Stigmatization and Mental Health Impact of Chronic Pediatric Skin Disorders.

Importance: Chronic skin disorders in children frequently are visible and can cause stigmatization. However, the extent of stigmatization from chronic skin disease and association with mental health needs further study. Objective: To examine the extent of stigma, dependence on disease visibility and severity, and association with mental health and quality of life (QOL) in chronic pediatric skin disease. Design, Setting, and Participants: A cross-sectional, single-visit study was conducted at 32 pediatric dermatology centers in the US and Canada from November 14, 2018, to November 17, 2021. Participants included patients aged 8 to 17 years with chronic skin disease and 1 parent. Main Outcomes and Measures: Using the Patient-Reported Outcomes Measurement Instrumentation System (PROMIS) Stigma-Skin, the extent of stigma with child-, caregiver-, and physician-assessed disease visibility (primary outcome) and severity was compared, as well as reduced QOL (assessed by Skindex-Teen), depression, anxiety, and poor peer relationships (PROMIS child and proxy tools) (secondary outcomes). Results: The study included 1671 children (57.9% female; mean [SD] age, 13.7 [2.7] years). A total of 56.4% participants had self-reported high disease visibility and 50.5% had moderate disease severity. Stigma scores significantly differed by level of physician-assessed and child/proxy-assessed disease visibility and severity. Among children with chronic skin disorders, predominantly acne, atopic dermatitis, alopecia areata, and vitiligo, only 27.0% had T scores less than 40 (minimal or no stigma) and 43.8% had at least moderate stigma (T score ≥45) compared with children with a range of chronic diseases. Stigma scores correlated strongly with reduced QOL (Spearman ρ = 0.73), depression (ρ = 0.61), anxiety (ρ = 0.54), and poor peer relationships (ρ = -0.49). Overall, 29.4% of parents were aware of bullying of their child, which was strongly associated with stigma (Cohen d = -0.79, with children who were not bullied experiencing lower levels of stigma). Girls reported more stigma than boys (Cohen d = 0.26). Children with hyperhidrosis and hidradenitis suppurativa were most likely to have increased depression and anxiety. Conclusions and Relevance: The findings of this study suggest that physician assessment of disease severity and visibility is insufficient to evaluate the disease impact in the patient/caregiver. Identifying stigmatization, including bullying, and tracking improvement through medical and psychosocial interventions may be a key role for practitioners.

Pediatric Dermatology in Canada: A Broad Review of Population Needs, Workforce and Training With Proposed Solutions.

INTRODUCTION: The need for pediatric dermatology services is increasing across Canada. In parallel, the complexity of treatment with novel targeted therapeutics has increased. Currently, there is no accredited and limited non-accredited fellowship training access to pediatric dermatology in Canada. HYPOTHESIS: Understanding the current state of pediatric dermatology training in Canada will provide insight into opportunities for strategic improvement. METHODS: A survey was distributed to 44 pediatric dermatology providers. In addition, a review of the burden of pediatric skin disease and education/training in Canada was performed. RESULTS: Thirty-four specialists responded to the survey (77% response rate). One third of current pediatric dermatology providers are over 50 years old and half of these (15%) plan to retire within the next 5 years. Half of respondents were dermatologists, 35% were pediatricians, and 11% were double boarded. Almost all respondents practiced in an academic setting (94%). Most had further fellowship training in pediatric dermatology (82.4%) but only 57% achieved this training in Canada, due to lack of accredited or non-accredited funded fellowship positions. CONCLUSION: There is a high and growing need for pediatric dermatology specialty care in a diverse range of settings. The current provider population and training programs are insufficient to meet current and future demands. We highlighted solutions to close this gap between supply and demand including increased double board certification in Pediatrics and Dermatology, a protected pediatric stream within existing Dermatology residency training programs and accredited fellowships in Pediatric Dermatology for both dermatologists and pediatricians.

A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation.

B-cell lymphoma/leukemia 11B (BCL11B) is a C2H2 zinc finger transcription factor that is critically important for regulating the development and function of a variety of systems including the central nervous system, the skin, and the immune system. Germline heterozygous variants are associated with a spectrum of clinical disorders, including severe combined immunodeficiency as well as neurological, craniofacial, and dermal defects. Of these individuals, ~50% present with severe allergic disease. Here, we report the detailed clinical and laboratory workup of one of the most severe BCL11B-dependent atopic cases to date. Leveraging a zebrafish model, we were able to confirm a strong T-cell defect in the patient. Based on these data, we classify germline BCL11B-dependent atopic disease as a novel primary atopic disorder.

Barriers to healthcare access in pediatric dermatology: A systematic review.

Barriers to healthcare access are healthcare inequities that have been widely studied across different medical specialties. No studies have previously evaluated the state of barriers to healthcare access research in pediatric dermatology. A systematic review was conducted to examine the types of barriers identified within pediatric dermatology literature. Relevant information was extracted and categorized into the themes of systemic, sociocultural, or individual barriers. The systemic barriers we found include finances, wait times, and geography. The sociocultural barriers included culture beliefs and communication. Patient beliefs and health knowledge were found as individual barriers. The small number and limited scope of studies we identified suggest that barriers to healthcare access in pediatric dermatology remain an understudied topic. Additional research is needed to further characterize these barriers to dermatologic care, as well as the impact of any interventions designed to overcome them.

Diversity in pediatric dermatology: A report from the Pediatric Dermatology Research Alliance and a call to action.

BACKGROUND/OBJECTIVES: The Pediatric Dermatology Research Alliance (PeDRA) connects pediatric dermatologists, trainees, basic scientists, allied health professionals, and patient advocates to improve the lives of children with skin disease through research. As a training pipeline for future pediatric dermatologists and steward of research in the field, PeDRA has a responsibility to examine its history and take actionable steps to diversify its membership, grant recipients, study leads, research priorities, and leadership. METHODS: In 2020, PeDRA formed an Equity, Diversity, and Inclusion Task Force to address this need. In an effort to assess PeDRA's past and plan for PeDRA's future, a review of PeDRA's membership, leadership, grant awardees, and research topics was conducted. RESULTS/CONCLUSIONS: Results demonstrated gaps in PeDRA's current operational efforts to diversify the pediatric dermatology workforce and identified areas for improvement. Recommendations are proposed as a call to action for the community.

Ulcerated amelanotic melanoma of the ear in an 11 year old with Fitzpatrick VI skin type: A case report.

Melanoma is rare in pediatric patients and even more so in those with darker Fitzpatrick skin types. Although risk factors for conventional melanoma are similar in both adult and pediatric cases, the presentation of melanoma in pediatric patients is often distinct from adults. Here, we describe a case of amelanotic ulcerated nodular melanoma with regional lymph node metastases treated with nivolumab in a patient with Fitzpatrick skin type VI.

Integrating dermatology services into a social pediatrics network: 8 years of experience in the RICHER (Responsive, Interdisciplinary/Intersectoral, Child/Community, Health, Education and Research) program.

Social pediatric initiatives aim to improve health outcomes for vulnerable children by working in the community to empower families, to enhance protective factors that mitigate adverse childhood experiences (ACEs), and to deliver place-based health care. In 2012, pediatric dermatology was added as a component of the Responsive, Interdisciplinary Intersectoral Child and Community Health Education and Research (RICHER) social pediatric program in Vancouver, BC. We share our experience with inclusion of pediatric dermatology in a well-established social pediatric program as well as lessons we have learned in the first 8 years of our partnership. Partnership, bridging trust, knowledge sharing, empowerment, consistency, and flexibility were found to be central elements in the success of this endeavor.

Trametinib therapy for children with neurofibromatosis type 1 and life-threatening plexiform neurofibroma or treatment-refractory low-grade glioma.

PURPOSE: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. METHODS: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. RESULTS: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. CONCLUSION: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

Treatment practices in the management of scabies in infants younger than two months.

BACKGROUND/OBJECTIVES: Efficacy and safety data of scabies treatments in infants are limited. Although topical permethrin is used in the treatment of scabies in adults, it is not approved for use in infants younger than 2 months of age in many parts of the world. This study aimed to describe treatment practices in the management of scabies in infants younger than 2 months. METHODS: An online survey was developed and distributed to physicians worldwide through the Society of Pediatric Dermatology and the Pediatric Dermatology Research Alliance. Data collected included demographics, medication availability, experience using medications, deterrents to medication use, medication administration preferences, perceived and experienced medication side effects, and preferred treatment agent in this population. RESULTS: In total, 57 physicians from seven countries responded. The majority of respondents were board-certified in pediatric dermatology (48/57, 84.2%) and resided in the United States (44/57, 77.2%). Respondents had experience using permethrin (47/57, 82.5%) and precipitated sulfur (35/57, 61.4%) most frequently. Most (38/57, 66.7%) preferred permethrin as their treatment of choice. Among those who did not use permethrin, potential side effects (8/10, 80%) were most frequently reported as a deterrent from its use. However, only 4.3% (22/47) of those who used permethrin reported side effects, including itching, erythema, and xerosis. CONCLUSIONS: Permethrin is frequently used in the treatment of infants younger than 2 months with scabies. Furthermore, our results demonstrate that permethrin is the preferred treatment agent among sampled dermatologists for infants younger than 2 months. Few side effects were reported, and none were serious.

Exome sequencing enables diagnosis of X-linked hypohidrotic ectodermal dysplasia in patient with eosinophilic esophagitis and severe atopy.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical and genetic heterogeneity between different ectodermal dysplasia types and evidence of incomplete penetrance and variable expressivity increase the potential for misdiagnosis. We describe a family with X-linked hypohidrotic ectodermal dysplasia (XLHED) presenting with variable expressivity of symptoms between affected siblings. In addition to the classical signs of hypohidrosis, hypotrichosis and hypodontia, the index patient-a 5 year old boy, also presented with a severe atopy phenotype that was not observed in the other two affected brothers. Exome sequencing in the index and the mother identified a pathogenic nonsense variant in EDA (NM_001399.4: c.766 C>T; p. Gln256Ter). This study highlights how exome sequencing was crucial in establishing a precise molecular diagnosis of XLHED by enabling us to rule out other differential diagnoses including NEMO deficiency syndrome, that was initially presented as a clinical diagnosis to the family.

Skin diseases in displaced populations: a review of contributing factors, challenges, and approaches to care.

There are 70.8 million persons displaced worldwide due to war, persecution, and violence. Eighty percent of displaced persons reside in low- and middle-income countries with limited healthcare resources. Cutaneous diseases are commonly reported among displaced persons owing to numerous interrelated factors such as inadequate housing, overcrowding, food insecurity, environmental exposures, violence including torture, and breakdown of healthcare infrastructure. Diagnosis and management of these conditions, as well as an understanding of the context in which they present, is crucial to providing dermatologic care for displaced populations worldwide. Herein, we define displaced populations and, within this context, review the epidemiology of skin diseases, discuss pertinent skin conditions, examine challenges to care provision, and present approaches for improving dermatologic care. Inflammatory and communicable infectious disorders are the most common skin diseases seen in displaced populations. Other relevant conditions include skin manifestations of heat injuries, cold injuries, immersion foot syndromes, macronutrient and micronutrient deficiencies, torture, and sexual and gender-based violence. Provision of dermatologic care to displaced populations is hampered by limited diagnostic and therapeutic resources and specialist expertise. Medical screening for cutaneous disorders, context-relevant dermatology training, and telemedicine are potential tools to improve diagnosis and management of skin diseases in displaced populations.

Clinical Insights About Topical Treatment of Mild-to-Moderate Pediatric and Adult Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition, also referred to as atopic eczema, that is identified by itching and recurrent eczematous lesions. It often starts in infancy where it affects up to 20% of children but is also highly prevalent in adults. AD inflicts a significant psychosocial burden on patients and their families and increases the risk of other immune-mediated inflammatory conditions, such as asthma and allergic rhinitis, food allergy, and mental health disorders. It is a lifelong condition associated with epidermal barrier dysfunction and altered immune function. Through the use of emollients and anti-inflammatory agents, current prevention and treatment therapies attempt to restore epidermal barrier function. Acute flares are treated with topical corticosteroids. Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCSs) are used for proactive treatment to prevent remission. There remains a need and opportunity to improve AD care through future research directed toward an improved understanding of the heterogeneity of the disease and its subtypes, the role of autoimmunity in its pathogenesis, the mechanisms behind disease-associated itch and response to specific allergens, and the comparative effectiveness and safety of therapies.

A two-year, double-blind, randomized placebo-controlled trial of oral green tea polyphenols on the long-term clinical and histologic appearance of photoaging skin.

BACKGROUND: Green tea polyphenols (GTPs) have significant antioxidant and antiinflammatory activities, and prior short-term studies suggest that these compounds may improve photoaging skin. OBJECTIVES: To evaluate the long-term effects of oral GTPs on the clinical and histologic characteristics of photoaging skin. MATERIALS AND METHODS: Double-blind, placebo-controlled trial of 56 women aged 25 to 75 randomized to 250 mg GTPs or placebo twice daily for 2 years. A blinded dermatologist scored the appearance of photodamaged facial skin at 0, 6, 12, and 24 months. A blinded dermatopathologist scored the histologic characteristics of sun-exposed arm skin at 0 and 24 months. RESULTS: Clinical assessment of facial skin revealed that the GTP group had significant improvement in overall solar damage at 6 months (p=.02) and significant improvement in erythema and telangiectasias at 12 months (p=.02). The placebo group did not have significant improvements in these parameters at 6 months or 12 months. There were no statistically significant differences in other photoaging parameters at 6, 12, or 24 months in the GTP or placebo groups. Histopathologic analysis of sunexposed arm skin showed no statistically significant difference in photoaging parameters in the GTP group or the placebo group at 24 months. CONCLUSIONS: Long-term supplementation with oral GTPs was not superior to placebo in improving clinical or histologic photoaging parameters after 24 months of use.

Supplementation with CoQ10 lowers age-related (ar) NOX levels in healthy subjects.

Our work has identified an aging-related ECTO-NOX activity (arNOX), a hydroquinone oxidase which is cell surface located and generates superoxide. This activity increases with increasing age beginning >30 y. Because of its cell surface location and ability to generate superoxide, the arNOX proteins may serve to propagate an aging cascade both to adjacent cells and to oxidize circulating lipoproteins as significant factors determining atherogenic risk. The generation of superoxide by arNOX proteins is inhibited by Coenzyme Q10 as one basis for an anti-aging benefit of CoQ10 supplementation in human subjects. In a preliminary pilot study, 25 female subjects between 45 and 55 y of age were recruited at Stanford University from the Palo Alto, CA area. Informed consent was obtained. Ten of the subjects received Coenzyme Q10 supplementation of 180 (3 x 60 mg) per day for 28 days. Serum, saliva and perspiration levels of arNOX were determined at 7, 14 and 28 days of CoQ10 supplementation and compared to the initial baseline value. Activity correlated with subject age up to a maximum between age 50 and 55 years of age for saliva and perspiration as well and then declined. With all three sources, the arNOX activity extrapolated to zero at about age 30. Response to Coenzyme Q10 also increased with age being least between ages 45 and 50 and greatest between ages 60 and 65. With all three biofluids, arNOX activity was reduced between 25 and 30% by a 3 x 60 mg daily dose Coenzyme Q10 supplementation. Inhibition was the result of Coenzyme Q10 presence.