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.

Arteriovenous malformations as a presenting sign of PTEN hamartoma tumor syndrome: A case series.

High-flow vascular malformations have been associated with multiple syndromes including capillary malformation-arteriovenous malformation (CM-AVM) syndrome, hereditary hemorrhagic telangiectasia syndrome, and less commonly, phosphatase and tensin homolog hamartoma tumor syndrome (PHTS). We present a series of three patients with clinically challenging complex AVMs who were found to have underlying PHTS. In all patients, diagnosis was delayed, and the presence of the AVM prompted sampling and genetic testing for PHTS in the absence of other clinical features of the condition. This series highlights the importance of screening for PHTS in the setting of high-flow vascular malformations.

Use of dupilumab for atopic dermatitis in young transplant patients-A case series of 3 patients.

Patients who undergo solid organ transplantation are at an increased risk of developing atopic dermatitis, potentially due to long-term use of calcineurin inhibitors which results in a shift towards the Th2 immune response. The effectiveness and safety of dupilumab for atopic dermatitis in posttransplant patients is not established. Previous reports of dupilumab use in posttransplant patients have been in adult patients. In this series, we report three young posttransplant patients treated successfully with dupilumab.

Transition of care in patients with epidermolysis bullosa: A survey study.

There are little published data on the transition of care in EB. We conducted a survey study recruiting EB patients from the Dystrophic EB Research Association (debra) website and centers caring for high numbers of EB patients in the United States and internationally from Sept 17, 2019 to Nov 3, 2021. The majority of participants had not discussed the transition of care with their healthcare providers, nor the healthcare needs to be required as an adult. Ongoing pediatric subspecialty care was reported by 12% of adults, most commonly in pediatric dermatology. Identified barriers to transition included the perceived lack of adult providers' knowledge about EB patient healthcare needs. The results suggest the need for transition guidelines, early discussions with families about transition, and practical information for the adult providers accepting care.

Expanding the clinical spectrum of SOX18-related Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome.

Pathogenic variants in SOX18 are associated with hypotrichosis-lymphedema-telangiectasia-renal defects syndrome (HLTRS) and hypotrichosis-lymphedema-telangiectasia syndrome (HLTS). Eleven patients with SOX18 related HLTRS/HLTS have been previously described. Cardinal features include varying degrees of hypotrichosis, lymphedema and telangiectasias. We report a 15-year-old female patient with a likely de novo SOX18 pathogenic variant identified on duo exome sequencing. In addition to the classic features, the currently reported patient presented with novel clinical features including musculoskeletal abnormalities and strikingly poor wound healing. Chronic skin ulcers have been a major cause of morbidity for the patient and have led to significant functional limitation. Further, our experience with wound management has been detailed. We hope to improve understanding of the clinical spectrum of this ultra-rare disorder by reviewing the phenotypic features in all reported patients including our patient.

Diagnosis and Management of Plantar Dermatoses.

Plantar dermatoses (PD) are common, occurring either spontaneously on healthy skin or developing secondarily from previously established foot disease. PD share similar symptoms and morphology, making them challenging to differentiate. A few of the most frequently encountered PD include tinea pedis, psoriasis, contact dermatitis, dyshidrotic dermatitis (or recurrent vesicular palmoplantar dermatitis), and juvenile plantar dermatosis. This review offers practical advice for diagnosing and treating the most common PD in the primary care office.

Interrogation of RDEB Epidermal Allografts after BMT Reveals Coexpression of Collagen VII and Keratin 15 with Proinflammatory Immune Cells and Fibroblasts.

Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating genodermatosis characterized by dysfunctional collagen VII protein resulting in epithelial blistering of the skin, mucosa, and gastrointestinal tract. There is no cure for RDEB, but improvement of clinical phenotype has been achieved with bone marrow transplantation and subsequent epidermal allografting from the bone marrow transplant donor. Epidermal allografting of these patients has decreased wound surface area for up to 3 years after treatment. This study aimed to determine the phenotype of the epidermal allograft cells responsible for durable persistence of wound healing and skin integrity. We found that epidermal allografts provide basal keratinocytes coexpressing collagen VII and basal stem cell marker keratin 15. Characterization of RDEB full-thickness skin biopsies with single-cell RNA sequencing uncovered proinflammatory immune and fibroblast phenotypes potentially driven by the local environment of RDEB skin. This is further highlighted by the presence of a myofibroblast population, which has not been described in healthy control human skin. Finally, we found inflammatory fibroblasts expressing profibrotic gene POSTN, which may have implications in the development of squamous cell carcinoma, a common, lethal complication of RDEB that lacks curative treatment. In conclusion, this study provides insights into and targets for future RDEB studies and treatments.

Conradi-Hünermann-Happle syndrome associated with severe hypocalcemia in a newborn.

Conradi-Hünermann-Happle syndrome is rare X-linked dominant syndrome associated with stippled epiphyseal calcifications, congenital cataracts, Blaschkoid ichthyosiform scaling, and follicular atrophoderma. This case describes a novel finding of hypocalcemia and hypoparathyroidism in an infant with Conradi-Hünermann-Happle syndrome.

Worsening ulceration of infantile hemangioma after initiation or escalation of propranolol.

For infantile hemangiomas (IH) requiring treatment, including those in high-risk locations or in the setting of ulceration, oral propranolol is first-line therapy. Here, we present three cases of infantile hemangioma with worsening ulceration following initiation or escalation of oral propranolol at standard doses.

Successful management of an arteriovenous malformation with trametinib in a patient with capillary-malformation arteriovenous malformation syndrome and cardiac compromise.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant condition characterized by multifocal, noncontiguous pink patches on the skin that often have a surrounding pale halo. In some cases, an association with a fast flow, arteriovenous malformation (AVM) can be identified. Here, we describe a case report of a 16-year-old woman with CM-AVM syndrome and significant cardiac compromise successfully treated with trametinib, a mitogen-activated protein kinase (MEK) inhibitor.

Revertant Mosaicism in Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is a group of genetic blistering diseases characterized by mechanically fragile skin and mucocutaneous involvement. Historically, disease management has focused on supportive care. The development of new genetic, cellular, and recombinant protein therapies has shown promise, and this review summarizes a unique gene and cell therapy phenomenon termed revertant mosaicism (RM). RM is the spontaneous correction of a disease-causing mutation. It has been reported in most EB subtypes, some with relatively high frequency, and has been observed in both keratinocytes and fibroblasts. RM manifests as identifiable patches of unaffected, blister-resistant skin and can occur through a variety of molecular mechanisms, including true back mutation, intragenic crossover, mitotic gene conversion, and second-site mutation. RM cells represent a powerful autologous platform for therapy, and leveraging RM cells as a therapeutic substrate may avoid the inherent mutational risks of gene therapy/editing. However, further examination of the genomic integrity and long-term functionality of RM-derived cells, as well in vivo testing of systemic therapies with RM cells, is required to realize the full therapeutic promise of naturally occurring RM in EB.

THE demographics and trends in pediatric melanoma in the United States: An analysis of the National Cancer Database.

BACKGROUND/OBJECTIVE: Relative to adults, rates of melanoma are lower in children. Due to its rarity, it is difficult to assess the incidence, trends, and outcomes of this malignancy. Much of our understanding comes from single institution or regional cancer registries which may not be large enough to detect subtleties in the burden of pediatric melanoma. METHODS: Data from the 2004 to 2016 National Cancer Database were analyzed; this database captures approximately 70% of all cancer diagnoses in the United States. RESULTS: Our analysis consisted of 1903 cases. A majority were White (89.8%), the mean age was 12.4 years, and the ratio of females: males was 1.2:1.0. The most common anatomic location was the trunk (31.1%). Between 2004 and 2016, a decreasing trend in the number of new melanoma cases was observed. Comparing histologic subtype by age, there was an increased percentage of nodular and epithelioid and spindle cell tumors in the pre-teen children and a greater percentage of superficial spreading tumors in teenagers. Overall, a majority of cases were stage 0 or I (56.9%), with relatively few stage IV cases (2.0%). A 5-year all-cause survival of greater than 90% was observed for stage I-III tumors, with stage IV tumors having a 5-year all-cause survival of 34.4%. CONCLUSION: Comparable to previous studies, pediatric melanoma occurred most often in Whites, females, and adolescents. However, we detected a decreasing trend in new cases, noted differences between histologic subtype and age, and observed a 5-year all-cause survival rate of greater than 90% for stage I-III tumors.

Cutaneous findings in Fanconi anemia.

BACKGROUND: Fanconi anemia (FA) is a genetic disorder that results in bone marrow failure, physical abnormalities, and solid organ malignancies. The diagnosis of FA is often delayed because the early disease characteristics have not been well established. OBJECTIVE: To outline the spectrum of cutaneous findings seen in patients with FA. METHODS: A cross-sectional study in which patients with FA received a full-body skin examination. Patient characteristics are summarized with mean (SD) for continuous and count (%) for categorical variables. Poisson regression and logistic regression models were used to examine the relationships between pigmentary changes and patient characteristics. RESULTS: At least 1 cutaneous pigmentary alteration was present in 96.8% of patients, most arising before the teenage years. The most common finding was café-au-lait macules. Other findings included hypopigmented macules, skin-fold freckle-like macules, extensive sun-exposed freckling, and both hypopigmented and hyperpigmented pigment macules. LIMITATIONS: Patients received a single assessment, so the number of pigmentary changes could not be assessed over time. CONCLUSIONS: Characteristic morphology of FA includes faint and ill-defined café-au-lait macules, hypopigmented skin-fold freckle-like macules and the concurrence of hypopigmented and hyperpigmented macules. The recognition of these findings could aid clinicians in making earlier diagnoses.

Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study.

BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.