Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

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.

Development of SkinTracker, an integrated dermatology mobile app and web portal enabling remote clinical research studies.

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.

Research Fever in Dermatology-A Symptom of a Larger Problem.

This Viewpoint offers potential solutions to research "fever," which is characterized as a symptom of larger problems in our health care and educational systems rather than the fault of residency applicants.

Nagashima-type palmoplantar keratoderma: Case series and two novel variants.

Nagashima-type palmoplantar keratoderma (PPK) is an autosomal recessive PPK. We report four patients, highlight two new genetic variants, and emphasize the possibility of misdiagnosing the condition. Concomitant atopic dermatitis, specifically, may make correct diagnosis challenging. Clinicians should consider the diagnosis of Nagashima-type PPK in patients presenting with mild PPK with transgrediens and understand the importance of individualized multimodal treatment regimens.

Long-pulsed neodymium-doped yttrium aluminum garnet for hair reduction in pediatric microtia repair.

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.

Multicenter retrospective review of pulsed dye laser in nonulcerated infantile hemangioma.

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.

Milestones 2.0: An advancement in competency-based assessment for dermatology.

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.

Successful use of telemedicine for evaluation of infantile hemangiomas during the early COVID-19 pandemic: A cross-sectional study.

BACKGROUND/OBJECTIVES: The COVID-19 pandemic prompted a rapid expansion in the use of telemedicine. This study aimed to assess the experiences of hemangioma specialists utilizing telemedicine during the COVID-19 pandemic to evaluate and manage infantile hemangiomas (IH), including perceived effectiveness of different modalities and barriers to care delivery. METHODS: Multicenter cross-sectional study asking providers to describe their experiences using telemedicine for initial evaluation of IH from March to September 2020. RESULTS: The study included 281 patients from 15 medical centers internationally. Median time from referral to evaluation was 17 days. Median physician confidence in performing evaluations via telemedicine was 95.0 (IQR 90.0-100.0). Most evaluations were performed via video communication with photographs or audio communication with photographs; when not initially available, photographs were requested in 51.4%. Providers preferred follow-up modalities that included photographs. CONCLUSIONS: Physicians with extensive expertise in managing IH are confident in their abilities to assess and manage IH via telemedicine including initiating treatment in patients without risk factors for beta-blocker therapy. There was a preference for hybrid modalities that included photographs. The data suggest that telemedicine can be effective for managing IH and may decrease wait times and improve specialist reach to underserved areas.

S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome.

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 ß-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.

Mapping of Segmental and Partial Segmental Infantile Hemangiomas of the Face and Scalp.

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.

Consensus recommendations for the use of retinoids in ichthyosis and other disorders of cornification in children and adolescents.

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.

Management of infantile hemangiomas during the COVID pandemic.

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.

The biker-glove pattern of congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are common birthmarks with 20% occurring on the limbs. We describe 4 patients with acral CMN with a "biker-glove" distribution with sparing of the distal digits, as has previously been described in acral infantile hemangiomas (IH). The existence of the biker-glove pattern suggests that CMN arise from early mutations in melanocyte precursors and supports the recently described Kinsler-Larue hypothesis of mesenchymal distribution of melanocyte migration occurring in a circular field from a central point. Developmental errors in mesenchymal precursors with similar migration patterns may explain this shared pattern among CMN and IH.

Topical timolol: An effective treatment option for agminated pyogenic granuloma.

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.

Hearing loss in PHACE syndrome: clinical and radiologic findings.

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.

Sirolimus for management of complex vascular anomalies - A proposed dosing regimen for very young infants.

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.

Infantile hemangiomas with conjunctival involvement: An underreported occurrence.

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.