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Adena Rosenblatt,1 Erin F Mathes,2 Kristina W Rosbe31Department of Pediatrics, University of California, San Francisco, 2Division of Pediatric Dermatology, Departments of Dermatology and Pediatrics, University of California, San Francisco, 3Division of Pediatric Otolaryngology, Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, CA, USAAbstract: Infantile hemangiomas (IH) are benign vascular tumors consisting of a collection of immature cells, including progenitor stem cells and disorganized blood vessels. They are the most common benign tumors in childhood. Recently, there have been significant, exciting advancements in the understanding of the pathogenesis and treatment of infantile hemangiomas, which are discussed in this review. The decision to initiate treatment for IH is based on many factors, including size and location, functional compromise, psychosocial implications, and risks and benefits of the proposed therapy. For most families of children with hemangiomas, education about the natural history of IH and reassurance are often the only "treatment" required. A minority of patients with large, complex lesions or lesions that cause functional compromise require early intervention. These patients and families benefit from a multidisciplinary approach to care in vascular birthmark centers. Ongoing multi-institutional clinical trials will provide further important data on the efficacy and safety of hemangioma treatments.Keywords: progenitor stem cell, glucose transporter 1, PHACES, LUMBAR, infantile hemangioma

Background: The incidence of localized intravascular coagulopathy (LIC) in venous malformations varies with lesion size and location, as well as the presence of palpable phleboliths. The development of LIC can cause pain and hemorrhage and can progress to disseminated intravascular coagulopathy (DIC) and thromboembolic disease resulting in death in some cases. Early recognition of LIC can relieve symptoms and prevent progression to life-threatening complications. Objective: The aim of this work was to identify MRI features of venous malformation associated with LIC. We hypothesized that venous malformations with larger capacitance, slower flow and less physiological compression (greater stasis) were more likely to be associated with LIC. Materials and methods: In this HIPAA-compliant and IRB-approved study, we retrospectively reviewed clinical records and MRI for consecutive patients undergoing evaluation of venous malformations at our multidisciplinary Birthmarks and Vascular Anomalies Center between 2003 and 2013. Inclusion required consensus diagnosis of venous malformation and availability of laboratory data and MRI; patients on anticoagulation or those previously undergoing surgical or endovascular treatment were excluded. LIC was diagnosed when D-dimer exceeded 1,000 ng/mL and/or fibrinogen was less than 200 mg/dL. Two board-certified radiologists assessed the following MRI features for each lesion: morphology (spongiform vs. phlebectatic), presence of phleboliths, size, location (truncal vs. extremity), and tissue type(s) involved (subcutis, muscle, bone and viscera). Univariate logistic regression analyses were used to test associations between LIC and MRI findings, and stepwise regression was applied to assess the significance of the individual imaging predictors. Results: Seventy patients, 37 with LIC, met inclusion criteria during the 10-year study period (age: 14.5 +/- 13.6 years [mean +/- standard deviation]; 30 male, 40 female). Both elevated D-dimer and low fibrinogen were associated with the presence of phleboliths, larger lesion sizes and visceral involvement on MRI (all P < 0.05). In stepwise regressions, lesion size (P < 0.001), the presence of phleboliths (P = 0.005) and lesion morphology (P = 0.006) were all significant predictors of LIC. Conclusion: LIC is associated with larger lesion size, visualized phleboliths, truncal location and spongiform morphology on MRI in venous malformations, suggesting that lesions with larger capacitance, slower flow and less physiological compression are more likely to be associated with coagulopathy.

Background: Board-certified dermatologists experience diverse practice gaps., Objective: Identify the top self-selected focused Practice Improvement (fPI) modules completed over time by board-certified dermatologists during the program's first 8 years., Methods: Cohort study of dermatologists certified by American Board of Dermatology (ABD) completing fPI modules from 2016 to 2023. This descriptive analysis reports modules completed by topic, subspecialty, relevance, and self-reported changes to subsequent patient care related to modules., Results: 19143 fPI modules were completed by 7378 unique ABD diplomates, representing 48.8% of all current ABD-certified dermatologists (n = 15118). Modules were rated relevant by 18917 participants (99%). Care gaps requiring improvement efforts and performance remeasurement occurred in 2919 (15.2%) completed modules. Acne and medication-related laboratory monitoring were popular topics requiring improvement. Diplomates reported care improvements resulting from completing modules in 8397 instances (43.9%), and improved patient outcomes in at least one patient 5310 times (27.7%). Finally, diplomates stated they would recommend fPI modules to peers 18633 (97.3%) times., Limitations: Dermatologists who started but did not complete modules would not have rated the module. Attribution bias on care impact is possible and potentially overestimated., Conclusion: The ABD fPI program is helping board-certified dermatologists identify and improve gaps in care with reported patient outcome improvements., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To characterize long-term outcomes of PHACE syndrome., Study Design: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains., Results: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD., Conclusions: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood., Competing Interests: Declaration of Competing Interest Supported by the 2021 Research Fellowship from the Pediatric Dermatology Research Alliance (PeDRA) as well as the 2021-2022 University of California San Francisco Yearlong Research Fellowship. The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In-person dermatology clinical research studies often face recruitment and participation challenges due to travel-, time-, and cost-associated barriers. Studies incorporating virtual/asynchronous formats can potentially enhance research subject participation and satisfaction, but few mobile health tools are available to enable remote study conduct. We developed SkinTracker, a patient-facing mobile app and researcher-facing web platform, that enables longitudinal collection of skin photos, patient reported outcomes, and biometric health and environmental data., Methods: Eight design thinking sessions including dermatologists, clinical research staff, software engineers, and graphic designers were held to create the components of SkinTracker. Following iterative prototyping, SkinTracker was piloted across six adult and four pediatric subjects with atopic dermatitis (AD) of varying severity levels to test and provide feedback on SkinTracker for six months., Results: The SkinTracker app enables collection of informed consent for study participation, baseline medical history, standardized skin photographs, patient-reported outcomes (e.g., Patient Oriented Eczema Measure (POEM), Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI)), medication use, adverse events, voice diary to document qualitative experiences, chat function for communication with research team, environmental and biometric data such as exercise and sleep metrics through integration with an Apple Watch. The researcher web portal allows for management and visualization of subject enrollment, skin photographs for examination and severity scoring, survey completion, and other patient modules. The pilot study requested that subjects complete surveys and photographs on a weekly to monthly basis via the SkinTracker app. Afterwards, participants rated their experience in a 7-item user experience survey covering app function, design, and desire for participation in future studies using SkinTracker. Almost all subjects agreed or strongly agreed that SkinTracker enabled more convenient participation in skin research studies compared to an in-person format., Discussion: To our knowledge, SkinTracker is one of the first integrated app- and web-based platforms allowing collection and management of data commonly obtained in clinical research studies. SkinTracker enables detailed, frequent capture of data that may better reflect the fluctuating course of conditions such as AD, and can be modularly customized for different skin conditions to improve dermatologic research participation and patient access., Competing Interests: TB has received research grant funding from Novartis and Regeneron and is a principal investigator for trials sponsored by Abbvie, Castle, CorEvitas, Dermavant, Galderma, Mindera, and Pfizer. She has served as an advisor for Abbvie, Arcutis, Boehringer-Ingelheim, Bristol Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, Sun, and UCB. WL has received research grant funding from Abbvie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. AK, PD, and ND were employed by RedBlink Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jin, Hong, Elhage, Braun, Spencer, Chung, Yeroushalmi, Hadeler, Mosca, Bartholomew, Hakimi, Davis, Thibodeaux, Wu, Kahlon, Dhaliwal, Mathes, Dhaliwal, Bhutani and Liao.)

Microtia is the term for congenital malformation of the ear in which the external and internal ear are absent or malformed. Surgical reconstruction is a common management approach and occasionally requires hair reduction of the newly constructed auricle. Few studies have investigated lasers for this purpose. We conducted a retrospective chart review of patients seen at a single institution between 2012 and 2021 who underwent laser hair reduction with long-pulsed neodymium-doped yttrium aluminum garnet laser (Nd:YAG). Efficacy ratings were done through review of clinical photographs. Twelve patients were identified with 14 total ears treated. The number of laser treatments varied from 1 to 9 sessions with an average of 5.1 treatments. The majority (8/12) had an "excellent" or "very good" response, one patient had a "good" response, and three were lost to follow-up. Other than pain, there were no side effects documented. Nd:YAG laser was both effective and safe in our pediatric cohort, without any cutaneous side effects in patients with darker skin., (© 2023 Wiley Periodicals LLC.)

Background/objectives: We sought to describe the experience among members of the Hemangioma Investigator Group with pulsed dye laser (PDL) in the treatment of nonulcerated infantile hemangioma (IH) in pediatric patients in the pre- and post-beta-blocker era., Methods: A multicenter retrospective cohort study was conducted in patients with nonulcerated IH treated with laser therapy. Patient demographics, IH characteristics, indications for/timing of laser therapy, as well as laser parameters were collected. Responses to laser therapy were evaluated using a visual analog scale (VAS)., Results: One hundred and seventeen patients with IH were treated with PDL. 18/117 (15.4%) had early intervention (defined as <12 months of life), and 99/117 (84.6%) had late intervention (≥12 months of life). In the late intervention group, 73.7% (73/99) had additional medical management of their IH. The mean age at PDL initiation for the late intervention group was 46.7 ± 35.3 months of life (range 12-172 months) with total number of treatments to maximal clearing of 4.2 ± 2.8 (range 1-17). Those who received propranolol prior to PDL received fewer sessions (1.1 fewer sessions, approaching significance [p = .056]).     On the VAS, there was a mean 85% overall improvement compared to baseline (range 18%-100%), with most improvement noted in erythema and/or telangiectasias. The incidence of adverse effects was 6/99 (6.1%)., Conclusions: PDL is a useful tool in the treatment of IH, with notable improvement of telangiectasia and erythema and low risk of complications.   PDL is often introduced after the maximal proliferative phase., (© 2022 Wiley Periodicals LLC.)

In 2013, Next Accreditation System and Milestones became the competency-based assessment framework required for all specialties accredited by the Accreditation Council for Graduate Medical Education. Dermatology residency programs implemented Milestones 1.0 in the 2013-2014 academic year. The Accreditation Council for Graduate Medical Education committed to review and revise Milestones 1.0 within 3 to 5 years. Subsequently, feedback from key stakeholders influenced the goals for revision, including reducing complexity, enhancing community engagement, and providing additional resources for programs. In 2019, the Dermatology Milestones 2.0 work group streamlined the specialty-specific patient care and medical knowledge subcompetencies. The harmonized milestones allowed for greater uniformity across specialties in systems-based practice, practice-based learning and improvement, professionalism, and interpersonal communication and skills. The work group developed a supplemental guide with specialty-specific context to help program directors, clinical competency committee members, and other faculty understand individual milestones. Dermatology Milestones 2.0 reduces the number of subcompetencies from 28 to 21. Milestones 2.0 represents an advancement in competency-based assessment for dermatology. The first year of reporting for Dermatology Milestones 2.0 is 2021., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease (MBTPS1, S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid β-oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA/ETFB. Our study discovered that mutations in MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Importance: Recognizing segmental infantile hemangioma (IH) patterns is important for risk stratification and provides clues to pathogenesis. Previously, segmental hemangiomas were mapped to 4 facial regions, 3 corresponding to known facial metameres., Objectives: To refine existing maps of facial segmental IHs, examine so-called indeterminate hemangiomas as they relate to known segmental patterns, and define a novel pattern of segmental scalp hemangiomas., Design, Setting, and Participants: This retrospective cohort study was conducted at 4 pediatric dermatology centers (University of California, San Francisco; Indiana University; Medical College of Wisconsin; and Northwestern University/Ann & Robert H. Lurie Children's Hospital of Chicago) using photographic archives of patients younger than 12 years with segmental and indeterminate hemangiomas on the face and scalp. Clinical images were used to map hemangioma distribution onto standardized facial templates. Heat map densiometry identified recurrent patterns that were compared with previously published patterns of facial segmental hemangiomas. Patterns of indeterminate hemangiomas were compared with those of segmental hemangiomas. Data collection took place in 2017, and analysis took place from 2017 to 2019., Main Outcomes and Measures: Distribution and patterning of segmental and indeterminate IHs of the face and scalp., Results: A total of 549 IHs were mapped. The borders of the frontotemporal (S1) and frontonasal (S4) segments agreed with previous segmental maps; however, the maxillary (S2) and mandibular (S3) segment borders differed with respect to the preauricular skin. In contrast with previous reports, preauricular skin segregated with the mandibular (S3) rather than the maxillary (S2) segment. Indeterminate hemangiomas occurred within and respected the same borders as segmental hemangiomas. Hemangiomas on the lateral scalp commonly occurred in a C shape extending from the posterior auricular region., Conclusions and Relevance: This cohort study provides an updated map of facial segmental IHs with redefined maxillary (S2) and mandibular (S3) segment borders. It provides evidence that indeterminate hemangiomas are partial segmental hemangiomas respecting anatomic boundaries of their larger segmental counterparts. A newly recognized C-shaped pattern of segmental scalp hemangioma is reported.

Topical and systemic retinoids have long been used in the treatment of ichthyoses and other disorders of cornification. Due to the need for long-term use of retinoids for these disorders, often beginning in childhood, numerous clinical concerns must be considered. Systemic retinoids have known side effects involving bone and eye. Additionally, potential psychiatric and cardiovascular effects need to be considered. Contraceptive concerns, as well as the additive cardiovascular and bone effects of systemic retinoid use with hormonal contraception must also be deliberated for patients of childbearing potential. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address these issues and to establish best practices regarding the use of retinoids in ichthyoses based on available evidence and expert opinion., (© 2020 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

The COVID-19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long-term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA-approved monitoring guidelines, clinical practice guidelines, and relevant, up-to-date publications regarding initiation and monitoring of beta-blocker therapy were used to inform the recommendations. Clinical decision-making guidelines about when telehealth is an appropriate alternative to in-office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided., (© 2020 Wiley Periodicals LLC.)

We present three patients with agminated pyogenic granulomas who experienced significant decrease in size and bleeding with treatment with topical timolol solution with minimal side effects. One patient had complete clinical resolution. For patients with agminated pyogenic granuloma who may otherwise have limited treatment options, timolol is an effective potential solution., (© 2018 Wiley Periodicals, Inc.)

Purpose: To characterize the types of hearing loss, auditory-related imaging findings, and hemangioma characteristics in patients with Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and abnormalities of the Eye (PHACE) syndrome., Methods: Retrospective medical records, audiologic data, and imaging review of all patients presenting to a tertiary care children's hospital with a proven diagnosis of PHACE syndrome from 2005 to 2016., Results: Twelve patients were identified with hearing and imaging data. 5/12 had hearing loss, 1 had unilateral severe sensorineural loss with minor conductive component, 1 had unilateral moderate sensorineural loss with minor conductive component, 1 had mild bilateral conductive loss, 1 had bilateral hearing loss (left severe mixed and right severe sensorineural), and 1 had moderate bilateral conductive loss. All patients passed their newborn hearing screening. Of the 5 patients with hearing loss, 3 had IAC hemangiomas (1 bilateral), 3 had enlarged IACs with prominent posterior petrous bones (1 bilateral), 2 had dysgenesis of the cerebellar vermis and hemispheres, there was 1 patient each with a deformed pinna and middle ear and mastoid effusions, and 1 patient had no abnormal auditory-related imaging findings. Patients with hearing loss were more likely to have more areas of cutaneous hemangioma involvement (mean 6.4 vs 3.1, p = .05). Laterality of hearing impairment correlated with the side of cutaneous hemangioma in all patients with hearing loss. Treatment with systemic propranolol did not improve hearing., Conclusions: Patients with PHACE are at risk for hearing loss and may demonstrate radiologic abnormalities within the ear structures, although the type of hearing loss, imaging findings, and their respective correlation vary. While our results are limited by our small sample size, comprehensive audiology evaluations (as opposed to newborn screening testing only) should be considered for PHACE patients who have extensive cutaneous hemangioma or auditory-related imaging abnormalities, such as internal auditory canal hemangiomas.

Neonates with vascular anomalies causing airway compromise and other complications require early initiation of medical therapy. Sirolimus has emerged as a safe and effective treatment, but standard recommendations for dosing start at seven months. Guidelines are needed for dosing in very young infants, who have reduced hepatic metabolism of sirolimus. We present our experience treating six neonates (mean age 14.8 days) with complicated vascular anomalies. Standard dosing caused supratherapeutic levels in this population. Our modified dosing regimen has resulted in safe therapeutic concentrations. Properly dosed, sirolimus is a viable and potentially lifesaving option for neonates with severe morbidity from vascular anomalies., (Copyright © 2017. Published by Elsevier B.V.)

Background/objectives: Infantile hemangiomas (IHs) involving the conjunctiva are only anecdotally reported in the literature and little is known about their clinical course. In a retrospective case series we aimed to better delineate the clinical presentation, complications, and response to treatment of this uncommon subtype of IH. A classification of conjunctival IH is proposed., Methods: Medical charts at three academic pediatric dermatology institutions were retrospectively analyzed. Data were collected on the clinical characteristics, ophthalmologic findings, treatments, and outcomes of 22 individuals with conjunctival IH., Results: Growth characteristics of conjunctival IH closely mirrored those of their cutaneous counterparts. Ophthalmologic abnormalities were associated with the IH in six individuals (27%); in three, they were considered severe. Seventeen subjects (77%) required treatment, most commonly because of risk of ocular compromise. All treated individuals responded favorably to topical timolol or systemic propranolol., Conclusion: Conjunctival IH have clinical characteristics similar to those of cutaneous IH and respond readily to beta-blocker treatment. Ocular complications may occur in a minority of individuals receiving treatment., (© 2017 Wiley Periodicals, Inc.)

Background/objectives: There is a lack of primary care provider (PCP) understanding of atopic dermatitis (AD) treatments and topical steroid use. We designed an AD management algorithm for pediatric PCPs. We hypothesized that the algorithm would improve pediatric PCPs' knowledge of AD diagnosis and management., Methods: Pediatric primary care resident and attending physicians at three residency programs were invited to participate in an electronic AD algorithm survey that contained demographic and 19 knowledge-based questions. Participants were randomized to intervention and control groups, with the intervention group receiving a short lecture and copy of our algorithm to use in an inpatient or outpatient setting for 2 months. Changes in scores between preintervention and postintervention surveys were compared., Results: Of the 54 participants, those in the intervention group (n = 26) performed significantly better than those in the control group (n = 28) after controlling for pretest scores (β = 1.19 [95% confidence interval 0.07, 2.32], p = 0.04). The intervention group had a higher average score on the posttest knowledge questions (71% correct) than the control group (65% correct) (p = 0.06). The majority of physicians who received the algorithm agreed or strongly agreed that they liked using the algorithm., Conclusion: The use of a management algorithm improved physician knowledge about the diagnosis and treatment of AD and was well accepted by physicians. Use of this management algorithm may lead to better recognition and management of AD, particularly earlier recognition of and therapy for superinfection, improving treatment outcomes and quality of life for patients and families., (© 2017 Wiley Periodicals, Inc.)

Background: The inflammatory infiltrate seen in biopsy specimens obtained from patients with subcutaneous fat necrosis of the newborn (SCFN) has classically been described as consisting mostly of histiocytes. However, we encountered patients with SCFN whose biopsy specimens revealed mostly neutrophils, prompting infection to be an initial consideration., Objectives: We sought to describe cases of SCFN in which neutrophils formed the majority of the infiltrate at our institution and in the literature., Methods: We performed a retrospective analysis of patients with SCFN reported at our institution and a literature review of SCFN., Results: Thirteen cases of SCFN were identified at our institution. In 2 of 13 cases, neutrophils composed >75% of the inflammatory infiltrate, and both lesions were 1 day old. From the literature review, neutrophils were mentioned as a component of the infiltrate in 10 of 124 cases, but in none were neutrophils described as forming the majority of the infiltrate., Limitations: This study is limited by its retrospective nature and small sample size., Conclusions: Neutrophils can comprise most of the inflammatory cells in patients with SCFN, especially early in the course of the disease. This variant of SCFN can be easily mistaken for infection., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Kaposiform hemangioendothelioma (KHE) is an infiltrative vascular tumor that classically presents in infancy. Management typically focuses on treating Kasabach-Merritt phenomenon (KMP), a disorder of severe and at times life-threatening platelet trapping. However, the morbidity of KHE extends beyond KMP. The infiltrative nature of the tumor can lead to long-term disability and often makes complete surgical resection impossible. We report the case of a 10-year-old boy with a KHE of his right distal thigh who was unable to walk without assistance due to fibrotic change and right knee contracture. He had no laboratory evidence of KMP at the time of representation. Rapamycin was started in hopes of reducing the tumor burden. Within 2 months of therapy, fibrotic areas softened, his contracture nearly resolved, and there was marked improvement in his mobility. Rapamycin has been previously reported to be effective in managing cases of KHE complicated by KMP. Our report emphasizes the role for rapamycin in the treatment of KHE in the absence of KMP through the inhibition of vasculogenesis and fibrotic pathways., (© 2016 Wiley Periodicals, Inc.)

PHACE syndrome is a rare neurocutaneous disorder characterized by posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, and abnormalities of the eye. Thyroid disorders associated with PHACE syndrome have been described, although there are limited reports of this rare occurrence. We report a case of PHACE syndrome with congenital hypothyroidism in an infant, for which absent thyroid gland was diagnosed at magnetic resonance imaging., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A brother and sister developed a previously undescribed constellation of autoimmune manifestations within their first year of life, with uncontrollable bullous pemphigoid, colitis, and proteinuria. The boy had hemophilia due to a factor VIII autoantibody and nephrotic syndrome. Both children required allogeneic hematopoietic cell transplantation (HCT), which resolved their autoimmunity. The early onset, severity, and distinctive findings suggested a single gene disorder underlying the phenotype. Whole-exome sequencing performed on five family members revealed the affected siblings to be compound heterozygous for two unique missense mutations in the 70-kD T cell receptor ζ-chain associated protein (ZAP-70). Healthy relatives were heterozygous mutation carriers. Although pre-HCT patient T cells were not available, mutation effects were determined using transfected cell lines and peripheral blood from carriers and controls. Mutation R192W in the C-SH2 domain exhibited reduced binding to phosphorylated ζ-chain, whereas mutation R360P in the N lobe of the catalytic domain disrupted an autoinhibitory mechanism, producing a weakly hyperactive ZAP-70 protein. Although human ZAP-70 deficiency can have dysregulated T cells, and autoreactive mouse thymocytes with weak Zap-70 signaling can escape tolerance, our patients' combination of hypomorphic and activating mutations suggested a new disease mechanism and produced previously undescribed human ZAP-70-associated autoimmune disease., (© 2016 Chan et al.)

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., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Areas of blanched skin in children may be seen as an independent finding or in association with vascular birthmarks. We performed a retrospective chart review to identify and describe infants with areas of ventral midline blanching in the presence of segmental infantile hemangiomas. We identified nine full-term infants with partial or full segmental hemangiomas and areas of midline ventral blanching. Additional ventral wall defects were seen in five patients. Six had cardiac anomalies and six had intracranial anomalies. Five were diagnosed with definite PHACE (posterior fossa, hemangioma, arterial, cardiac, and eye abnormalities) syndrome and three had possible PHACE syndrome. Eight were complicated by ulceration. Treatment varied according to the case. Ventral blanching, even in the absence of overt midline defects, can be seen in infants with segmental hemangiomas at risk for PHACE syndrome. We hypothesize that midline blanching may represent a minor manifestation of a developmental ventral defect., (© 2014 Wiley Periodicals, Inc.)

Background: Mycoplasma pneumoniae infection is associated with extrapulmonary complications, including mucocutaneous eruptions. These eruptions, which have been termed either "Stevens-Johnson syndrome" or "erythema multiforme" in the literature, may differ from drug-induced Stevens-Johnson syndrome or viral-associated erythema multiforme., Objective: We sought to review the literature characterizing morphology and disease course of M pneumoniae-associated mucocutaneous disease., Methods: A comprehensive literature search identified 95 articles with 202 cases., Results: Patients were often young (mean age: 11.9 years) and male (66%). Cutaneous involvement ranged from absent (34%), to sparse (47%), to moderate (19%). Oral, ocular, and urogenital mucositis was reported in 94%, 82%, and 63% of cases, respectively. Treatments included antibiotics (80%), systemic corticosteroids (35%), supportive care alone (8%), and/or intravenous immunoglobulin (8%). Complications included mucosal damage (10%), cutaneous scarring (5.6%), recurrence (8%), and mortality (3%)., Limitations: Mild cases may not have been published; thus this review may have a bias toward more severe disease., Conclusion: M pneumoniae-associated mucocutaneous disease has prominent mucositis and sparse cutaneous involvement, although cutaneous involvement varies. Because of the distinct morphology, mild disease course, and potentially important clinical implications regarding treatment, we propose a revision of the nomenclature system and suggest the term "Mycoplasma-induced rash and mucositis" for these cases., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2014 by the American Academy of Pediatrics.)

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., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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.

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., (© 2013 Wiley Periodicals, Inc.)

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.

Molluscum contagiosum is very common. In this article we discuss the use of cantharidin as a treatment option for molluscum contagiosum and give detailed information about distribution sources, how to apply it, and caveats regarding its use.Molluscum contagiosum is a common viral disease of childhood caused by a poxvirus, which presents with small, firm, dome-shaped, umbilicated papules. It is generally benign and self-limited, with spontaneous resolution within 6 months to several years. Watchful waiting can often be an appropriate management strategy; however, some patients either desire or require treatment. Reasons for actively treating molluscum contagiosum may include alleviation of discomfort and itching (particularly in patients where an eczematous eruption - the so-called "molluscum eczema" - is seen in association) or in patients with ongoing atopic dermatitis where more lesions are likely to be present. Other reasons for treatment include limitation of spread to other areas and people, prevention of scarring and superinfection, and elimination of the social stigma of visible lesions. No one treatment is uniformly effective.Treatment options include destructive therapies (curettage, cryotherapy, cantharidin, and keratolytics, among others), immunomodulators (imiquimod, cimetidine, and Candida antigen), and antivirals (cidofovir). In this article we discuss and describe our first-line treatment approach for those molluscum needing treatment - cantharidin., (Copyright 2010, SLACK Incorporated.)

The triad of fever, rash, and arthritis in a hospitalized child suggests an inflammatory, infectious, or postinfectious process in most cases; however, malignancy must be considered. The most common causes in this age group are inflammatory conditions, including Kawasaki disease, Henoch-Schönlein Purpura, serum sickness-like reaction, and juvenile idiopathic arthritis. Other rarer inflammatory processes can present with this triad of symptoms such as Cryopyrin-related diseases (autoinflammatory disorders), urticarial vasculitis, and systemic lupus erythematosus. We will discuss the differential diagnosis and inpatient management of fever, rash, and arthritis in a young child, focusing on inflammatory conditions. The important features which can help distinguish these conditions include the nature of the rash, associated signs or symptoms, time course of the eruption, and characteristic laboratory and/or histologic findings.

Cilia, or eyelashes, are unique hair follicles normally found at the eyelid margin. The spectrum of cilial anomalies includes cilial row duplication, agenesis, and ectopic placement. Ectopic cilia are the most rare of cilial anomalies. We report a case of a 2-and-a-half-year-old girl with ectopic cilia of the anterior tarsal plate, an extremely rare, congenital anomaly that is most often not associated with other findings and likely results from an event during embryogenesis.

Objective: To describe the scope of the University of California, San Francisco (UCSF), Vascular Anomalies Clinic (VAC), including the types of diagnoses, characteristics, and management of patients seen in the clinic., Design: Case series., Setting: Referral, outpatient, multidisciplinary clinic in a university system., Patients: Consecutive sample of 175 patients seen in the VAC at UCSF from January 2001 to July 2003., Main Outcome Measures: Diagnosis before and after clinic visit, symptoms, treatment recommendations, age of onset, age at clinic visit, location of lesion, sex, and type of referring physician., Results: A total of 96% of patients had cutaneous involvement, 71% of patients had vascular malformations, and 14% had infantile hemangiomas. Fifty-eight percent of patients were referred from outside the UCSF system. Of the patients who had not been previously seen by members of the VAC team or UCSF dermatologists, only 22% had been assigned correct specific diagnoses before coming to the VAC, and 13% had incorrect specific diagnoses before coming to the VAC. Fifty-six percent of vascular malformations were first noted at birth and 17% were noted at later than 10 years of age. Eighty-seven percent of patients were symptomatic from their vascular lesion. Sixty-six percent of patients underwent prior magnetic resonance imaging of their lesion. Further diagnostic workup was recommended in 43% of cases, and treatment recommendations were made in 83% of cases., Conclusions: Significant confusion still exists regarding the appropriate terminology, diagnosis, and management of vascular anomalies. Multidisciplinary clinics effectively address these complicated and troubling disorders by providing accurate diagnoses, clear treatment recommendations, and counseling from a team of specialists.