/probable JDM (n = 234, 82%), possible JDM (n = 43, 15%,), or rash only (n = 9, 3%). The group was predominantly white (71%) and had a girl:boy ratio of 2:1. Although the mean age at onset was 6.7 years for girls and 7.3 years for boys, 25% of the children were 54 years old at disease onset. In the 3 months before onset, 57% of the children had respiratory complaints, 30% had gastrointestinal symptoms, and 63% of children with these symptoms of infection were given antibiotics.Conclusion. This study provides evidence that JDM affects young children. The symptoms of the typical rash and weakness often follow a history of respiratory or gastrointestinal complaints. These data suggest that the response to an infectious process may be implicated in JDM disease pathogenesis.