Attenuation of Atopic Dermatitis in Newborns, Infants, and Children With Prescription Treatment and Ceramide-Containing Skin Care: A Systematic Literature Review and Consensus.

BACKGROUND: Atopic dermatitis (AD) typically starts in infancy and early childhood. The chronic skin disorder is associated with recurrent flares, pruritus, and genetic predisposition. Daily use of moisturizers that contain lipids, such as ceramides, reduces the rate of AD flares and the need for topical steroid treatment. We aimed to provide insights on AD attenuation to tailor AD prescription therapy, skin care, and maintenance treatment to improve pediatric patients with AD and families. METHODS: A panel of 6 pediatric dermatologists and dermatologists who treat neonates, infants, and children developed a consensus paper on AD attenuation for pediatric patients. The modified Delphi process comprised a face-to-face panel meeting and online follow-up to discuss the systematic literature search results and draw from clinical experience and opinion of the panel to adopt and agree on 5 statements.  Results: Understanding the functional properties of newborn and infant skin, discussing skincare product use with parents, and recommending tailored prescription and skincare routines can improve newborn, infant, and children’s skin health. Studies on the prophylactic application of moisturizers initiated in early infancy suggest moisturizers may delay rather than prevent AD, especially in high-risk populations and when used continuously. Increasingly there is evidence that moisturizer application reduces the severity of AD and extends the time to flares, which may help attenuate the atopic march. The protective effect of skin care for AD has been observed in studies where its daily use is ongoing; these beneficial effects may be lost in less than 1year after cessation. It is therefore important to emphasize that skin care should be routinely used when counseling patients and caregivers.  Conclusion: Healthcare providers can improve patient outcomes in atopic-prone infants and children by providing instructions regarding the daily benefits of applying skin care with gentle cleansers and moisturizers. Using gentle cleansers and moisturizers containing barrier lipids from birth onward may delay AD occurrence and mitigate severity in predisposed infants.J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7894.

Dermatology in Contemporary Times: Building Awareness of Social Media's Association With Adolescent Skin Disease and Mental Health.

BACKGROUND: The contribution of psychological disorders to the burden of skin disease has been poorly explored in adolescent patients. The review aims to provide insights into the psychological, social, occupational, and social medias' association with acne, atopic dermatitis (AD), and aesthetics in adolescent patients. METHODS: The project used a modified Delphi process comprising face-to-face discussions followed up online.  The systematic literature search results informed the 14 draft statements. During an expert panel meeting, the draft statements underwent the panel's evaluation at a workshop, followed by a plenary discussion adopting five statements using evidence from the literature coupled with the panel's opinions and experiences.  Results: Studies reported an association between poor sleep, social impairment, and mental health disorders, including body dysmorphic disorder (BDD) with acne or AD in adolescents with acne or AD. Education for patients and parents may improve self-management skills and self-responsibility, promoting better outcomes for acne and AD. The use of certain types of social media can contribute to unrealistic expectations regarding the outcomes of cosmetic procedures. Social media use may also be associated with, and potentially contribute to unrealistic appearance expectations and certain mental health conditions. However, social media use may have benefits, such as connection, diversity, social support, increased self-esteem, safe identity experimentation, and an increased opportunity for self-disclosure.  Conclusions: The association with negative life events, BDD, suicidal ideation, depression, and anxiety are thought to be high for adolescent patients with acne or AD. Using social media for information has both positive and negative aspects. Awareness of the risks and benefits of receiving health information about dermatological disease among adolescents needs to be improved through the education of patients and clinicians. Action-oriented items need to be developed to help dermatologists address these issues in clinical practice.Rieder EA, Andriessen A, Cutler V, et al. Dermatology in contemporary times: building awareness of social media's association with adolescent skin disease and mental health. J Drugs Dermatol. 2023;22(8):817-825. doi:10.36849/JDD.7596.

Racial and Ethnic Variations in Skin Barrier Properties and Cultural Practices in Skin of Color Newborns, Infants, and Children.

BACKGROUND: The skin of newborns and infants of all races/ethnicity is more susceptible to skin barrier disruption than adult skin. This consensus paper offers insights into potential skincare implications for using gentle cleansers and moisturizers for skin of color (SOC) newborns, infants, and children. METHODS: Six pediatric dermatologists and dermatologists used a Delphi communication technique to adopt 5 statements for SOC newborns, infants, and children on skin barrier integrity and the importance of skin care to promote a healthy skin barrier.  Results: Regardless of ethnicity, newborn and infant skin is still developing and more susceptible to infections and chemical and thermal damage. A growing body of evidence supports skincare starting early in life, recognizing that the ongoing daily use of gentle cleansers and moisturizers containing barrier lipids, such as ceramides, promotes a healthy skin barrier. Understanding cultural differences in everyday skincare practices for SOC newborns, infants, and children is critical for developing an evidence base to substantiate skincare practices.  Conclusions: Closing knowledge gaps in the clinical presentation, cultural differences, and approach to treating skin conditions using skincare for SOC newborns, infants, and children may improve patient outcomes.   Schachner  LA, Andriessen A, Benjamin  L, et al. Racial/ethnic variations in skin barrier properties and cultural practices in skin of color newborns, infants and children. J Drugs Dermatol. 2023;22(7):657-663. doi:10.36849/JDD.7305.

Laboratory Safety from a Randomized 16-Week Phase III Study of Dupilumab in Children Aged 6 Months to 5 Years with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND AND OBJECTIVE: Previous studies of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents, and severe atopic dermatitis in children aged 6 to < 12 years demonstrate no clinically important changes in laboratory parameters. The objective of this study was to assess laboratory outcomes in children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis treated with dupilumab. METHODS: In this randomized, placebo-controlled, phase III trial of dupilumab, 161 children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis were enrolled from 31 sites in Europe and North America and randomized 1:1 to receive subcutaneous placebo or dupilumab (5 kg to < 15 kg: 200 mg; 15 kg to < 30 kg: 300 mg) every 4 weeks plus topical corticosteroids for 16 weeks. Hematology, serum chemistry, and urinalysis assessments were analyzed on blood and urine samples collected at screening and weeks 4 and 16; descriptive statistics are provided. RESULTS: No clinically meaningful changes in laboratory parameters were observed. While two cases of eosinophilia and one case each of neutropenia and leukocytosis were reported as treatment-emergent adverse events in the dupilumab plus topical corticosteroids group, these events were not associated with clinical symptoms and did not lead to treatment discontinuation or study withdrawal. CONCLUSIONS: These results suggest that routine laboratory monitoring of children aged 6 months to < 6 years treated with dupilumab plus topical corticosteroids is not required. Limitations of this study include short study duration, and exclusion of patients with abnormalities in laboratory test results at screening. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03346434, part B.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that often causes itchy rashes. To reduce persistent AD signs and symptoms, patients may need to take medications that require laboratory monitoring. This can add to treatment burden, especially among infants and children. Dupilumab is a drug that specifically targets key molecules that underlie AD and has been tested in several clinical trials, now in patients 6 months and older. Studies in adults, adolescents, and children as young as 6 years of age with moderate-to-severe AD have shown that dupilumab can be used without the need for regular laboratory tests. In this study, the authors analyzed blood and urine samples collected during a clinical trial of dupilumab in 161 infants and children aged 6 months to 5 years with moderate-to-severe AD. Routine laboratory tests revealed no clinically meaningful changes in patients' blood and urine following treatment with dupilumab. In general, the laboratory results in these patients were similar to those in adults, adolescents, and children aged 6­11 years treated with dupilumab. Taken together, these findings suggest that dupilumab can be used for the continuous treatment of moderate-to-severe AD without the need for routine laboratory monitoring. Video abstract: Does dupilumab treatment require routine laboratory monitoring in infants and young children with atopic dermatitis? (MP4 128,088 KB).

Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa.

BACKGROUND: Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in COL7A1, which encodes type VII collagen (C7). Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering COL7A1. METHODS: We conducted a phase 3, double-blind, intrapatient randomized, placebo-controlled trial involving patients 6 months of age or older with genetically confirmed dystrophic epidermolysis bullosa. For each patient, a primary wound pair was selected, with the wounds matched according to size, region, and appearance. The wounds within each pair were randomly assigned in a 1:1 ratio to receive weekly application of either B-VEC or placebo for 26 weeks. The primary end point was complete wound healing of treated as compared with untreated wounds at 6 months. Secondary end points included complete wound healing at 3 months and the change from baseline to weeks 22, 24, and 26 in pain severity during changes in wound dressing, assessed with the use of a visual analogue scale (scores range from 0 to 10, with higher scores indicating greater pain). RESULTS: Primary wound pairs were exposed to B-VEC and placebo in 31 patients. At 6 months, complete wound healing occurred in 67% of the wounds exposed to B-VEC as compared with 22% of those exposed to placebo (difference, 46 percentage points; 95% confidence interval [CI], 24 to 68; P = 0.002). Complete wound healing at 3 months occurred in 71% of the wounds exposed to B-VEC as compared with 20% of those exposed to placebo (difference, 51 percentage points; 95% CI, 29 to 73; P<0.001). The mean change from baseline to week 22 in pain severity during wound-dressing changes was -0.88 with B-VEC and -0.71 with placebo (adjusted least-squares mean difference, -0.61; 95% CI, -1.10 to -0.13); similar mean changes were observed at weeks 24 and 26. Adverse events with B-VEC and placebo included pruritus and chills. CONCLUSIONS: Complete wound healing at 3 and 6 months in patients with dystrophic epidermolysis bullosa was more likely with topical administration of B-VEC than with placebo. Pruritus and mild systemic side effects were observed in patients treated with B-VEC. Longer and larger trials are warranted to determine the durability and side effects of B-VEC for this disease. (Funded by Krystal Biotech; GEM-3 ClinicalTrials.gov number, NCT04491604.).

Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis. METHODS: This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434. FINDINGS: Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation. INTERPRETATION: Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults. FUNDING: Sanofi and Regeneron Pharmaceuticals.

Safety and Efficacy of VP-102 (Cantharidin, 0.7% w/v) in Molluscum Contagiosum by Body Region: Post hoc Pooled Analyses from Two Phase III Randomized Trials.

TRIAL REGISTRATION: >ClinicalTrials.gov identifier nos. NCT03377790 (for CAMP-1) and NCT03377803 (for CAMP-2). BACKGROUND: VP-102 is drug-device combination product containing cantharidin (0.7% w/v) and has undergone Phase III clinical trials for the treatment of molluscum contagiosum (molluscum). Efficacy and safety may differ by body region due to variable skin anatomy. OBJECTIVE: We investigated the pooled safety and efficacy of VP-102 by affected body region. METHODS: Individuals at least two years of age with molluscum were randomized to topical VP-102 or vehicle once every 21 days until clear (maximum of four applications). Participants were assigned to body region groups where lesions were present at baseline. Body region lesion counts were recorded at each visit. Efficacy was measured by the percentage of participants with complete clearance of lesions by region. Pre-specified adverse events (AEs) were analyzed for those treated in the region on that visit. RESULTS: Participants had a mean of two regions affected at baseline. Complete clearance was significantly higher in the VP-102-treated group than with vehicle application in all regions at the last visit (P<0.01 for each region). The incidence of pre-specified AEs was consistent across regions. However, these analyses were post hoc, and individual lesions were not tracked for efficacy. CONCLUSION: VP-102 treatment shows consistent safety and efficacy across molluscum body regions.

A Case Report of a Rapidly Growing Giant Pilomatrixoma on the Posterior Shoulder in a 12-Year-Old Male Patient.

INTRODUCTION: Giant pilomatrixomas are quite rare and can be clinically challenging to diagnose. CASE PRESENTATION: Here, we report a case of a rapidly growing mass on the shoulder of a 12-year-old previously healthy boy. The lesion on his right shoulder appeared as a painless, pink-blue-colored solitary mass that started 6 months ago and rapidly enlarged to 4.5 × 6 cm in size. Previous biopsy results were inconclusive, showing only hypercellular spindle cell proliferation in a collagenous stroma. There was concern for malignancy versus mixed lymphatic venous malformation or benign soft tissue tumor. An excisional biopsy was done and demonstrated features of a pilomatrixoma. Complete surgical removal with clear margins was curative. CONCLUSION: Diagnosis and management of rapidly enlarging skin lesions in children can be difficult for clinicians and dermatopathologists. Excisional biopsy can be both diagnostic and therapeutic. A timely exclusion of malignancy is of utmost importance.

Treatment of Impetigo in the Pediatric Population: Consensus and Future Directions.

BACKGROUND: Impetigo is a common contagious superficial bacterial skin infection. Treatment of localized lesions can be achieved through topical antibiotics. Oral antibiotics are reserved for extensive disease. Increasing antimicrobial resistance to existing therapies have raised concerns. Antimicrobial stewardship, achieved through the responsible use of antibiotics, is an important measure to re-duce bacterial resistance. This review highlights treatment options for impetigo and shares consensus statements to help guide the management of impetigo in the pediatric population. OBJECTIVE: An expert panel of dermatologists and pediatricians convened in February 2019 to establish evidence-based consensus on the management of impetigo in the pediatric patient population. METHODS: The consensus was created in accordance with the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Prior to the consensus meeting, a systematic literature review was conducted, with the selected literature deemed clinically relevant to the consensus statements. Statements were further refined and assessed systematically following established standards. The consensus process consisted of a modified Delphi approach. The consensus was established through a minimal 75% “agree” rate. RESULTS: Thirteen consensus statements were developed addressing clinical challenges, existing treatment options and their limita-tions, and new therapeutic alternatives. CONCLUSION: Bacterial resistance to antimicrobials commonly used in treating impetigo has been reported. Antimicrobial stewardship is critical to optimize patient outcomes and to prevent the development of resistance. Healthcare providers should be aware of local resistance patterns in impetigo to help guide therapy. The use of newer safe and effective topical antibiotic alternatives as a first-line treatment should be an important step in antimicrobial stewardship.J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4679.

Cutaneous microbiome effects of fluticasone propionate cream and adjunctive bleach baths in childhood atopic dermatitis.

BACKGROUND: Patients with atopic dermatitis (AD) are prone to skin infections, with microbes such as Staphylococcus aureus suspected of contributing to pathogenesis. Bleach baths might improve AD by reducing skin microbial burden. OBJECTIVE: We sought to characterize the microbiota of lesional and nonlesional skin in young children with AD and control subjects and compare changes after treatment with a topical corticosteroid (TCS) alone or TCS + dilute bleach bath. METHODS: In a randomized, placebo-controlled, single-blinded clinical trial in 21 children with AD and 14 healthy children, lesional and nonlesional AD skin was examined at baseline and after 4-week treatment with TCS alone or TCS plus bleach bath. Microbial DNA was extracted for quantitative polymerase chain reaction of predominant genera and 16S rRNA sequencing. RESULTS: At baseline, densities of total bacteria and Staphylococcus, including Staphylococcus aureus, were significantly higher at the worst AD lesional site than nonlesional (P = .001) or control (P < .001) skin; bacterial communities on lesional and nonlesional AD skin significantly differed from each other (P = .04) and from control (P < .001). After TCS + bleach bath or TCS alone, bacterial compositions on lesional skin normalized (P < .0001), resembling nonlesional skin, with microbial diversity restored to control skin levels. LIMITATIONS: The 4-week time period and/or the twice-weekly baths may not have been sufficient for additional impact on the cutaneous microbiome. More detailed sequencing may allow better characterization of the distinguishing taxa with bleach bath treatment. CONCLUSIONS: Treatment with a TCS cream suffices to normalize the cutaneous microbiota on lesional AD; after treatment, bacterial communities on lesional skin resemble nonlesional skin but remain distinct from control.

Evaluation and treatment of the newborn with epidermolysis bullosa.

Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin diseases characterized by increased skin fragility and variable degrees of extracutaneous involvement. The clinical spectrum ranges from localized skin disease to a life-threatening and disabling disease with extensive extracutaneous involvement. All four major types of EB, namely EB simplex, Junctional EB, Dystrophic EB and Kindler syndrome, can present with blistering and erosions at birth and cannot be distinguished clinically in the newborn period. The extensive differential diagnosis of blistering and erosions in the neonate must be considered and common etiologies ruled out. The diagnosis of EB can be confirmed via a skin biopsy for immunoflourescence mapping. This review discusses the four major subtypes of EB and their associated extracutaneous features. The evaluation of a newborn suspected of having EB, including diagnosis and management, is also reviewed.

Management of severe atopic dermatitis in children.

Severe childhood atopic dermatitis refers to the presence of recurrent, widespread, eczematous dermatitis that significantly interferes with the daily activities and/or the quality of life of the affected child and family. The vast majority of children with severe, long-standing atopic dermatitis can be managed with the appropriate use of topical treatments, including long-term maintenance therapy and adjunctive treatments. In the recalcitrant patient, second line therapies such as narrowband ultraviolet light therapy and systemic immunosuppressants such as cyclosporine, azathioprine, mycophenolate moefetil, and methotrexate have been shown to be safe and effective in children with severe atopic dermatitis and can lead to sustained clinical improvement. To date, biologic therapy has not been uniformly effective in childhood atopic dermatitis. Management of severe childhood atopic dermatitis, including topical and adjunctive treatments and second-line therapies including systemic immunosuppressants will be reviewed here.

Ulcerative sarcoidosis.

Sarcoidosis is a multi-system, granulomatous disease, which affects the skin in approximately 20 to 30 percent of cases. Recognition of cutaneous sarcoidosis can be challenging because of the wide range of skin lesion morphologies. Ulcerative sarcoidosis is uncommon. We present a 35-year-old woman with pretibial ulcerative sarcoidosis, indurated tattoos, and hilar lymphadenopathy.

Abortive segmental perineal hemangioma.

A six-week-old girl presented with a segmental, focally atrophic, vascular patch in the diaper area, present since birth. It had undergone minimal proliferation, but had ulcerated. Evaluation to rule out LUMBAR (Lower body hemangioma/Lipoma or other cutaneous anomalies, Urogenital anomalies, Myelopathy, Bony deformities, Anorectal/Arterial anomalies, and Renal anomalies) syndrome, which included ultrasound and Doppler examination of the abdomen, spine, and pelvis, was negative. We report a unique case of an ulcerated, segmental abortive hemangioma of the anogenital area with excellent clinical response to topical timolol gel.

Positive patch- and photopatch-test reactions to methylene bis-benzotriazolyl tetramethylbutylphenol in patients with both atopic dermatitis and chronic actinic dermatitis.

Ultraviolet filters are the most common topical photoallergens. Although currently not available on the US market, methylene bis-benzotriazolyl tetramethylbutylphenol (referred to as bisoctrizole on product labels) represents a new class of UV filters that have both organic and inorganic properties and are widely available in different preparations in Europe, South America, and Asia. We report two patients with atopic dermatitis and chronic actinic dermatitis who had positive patch- and photopatch-test reactions, which suggested both an allergic contact and a photoallergic contact dermatitis from bisoctrizole. Neither patient could identify previous or current contact with the chemical; nonetheless, it is possible that either the allergic contact or photoallergic contact dermatitis from bisoctrizole led to their chronic actinic dermatitis.

Epidermal nevus.

A healthy 25-year-old man presented with a widespread, non-organoid, non-epidermolytic epidermal nevus. In addition to extensive hyperpigented patches and thin plaques following Blaschko lines, there were superimposed psoriasiform plaques on the elbows and warty plaques on the upper trunk. Striate palmar keraoderma also was evident. We review the clinical morphologies, sites of involvement, histopathologic findings (presence or absence of epidermolytic hyperkeratosis), and syndromal associations of non-organoid EN with underlying mutations in different genes.

Erythema dyschromicum perstans.

A 39-year-old Hispanic man presented with widespread, symmetric, hyperpigmented, brown-gray-blue, oval-to-circular, discrete and coalescing patches on the upper extremities, trunk, neck and face, many with an associated annular erythematous border. Histopathologic features showed an interface dermatitis, thin lichenoid and superficial perivascular infiltrates, and dermal melanophages. These changes were consistent with a diagnosis of erythema dyschromicum perstans (EDP). The etiology of EDP is unknown, but many associations have been described. The rim of erythema that appears during the inflammatory phase of the disorder distinguishes it from other disorders of hyperpigmentation. There is no consistently effective treatment for EDP. We highlight the use of narrow-band UV B phototherapy in the treatment of this disorder, which has shown good success in our patient thus far.