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Objective: Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure., Methods: LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter-rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment., Results: LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA-Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate-to-excellent inter-rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation., Conclusion: We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies., (© 2023 American College of Rheumatology.)

Objective: To perform a comparative effectiveness feasibility study in juvenile localized scleroderma (LS), using standardized treatment regimens (consensus treatment plans; CTP)., Methods: A prospective, multicenter 1-year pilot observational cohort study was performed by Childhood Arthritis and Rheumatology Research Alliance (CARRA) LS workgroup members. Patients with active, moderate to severe juvenile LS were treated with one of 3 CTP: methotrexate alone, or in combination with intravenous (30 mg/kg/dose for 3 mos) or oral corticosteroids (2 mg/kg/day tapered by 48 weeks)., Results: Fifty patients, with demographics typical for juvenile LS, were enrolled, and 44 (88%) completed the study. Most had extracutaneous involvement. Patients improved in all 3 CTP, with > 75% having a major or moderate level of improvement compared to baseline. Damage accrued in some patients. Major deviations from prescribed regimen resulted from medication intolerance (n = 6; 14%) or treatment failure (n = 11; 25%); failures occurred in all 3 CTP. Significant responses to treatment were demonstrated by LS skin scoring measures and overall physician assessments, with differences in response level identified in some patient subsets. Response differences were associated with baseline disease activity level, LS subtype, skin disease extent, and extracutaneous involvement., Conclusion: This study demonstrates the feasibility of conducting juvenile LS comparative effectiveness studies. The CTP were found to be safe, effective, and tolerable. Our assessments performed well. Because damage is common and may progress despite effective control of activity, we recommend initial treatment efficacy be evaluated primarily by activity measures. Potential confounders for response were identified that warrant further study.

Background: We designed and initiated a pilot comparative effectiveness study for juvenile localized scleroderma (jLS), for which there is limited evidence on best therapy. We evaluated the process we used, in relation to the specific protocol and to the general task of identifying strategies for implementing studies in rare pediatric diseases., Methods: This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize clinical assessments, generate and refine disease activity and damage measures, and monitor the study. Patients were initiated on one of three standardized methotrexate-based treatment regimens (consensus treatment plans, CTPs) and monitored for 1 year. An optional bio-banking sub-study was included., Results: The target enrollment of 50 patients was achieved over 26 months at 10 sites, with patients enrolled into all CTPs. Enrolled patients were typical for jLS. Study eligibility criteria were found to perform well, capturing patients thought appropriate for treatment studies. Minor modifications to the eligibility criteria, primarily to facilitate recruitment for future studies, were discussed with consensus agreement reached on them by the jLS group. There were marked differences in site preferences for specific CTPs, with half the sites treating all their patients with the same CTP. Most patients (88%) completed the study, and 68% participated in the bio-banking substudy., Conclusions: We demonstrate the feasibility of our approach for conducting comparative effectiveness research in a rare pediatric disease. Multi-center collaboration by dedicated investigators who met regularly was a key factor in the success of this project. Other factors that facilitate these studies include having a sufficient number of investigators to enroll in each regimen, and streamlining study approval and management.

Most children with idiopathic central hypoventilation have symptoms at birth or shortly thereafter and have mutations of the PHOX2B gene. Those whose symptoms appear later usually have obesity and hypothalamic abnormalities. We describe a case of a boy who presented at 5 years of age with severe idiopathic central hypoventilation, but no obesity or hypothalamic abnormalities, and who tested negative for mutation of the PHOX2B gene. This case illustrates the heterogeneity of childhood idiopathic central hypoventilation syndromes and indicates the multifactorial etiology of these syndromes.