ObjectiveAutoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes.MethodsA subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers.ResultsExisting consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis.ConclusionsDiagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts.

Objective. To develop and apply a model that allows prediction of current and future supply and demand for rheumatology services in the US.Methods. A supply model was developed using the age and sex distribution of current physicians, retirement and mortality rates, the number of fellowship slots and fill rates, and practice patterns of rheumatologists. increase the number of people with rheumatic disorders, growth in the Gross Domestic Product, and flat rheumatology supply due to fixed numbers entering the workforce and to retirements. The productivity of younger rheumatologists and women, who will make up a greater percentage of the future workforce, may also have important effects on supply. Unknown effects that could influence these projections include technology advances, more efficient practice methods, changes in insurance reimbursements, and shifting lifestyles. Current data suggest that the pediatric rheumatology workforce is experiencing a substantial excess of demand versus supply.Conclusion. Based on assessment of supply and demand under current scenarios, the demand for rheumatologists is expected to exceed supply in the coming decades. Strategies for the profession to adapt to this changing health care landscape include increasing the number of fellows each year, utilizing physician assistants and nurse practitioners in greater numbers, and improving practice efficiency.The American College of Rheumatology (ACR) created the Workforce Study Advisory Group and retained The Lewin Group to conduct a new workforce study of US rheumatologists in 2005, to project demand for rheumatology services, in order to guide policy regarding rheumatology manpower for the next 2 decades. The Lewin Group is an applied research and consulting group specializing in health policy issues. While workforce projections are not an exact science, they attempt to model future needs using information and assumptions from the present.

Objective. To assess the reliability and validity of the Disease Activity Score (DAS), an instrument used to evaluate children with juvenile dermatomyositis (JDM). Methods. Psychometric study of internal consistency, reliability, rater agreement, and the relationship with measures of muscle strength and disability was conducted. Results. The DAS ratings are internally consistent (reliability ‫؍‬ 0.89) and describe a wide range of disease activity. The pediatric rheumatologists in this study agree on the presence of most of the disease indicators. Their disagreements tend to cancel each other, resulting in highly correlated (r ‫؍‬ 0.79) overall measures across raters. Estimates of muscle weakness using the DAS and ratings of muscle strength obtained independently from therapists are highly related (r ‫؍‬ ؊0.77), but estimates of disease activity and disability are weakly related (r ‫؍‬ 0.20). Conclusion. The DAS exhibits evidence of good reliability and validity. The combination of skin and muscle strength assessments makes this easily administered instrument a useful addition in the evaluation of children with JDM. KEY WORDS. Juvenile dermatomyositis; Disease activity; Reliability; Validity. INTRODUCTIONJuvenile dermatomyositis (JDM) is the most common of the pediatric inflammatory myopathies, with an annual incidence of 3.2 per 1 million children in the US (1) and a mean age at diagnosis of 6.3 years (SD ϭ 3.4 years) (2,3).There are few validated assessments of either clinical (4) or laboratory-based (5) data that reliably evaluate the disease activity in children diagnosed with JDM. The assessments that are available focus on muscle strength and do not quantify levels of cutaneous involvement. Because the measurement of muscle strength is problematic in children who are younger than 4 years, such assessments are typically used for examinations of children who are older. As a result of this dearth of information, recent publications have focused on identifying the important variables in assessing disease activity as well as tissue damage (6 -9). Recently, we have documented that the cutaneous manifestations in JDM are strongly associated with evidence of systemic derangement of blood vessel morphology, thus strengthening the importance of the inclusion of the extent and severity of skin involvement in the assessment of disease activity (10). Several laboratory-based methods are now available as markers for disease activity, but no single test has yet proven to be a reliable indicator (5,8,11). Thus, there is an urgent need for a disease activity assessment that can measure more than muscle strength and be used to evaluate children of all ages who are diagnosed with JDM.The Juvenile Myositis Clinic at Northwestern University Medical School's Children's Memorial Hospital (Chicago, Illinois) has evaluated more than 210 children with JDM during the past 2 decades. In this time, a rapid assessment of each child's clinical status has evolved and been described as a measure of disease activity (to differentiate it fro...

Objective. To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE).Methods. One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models.Results. Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score.Conclusion. Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhoodonset SLE disease activity.

We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of disease activity in lupus nephritis. NGAL in serial plasma (PNGAL) and urine (UNGAL) samples was measured by enzyme-linked immunosorbent assay (ELISA) in 85 participants with pediatric systemic lupus erythematosus (pSLE), healthy children (n = 50), and children with juvenile idiopathic arthritis (JIA) (n = 30). Disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Plasma and urinary NGAL were significantly increased in subjects with pSLE compared with those with JIA or with healthy controls (all p < 0.03), and unrelated to subjects' age, weight, or height. Plasma and urinary NGAL were stable in pSLE subjects with unchanged disease activity. The pSLE subjects with worsening global or renal disease activity had a mean +/- standard error (SE) increase of UNGAL (in ng/ml) of 11.5 +/- 6.4 or 36.6 +/- 12.1 (p < 0.01), corresponding to a 156% or 380% increase, respectively. PNGAL increased with worsening disease but to a much lesser degree than UNGAL [global disease activity (mean +/- SE): 7.3 +/- 6.2 or 21%; renal disease activity: 20.2 +/- 6.0 or 51%; both p = not significant]. In conclusion, NGAL in urine but not in plasma represents a novel biomarker for renal disease activity in pSLE.

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.

Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS-proteins for detecting activity of LN over time. Using surface-enhanced or matrix assisted laser desorption/ ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), α1-acid-glycoprotein (AGP), lipocalintype prostaglandin-D synthetase (L-PGDS), albumin and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African-American) and 30 controls with juvenile idiopathic arthritis. All urinary PS-proteins were significantly higher with active versus inactive LN or in patients without LN (all p<0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 months before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001) and L-PGDS (p < 0.01) occurred, indicating that these PS-proteins are biomarkers of LN activity and may help anticipate the future course of LN.Corresponding Author: Hermine Brunner, MD, Cincinnati Children's Hospital Medical Center, William Rowe Division of Rheumatology, E 4010, 3333 Burnet Avenue, Cincinnati, Phone: (513) FAX: (513) NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptSystemic Lupus Erythematosus (SLE) is an inflammatory autoimmune disease and lupus nephritis (LN) is one of the main determinants of poor prognosis (1). Currently, LN is gauged by measuring circulating and excreted indicators of renal dysfunction, with supporting information from kidney biopsies. The latter constitute the current standard for diagnosing LN, providing a direct assessment of the presence, severity and activity of LN, and the degree of renal damage (2). Due to the invasive nature of kidney biopsies, clinicians base LN activity and its therapy on the results of urinary protein excretion, urinary sediment, creatinine clearance and serum albumin. These traditional markers are not accurate in assessing whether active LN is present or not, and none of them is predictive, i.e. can anticipate the course of LN.Using Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF MS) technology, we previously identified a LN urinary protein signature (PS), consisting of eight candidate biomarkers at the mass-to-charge ratios (m/z) of 2. 763, 22, 23, 44, 56, 79, 100, and 133 kDa (3).In this study, we present the identification of the specific proteins contained in this PS of children with LN. We further assayed plasma and urine samples of SLE patients and controls with juvenile idiopathic arthritis (JIA) to investigate the concurrent and predictive validity of the PS-proteins to serve as biomarkers of LN activity....

Objective. To examine the strength of the association between different measures of health-related quality of life (HRQOL), disability, pain, and well-being in children with chronic arthritis. To evaluate whether HRQOL scores vary as a function of disability status beyond chance. To assess the quality of the parent proxy report for HRQOL as compared with disability, pain, and well-being. There was fair to good agreement and moderate consistency of the HRQOL ratings (SG: fair consistency) between patients and parents with marked differences between health domains. Conclusion. HRQOL measured by the PedsQL, JAQQ, and VAS are moderately to highly correlated with each other in children with chronic arthritis. The children's HRQOL significantly decreases with increasing disability. Despite more pronounced differences for some health domains, parents are moderate to good proxy reporters of HRQOL, disability, and well-being of children with chronic arthritis.