Susan J. Bayliss

“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.

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation

Capillary malformation–arteriovenous malformation (CM–AVM) is an autosomal‐dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast‐flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM–AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM–AVM (n = 100), common CM(s) (port‐wine stain; n = 100), Sturge–Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty‐eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM–AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the “second‐hit” hypothesis as a pathophysiological mechanism for CM–AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild‐type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM–AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast‐flow lesions warrants careful clinical and radiologic examination, and regular follow‐up.

Cutis laxa: A review

Cutis laxa is a rare disorder of elastic tissue resulting in loose, redundant, hypoelastic skin. Both acquired and inherited forms exist, some of which have significant systemic manifestations. Here, we review the various forms of cutis laxa, with focus on the inherited forms. Recent molecular studies have provided many new insights into the causes of cutis laxa and revealed greater genetic heterogeneity than previously appreciated.

Milia : A review and classification

Milia are frequently encountered as a primary or secondary patient concern in pediatric and adult clinics, and in general or surgical dermatology practice. Nevertheless, there are few studies on the origin of milia and, to our knowledge, there is no previous comprehensive review of the subject. We review the various forms of milia, highlighting rare variants including genodermatosis-associated milia, and present an updated classification.

Oral propranolol for treatment of periocular infantile hemangiomas.

OBJECTIVE To evaluate the efficacy and adverse effects of oral propranolol for treatment of periocular infantile hemangioma. METHODS Participants were treated with oral propranolol 3 times daily, with outpatient monitoring of adverse effects. The starting dosage was 0.5 mg/kg/d for 1 week, then 1 mg/kg/d for the following week, then 2 mg/kg/d for the remaining duration of treatment. Serial examinations and external photography documented the size of the hemangiomas. Complete ophthalmic examinations included assessing for amblyopia with cycloplegic refraction and visual diagnostic testing. Amblyopia was treated with part-time occlusion therapy. RESULTS Nineteen periocular hemangiomas from 17 children (71% girls) were studied. The median age at the start of treatment was 4.5 months (interquartile range, 2.2-5.6 months). The median treatment duration was 6.8 months (interquartile range, 4.1-7.2 months). Treatment with oral propranolol reduced the size of all hemangiomas. Median change in the surface area was 61% (interquartile range, 32%-64%) of the original size. Mild rebound growth that did not necessitate retreatment was found in 2 patients (12%). One patient (6%) experienced a benign episode of bradycardia. Seven patients (41%) had amblyopia. CONCLUSIONS Oral propranolol for treatment of infantile hemangiomas was effective in all patients, with 33% reduction in astigmatism and 39% reduction in surface area. Vision equalized in all but 1 child, who receives ongoing amblyopia therapy. Our results suggest that early treatment with propranolol is remarkably effective in treating and preventing loss of visual acuity associated with periocular infantile hemangiomas.

The genetics of hair shaft disorders.

Many of the genes causing hair shaft defects have recently been elucidated. This continuing medical education article discusses the major types of hair shaft defects and associated syndromes and includes a review of histologic features, diagnostic modalities, and findings in the field of genetics, biochemistry, and molecular biology. Although genetic hair shaft abnormalities are uncommon in general dermatology practice, new information about genetic causes has allowed for a better understanding of the underlying pathophysiologies.

Neutrophilic Dermatoses in Children

Abstract:  The neutrophilic dermatoses are rare disorders, especially in children, and are characterized by neutrophilic infiltrates in the skin and less commonly in extracutaneous tissue. The neutrophilic dermatoses share similar clinical appearances and associated conditions, including inflammatory bowel disease, malignancies, and medications. Overlap forms of disease demonstrating features of multiple neutrophilic dermatoses may be seen. The manuscript attempts to provide an up‐to‐date review of (i) classical neutrophilic dermatoses, focusing on distinctive features in children and (ii) neutrophilic dermatoses which may largely be pediatric or genodermatosis‐associated (Majeed, SAPHO [synovitis, severe acne, sterile palmoplantar pustulosis, hyperostosis, and osteitis] syndrome, PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), PFAPA (periodic fever with aphthous stomatitis, pharyngitis, and cervical adenopathy), and other periodic fever syndromes, and congenital erosive and vesicular dermatosis healing with reticulated supple scarring).

Aquagenic Wrinkling of the Palms in Cystic Fibrosis Comparison With Controls and Genotype-Phenotype Correlations

OBJECTIVE To determine the prevalence of aquagenic wrinkling of the palms (AWP) in patients with cystic fibrosis (CF) compared with control patients, and evaluate for genotype-phenotype correlations. Since its first description over 30 years ago, AWP has frequently been anecdotally associated with CF, but this association has not been confirmed in a rigorous prospective case-control study. DESIGN Blinded comparison. SETTING The CF and dermatology clinics at St Louis Childrens Hospital. PARTICIPANTS Forty-four individuals with CF from a CF clinic and 26 controls from a dermatology clinic. Intervention Participants were tested for AWP using 3 minutes of water immersion with room-temperature tap water. Main Outcome Measure The degree of AWP was scored from 0 (no wrinkling) to 4 (severe wrinkling) by 3 blinded physicians. For genotype-phenotype correlations, patients with CF were divided into those homozygous for the DeltaF508 mutation and those with other genotypes. RESULTS The mean AWP score of the CF group was significantly higher than the mean score of the control group (1.5 vs 0.6; P < .001). Patients with CF who were homozygous for the DeltaF508 mutation (n = 27) had significantly higher scores than patients with CF who were not homozygous for the DeltaF508 mutation (n = 17) (1.7 vs 1.1; P = .02). The 17 patients with CF who were not homozygous for the DeltaF508 mutation still had higher scores than the control group (1.1 vs 0.6; P = .03). There was no correlation between sweat chloride concentrations measured at the time of diagnosis and AWP score. CONCLUSIONS Our results confirm the association between AWP and CF. Among patients with CF, greater AWP occurs in those who are homozygous for the DeltaF508 mutation.

Morphologic Features and Natural History of Scalp Nevi in Children

OBJECTIVE To characterize the clinical changes in clinically distinctive scalp nevi over time in children to help guide management and avoid misdiagnosis as melanoma. DESIGN Cohort study. SETTING Washington University School of Medicine pediatric dermatology clinics. Patients Of 93 patients younger than 18 years with photographically documented, clinically distinctive scalp nevi, 28 (30%) consented to participate. Minimum follow-up from the initial visit was 1 year. Collectively, these patients had 44 scalp nevi at the initial visit. No patient had a personal diagnosis of melanoma or dysplastic nevus syndrome. MAIN OUTCOME MEASURES Clinical changes in scalp nevi as determined using the ABCDE scoring system (ie, asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution/elevation from initial to follow-up images) on initial and follow-up photographs of scalp nevi. RESULTS Overall, 77% of the clinically distinctive scalp nevi (34 of 44) showed clinical signs of change during mean follow-up of 2.8 years. Of those with changes, 18 (53%) became more atypical and 16 (47%) became less atypical since the initial examination. None of the changes were concerning for melanoma. The mean total scalp nevus count was 2.6. Scalp nevi represented approximately 6% of total-body nevi. The number of scalp nevi increased with age. Boys had 1.5 times the number of scalp nevi as girls (P = .03). CONCLUSIONS Scalp nevi are clinically dynamic in childhood. These changes include an increase or a decrease in atypical features and occur in all age groups. This preliminary study does not support excisional biopsies but does support physician evaluation of scalp nevi evolution and serial photography of clinically distinctive lesions.

Cutaneous effects of thiotepa in pediatric patients receiving high-dose chemotherapy with autologous stem cell transplantation

High-dose thiotepa, a polyfunctional alkylating agent used in the treatment of solid tumors in children and adults, has been reported to cause a variety of reactions in the skin, including erythema, blistering, and hyperpigmentation. Reports vary in descriptions of the prevalence, severity, and nature of cutaneous reactions to thiotepa. To further characterize the cutaneous effects of thiotepa in children, we performed a chart review of 38 pediatric patients treated with a thiotepa-based chemotherapy regimen before autologous stem cell transplantation. Although cutaneous symptoms were documented in all patients, a consistent pattern of diffuse erythema with progression to desquamation and hyperpigmentation occurred in nearly 80% of the patients. Intertriginous and occluded areas were often the initial areas to be affected. Recognition of this association will improve the care of this patient population. This study was limited by reliance on chart data and lack of follow-up by a dermatologist.