Faculty Bibliography

This report describes a case of chronic neutrophilic urticarial dermatosis as a presenting feature of systemic juvenile idiopathic arthritis. When encountered in children, neutrophilic urticarial dermatosis should raise suspicion of autoimmune or autoinflammatory disease.

BACKGROUND:A standardized set of quality measures for juvenile idiopathic inflammatory myopathies (JIIM) is not in use. Discordance has been shown between the importance ascribed to quality measures between patients and families and physicians. The objective of this study was to assess and compare the importance of various aspects of high quality care to patients with JIIM and their families with healthcare providers, to aid in future development of comprehensive quality measures. METHODS:Surveys were developed by members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Juvenile Dermatomyositis Workgroup through a consensus process and administered to patients and families through the CureJM Foundation and to healthcare professionals through CARRA. The survey asked respondents to rate the importance of 19 items related to aspects of high quality care, using a Likert scale. RESULTS:Patients and families gave generally higher scores for importance to most of the quality measurement themes compared with healthcare professionals, with ratings of 13 of the 19 measures reaching statistical significance (p < 0.05). Of particular importance, however, was consensus between the groups on the top five most important items: quality of life, timely diagnosis, access to rheumatology, normalization of functioning/strength, and ability for self care. CONCLUSIONS:Despite overall differences in the rating of importance of quality indicators between patients and families and healthcare professionals, the groups agreed on the most important aspects of care. Recognizing areas of particular importance to patients and families, and overlapping in importance with providers, will promote the development of standardized quality measures with the greatest potential for improving care and outcomes for children with JIIM.

Cutaneous lupus erythematosus (CLE) refers to skin manifestations of the autoimmune disease lupus erythematosus (LE). Skin involvement is one of the most common presenting signs of systemic lupus erythematosus (SLE) and its evaluation can be critical in making a diagnosis and monitoring disease progression. Patients may also present with isolated CLE without systemic disease. The visible lesions of CLE can be disfiguring and distressing to patients. While CLE has been extensively researched in the adult population, few studies exist in the pediatric population. The development of a validated disease severity tool is crucial for monitoring the natural history of skin involvement in lupus registry studies. There is also a great need for new therapeutic agents, and demonstrating the efficacy of these agents will require clinical trials with reliable outcome measures. The CLASI is a reliable outcome measure for CLE in the adult population, where it is commonly used in clinical trials for SLE. However, no study has validated this assessment tool in children, potentially limiting the conduct of clinical trials in pediatric SLE. The study will include at least five pediatric dermatologists and five rheumatologists to independently evaluate patients with pediatric cutaneous lupus. The study will take place at the autoimmune disease clinic of the University of Pennsylvania, on March 3rd, 2018. The physicians will be given a training session on the assessment of cutaneous lupus using 2 measurement tools: the CLASI and the Physician Global Assessment (PGA), which allow grading of skin activity and skin damage, as well as a score for the overall findings. One cohort of physicians will apply the PGA before the CLASI and the other cohort will apply the CLASI before the PGA. Inter-rater reliability within each physician group will be determined by intraclass correlation coefficient (ICC), type ICC and its confidence interval. While many pediatric dermatologists and rheumatologists have shown strong interest in participation, there have been difficulties recruiting pediatric CLE patients with currently active disease who are willing to travel to Philadelphia. However we have reached out to over ten institutions and all physicians are actively searching for interested patients and we have identified several patients who will participate. The primary benefit of this study is the validation of a standardized instrument that can be applied to pediatric cutaneous lupus to facilitate epidemiologic studies and provide a critical tool for clinical trials. Secondary benefits include more standardized documentation of skin disease activity and damage between specialties to help facilitate clinical practice and interdisciplinary collaboration

BACKGROUND: Juvenile dermatomyositis (JDM) is the most common form of the idiopathic inflammatory myopathies in children. A subset of children have the rash of JDM without significant weakness, and the optimal treatments for these children are unknown. The goal of this study was to describe the development of consensus clinical treatment plans (CTPs) for children with JDM who have active skin rashes, without significant muscle involvement, referred to as skin predominant JDM in this manuscript. METHODS: The Children's Arthritis and Rheumatology Research Alliance (CARRA) is a North American consortium of pediatric rheumatology health care providers. CARRA members collaborated to determine consensus on typical treatments for JDM patients with skin findings without significant weakness, to develop CTPs for this subgroup of patients. We used a combination of Delphi surveys and nominal group consensus meetings to develop these CTPs. RESULTS: Consensus was reached on patient characteristics and outcome assessment, and CTPs were developed and finalized for patients with skin predominant JDM. Treatment option A included hydroxychloroquine alone, Treatment option B included hydroxychloroquine and methotrexate, and Treatment option C included hydroxychloroquine, methotrexate and corticosteroids. CONCLUSIONS: Three CTPs were developed for use in children with skin predominant JDM, which reflect typical treatment approaches. These are not considered to be specific recommendations or standard of care. Using the CARRA network and prospective data collection, we will be able to apply statistical methods in the future to allow comparisons of JDM patients following these consensus treatment plans.

OBJECTIVE: Juvenile dermatomyositis (JDM) is the most common form of idiopathic inflammatory myopathy in children. While outcomes are generally thought to be good, persistence of skin rash is a common problem. The goal of this study was to describe the development of clinical treatment plans (CTP) for children with JDM characterized by persistent skin rash despite complete resolution of muscle involvement. METHODS: The Childhood Arthritis and Rheumatology Research Alliance, a North American consortium of pediatric rheumatologists and other healthcare providers, used a combination of Delphi surveys and nominal group consensus meetings to develop CTP that reflected consensus on typical treatments for patients with JDM with persistent skin rash. RESULTS: Consensus was reached on patient characteristics and outcome assessment. Patients should have previously received corticosteroids and methotrexate (MTX). Three consensus treatment plans were developed. Plan A added intravenous immunoglobulin (IVIG) if it was not already being used. Plan B added mycophenolate mofetil, while Plan C added cyclosporine. Continuation of previous treatments, including corticosteroids, MTX, and IVIG, was permitted in plans B and C. CONCLUSION: Three consensus CTP were developed for use in children with JDM and persistent skin rash despite complete resolution of muscle disease. These CTP reflect typical treatment approaches and are not to be considered treatment recommendations or standard of care. Using prospective data collection and statistical methods to account for nonrandom treatment assignment, it is expected that these CTP will be used to allow treatment comparisons, and ultimately determine the best treatment for these patients.

BACKGROUND: Acute urinary retention (AUR) is a rare diagnosis both in pediatric and adult female populations, especially when compared to adult males. AUR occurs in women at a rate of 7 in 100,000 per year in a 1:13 female to male ratio. Multiple studies have shown that within the pediatric population AUR is far less common in females and is caused by different pathologies than AUR in adult women. CASE REPORT: We report the case of an 11 year-old prepubescent female who presented to the emergency department with acute urinary retention found to be caused by a mature cystic ovarian teratoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case is unique in that it describes an ovarian mass leading to AUR which has not previously been described in the pediatric literature. We will review the causes of AUR in the pediatric female population and compare these to the causes of AUR in other populations.

OBJECTIVE: Epidemiological associations suggest vitamin D may play a role in inflammation and atherosclerosis. Using frozen serum and data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed associations between 25-hydroxyvitamin D [25(OH)D] and measures of systemic lupus erythematosus (SLE) disease activity and cardiovascular risk. METHODS: Baseline APPLE serum samples were used to measure 25(OH)D levels. Logistic regression models for vitamin D deficiency [25(OH)D levels <20 ng/mL] were constructed using baseline variables collected as part of the trial, including race, season, latitude, disease duration, disease activity, high-sensitivity C-reactive protein (hsCRP), proteinuria, fasting lipids and carotid intima medial thickness (CIMT). RESULTS: Samples were available from 201 of 221 APPLE subjects; 61/201 (30%) had vitamin D deficiency at baseline. In univariable analysis, baseline vitamin D deficiency was associated with season (p<0.01), minority status (p<0.01), body mass index (p=0.04), duration of SLE (p<0.01), SLICC damage index (p=0.04), hsCRP (p<0.01), mean-max CIMT (p=0.01), LDL-cholesterol (p=0.03) and timed urine protein (p=0.03). In multivariable modelling, vitamin D deficiency was associated with age, latitude, season, minority status, proteinuria and hsCRP. CONCLUSIONS: Vitamin D deficiency is common in paediatric lupus and is independently associated with elevated hsCRP, a marker of inflammation that predicts cardiovascular disease risk. Although association is not proof of causation, this association is novel in the paediatric SLE population and suggests that vitamin D deficiency may contribute to heightened inflammation and cardiovascular risk in this population. TRIAL REGISTER NUMBER: NCT00065806.

OBJECTIVE: Epidemiological associations suggest that vitamin D status may play a role in inflammation and progression of atherosclerosis. Using frozen serum, carotid intima medial thickness (CIMT) measurements and other existing data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed interactions between serum 25-hydroxyvitamin D (25(OH)D), atorvastatin randomisation and CIMT progression rate. METHODS: Participants in the 3-year APPLE trial were randomised to placebo or atorvastatin and CIMT progression rate was measured. Baseline frozen serum was used to measure 25(OH)D concentrations. Mixed effect longitudinal models for CIMT progression at 3 years were used to evaluate interaction between vitamin D deficiency (serum 25(OH)D <20 ng/mL) at baseline and atorvastatin or placebo treatment, adjusting for key systemic lupus erythematosus disease variables and cardiovascular risk factors. RESULTS: 201/221 APPLE participants had available samples and were included in this analysis; 61/201 (30%) had vitamin D deficiency at baseline. In adjusted longitudinal modelling, there was significant interaction between baseline vitamin D deficiency and atorvastatin randomisation in 3-year progression of mean-max CIMT. In four out of six carotid segments, there was a greater decrease in mean-max CIMT progression rate in subjects who were treated with atorvastatin compared with placebo if they had baseline serum 25(OH)D levels >/=20 ng/mL. CONCLUSIONS: Subjects with serum 25(OH)D >/=20 ng/mL had less mean-max CIMT progression following 3 years of atorvastatin treatment. Results from secondary analyses must be interpreted cautiously, but findings suggest that underlying vitamin D deficiency may be involved in response to atorvastatin in atherosclerosis prevention. TRIAL REGISTRATION NUMBER: NCT00065806.