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Background: Transition from pediatric to adult care can be a challenging process which leaves young people vulnerable to interruptions of care and worsening disease status. Efforts to improve transition processes and outcomes have included development of individualized transition plans, creation of transition clinics, and utilization of transition coordinators. Few interventions have assessed transition outcomes quantitatively., Methods: We assessed transition outcome and satisfaction of a social worker-centered transition program in a pediatric rheumatology clinic. The social worker met with patients who were 16 years or older and their families, provided transition education materials, assisted patients in developing an individualized transition plan, assisted in making appointments with an adult rheumatologist at time of transfer of care, and followed up with patients to assess transition outcomes. Patients were contacted 6-8 months after initial appointment with the adult rheumatologist to assess whether they remained in the care of the adult provider. Participants then completed a questionnaire to rate their satisfaction with the transition program., Results: 210 adolescents and young adults participated in the transition program. Twenty-six similarly aged patients were eligible for transition services but did not participate in the program and were used as controls. Of the patients who participated in the program, 42% were considered to have transitioned successfully to adult care compared to 23% of controls (p-value = 0.002) of all patients. In the survey of satisfaction, 81% of participants said that they were satisfied with the transition process., Conclusions: This study shows that a social worker transition coordinator can significantly improve the rate of pediatric rheumatology patients who successfully transition to adult care. Furthermore, patients are largely satisfied with this process.

Background: We tested the hypothesis that the course and outcome of juvenile dermatomyositis (JDM) in children seen at one center with the JDM disease onset at or below three years of age is different from that in the children with disease onset at greater than three years of age., Methods: Institutional Review Board approval was obtained to retrospectively review the charts of 78 patients from age 0-18 years with JDM seen in the pediatric rheumatology clinic at Nationwide Children's Hospital in Columbus, Ohio over the past 23 years from January 1988. The diagnosis was made by the treating pediatric rheumatologist. Not all the patients met the Bohan and Peter criteria, as muscle biopsy and EMG were not always performed and we utilized a modified JDM criteria. The data regarding disease course and outcome were collected as of the last clinic follow-up or to July 1, 2010. We used the Wilcoxon Two-Sample test to compare numerical variables between two age groups, and used logistic regression to compare categorical variables between two age groups in SAS 9.1.3. Minitab-16 was used to calculate various mean, median, modes, standard deviations and range. For survival analysis, we used Kaplan-Meier method with log-rank test., Results: The mean age of onset in the two groups at Nationwide Children's Hospital was 27 months and 91 months. The mean times between onset of symptoms to diagnosis in the younger and older age groups was 5.6 months and 4.5 months, respectively, not a statistically significant difference. The younger onset group had more females (p=0.05) and their disease onset occurred less frequently during the typical winter-spring seasons (p=0.031). The younger onset group was more likely to have a preceding fever (p=0.029) and family history of autoimmune diseases (p=0.012). The younger onset group was less likely to have heliotrope rash (p=0.04), Gottron's sign (p=0.049), capillary loop abnormalities (p=0.010), or elevations in creatine kinase (CK, p=0.022), aspartate aminotransferase (AST, p=0.021) or aldolase (p=0.035). The younger onset group was treated less often with pulse methylprednisolone at diagnosis (p=0.043) and less often with hydroxychloroquine (p=0.035). There were no differences between the two groups regarding initial oral steroid dose (p=0.8017), number of patients who received methotrexate at diagnosis (p=0.709), and the number who ever received other immunosuppressants (p=0.323). The mean and maximum duration (mean duration 24.3 months vs. 35.2 months, maximum duration 51 vs. 124 months in younger and older onset group respectively) of methotrexate therapy, and the mean and maximum duration of oral steroid therapy (Mean duration 16.8 months vs. 33.3 months, maximum duration 50 vs. 151 months in younger and older onset group respectively), was shorter in the younger group. The younger onset patients were less likely to have active disease at 5 years (9% vs. 35.7%, p=0.015) and 10 years post-diagnosis (9% vs. 45.1%, p=0.011, Table 7). The younger patients were less likely to have osteonecrosis (p=0.023). Two disease-related deaths occurred in the younger group, none in the older group. The results of the survival analysis showed that the difference between the age groups was statistically significant (p < 0.012). The sex and race were not significant (p> 0.26 and p>0.95, respectively)., Conclusions: There were significant differences between JDM patients with disease onset at or below age three years at our center, compared to their older counterparts. Younger patients in our cohort had fewer typical findings at diagnosis and a milder disease course without needing as long a duration of corticosteroids and immunosuppression. Patients with a younger onset had a higher mortality rate but mortalities were unusual and numbers small. The younger group had a similar complication rate compared to the older onset patients, except for osteonecrosis which was higher in the older onset group. These findings differ from the previous reports that a younger age of onset in JDM is often associated with a more severe disease, as results at our center suggest that children with younger onset JDM appear to be atypical but may do well compared to the older JDM patients.

Susac's Syndrome (SS) consists of the clinical triad of encephalopathy, branch retinal artery occlusion (BRAO), and hearing loss (HL). It is an autoimmune endotheliopathy affecting the precapillary arterioles of the brain, retina, and inner ear (cochlea and semicircular canals). The age range extends from 7 to 72 years, but young women (20-40) are most vulnerable. Headache routinely accompanies the encephalopathy and may be constant (best explained by leptomeningeal involvement), migrainous, or both. Multifocal neurological manifestations--particularly bilateral long-tract signs--commonly accompany the encephalopathy, which is laden with psychiatric features, confusion, memory loss and other cognitive changes. Left untreated, dementia can ensue. SS has an unexplained proclivity for attacking the central corpus callosum. In its encephalopathic form, pathognomonic callosal lesions permit an immediate diagnosis. We believe that the diagnosis of SS can be made when only the encephalopathy and pathognomonic MRI lesions are present; the BRAO and HL need not be present. We have also found the "string of pearls" MRI finding--the studding of the internal capsules with microinfarcts--to be most helpful--if not pathognomonic. This sign is always associated with the clusters of corpus callosum lesions, is especially striking on diffusion weighted imaging, and is associated with long-tract findings. We discuss the newly appreciated BRAO subset of SS and offer preliminary treatment suggestions for this subset. We also call attention to our development of an International Collaborative Study of SS and an educational website (http://www.ucalgary.ca/susac)., (Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.)

Objective: To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables., Methods: Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the "gold standard measure," chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions., Results: The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process., Conclusion: We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM., (Copyright © 2010 by the American College of Rheumatology.)

Objectives: Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater reliability of the CAT, and the frequency of lesions endorsed in a large population of juvenile IIM patients., Methods: The CAT includes 10 activity, 4 damage and 7 combined lesions. Thirty-two photographic slides depicting IIM skin lesions were assessed by 11 raters. One hundred and twenty-three children were assessed by 11 paediatric rheumatologists at 10 centres. Inter-rater reliability was assessed using simple agreements and intra-class correlation coefficients (ICC)., Results: Simple agreements in recognizing lesions as present or absent were generally high (0.5-1.0). ICCs for CAT lesions were moderate (0.4-0.75) in both slides and real patients. ICCs for the CAT activity and damage scores were 0.71 and 0.81, respectively. CAT activity scores ranged from 0 to 44 (median 7, potential range 0-96) and CAT damage scores ranged from 0 to 13 (median 1, potential range 0-22). The most common cutaneous lesions endorsed were periungual capillary loop changes (63%), Gottron's papules/sign (53%), heliotrope rash (49%) and malar/facial erythema (49%)., Conclusions: Total CAT activity and damage scores have moderate to good reliability. Assessors generally agree on the presence of a variety of cutaneous lesions. The CAT is a promising, semi-quantitative tool to comprehensively assess skin disease activity and damage in IIM.

Objective: To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care., Methods: An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease., Results: A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation., Conclusion: This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.

Objective: To examine the effects of daily supplementation with calcium (Ca) in combination with vitamin D on total body and lumbar spine bone mineral density (BMD) in patients with juvenile rheumatoid arthritis (JRA) who had not taken corticosteroids for at least 3 months prior to the beginning of the study., Methods: One hundred ninety-eight children and adolescents (141 girls and 57 boys) with JRA, ages 6 to 18 years, with a mean +/- SD age of 11.7 +/- 3.3 years and a mean +/- SD disease duration of 5.6 +/- 3.8 years at the beginning of the study, were enrolled in this randomized double-blind, placebo-controlled trial to receive either daily oral supplements of 1,000 mg of Ca and 400 IU of vitamin D (n = 103) or matched placebo tablets and 400 IU of vitamin D (n = 95) for 24 months. Total body BMD (TBBMD) was measured by dual x-ray absorptiometry at baseline and every 6 months for 24 months., Results: At baseline, the mean +/- SD TBBMD was 0.89 +/- 0.14 gm/cm2 among patients randomized to the Ca group and 0.87 +/- 0.14 gm/cm2 among those randomized to placebo (P = 0.445). At 24 months, the mean +/- SD TBBMD among those receiving Ca was 0.95 +/- 0.13 gm/cm2, compared with 0.92 +/- 0.14 gm/cm2 among those receiving placebo. A longitudinal random-effects mixed model analysis that controlled for differences in the subject's initial BMD, sex, Tanner stage, adherence to the study medication regimen, and body composition revealed significantly higher TBBMD among patients who received Ca compared with patients who received placebo during the study period (P = 0.03)., Conclusion: Ca supplementation resulted in a small, but statistically significant, increase in TBBMD compared with placebo in children with JRA.

Objective: To assess for novel markers of muscle damage using urinary muscle metabolites by 1H magnetic resonance spectroscopy in patients with juvenile idiopathic inflammatory myopathy (IIM)., Methods: Creatine (Cr), choline (Cho), betaine (Bet), glycine (Gly), trimethylamine oxide (TMAO), and several other metabolites were measured in first morning void urine samples from 45 patients with juvenile IIM and from 35 healthy age-matched controls, and correlated with measures of myositis disease activity and damage. Urinary metabolite to age-adjusted creatinine (Cn) ratios were examined., Results: Age-adjusted initial Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios were higher in patients with juvenile IIM than controls (P < 0.01). Cr:Cn ratios showed significant correlations with physician-assessed global disease damage (Spearman rs = 0.37; P = 0.01), Steinbrocker functional class (rs = 0.35; P = 0.02), serum Cr (rs = 0.72; P = 0.001), and lactate dehydrogenase (rs = 0.34; P = 0.03) levels. Cho:Cn (rs = 0.3; P = 0.05), Gly:Cn (rs = 0.33; P = 0.03), and TMAO:Cn (rs = 0.36; P = 0.02) ratios showed a significant correlation with serum aldolase levels. Cho:Cn ratios also showed a significant correlation with aspartate aminotransferase levels (rs = 0.35; P = 0.02). A linear regression model was used to evaluate the factors influencing urinary Cr:Cn ratios in the 43 patients with data sets available at the initial visit. The regression model explained 73% of the variation in Cr:Cn ratios. The most significant factor was the physician-assessed global disease damage (R2 = 0.50, P = 0.015)., Conclusion: Urinary Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios are elevated in juvenile IIM and Cr:Cn correlates strongly with global disease damage. The Cr:Cn ratio may have potential utility as a marker of myositis disease damage.

Objective: To describe the health and functional status of children with juvenile rheumatoid arthritis (JRA) diagnosed in the early 1990s., Methods: Patients were obtained from the Pediatric Rheumatology Disease Registry, a database of patients seen in pediatric rheumatology centers across the United States. Questionnaires designed to be filled out after retrospective chart review were sent to pediatric rheumatologists caring for children diagnosed with JRA between 1992 and 1997., Results: We studied 703 patients -- 376 with pauciarticular onset (pauci), 232 with polyarticular onset (poly), and 95 with systemic onset JRA (systemic). At 1 year after diagnosis, half of the pauci and systemic patients no longer required medication, compared to 78% of the poly patients; 98% of the patients functioned in Steinbrocker classes I and II. Six percent of pauci, 27% of poly, and 11% of systemic patients had limitations in school function. Nearly 1/3 of poly patients already had joint space narrowing on radiograph. By 5 years after diagnosis, all pauci, 88% of poly, and 70% of systemic patients were in Steinbrocker classes I and II; but 6% of pauci, 28% of poly, and 44% of systemic patients had limitations in school function. Nearly 2/3 of poly and systemic patients had joint space narrowing., Conclusion: In these children treated prior to the era of biologic therapy, at 5 years after onset, > 25% of poly and nearly half of systemic patients had functional limitations that required modifications in their school schedule. Radiographically evident joint space damage was seen within a year of onset in poly patients, and by 5 years 2/3 of poly and systemic patients had damage.

Objective: The aims of this study were: (1) to assess functional status, emotional well-being and quality of life in patients with polyarticular and systemic juvenile rheumatoid arthritis (JRA) treated with etanercept, and (2) to determine the prevalence and significance of adverse events associated with etanercept therapy., Patients and Methods: All JRA patients (n = 21) who received etanercept in our rheumatology clinic over a 14-month period were evaluated. Patient demo-graphics, type of arthritis, dosing regimens, family history, measures of joint function and laboratory parameters were obtained for each patient. A questionnaire that comprised validated functional assessment and quality-of-life measures (the Childhood Health Assessment Questionnaire [CHAQtrade mark], the Juvenile Arthritis Function Assessment Report [JAFAR 5trade mark] and the Pediatric Quality of Life Inventory Version 4 [PedsQL Generic Scaletrade mark] scales) was administered to patients and parents to assess physical and emotional function, pain, adverse drug events and quality of life at each clinic visit., Results: Functional status and quality of life improved in patients with poly-articular and systemic disease. A significant difference between pre- and post-etanercept functional assessment (JAFARtrade mark and CHAQtrade mark) and quality-of-life assessment by parents and patients was found (p = 0.009, p = 0.002, p

The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is important to allow for the evaluation of practice patterns for future outcome studies. A survey of nine pediatric rheumatologists was performed between September 1999 and February 2000. Each of the physicians prospectively recorded demographic and treatment information on consecutively sampled JRA patients (n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in 35%, and systemic onset JRA in 19% of the children. Naproxen was the most frequently prescribed medication (55% of the patients), followed by methotrexate (MTX), which was used in 39% of the patients. Folic acid supplementation (1 mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used in 11% of the children. Eleven percent of the patients received corticosteroids, and 13% of children on corticosteroids took calcium supplements. Uveitis was present in 8% and had a chronic course in 79% of those cases. Although systemic medications were used in 50% of the children with uveitis to control eye inflammation, severe damage to the eyes developed in 30% of them. Fourteen percent of the patients required gastroprotective medications. Compared with findings of a similar survey performed in 1993, there was no significant change in the frequency of use of naproxen, but nabumetone is now more often prescribed, and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among second-line agents used for JRA have also occurred, although there was no change in the frequency of use of MTX or corticosteroids. JRA continues to be a treatment challenge for the practicing pediatric rheumatologist. Patients often show incomplete response to the currently available medications. Therefore, new therapeutic agents need to be evaluated for their use in JRA, and the treatment of JRA associated uveitis especially needs to be improved.

Objective: To examine the validity of the Childhood Health Assessment Questionnaire (CHAQ) in patients with juvenile idiopathic inflammatory myopathy (IIM)., Methods: One hundred fifteen patients were enrolled in a multicenter collaborative study, during which subjects were assessed twice, 7-9 months apart. Physical function was measured using the CHAQ. Internal reliability was assessed using adjusted item-total correlations and item endorsement rates. Construct validity was assessed by comparing predicted and actual correlations of the CHAQ with other measures of physical function and disease activity. Responsiveness was assessed by calculating effect size (ES) and standardized response mean (SRM) in a group of a priori defined "improvers.", Results: Item-total correlations were high (rs range = 0.35-0.81), suggesting all items were related to overall physical function. Manual muscle testing and the Childhood Myositis Assessment Scale correlated moderate to strongly with the CHAQ (r = -0.64 and -0.75, both p < 0.001). Moderate correlations were also seen with the physician global assessment of disease activity (rs = 0.58, p < 0.001), parent global assessment of overall health (rs = -0.65, p < 0.001), Steinbrocker function class (rs = 0.69, p < 0.001), and global skin activity (rs = 0.40, p < 0.001), while global disease damage and skin damage had low correlations (rs = 0.13 and 0.07, p > or =0.17). Responsiveness of the CHAQ was high, with ES = 1.05 and SRM = 1.20., Conclusion: In this large cohort of patients with juvenile IIM, the CHAQ exhibited internal reliability, construct validity, and strong responsiveness. We conclude that the CHAQ is a valid measure of physical function in juvenile IIM, appropriate for use in therapeutic trials, and potentially in the clinical care of these patients.

Myasthenia gravis has been associated with other autoimmune disorders. We report two children with myasthenia gravis and another autoimmune disease: an 18-month-old boy with ocular myasthenia gravis and Hashimoto's disease and a 14-year-old girl presenting with autoimmune polymyositis, then generalized myasthenia gravis 2 years later. The rare combinations of myasthenia gravis and Hashimoto's disease or polymyositis in children are discussed, and we also briefly review myasthenia gravis and other associated autoimmune diseases in children.

The complement component C4 genes located in the major histocompatibility complex (MHC) class III region exhibit an unusually complex pattern of variations in gene number, gene size, and nucleotide polymorphism. Duplication or deletion of a C4 gene always concurs with its neighboring genes serine/threonine nuclear protein kinase RP, steroid 21-hydroxylase (CYP21), and tenascin (TNX), which together form a genetic unit termed the RCCX module. A detailed molecular genetic analysis of C4A and C4B and RCCX modular arrangements was correlated with immunochemical studies of C4A and C4B protein polymorphism in 150 normal Caucasians. The results show that bimodular RCCX has a frequency of 69%, whereas monomodular and trimodular RCCX structures account for 17.0 and 14.0%, respectively. Three quarters of C4 genes harbor the endogenous retrovirus HERV-K(C4). Partial deficiencies of C4A and C4B, primarily due to gene deletions and homoexpression of C4A proteins, have a combined frequency of 31.6%. This is probably the most common variation of gene dosage and gene size in human genomes. The seven RCCX physical variants create a great repertoire of haplotypes and diploid combinations, and a heterozygosity frequency of 69.4%. This phenomenon promotes the exchange of genetic information among RCCX constituents that is important in homogenizing the structural and functional diversities of C4A and C4B proteins. However, such length variants may cause unequal, interchromosomal crossovers leading to MHC-associated diseases. An analyses of the RCCX structures in 22 salt-losing, congenital adrenal hyperplasia patients revealed a significant increase in the monomodular structure with a long C4 gene linked to the pseudogene CYP21A, and bimodular structures with two CYP21A, which are likely generated by recombinations between heterozygous RCCX length variants.

Objective: To develop, validate, and determine the measurement characteristics of a quantitative tool for assessing the severity of muscle involvement in children with idiopathic inflammatory myopathies., Methods: The Childhood Myositis Assessment Scale (CMAS) was developed from 2 existing observational functional assessment tools to assess muscle function in the areas of strength and endurance across a wide range of ability and ages. The 14 ordinal items included were chosen to assess primarily axial and proximal muscle groups and are ranked with standard performance and scoring methods. Following the development of the CMAS, a training video and written instructions were developed and reviewed by the physicians participating in this study. Subsequently, utilizing a randomized block design, 12 physicians independently scored 10 children (9 with dermatomyositis, 1 with polymyositis; ages 4-15 years) twice in one day (morning and afternoon) on the CMAS. A pediatric physical therapist performed quantitative manual muscle strength testing (MMT) twice on each child (morning and afternoon), including the neck, trunk, and proximal and distal extremity muscle groups., Results: The CMAS has a potential range of 0-51, with higher scores indicating greater muscle strength and endurance. The observed mean for the 10 patients was 36.4 (median 44, SD 14.1, observed range 5-51). The total score for the CMAS correlated with the physician's global assessment (by visual analog scale) of disease activity, the MMT score, serum creatine kinase level, and the Juvenile Arthritis Functional Assessment Report score. The score on the CMAS was not correlated with patient age. Interrater reliability (Kendall's coefficient of concordance) ranged from 0.77 to 1.0 for individual items (all P < 0.001), and overall, it was 0.95 (P < 0.001). Intrarater reliability for the individual physicians was measured by correlation of the CMAS scores for each patient on 2 separate evaluations and ranged from 0.97 to 0.99, with an overall correlation for all physicians of 0.98 (all P < 0.001)., Conclusion: The CMAS demonstrated an acceptable range of observed scores, excellent convergent validity, and excellent inter- and intrarater reliability. The CMAS is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies. It can be used in routine clinical care as well as therapeutic trials.

This was a single-center, open-label, single-dose pharmacokinetic study of etodolac in pediatric and adolescent patients with stable juvenile rheumatoid arthritis (JRA). Eleven male and female patients with JRA (8.1 to 14.8 years of age, weighing 26.4 to 59.5 kg) received a single oral dose of etodolac (200, 300, or 400 mg based on body weight). Clinical laboratory measurements, measurement of vital signs, and physical examinations were performed to monitor safety. Concentrations of etodolac were determined in plasma using high-performance liquid chromatography with ultraviolet detection with a limit of quantitation of 0.2 mg/L and were analyzed using a noncompartmental pharmacokinetic method. Pharmacokinetic parameters observed were consistent in magnitude and degree of variability with data from healthy adult subjects receiving a single 400- or 600-mg dose of etodolac. Although the mean fraction of unbound drug in patients with JRA was higher than in healthy adults, the oral clearance was independent of age. No serious adverse events occurred during this study. Etodolac yielded consistent pharmacokinetic values among stratified dose subgroups. Single doses of all etodolac treatments were well tolerated in both pediatric and adolescent patients.

The RCCX module of the human MHC class III region is comprised of four genes arranged in tandem: RP, complement C4, steroid 21-hydroxylase (CYP21), and tenascin X (TNX). Variations in the number and genes of the RCCX modules may lead to genetic and/or autoimmune diseases. Restriction fragment length polymorphism (RFLP) analysis was utilized to determine the RCCX modular variation in patients with juvenile rheumatoid arthritis (JRA). In JRA patient L1, RFLP analysis suggested the presence of a bimodular RCCX structure containing both C4A long and C4B short genes, yet missing the markers for the CYP21A and TNXA genes usually located between the C4A and C4B genes. The 7.5-kb genomic fragment spanning the CYP21-TNX-RP2 genes was cloned and sequenced, revealing that a genetic recombination occurred between TNXA of a bimodular RCCX chromosome and TNXB of a monomodular RCCX chromosome. This recombination results in a new MHC haplotype with a CYP21B gene and a TNXB/TNXA-RP2 recombinant between the two C4 genes. Elucidation of the breakpoint region provides further evidence for the instability of the MHC class III gene region as a result of the RCCX modular variation.

Objective: To determine the reliability, content validity, and responsiveness of physician global assessments of disease activity and damage in the juvenile idiopathic inflammatory myopathies (IIM), and to investigate concordance among physician, parent, and patient global ratings., Methods: Sixteen pediatric rheumatologists rated 10 juvenile IIM paper patient cases for global disease activity and damage, and assessed the importance of 51 clinical and laboratory parameters in formulating their global assessments. Then, 117 juvenile IIM patients were enrolled in a protocol to examine the relationship between Likert and visual analog scale global assessments, their sensitivity to change, and the comparability of physician, parent, and patient global ratings., Results: Pediatric rheumatologists demonstrated excellent interrater reliability in their global assessments of juvenile IIM disease activity and damage (97.7% and 94.7% agreement among raters, respectively), and agreed on a core set of clinical parameters in formulating their judgments. Likert scale ratings correlated with those on a visual analog scale, and both were comparable in responsiveness (standardized response means -0.56 for disease activity, 0.02 [Likert] and 0.14 [visual analog] for damage, measured over 8 months). Parent global ratings of disease activity correlated with physician assessments, but were not colinear (Spearman's correlation [r] = 0.41-0.45). Patient global disease activity assessments correlated with those done by parents (r = 0.57-0.84) and physicians (r = 0.37-0.63), but demonstrated less responsiveness (standardized response means -0.21 and -0.12, respectively, over 8 months)., Conclusion: Physician global assessments of juvenile IIM disease activity and damage demonstrated high interrater reliability and were shown to be comprehensive measures. Both physician and parent disease activity assessments should be considered valuable as quantitative measures for evaluating therapeutic responses in juvenile IIM patients.

This survey was performed to review medication usage by pediatric rheumatologists in the care of patients with juvenile rheumatoid arthritis (JRA). Prospective data from 50 patients per physician with JRA were recorded by six pediatric rheumatologists in the Fall of 1993. Naproxen was used most frequently-in 48% of all patients. Next in order of frequency were methotrexate (39%), prednisone (15%), tolmetin (12%), indomethacin (11%) and folic acid (10%). Salicylates (acetylsalicylic acid, trisalicylate and salsalate) were used in 7%, and myochrysine was used in 2% of patients. Overall, nonsteroidal anti-inflammatory drugs were used in 93% of all patients, slower-acting antirheumatic drugs (SAARDs) were used in 54% and prednisone in 15%.Medication usage varied by disease type in predictable ways but also varied by physician in ways that could not be accounted for by population differences. Methotrexate was the most-often used of all SAARDs and supplanted myochrysine in JRA. Naproxen was the most often used NSAID in the treatment of JRA and had largely supplanted salicylates. With the arrival of practice guidelines, reasons for and impact of these changes (as well as the interesting variations between physicians) will need to be examined.

Mixed connective tissue disease (MCTD) is characterized by features of more than one of the rheumatic disorders with antinuclear antibodies in a speckled pattern and with antibodies to nuclear ribonucleoprotein (nRNP). MCTD is uncommon in children and long-term follow-up studies in children are infrequently reported. A retrospective review of clinical experience at five pediatric rheumatology centers provided 11 patients who met the following inclusion criteria: (1) Kasukawa's criteria for MCTD1; (2) presentation younger than 18th birthday; (3) greater than five years of follow-up; (4) completion of data collection form. The widely varying outcomes of these 11 children with MCTD on long-term follow-up may lend doubt that this is a unique and distinctive rheumatologic disorder.

Kawasaki's disease (mucocutaneous lymph node syndrome) is an acute febrile illness primarily affecting children. Slit-lamp examinations of six children with kawasaki's disease, ranging in age from 22 months to 16 years, showed that five had anterior uveitis during the acute phase of the illness. Two of the children were treated with corticosteroids and cycloplegic drugs and three received no treatment. In all five, the anterior uveitis resolved completely within a few weeks.

Many concerns and difficult challenges are presented by JRA, particularly by the more severe forms of the disease. However, the child, family, school, and multidisciplinary team of health professionals can collaborate to better understand and meet these challenges. Often, in the process, important life lessons are learned and perspectives are gained which ultimately strengthen the child and family.

Two patients had onset of juvenile gouty arthritis at ages 16 and 1 1/2 years, respectively. Both had mild renal insufficiency, with creatinine clearances of 46 and 54 mL/min/1.73 sq m, respectively. Their presenting hyperuricemia (13.8 and 11 mg/dL, respectively) was out of proportion to the degree of renal insufficiency. Clinical and laboratory studies did not suggest an inborn error of purine metabolism, glycogen storage disease type I, or any myeloproliferative disorder. Neither patient had a family history of gout or inherited renal disease. Although juvenile gouty arthritis is rare, it must be considered in the differential diagnosis of episodic arthritis in children, especially if renal impairment, even mild, is present.

We report two patients with infantile onset of evanescent rash, fever, arthropathy with severe deformities, periosteal changes, chronic meningitis, hydrocephalus, convulsions, developmental delay, papilledema, unusual uveitis, and lymphadenopathy. A few patients with similar findings have been previously reported. Although some similarity exists between findings in these patients and in others with systemic juvenile rheumatoid arthritis, they appear to differ both in regard to the nature and severity of the clinical and pathologic features. We suggest that this group of patients has a separate rheumatic disorder not yet included in the standard classifications of the childhood rheumatic diseases.

We recalled 15 patients who had had Kawasaki's disease with documented bilateral conjunctival injection but who had not undergone slit-lamp examinations during the acute phase of the illness. Although anterior uveitis has been found in the acute phase of Kawasaki's disease, results of the follow-up studies (including slit-lamp examination, visual acuity testing, and assessment of pupillary reaction, muscle balance, and intraocular pressure) were normal in all 14 children.

Kawasaki disease or mucocutaneous lymph node syndrome is an acute febrile illness primarily affecting children. The principal signs and symptoms recognizable during the acute phase of the illness are described. Kawasaki disease is fatal in up to 3% of cases due to cardiac complications secondary to a systemic vasculitis. In a prospective series, ophthalmologic examinations on 10 children with Kawasaki disease showed that eight had anterior uveitis during the acute phase of the illness. All cases resolved within two to eight weeks. Because of these findings, 15 patients who had had Kawasaki disease with documented bilateral conjunctival injection, but who had never undergone slit-lamp examinations, were recalled for ophthalmologic evaluation. Results of these follow-up examinations were normal in all 15 children.

This review informs clinicians about current clinical usage and pharmacokinetics of newer NSAIDs and aspirin. To understand the effects of these drugs, a review of prostaglandin synthesis and actions is provided.

Concern that salicylates may play a role in the pathogenesis of Reye syndrome has raised the question of whether children receiving salicylate therapy for connective tissue disease are at risk for development of Reye syndrome. Of 176 patients with biopsy-confirmed Reye syndrome studied between January 1969 and June 1983, six had connective tissue disease at the time of development of Reye syndrome, and all six were receiving salicylates. Compared with the general population, children receiving salicylate therapy for connective tissue disease may be at increased risk for the development of Reye syndrome.