Cutaneous manifestations of childhood Eosinophilic Granulomatosis with Polyangiitis (cEGPA): A case-based review.

BACKGROUND/OBJECTIVES: This study seeks to better define the clinical presentation and histopathology of cutaneous manifestations in childhood eosinophilic granulomatosis with polyangiitis (cEGPA). METHODS: Case reports were collected from Ovid Medline Database and PubMed using keyword identifiers from 1946 to 2017. Adult patients ≥ 18 years and cases not diagnosed with EGPA by the author were excluded. Sixty-five case reports of cEGPA were initially identified. These were reviewed individually, and fifty cases were determined to meet the American College of Rheumatology criteria for EGPA. No case series examining the cutaneous morphology and histopathology were identified. Cutaneous morphology, lesion location, and cutaneous histopathology results were recorded. Results were analyzed using summary statistics. RESULTS: Sixty-four percent (32/50) of cEGPA patients presented with cutaneous manifestations. Twenty-nine cases provided specific morphological descriptions and lesion location. Common manifestations included purpura (15/29), subcutaneous nodules (8/29), and a macular/papular/maculopapular rash (8/29). However, twelve different cutaneous morphologies were identified in this review. Lesions occurred most commonly on the extremities (26/29). Twenty-two cases reported corresponding cutaneous histopathology, which revealed extravascular eosinophils (15/22), vasculitis (13/22), and granulomas (5/22). Only one biopsy sample (1/22) had all three classical EGPA characteristics of granulomas, extravascular eosinophils, and vasculitis. CONCLUSION: With nearly two-thirds of cEGPA patients presenting with cutaneous manifestation, this study highlights the importance of clinical recognition of this disease by dermatologists. While the varied morphology of skin lesions and rarity of this disease makes cEGPA a difficult diagnosis, prompt recognition and treatment will improve outcomes in this patient population.

Epidemiology, Pathophysiology, and Management Strategies of Neonatal Wound Care.

Guidelines for neonatal skin care are scarce, and there is no consensus on the best management practices for neonatal skin breakdown. This review presents the pathology and phases of wound healing, reasons for neonatal skin fragility, and approaches to recognition of commonly encountered neonatal wounds. This review also provides general strategies for neonatal wound prevention, care, dressing, and management to avoid further damage to the fragile neonatal skin. The importance and role of retaining moisture in expediting wound healing is discussed, as well as updated classifications on how to grade and assess pressure ulcers and the role of negative pressure wound therapy and silver dressings. Lastly, this review discusses prevention and treatment options for surgical wounds, intravenous extravasation wounds, congenital wounds, and thermal injuries, in addition to how to differentiate these wounds from the common diaper dermatitis and contact dermatitis.

Utility of Dermatology Extension for Community Healthcare Outcomes (ECHO) sessions in the adult and paediatric population.

INTRODUCTION: Primary care provider (PCP) competency in dermatology is inadequate despite the high volume of patients with skin conditions. Better education and access to dermatology expertise is vital to improve patient care. We present a comprehensive case-based evaluation of Dermatology Extension for Community Healthcare Outcomes (ECHO) sessions, an innovative videoconferencing educational model, by determining the diagnostic and treatment accuracy of dermatological conditions by PCPs over a 2-year period. METHODS: This is a retrospective cross-sectional study evaluating the use and impact of Dermatology ECHO over a 2-year period. Outcomes assessed include patient demographics, PCPs' diagnostic accuracy, and expert treatment impact. Results were analysed using summary statistics and Pearson's chi-square test to describe the adult and paediatric populations. RESULTS: One hundred and sixty-seven adult cases and 56 paediatric cases were presented in 2016-2017. Among the 223 cases, 137 adult and 44 paediatric cases were complete and eligible for analysis. The mean lesion duration was 3.3 years in adults and 2.9 years in children prior to presentation. Upon case presentation, almost half (43.8%) of the adult cases were incorrectly diagnosed by their PCP with 18.8% receiving a partially correct diagnosis. PCPs had greater diagnostic accuracy in children (45% correct diagnosis, 27.5% partially correct, 27.5% incorrect). Expert treatment recommendations benefited 83.6% of adult cases and 72.5% of paediatric cases. DISCUSSION: This study highlights the need for better dermatology access and teaching opportunities among PCPs in Missouri. Dermatology ECHO provides a platform for didactic learning and case presentations to improve dermatology competency among PCPs.

An essential role for MEF2C in the cortical response to loss of sleep in mice.

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep-loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss in C57BL/6J mice. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function.

MEF2C Hypofunction in Neuronal and Neuroimmune Populations Produces MEF2C Haploinsufficiency Syndrome-like Behaviors in Mice.

BACKGROUND: Microdeletions of the MEF2C gene are linked to a syndromic form of autism termed MEF2C haploinsufficiency syndrome (MCHS). MEF2C hypofunction in neurons is presumed to underlie most of the symptoms of MCHS. However, it is unclear in which cell populations MEF2C functions to regulate neurotypical development. METHODS: Multiple biochemical, molecular, electrophysiological, behavioral, and transgenic mouse approaches were used to characterize MCHS-relevant synaptic, behavioral, and gene expression changes in mouse models of MCHS. RESULTS: We showed that MCHS-associated missense mutations cluster in the conserved DNA binding domain and disrupt MEF2C DNA binding. DNA binding-deficient global Mef2c heterozygous mice (Mef2c-Het) displayed numerous MCHS-related behaviors, including autism-related behaviors, changes in cortical gene expression, and deficits in cortical excitatory synaptic transmission. We detected hundreds of dysregulated genes in Mef2c-Het cortex, including significant enrichments of autism risk and excitatory neuron genes. In addition, we observed an enrichment of upregulated microglial genes, but this was not due to neuroinflammation in the Mef2c-Het cortex. Importantly, conditional Mef2c heterozygosity in forebrain excitatory neurons reproduced a subset of the Mef2c-Het phenotypes, while conditional Mef2c heterozygosity in microglia reproduced social deficits and repetitive behavior. CONCLUSIONS: Taken together, our findings show that mutations found in individuals with MCHS disrupt the DNA-binding function of MEF2C, and DNA binding-deficient Mef2c global heterozygous mice display numerous MCHS-related phenotypes, including excitatory neuron and microglia gene expression changes. Our findings suggest that MEF2C regulates typical brain development and function through multiple cell types, including excitatory neuronal and neuroimmune populations.