OBJECTIVE: To characterize the atypical cutaneous presentations in the coxsackievirus A6 (CVA6)–associated North American enterovirus outbreak of 2011–2012.METHODS: We performed a retrospective case series of pediatric patients who presented with atypical cases of hand, foot, and mouth disease (HFMD) from July 2011 to June 2012 at 7 academic pediatric dermatology centers. Patients were included if they tested positive for CVA6 or if they met clinical criteria for atypical HFMD (an enanthem or exanthem characteristic of HFMD with unusual morphology or extent of cutaneous findings). We collected demographic, epidemiologic, and clinical data including history of skin conditions, morphology and extent of exanthem, systemic symptoms, and diagnostic test results.RESULTS: Eighty patients were included in this study (median age 1.5 years, range 4 months–16 years). Seventeen patients were CVA6-positive, and 63 met clinical inclusion criteria. Ninety-nine percent of patients exhibited a vesiculobullous and erosive eruption; 61% of patients had rash involving >10% body surface area. The exanthem had a perioral, extremity, and truncal distribution in addition to involving classic HFMD areas such as palms, soles, and buttocks. In 55% of patients, the eruption was accentuated in areas of eczematous dermatitis, termed “eczema coxsackium.” Other morphologies included Gianotti-Crosti–like (37%), petechial/purpuric (17%) eruptions, and delayed onychomadesis and palm and sole desquamation. There were no patients with serious systemic complications.CONCLUSIONS: The CVA6-associated enterovirus outbreak was responsible for an exanthem potentially more widespread, severe, and varied than classic HFMD that could be confused with bullous impetigo, eczema herpeticum, vasculitis, and primary immunobullous disease.

Research from JAMA Pediatrics — Synbiotics for Prevention and Treatment of Atopic Dermatitis — A Meta-analysis of Randomized Clinical Trials

BACKGROUND AND OBJECTIVES: Propranolol is first-line therapy for problematic infantile hemangiomas (IHs). Rebound growth after propranolol discontinuation is noted in 19% to 25% of patients. Predictive factors for rebound are not completely understood and may alter the management approach. The goal of the study was to describe a cohort of patients with IHs treated with propranolol and to identify predictors for rebound growth. METHODS: A multicenter retrospective cohort study was conducted in patients with IHs treated with propranolol. Patient demographic characteristics, IH characteristics, and specifics of propranolol therapy were obtained. Episodes of rebound growth were recorded. Patients’ responses to propranolol were evaluated through a visual analog scale. RESULTS: A total of 997 patients were enrolled. The incidence of rebound growth was 231 of 912 patients (25.3%). Mean age at initial rebound was 17.1 months. The odds of rebound among those who discontinued therapy at <9 months was 2.4 (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.3 to 4.5; P = .004) compared with those who discontinued therapy between 12 to 15 months of life. Female gender, location on head and neck, segmental pattern, and deep or mixed skin involvement were associated with rebound on univariate analysis. With multivariate analysis, only deep IHs (OR: 3.3; 95% CI: 1.9 to 6.0; P < .001) and female gender (OR: 1.7; 95% CI: 1.1 to 2.6; P = .03) were associated. Of those with rebound growth, 83% required therapeutic modification including 62% of patients with modifications in their propranolol therapy. CONCLUSIONS: Rebound growth occurred in 25% of patients, requiring modification of systemic therapy in 15%. Predictive factors for rebound growth included age of discontinuation, deep IH component, and female gender. Patients with these predictive factors may require a prolonged course of therapy.

Background: Atopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics.Objectives: To characterize changes in the skin microbiome during treatment for AD.Methods: The skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification.Results: We included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment.Conclusions: There are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed.

The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization. Each patient's S. aureus population is dominated by a single lineage, with infrequent invasion by distant lineages. Mutations emerge within each lineage at rates similar to those of S. aureus in other contexts. Some variants spread across the body within months, with signatures of adaptive evolution. Most strikingly, mutations in capsule synthesis gene capD underwent parallel evolution in one patient and across-body sweeps in two patients. We confirm that capD negativity is more common in AD than in other contexts, via reanalysis of S. aureus genomes from 276 people. Together, these findings highlight the importance of the mutation level when dissecting the role of microbes in complex disease.