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This article reviews the clinical findings of epidermal nevi and their associated syndromes and provides an update on their pathogenic genetic changes as well as targeted therapies detailed to date.

IMPORTANCE: A 2010 prospective study of 108 infants estimated the incidence of PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome to be 31% in children with facial infantile hemangiomas (IHs) of at least 22 cm2. There is little evidence regarding the associations among IH characteristics, demographic characteristics, and risk of PHACE syndrome. OBJECTIVES: To evaluate demographic characteristics and comorbidities in a large cohort of patients at risk for PHACE syndrome and assess the clinical features of large head and neck IH that may be associated with a greater risk of a diagnosis of PHACE syndrome. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, retrospective cohort study assessed all patients with a facial, head, and/or neck IH who were evaluated for PHACE syndrome from August 1, 2009, to December 31, 2014, at 13 pediatric dermatology referral centers across North America. Data analysis was performed from June 15, 2017, to February 29, 2020. MAIN OUTCOMES AND MEASURES: The main outcome was presence or absence of PHACE syndrome. Data included age at diagnosis, sex, patterns of IH presentation (including size, segment location, and depth), diagnostic procedures and results, and type and number of associated anomalies. RESULTS: A total of 238 patients (mean [SD] age, 2.96 [4.71] months; 184 [77.3%] female) were included in the analysis; 106 (44.5%) met the criteria for definite (n = 98) or possible (n = 8) PHACE syndrome. A stepwise linear regression model found that a surface area of 25 cm2 or greater (odds ratio [OR] 2.99; 95% CI, 1.49-6.02) and involvement of 3 or more locations (OR, 17.96; 95% CI, 6.10-52.85) to be statistically significant risk factors for PHACE syndrome. Involvement of the parotid gland (OR, 0.39; 95% CI, 0.18-0.85) and segment S2 (OR, 0.38; 95% CI, 0.16-0.91) was associated with a lower risk. Race and ethnicity may also be associated with PHACE syndrome risk, although more studies are needed. CONCLUSIONS AND RELEVANCE: This cohort study further described factors associated with both a higher and lower risk of PHACE syndrome. The presence of multiple anatomical sites and large surface area were associated with greater risk, whereas S2 or parotid IHs were associated with lower, but still potential, risk. These findings can help in counseling families and decision-making regarding evaluation of infants with large head and neck IHs.

IMPORTANCE: Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB. OBJECTIVES: To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study. EXPOSURES: Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS). MAIN OUTCOMES AND MEASURES: Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB. RESULTS: Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 [81.0%]), followed by RDEB (218 of 283 [77.0%]), DDEB (71 of 104 [68.3%]), and EBS (100 of 194 [51.5%]). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died. CONCLUSIONS AND RELEVANCE: The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.

ABSTRACTTopical mupirocin is used widely to treat skin and soft tissue infections and to eradicate nasal carriage of methicillin-resistant Staphylococcus aureus(MRSA). Few studies to date have characterized the rates of S. aureusmupirocin resistance in pediatric populations. We retrospectively studied 358 unique S. aureusisolates obtained from 249 children seen in a predominantly outpatient setting by the Division of Pediatric Dermatology at a major academic center in New York City between 1 May 2012 and 17 September 2013. Mupirocin resistance rates and the associated risk factors were determined using a logistic regression analysis. In our patient population, 19.3% of patients had mupirocin-resistant S. aureusisolates at the time of their first culture, and 22.1% of patients with S. aureusinfection had a mupirocin-resistant isolate at some time during the study period. Overall, 31.3% of all S. aureusisolates collected during the study period were resistant to mupirocin. Prior mupirocin use was strongly correlated (odds ratio [OR] = 26.5; P= <0.001) with mupirocin resistance. Additional risk factors for mupirocin resistance included methicillin resistance, atopic dermatitis (AD), epidermolysis bullosa (EB), immunosuppression, and residence in northern Manhattan and the Bronx. Resistance to mupirocin is widespread in children with dermatologic complaints in the New York City area, and given the strong association with mupirocin exposure, it is likely that mupirocin use contributes to the increased resistance. Routine mupirocin testing may be important for MRSA decolonization strategies or the treatment of minor skin infections in children.

BACKGROUND Chlorhexidine gluconate–impregnated dressings have become widely adopted as a means to reduce the risk for catheter-associated bloodstream infections. These dressings release antiseptic under occlusion onto the skin surrounding catheter insertion sites. Although chlorhexidine gluconate is a known cause of contact dermatitis, the phenotypic range of this adverse effect of chlorhexidine gluconate–impregnated dressings in critically ill patients has not been described. OBSERVATIONS We report 7 cases of erosive irritant contact dermatitis due to chlorhexidine gluconate–impregnated transparent dressings. Six of these patients were children (age range, 4 months to 2 years); the adult was a critically ill 62-year-old man. Four patients were immunosuppressed after solid organ transplant and all were receiving blood pressure support at the time of this reaction. The insertion sites of femoral catheters were involved in all but 1 case; 3 catheter sites were involved in the adult patient. Results of extensive infectious workups were negative. All lesions resolved with discontinuation of the chlorhexidine gluconate–containing dressings, local wound care, and alternative antimicrobial dressings. CONCLUSIONS Erosive contact dermatitis is an underrecognized complication of chlorhexidine gluconate–impregnated dressings. Health care providers should be aware of this risk, particularly in young children and immunosuppressed and/or critically ill patients, who may be more susceptible to the irritant effects of these dressings. When the dressings are used, patients should be monitored closely for skin breakdown.

OBJECTIVES To develop instruments that measure the severity of infantile hemangiomas (Hemangioma Severity Scale [HSS]) and the complications of infantile hemangiomas for longitudinal use (Hemangioma Dynamic Complication Scale [HDCS]). DESIGN Instrument development and reliability study. SETTING Academic research. PARTICIPANTS The HSS and the HDCS were developed through the collaborative effort of members of the Hemangioma Investigator Group Research Core, an expert multi-institutional research group. After development of the scales, 13 pediatric dermatologists used the HSS to score 20 different hemangiomas. In addition, 12 pediatric dermatologists used the HDCS to score hemangioma-related complications for 24 clinical scenarios. Interrater and intrarater reliability was measured for both scales. MAIN OUTCOME MEASURES Interrater and intrarater reliability. RESULTS For the HSS, interrater reliability and intrarater reliability exceeded 99%. Similarly, the HDCS had a high rate of interrater agreement; for individual items, agreement among raters was 67% to 100%, with most clinical scenarios demonstrating greater than 90% agreement. Intrarater reliability was excellent for all individual items of the HDCS. CONCLUSION The HSS and the HDCS are reliable scales that can be used to measure the severity of infantile hemangiomas, including the severity of complications for longitudinal use.

OBJECTIVE To describe the clinical presentation and risk of PHACE syndrome in infants with large facial hemangiomas and concomitant airway hemangiomas. DESIGN The study involved a case series of infants with cutaneous hemangiomas and airway hemangiomas extracted from a prospective multicenter cohort study. Data regarding clinical features, diagnosis, treatment, and clinical course were obtained from medical charts and physician intake forms. All patients were evaluated for PHACE syndrome using a standardized protocol. SETTING Six academic pediatric dermatology clinics. PATIENTS The study included 17 patients younger than 1 year who were diagnosed as having large (>22 cm2) facial hemangiomas and airway hemangiomas. RESULTS Thirteen patients (76%) had hemangiomas in the bilateral mandibular distribution. Other observed facial patterns included limited involvement of the lip and chin, unilateral reticular frontotemporal and preauricular hemangiomas, and large unilateral hemifacial hemangiomas. Fourteen patients (82%) had symptomatic airway involvement. All symptomatic patients had subglottic airway hemangiomas. The airway hemangioma was circumferential in 10 patients (58%) and more focal in distribution in 7 patients (42%). All patients were treated with oral prednisolone. Eleven patients required additional multimodal therapy. Eight patients (47%) met the criteria for PHACE syndrome. CONCLUSIONS Airway hemangiomas represent a potentially fatal complication of infantile hemangiomas. Our data highlight cutaneous presentations in patients with subglottic hemangiomas and large (>22 cm2) cutaneous hemangiomas. PHACE syndrome was detected in 8 such patients (47%) in our series.

PHACES syndrome is a neurocutaneous disorder of unknown etiology. We studied the spectrum of associated congenital and progressive cerebral vascular anomalies.

Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins from arachidonic acid. This enzyme exists in at least two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and plays various physiological roles. However, COX-2 expression is induced by a variety of agents, which include pro-inflammatory agents and mitogens. Evidence exists to indicate that increased expression of COX-2 occurs in several types of epithelial neoplasms. In this study, we show the effect of chronic exposure of murine skin to carcinogenic UVB on cutaneous COX-2 expression. SKH-1 mice were irradiated with 180 mJ/cm2 UVB daily for five days a week for periods ranging from 1 to 20 weeks. Nontumor bearing skin areas of irradiated mice, skin of age-matched controls and benign papillomas and malignant tumors were assessed immunohistochemically for COX-2 expression in these mice. No epidermal staining occurred in any of the non-UVB-treated controls throughout the experiment. Epidermal COX-2 expression only occurred in UVB-irradiated mice. After 1 and 5 weeks of irradiation, patchy epidermal staining mostly confined to the granular layer and stratum corneum was observed. At week 9, staining intensity had increased, particularly in the granular layer. At week 13, staining was uniformly seen in all epidermal layers with particular prominence in the basal cell layer underlying areas of visible epidermal hyperplasia. It is of interest that the most intense staining was seen in the perinuclear region of keratinocytes and at the plasma membrane. At week 20, COX-2 staining was predominant in the granular layer, although in some tissue sections, the entire epidermis was positive. In benign papillomas, staining was confined to the superficial layers of the epidermis and in squamous cell carcinomas (SCCs), patchy staining in the granular and spinous layers predominated. In general, COX-2 expression was more intense in well-differentiated SCCs than in papillomas. In summary, our results indicate that COX-2 serves as an early marker of epidermal UVB exposure and its expression increases in benign papillomas and in SCCs. These results suggest that pharmacological intervention using specific COX-2 inhibitors could have anticarcinogenic effects in UVB-induced human skin cancer.