Erin F. Mathes

“Eczema Coxsackium” and Unusual Cutaneous Findings in an Enterovirus Outbreak

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.

Pediatric teledermatology: Observations based on 429 consults

BACKGROUND Store-and-forward teledermatology is an emerging means of access for patients with skin disease lacking direct access to dermatologists. OBJECTIVES We sought to examine the patient demographics, diagnostic concordance, and treatment patterns in teledermatology for patients younger than 13 years. METHODS We conducted a descriptive retrospective cohort study involving 429 patients. RESULTS Diagnoses were concordant in 48% of cases, partially concordant in 10%, and discordant in 42%. Management recommendations were concordant in 28% of cases, partially concordant in 36%, and discordant in 36%. Primary care providers tended to underuse topical steroids and overuse topical antifungals and systemic antibiotics. Only 1.4% and 6.0% of patients required repeated teledermatology consultation and in-person dermatology consultation, respectively. LIMITATIONS Limitations were the inability to generalize the data from the population studied and the chances of error and bias in teledermatology diagnoses. CONCLUSIONS Store-and-forward teledermatology can improve diagnostic and therapeutic care for skin disease in children who lack direct access to dermatologists.

Urticaria mimickers in children

Acute urticaria is a self‐limited cutaneous condition marked by transient, erythematous, and pruritic wheals. It is a hypersensitivity response that is often secondary to infection, medications, or food allergies in children. In contrast, the urticarial “mimickers” described in this review article are often seen in the context of fever and extracutaneous manifestations in pediatric patients. The differential diagnosis ranges from benign and self‐limited hypersensitivity responses to multisystem inflammatory diseases. Establishing the correct diagnosis of an urticarial rash in a pediatric patient is necessary to both prevent an unnecessary work up for self‐limited conditions and to appropriately recognize and evaluate multisystem inflammatory disorders. Herein, we describe two cases to illustrate the clinical manifestations, laboratory findings, histopathology and differential diagnoses for several mimickers of acute urticaria including: urticaria multiforme, serum sickness like reaction, Henoch‐Schönlein purpura, acute hemorrhagic edema of infancy, systemic onset juvenile idiopathic arthritis, cryopyrin associated periodic syndromes, and urticarial vasculitis.

Topical Timolol Maleate Treatment of Infantile Hemangiomas

BACKGROUND: There has been a dramatic increase in the off-label use of ophthalmic timolol maleate, a β-blocker used for infantile hemangioma (IH) treatment as a topical counterpart to oral propranolol. Its safety and efficacy in a pediatric population with IH have not been evaluated in a large cohort. Our goal was to retrospectively assess timolol’s effectiveness, discern characteristics associated with response, and document reported adverse events. METHODS: A multicenter retrospective cohort study of 731 patients treated with topical timolol was completed at 9 centers. Inclusion required an IH suitable for timolol in the treating physician’s judgment and access to clinical details including photographs. Logistic regression analysis and descriptive statistics were performed. Primary outcome measures were efficacy assessed by using visual analog scales for color and for size, extent, and volume from review of digital photographs taken as standard of care. RESULTS: Most IHs were localized (80.1%) and superficial (55.3%). Risk of disfigurement was the most common indication for therapy (74.3%). Duration of therapy (P < .0001), initial thinness (P = .008), and subtype (P = .031) were significant predictors of response. Best response occurred in superficial IHs <1 mm thick. Fifty-three (7.3%) required subsequent therapy with systemic β-blocker. Adverse events were mild, occurring in 25 (3.4%) patients. No cardiovascular side effects were documented. CONCLUSIONS: Timolol seems to be a well-tolerated, safe treatment option with moderate to good effectiveness, demonstrating best response in thin, superficial IHs regardless of pretreatment size. Timolol can be recommended as an alternative to systemic β-blockers and watchful waiting for many patients.

A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70

Chan et al. describe a combination of alleles with hypomorphic and activating mutations in the T cell signaling molecule ZAP-70 in a patient with autoimmunity.

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin.

Randomized controlled trial of spaced education for pediatric residency education.

BACKGROUND Spaced education (SE) has shown promise as an instructional tool that uses repeated exposure to the same questions, but information on its utility in graduate medical education is limited, particularly in assessing knowledge gain with outcome measures that are different from repeat exposure to the intervention questions. OBJECTIVE We examined whether SE is an effective instructional tool for pediatrics residents learning dermatology using an outcome measure that included both unique and isomorphic questions. METHODS We randomized 81 pediatrics residents into 2 groups. Group A completed an SE course on atopic dermatitis and warts and molluscum. Group B completed an SE course on acne and melanocytic nevi. Each course consisted of 24 validated SE items (question, answer, and explanation) delivered 2 at a time in 2 e-mails per week. Both groups completed a pretest and posttest on all 4 topics. Each group served as the comparison for the other group. RESULTS Fifty residents (60%) completed the study. The course did not have a statistically significant effect on the posttest scores for either group. Overall, test scores were low. Eighty-eight percent of residents indicated that they would like to participate in future SE courses. CONCLUSIONS Using primarily novel posttest questions, this study did not demonstrate the significant knowledge gains that other investigators have found with SE.

Headaches as a Presenting Symptom of Linear Morphea en Coup de Sabre

Linear morphea en coup de sabre (ECDS) is a form of localized scleroderma that predominantly affects the pediatric population, with a median age of 10 years at presentation. The existence of neurologic findings in association with ECDS has been well described in the literature. Here we describe 4 patients with ECDS who presented with headaches, which were typical migraines in 3 of the patients. The headaches preceded the onset of cutaneous findings by at least 6 months. Our patients’ cases emphasize both the importance of recognizing headaches as a harbinger of ECDS and the necessity of performing thorough cutaneous examination in patients with unexplained headaches or other neurologic disease.

What should primary care providers know about pediatric skin conditions? A modified Delphi technique for curriculum development

BACKGROUND There is limited access to pediatric dermatology in the United States, resulting in inadequate education and patient care. OBJECTIVE This Delphi study aimed to identify important objectives for a pediatric dermatology curriculum for general practitioners. METHODS A modified, 2-round Delphi technique was used to develop consensus on objectives developed by expert pediatric dermatologists. A panel of 20 experts (pediatric dermatologists, family practitioners, and general pediatricians) rated objectives using a 5-point Likert-type scale. Items with group medians 4.0 or greater with at least 70% agreement reached consensus. RESULTS In round 1, the expert panel rated 231 objectives from 16 categories for inclusion in an online curriculum. In round 2, experts were given group feedback and rated 235 objectives. A total of 170 items met consensus. Generally, objectives surrounding common conditions including acne, molluscum, warts, atopic dermatitis, and newborn skin met consensus whereas objectives on rare growths, birthmarks, and inherited conditions failed to meet consensus. LIMITATIONS The Delphi panel consisted of US-based physicians, most in urban areas with a dedicated pediatric specialist at their institution. CONCLUSIONS The accepted objectives encompass management of common conditions and referral of potentially dangerous diseases and can be used to develop a pediatric dermatology curriculum for primary care providers.

Hereditary Disorders of Cornification

The disorders of cornification (DOC) are a heterogeneous group of inherited conditions that involve abnormal keratinocyte differentiation resulting in dry, scaling, thickened skin, and variable degrees of associated inflammation. The general goals of therapy for children with DOC are to: (i) preserve function; (ii) maximize the quality of life by improving itch, sleep, and appearance; and (iii) prevent complications such as infection, dehydration, and poor growth. The mechanism of action, appropriate use, and side effects of specific therapies such as emollients, keratolytics, antimicrobials, bath additives, physical treatments, retinoids, retinoic acid, metabolism blocking agents, and targeted therapy are discussed. We then present the therapeutic ladders supported by evidence for selected DOC such as non-syndromic ichthyoses, Netherton syndrome, Sjogren-Larsson syndrome, Darier disease, and palmoplantar keratodermas.