Inpatient management of epidermolysis bullosa: Consensus-based hands-on instructions for neonates and postneonates.

BACKGROUND: Epidermolysis bullosa (EB), characterized by skin fragility and blistering, often requires hospitalization. Training for inpatient management of EB is limited, with no unified recommendations available in North America. OBJECTIVE: To develop consensus-derived best practices for hands-on inpatient management of EB in both the neonatal and postneonatal period. METHODS: A modified Delphi method (expert-based input via 2 surveys and a final review) was implemented. Available guidelines from EB Clinical Research Consortium centers were analyzed to determine areas of focus and formulate statements to be voted on by EB Clinical Research Consortium members, experienced EB nurses, and select family members. Study participants evaluated statements using a Likert scale: statements with at least 70% agreement were accepted; statements with 30% or more disagreement were rejected. RESULTS: Ten areas of focus were identified. Delphi participants included 15 dermatologists, 8 nurses, and 6 nonhealth care caregivers. Consensus was established on 103/119 neonatal statements and 105/122 postneonatal statements; no statements were rejected. Most recommendations applied to both age groups. LIMITATIONS: Recommendations may require adjustment based on individual patient's clinical context. CONCLUSION: Using the Delphi method, a consensus-derived resource for hospital-based health care professionals who manage patients with EB has been developed to improve the quality of inpatient care.

A solitary scalp mass as the presenting feature of clear cell sarcoma of the kidney in a pediatric patient.

Clear cell sarcoma of the kidney is a rare renal malignancy, accounting for 2%-4% of all pediatric renal tumors. In this case report, we describe a 9-year-old boy with an asymptomatic, solitary mass on the scalp, ultimately found to be metastatic clear cell sarcoma of the kidney. This report reviews indications for imaging scalp masses to facilitate making an accurate diagnosis and treatment planning.

Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study.

BACKGROUND: Epidermolysis bullosa (EB) is a heterogeneous group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Patients with EB are affected by mechanical fragility of epithelial surfaces including the skin and, as a result, extensive recurrent blistering is a characteristic of the condition. Chronic wounds predispose patients with EB to the development of squamous cell carcinoma, which is a major cause of premature death. OBJECTIVES: EASE was a double-blind, randomized, vehicle-controlled, phase III study to determine the efficacy and safety of the topical gel Oleogel-S10 (birch triterpenes) in EB. EASE was funded by Amryt Research Limited. METHODS: Patients with dystrophic EB, junctional EB or Kindler EB and a target partial-thickness wound lasting ≥ 21 days and < 9 months that was 10-50 cm2, were enrolled and randomized via computer-generated allocation tables 1 : 1 to Oleogel-S10 or control gel - both with standard-of-care dressings. Study gel was applied to all wounds at least every 4 days. The primary endpoint was the proportion of patients with first complete closure of target wound within 45 days. RESULTS: A total of 223 patients were enrolled and treated (109 treated with Oleogel-S10, 114 with control gel). The primary endpoint was met; Oleogel-S10 resulted in 41·3% of patients with first complete target wound closure within 45 days, compared with 28·9% in the control gel arm (relative risk 1·44, 95% confidence interval (CI) 1·01-2·05; P = 0·013). Adverse events (AEs) occurred with similar frequency for Oleogel-S10 (81·7%) compared with control gel (80·7%). AEs were predominantly of mild-to-moderate intensity (4·6% were severe). CONCLUSIONS: Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB. Oleogel-S10 was well -tolerated.

Diacerein 1% Ointment for the Treatment of Epidermolysis Bullosa Simplex: A Randomized, Controlled Trial.

BACKGROUND: In epidermolysis bullosa simplex (EBS), epithelial structural fragility results in blisters and erosions. Diacerein 1% ointment has been shown to reduce this blistering. OBJECTIVE: To evaluate the efficacy and safety of diacerein 1% ointment in the treatment of EBS. METHODS: A double-blind study of 54 patients with EBS were randomized to diacerein 1% or vehicle ointment once daily. The primary endpoint ( ≥60% reduction in body surface area of EBS) and the key secondary endpoint ( ≥2-point reduction in the Investigator’s Global Assessment) were evaluated at 8 weeks. RESULTS: There was no difference in the proportion of patients achieving either key efficacy endpoint between the diacerein 1% and vehicle groups (P>0.05). No difference in treatment emergent adverse events were noted between the groups. In post hoc analysis stratified by EBS subtypes, an IGA score of 0 or 1 was reported in 6 of 13 patients with severe EBS in the diacerein group (46.2%), compared with 2 of 13 patients with severe EBS in the vehicle group (15.4%); (relative risk= 3.08, 95% CI = 0.71, 13.4). CONCLUSIONS: Although there was no significant difference in outcomes between the groups, further study may elucidate the effects of diacerein on EBS lesions, especially in patients with severe EBS. Teng J, Paller AS, Bruckner AL, et al. Diacerein 1% ointment for the treatment of epidermolysis bullosa simplex: a randomized, controlled trial. J Drugs Dermatol. 2023;22(6):599-604. doi:10.36849/JDD.7108.

Retrospective chart review of patient socioeconomic status and language preference associated with live video telehealth in a pediatric dermatology practice.

Pediatric teledermatology rapidly expanded with the COVID-19 pandemic, and the impacts of this expansion on patients' access to care have not yet been entirely defined. In this retrospective study of 3027 patients in an academic pediatric dermatology practice, patients who identified as having a primary language other than English were less likely to access pediatric dermatology care during the COVID lockdown. This study did not identify a significant or meaningful difference in age, geography, socioeconomic status, ethnicity, or race between patients who were offered pediatric dermatology care that was either in-person or via synchronous telehealth. These findings are overall reassuring that there were not major disparities in telehealth utilization during the COVID shelter-in-place mandate, although highlight the need for institutions to ensure systems are in place to enhance telehealth access for patients with non-English primary language.

Assessing pain catastrophizing and functional disability in pediatric epidermolysis bullosa patients.

BACKGROUND/OBJECTIVES: The primary objective was to assess pain catastrophizing and functional disability in pediatric patients with epidermolysis bullosa (EB) and their parents/guardians. Secondary objectives included examining relationships between pain catastrophizing, functional disability, and correlations with other factors (e.g., age, disease severity, and percent of body surface area (BSA) involved). METHODS: Patients with EB ages 8-16 and their parents/guardians who were English or Spanish speaking completed a one-time online survey. Parent measures included: demographics questionnaire, Pain Catastrophizing Scale-Parent (PCS), and Parent Functional Disability Inventory (FDI). Child measures included: PCS child and child FDI. Higher scores on both scales indicate higher levels of catastrophizing and functional disability. RESULTS: Of 31 children, the mean age was 11.47 years and the majority (70.97%) had dystrophic EB. Mean scores were: 35.84 = PCS parent; 34.58 = PCS child; 30.87 = parent FDI; 29.77 = child FDI. Total scores for PCS parent, parent FDI, and child FDI increased significantly with disease severity and percentage of involved BSA (p < .01 for all). Total scores for PCS child increased significantly with percent of EB skin involvement (p = .04) but not disease severity. Older children reported more functional disability than their parents and younger children (p = .02). CONCLUSIONS: Our results demonstrate significant positive correlations between negative thoughts related to pain and the experience of functional difficulties in patients with EB and their caregivers. Psychological, psychiatric, and/or behavioral interventions to help managing chronic pain may be effective for patients with EB.

Characterization of wound microbes in epidermolysis bullosa: A focus on Pseudomonas aeruginosa.

The most common bacteria isolated from wound cultures in patients recorded in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) are Staphylococcus aureus and Pseudomonas aeruginosa. Given the prevalence of P. aeruginosa in this patient population and prior research implicating P. aeruginosa's potential role in carcinogenesis, we sought to further analyze patients with recorded wound cultures positive for Pseudomonas aeruginosa in the EBCCOD. We provide a descriptive analysis of this subset of patients and highlight potential avenues for future longitudinal studies that may have significant implications in our wound care management for patients with epidermolysis bullosa.

Cutaneous mosaic RASopathies associated with rhabdomyosarcoma.

Variants in RAS are known drivers of certain pediatric blood and solid cancers, including brain tumors. Though most RAS-driven cancers are thought to occur sporadically, genetic syndromes caused by germline RAS variants portend a slightly higher risk of rhabdomyosarcoma (RMS) development. Three new cases and a review of the literature demonstrate that in rare cases, certain somatic RAS variants are associated with an increased risk of RMS and that RMS development may be heralded by the presence of concomitant RAS-driven birthmarks. Further prospective studies are needed to establish incidence and recommend appropriate monitoring guidelines for patients at risk.

A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa.

BACKGROUND: Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE: To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS: A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS: A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%). LIMITATIONS: Retrospective design. CONCLUSIONS: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.

Anesthetic Management and Outcomes of Patients With Epidermolysis Bullosa: Experience at a Tertiary Referral Center.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare epithelial disorders caused by abnormal or absent structural proteins at the epidermal-dermal junction. As a result, patients experience blisters and wounds from mild shearing forces. Some forms of EB are complicated by resultant scarring and contractures. The perioperative anesthetic management of patients with EB is complex and requires a systems-based approach to limit harm. We reviewed our experience with providing general anesthesia to patients at our tertiary EB referral center, including adverse events related to anesthetic care, outcomes in the immediate perioperative period, and details of anesthetic management. METHODS: We retrospectively reviewed the charts of all patients with EB anesthetized at the Children's Hospital Colorado between January 2011 and December 2016. A subset of pediatric anesthesiologists cared for all patients using a standardized clinical care pathway. Patient demographics, detailed anesthetic methods, immediate perioperative outcomes, and adverse events were characterized. RESULTS: Over a 6-year period, 37 patients underwent 202 general anesthetics. Most patients (75.7%) had dystrophic EB (DEB). Female patients comprised 48.6%. The majority (56.7%) traveled >50 miles to receive care, and many (35.1%) traveled >150 miles for their care. Common adaptations to care included avoidance of electrocardiogram leads (88.6%) and temperature probes (91.6%). Nasal fiberoptic intubation (n = 160) was performed, or natural airway/mask (n = 27) was maintained for most patients. Supraglottic devices were not used for airway management during any of the anesthetics. Anesthesia preparation time was longer (average 25.8 minutes [standard deviation {SD} = 12.7]) than our average institutional time (14 minutes). Succinylcholine was never used, and nondepolarizing muscle relaxants were used in only 1.5% of patient encounters. Blood was transfused in 16.3% of cases and iron infused in 24.8%. Average length of stay in the postanesthesia care unit was comparable to our institutional average (average 40.1 [SD = 28.6] vs 39 minutes). New skin or mucosal injury occurred in 8 encounters (4%), and desaturation occurred in 43 cases (21.3%). There were no major adverse events. CONCLUSIONS: By using a specialized team and a standardized clinical care pathway, our institution was able to minimize adverse events caused by the anesthetic and surgical care of patients with EB. We recommend natural airway or nasal fiberoptic airway management, meticulous avoidance of shear stress on the skin, and a multidisciplinary approach to care. Supportive therapy such as perioperative blood transfusions and iron infusions are feasible for the treatment of chronic anemia in this population.

When is synchronous telehealth acceptable for pediatric dermatology?

BACKGROUND/OBJECTIVES: We evaluated the acceptance of synchronous (live video) telehealth for pediatric dermatology. METHODS: This was a prospective, single-center study of patient and dermatologist surveys paired at the encounter level for telehealth encounters with Children's Hospital Colorado Pediatric Dermatology Clinic between 21 April 2020 and 22 May 2020. RESULTS: Dermatologists were most receptive to a telehealth encounter for isotretinoin monitoring (96.6%) and non-isotretinoin acne (89.5%). In contrast, 71.8% and 58.8% of patients surveyed were open to telehealth for isotretinoin encounters and non-isotretinoin acne encounters, respectively. There was no significant correlation between patient and dermatologist satisfaction regarding a telehealth encounter (r = 0.09, CI [-0.09, 0.26], p = .34) or between patient and dermatologist preference for telehealth encounter (r = 0.07, CI [-0.11, 0.25] p = .46). Dermatologists reported needing a photo to aid their physical examination in 38/363 (10.7%) of encounters and preferred in-person examinations when an encounter would have benefitted from laboratories, procedures, dermatoscopic examination, examination by palpation, and accurate weights in infants. CONCLUSIONS: Synchronous, live-video telehealth is an effective method of healthcare delivery in certain situations for pediatric dermatology, but it does not replace in-person encounters. Families and dermatologists have different perceptions about its acceptance.

Ancestral patterns of recessive dystrophic epidermolysis bullosa mutations in Hispanic populations suggest sephardic ancestry.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis caused by mutations in the gene coding for type VII collagen (COL7A1). More than 800 different pathogenic mutations in COL7A1 have been described to date; however, the ancestral origins of many of these mutations have not been precisely identified. In this study, 32 RDEB patient samples from the Southwestern United States, Mexico, Chile, and Colombia carrying common mutations in the COL7A1 gene were investigated to determine the origins of these mutations and the extent to which shared ancestry contributes to disease prevalence. The results demonstrate both shared European and American origins of RDEB mutations in distinct populations in the Americas and suggest the influence of Sephardic ancestry in at least some RDEB mutations of European origins. Knowledge of ancestry and relatedness among RDEB patient populations will be crucial for the development of future clinical trials and the advancement of novel therapeutics.

Characterization of wound microbes in epidermolysis bullosa: Results from the epidermolysis bullosa clinical characterization and outcomes database.

BACKGROUND/OBJECTIVES: Patients with epidermolysis bullosa (EB) require care of wounds that are colonized or infected with bacteria. A subset of EB patients are at risk for squamous cell carcinoma, and bacterial-host interactions have been considered in this risk. The EB Clinical Characterization and Outcomes Database serves as a repository of information from EB patients at multiple centers in the United States and Canada. Access to this resource enabled broad-scale analysis of wound cultures. METHODS: A retrospective analysis of 739 wound cultures from 158 patients from 13 centers between 2001 and 2018. RESULTS: Of 152 patients with a positive culture, Staphylococcus aureus (SA) was recovered from 131 patients (86%), Pseudomonas aeruginosa (PA) from 56 (37%), and Streptococcus pyogenes (GAS) from 34 (22%). Sixty-eight percent of patients had cultures positive for methicillin-sensitive SA, and 47%, methicillin-resistant SA (18 patients had cultures that grew both methicillin-susceptible and methicillin-resistant SA at different points in time). Of 15 patients with SA-positive cultures with recorded mupirocin susceptibility testing, 11 had mupirocin-susceptible SA and 6 patients mupirocin-resistant SA (2 patients grew both mupirocin-susceptible and mupirocin-resistant SA). SCC was reported in 23 patients in the entire database, of whom 10 had documented wound cultures positive for SA, PA, and Proteus species in 90%, 50%, and 20% of cases, respectively. CONCLUSIONS: SA and PA were the most commonly isolated bacteria from wounds. Methicillin resistance and mupirocin resistance were reported in 47% and 40% of patients tested, respectively, highlighting the importance of ongoing antimicrobial strategies to limit antibiotic resistance.

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.

Skin cleansing and topical product use in patients with epidermolysis bullosa: Results from a multicenter database.

BACKGROUND/OBJECTIVES: Epidermolysis bullosa (EB) comprises a group of inherited skin blistering diseases. There is currently no cure, and management includes skin protection and prevention of infection. To date, there has been no systematic investigation of home skin care practices among EB patients on a multicenter scale. METHODS: This cross-sectional, observational study included data collected from patients with EB enrolled in the Epidermolysis Bullosa Characterization and Clinical Outcomes Database (EBCCOD) who provided answers to a patient-directed questionnaire between January 1, 2017, and December 31, 2017. RESULTS: Of 202 respondents, 130 (64.4%) had dystrophic EB, 51 (25.2%) had EB simplex, 21 (7.4%) had junctional EB, 3 (1.5%) had Kindler syndrome, and 3 (1.5%) had an unspecified subtype. Seventy-eight patients reported cleansing in plain water only (39%). Of those who used an additive in their cleansing water, 75 (57%) added salt, 71 (54%) added bleach, 36 (27%) added vinegar, and 34 (26%) endorsed the use of an "other" additive (multiple additives possible). Reported concentrations of additives ranged widely from 0.002% sodium hypochlorite and 0.002% acetic acid solutions, which are thought to have negligible effects on microbes, to 0.09% sodium hypochlorite and 0.156% acetic acid, concentrations shown to be cytotoxic. One hundred eighty-eight patients answered questions regarding topical product use (93%). Of those, 131 reported topical antimicrobial use (70%). Mupirocin and bacitracin were the most commonly reported topical antibiotics (59, 58 [31.4%, 30.9%], respectively). CONCLUSIONS: These findings highlight the variety of skin care routines and frequent use of topical antimicrobials among EB patients and have potential implications for antibiotic resistance. The reported range of bleach and vinegar additives to cleansing water, including cytotoxic concentrations, emphasizes the need for clear and optimized skin cleansing recommendations.

Approach and Safety of Esophageal Dilation for Treatment of Strictures in Children With Epidermolysis Bullosa.

OBJECTIVE: The aim of the study is to analyze a large series of esophageal balloon dilations in patients with epidermolysis bullosa (EB) to determine procedural approach and frequency of post-endoscopic adverse events (AEs). METHODS: Retrospective chart review for AE occurrence and clinical outcomes in children and adolescents with EB, age 1 to 19, who underwent esophageal dilation for esophageal stricture(s) from January 2003 to April 2016 at an academic, tertiary care, free-standing children's hospital. The primary outcome measure was occurrence of procedural AEs (defined as events occurring within 72 hours after endoscopic dilation procedure). RESULTS: A total of 231 fluoroscopy-guided esophageal balloon dilation procedures (209 anterograde, 20 retrograde, 2 both) were performed in 24 patients. Strictures were more common in the proximal portion of the esophagus with median stricture location 13 cm from the lips. From 2003 to 2012, 4.1% of dilations were retrograde. From 2013 to 2016, 20.2% of dilations were retrograde. AEs attributable to dilation occurred after 10.0% of procedures, and the most common AEs were vomiting, pain, and fever. No esophageal perforations, serious bleeding events, or deaths occurred secondary to dilation. The rate of post-dilation hospitalization was 6.9%. Dilation approach (anterograde vs retrograde) did not impact the likelihood of AEs. CONCLUSIONS: The characteristic esophageal lesion in EB is a single, proximal esophageal stricture. EB patients can safely undergo repeat pneumatic esophageal balloon dilations with minimal risk for severe complication. We observed a trend towards increased use of retrograde esophageal dilation.

Oxybutynin 3% gel for the treatment of primary focal hyperhidrosis in adolescents and young adults.

BACKGROUND/OBJECTIVES: There are no reliably effective, well-tolerated topical agents for the treatment of hyperhidrosis. We sought to evaluate the efficacy and tolerability of oxybutynin 3% gel in adolescents and young adults with primary focal hyperhidrosis. METHODS: Patients with severe axillary hyperhidrosis were treated with topical oxybutynin 3% gel for 4 weeks. Response to treatment was assessed by calculating change in Hyperhidrosis Disease Severity Score from baseline to weeks 1 and 4. Change in health-related quality of life was assessed using the Children's Dermatology Life Quality Index or the Dermatology Life Quality Index. Adverse effects were evaluated using patient diaries, investigator global review, and physical examination. RESULTS: Of 10 patients aged 13-24 enrolled, seven completed the study. Of those who completed the study, four (57.1%) reported reduction in axillary Hyperhidrosis Disease Severity Score at week 1 and all seven (100%) at week 4. Six patients (85.7%) reported reduction in Children's Dermatology Life Quality Index or Dermatology Life Quality Index score. Anticholinergic adverse effects were infrequent. The majority of treatment-related adverse events were mild to moderate in severity. One patient experienced a severe adverse event. CONCLUSION: Oxybutynin 3% gel reduced hyperhidrosis severity and improved health-related quality of life in this small pilot study. Safety and efficacy should be further evaluated in a large, prospective, placebo-controlled study.

Online education improves pediatric residents' understanding of atopic dermatitis.

BACKGROUND/OBJECTIVES: Pediatricians manage skin conditions such as atopic dermatitis (AD) but report that their dermatologic training is inadequate. Online modules may enhance medical education when sufficient didactic or clinical teaching experiences are lacking. We assessed whether an online module about AD improved pediatric residents' knowledge and changed their clinical management of AD. METHODS: Target and control cohorts of pediatric residents from two institutions were recruited. Target subjects took a 30-question test about AD early in their residency, reviewed the online module, and repeated the test 6 months and 1 year later. The control subjects, who had 1 year of clinical experience but had not reviewed the online module, also took the test. The mean percentage of correct answers was calculated and compared using two-sided, two-sample independent t tests and repeated-measures analysis of variance. For a subset of participants, clinical documentation from AD encounters was reviewed and 13 practice behaviors were compared using the Fisher exact test. RESULTS: Twenty-five subjects in the target cohort and 29 subjects in the control cohort completed the study. The target cohort improved from 18.0 ± 3.2 to 23.4 ± 3.4 correctly answered questions over 1 year (P < .001). This final value was greater than that of the control cohort (20.7 ± 4.5; P = .01). Meaningful differences in practice behaviors were not seen. CONCLUSION: Pediatric residents who reviewed an online module about AD demonstrated statistically significant improvement in disease-specific knowledge over time and had statistically significantly higher scores than controls. Online dermatology education may effectively supplement traditional clinical teaching.

Hereditary Progressive Mucinous Histiocytosis: New Insights Into a Rare Disease.

Hereditary progressive mucinous histiocytosis is a rare, benign, skin-limited form of non-Langerhans cell histiocytosis. We report on a 5-year-old boy who presented in infancy with self-resolving dermal nodules but later developed persistent and progressive erythematous papules on the face and scalp. Histologic evaluation revealed dermal aggregates of S-100/CD1a-negative histiocytes with abundant mucin. We present this case to highlight the evolution of the lesional morphology in infancy and early childhood and to stress the importance of histology in confirming this rare disorder.