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.).

A Consensus on Staphylococcus aureus Exacerbated Atopic Dermatitis and the Need for a Novel Treatment.

The skin microbiome is essential for skin barrier function because it inhibits pathogen colonization, and decreased microbiome diversity correlates with increased Staphylococcus aureus (S. aureus) burden and atopic dermatitis (AD) severity. Managing S. aureuss-driven AD in clinical practice remains problematic due to complications such as AD exacerbation, impetigo, abscesses, and invasive infections. This project used a modified Delphi process comprising face-to-face discussions followed by a blinded vote to define 5 final consensus statements. A panel of 6 pediatric dermatologists developed a consensus on S. aureus-driven AD exacerbation, challenges in current treatments for AD with secondary bacterial infections, and new developments to improve patient care and outcomes. The panel's 5 consensus statements provide recommendations for dermatologists, pediatricians, and healthcare providers treating patients with secondary infected AD. These recommendations underscore the importance of recognizing and managing S. aureus skin infection in AD clinical practice and promoting antibiotic stewardship to mitigate resistance. The panel defined a significant unmet need for a single topical AD therapy effective against all symptoms, including pruritus, S. aureus-driven AD exacerbation, infection, and inflammation, across AD severity levels. J Drugs Dermatol. 2024;23(10):825-832. doi:10.36849/JDD.8240.

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.

Appearance Dissatisfaction and Body Dysmorphic Disorder in the Dermatology Patient.

Dermatologists routinely see patients with inflammatory skin conditions and aesthetic concerns that involve substantial psychological comorbidity. However, most dermatologists do not receive formal training in this area, and many are unsure how to best help treat certain patients holistically. Body dysmorphic disorder (BDD) is a common and distressing psychiatric condition that disproportionately impacts dermatology patients, including patients living with chronic inflammatory skin conditions such as acne and atopic dermatitis. BDD is characterized by preoccupation with nonexistent or minimally noticeable flaws in physical appearance that cause clinically significant distress or impairment in functioning. Adolescent populations may be particularly vulnerable to clinically significant body image dissatisfaction, including BDD, due to the high prevalence of acne and the pervasive role of social media platforms. The rise of social media may exacerbate body image issues through repetitive exposure to idealized and often unrealistic beauty standards. Though screening questionnaires can assist dermatologists in recognizing BDD, dermatologists must collaborate with mental health providers to provide comprehensive care to vulnerable patients, including adolescents.J Drugs Dermatol. 2024;23(7):545-550.  doi:10.36849/JDD.8156.

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.

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.

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.

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.

Attentiveness and mental health in adolescents with moderate-to-severe atopic dermatitis without ADHD.

Patients with moderate-to-severe atopic dermatitis (AD) experience intense chronic itch and impaired sleep. Reports from parents and teachers suggest that AD patients may also have attention problems. However, attention has not yet been directly assessed in AD patients. We utilized an objective, computer-based continuous performance test (CPT) validated for use in attention-deficit/hyperactivity disorder (ADHD) diagnosis to formally evaluate attention in adolescent AD subjects. This was a single-visit, cross-sectional, non-interventional study of moderate-to-severe (Investigator's Global Assessment [IGA] ≥ 3) AD subjects aged 12-17 years without clinician-diagnosed ADHD. Attention was evaluated using two performance-based measures: Conners, CPT-3 and the Stroop Color and Word Test. The primary parameter was CPT-3 detectability (d') measure. Lesional severity measures included Eczema Area and Severity Index (EASI) and body surface area (BSA) involvement. Subjects completed self-report rating scales assessing sensory responsiveness patterns (Adult/Adolescent Sensory Profile [AASP]), itch (Peak Pruritus Numerical Rating Scale [PP-NRS]), skin pain, quality of life, sleep, anxiety, and depressive symptoms. A total of 44 subjects were included in the study (61.4% female; mean age 15.0 [SD 1.78] years; mean EASI 20.4 [SD 7.8]; mean PP-NRS 7.0 [SD 1.8]). Results indicated substantial disease impact on sleep, quality of life, and comorbid anxiety and depressive symptoms. The mean (SD) Conners, CPT-3 d' T-score was 48.7 (SD 10.7), similar to the expected mean from a randomly selected age/gender-matched sample of the general population (50 [SD 10], by definition). Overall, 13.6% of subjects exhibited a d' T-score ≥ 60 (clinically significant poor performance), which was not greater than the expected general population value (15.9%). Subject-level data review by two psychologists determined that only 2 subjects demonstrated an overall response pattern that clearly indicated attention deficit. Many subjects had atypical sensory responsiveness profiles: sensory hypersensitivity (38.6%), sensory avoidance (50%), and low registration (hypo-sensitivity, 36.4%). Adolescents with moderate-to-severe AD without existing ADHD diagnosis did not demonstrate greater attention problems on performance-based measures than would be expected in age/gender-matched peers.Trial registration NCT05203380.

Atopic dermatitis (often shortened to AD) is a long-term skin disease that causes intense itching. It affects patients' lives in many ways, including interrupting their sleep. Parents and teachers of young people with AD have sometimes suggested that AD may also cause attention problems. But this has never been tested properly.We measured the attention of 44 adolescents aged between 12 and 17 years who all had moderate-to-severe AD. We used computerized tests of attention that were developed for young people with ADHD (attention deficit hyperactivity disorder). Also, we made sure that none of the 44 patients had also been diagnosed with ADHD. The severity and extent of the patients' AD was measured by doctors. We also used some measures that allowed the patients to report how AD affected their lives, including things like itch, skin pain, quality of life, sleep, anxiety, and depression.The adolescent patients reported that AD had a negative effect on various areas of their lives, including sleep and quality of life, and that it resulted in anxiety and symptoms of depression. However, the results of the attention tests in adolescents with AD were similar to what would usually be expected in adolescents without AD. Only 2 of the 44 patients with AD were found to have clear evidence of attention problems.The study concluded that adolescents with moderate-to-severe AD did not have any greater attention problems than would usually be expected in adolescents without AD.

Dupilumab treatment reduces caregiver-reported skin pain in patients with moderate-to-severe atopic dermatitis aged 6 months to 5 years.

Background: Moderate-to-severe atopic dermatitis (AD) often has a profound impact on the quality of life of young children and their caregivers. One of the most burdensome symptoms reported by patients is skin pain. Methods: This post hoc analysis focuses on the impact of dupilumab treatment on skin pain in young children using data from the LIBERTY AD PRESCHOOL part B (NCT03346434), a 16-week randomized, double-blind, placebo-controlled, phase 3 study in 162 children aged 6 months to 5 years with moderate-to-severe AD receiving dupilumab or placebo, plus topical corticosteroids (TCS). Analyses were performed on the full analysis set and subgroups of patients who did not achieve an Investigator's Global Assessment score of 0 or 1 (IGA >1 subgroup), or who did not achieve a 75% improvement from baseline in the Eczema Area and Severity Index (1 and

Practical considerations relevant to treatment with the gene therapy beremagene geperpavec-svdt for dystrophic epidermolysis bullosa.

BACKGROUND/PURPOSE: Dystrophic epidermolysis bullosa (DEB), a rare genetic skin disease caused by loss-of-function mutations in COL7A1, the gene encoding type VII collagen (COL7), is characterized by skin blistering, scarring, and extracutaneous manifestations that markedly reduce patient quality-of-life. Beremagene geperpavec-svdt ('B-VEC') is a gene therapy employing a non-integrating, replication-defective herpes simplex virus type 1 (HSV-1)-based vector encoding two copies of full-length human COL7A1 to restore COL7 protein after topical administration to DEB wounds. B-VEC was approved in the United States in 2023 as the first topical gene therapy and the first approved treatment for DEB. However, few providers have experience with use of this gene therapy. METHODS: Data was obtained through literature review and the experience of providers who participated in the B-VEC clinical study or initiated treatment after B-VEC approval. RESULTS: This review discusses the burden of disease, describes the clinical trial outcomes of B-VEC, and provides physician and patient/caregiver recommendations as a practical guide for the real-world use of B-VEC, which can be administered in-office or at the patient's home. CONCLUSIONS: By continuing to optimize the practical aspects of B-VEC administration, the focus will continue to shift to patient-centric considerations and improved patient outcomes.

Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children: INTEGUMENT-1 and INTEGUMENT-2 Randomized Clinical Trials.

Importance: Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates. Objective: To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD. Design, Setting, and Participants: Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]). Intervention: Patients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks. Main Outcomes and Measures: The primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated. Results: Among 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; P < .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; P < .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; P < .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; P < .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site. Conclusions and Relevance: In 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability. Trial Registration: ClinicalTrials.gov Identifiers: NCT04773587, NCT04773600.

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).

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.

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.

Halo nevi in Turner syndrome.

Turner syndrome is a genetic disorder characterized by an abnormal or missing X-chromosome. Rarely reported cutaneous manifestations in Turner syndrome include hemangiomas, angiokeratomas, hirsutism, and halo nevi. A recent study demonstrated an increased prevalence of halo nevi in Turner syndrome when compared to vitiligo. We present a case of halo nevi with multiple melanocytic nevi in an 11-year-old patient with Turner syndrome on growth hormone.