IMPORTANCE Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, with limited treatment options. The efficacy and safety of dupilumab, a monoclonal antibody, approved for treatment in adolescent patients with inadequately controlled AD, remain unknown in this patient population. OBJECTIVE To assess the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled AD. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, parallel-group, phase 3 clinical trial was conducted at 45 US and Canadian centers between March 21, 2017, and June 5, 2018. A total of 251 adolescents with moderate to severe AD inadequately controlled by topical medications or for whom topical therapy was inadvisable were included. INTERVENTIONS Patients were randomized (1:1:1; interactive-response system; stratified by severity and body weight) to 16-week treatment with dupilumab, 200 mg (n = 43; baseline weight <60 kg), or dupilumab, 300 mg (n = 39; baseline weight Ն60 kg), every 2 weeks; dupilumab, 300 mg, every 4 weeks (n = 84); or placebo (n = 85). MAIN OUTCOMES AND MEASURES Proportion of patients with 75% or more improvement from baseline in Eczema Area and Severity Index (EASI-75) (scores range from 0 to 72, with higher scores indicating greater severity) and Investigator's Global Assessment (IGA) 0 or 1 on a 5-point scale (scores range from 0 to 4, with higher scores indicating greater severity) at week 16. RESULTS A total of 251 patients were randomized (mean [SD] age, 14.5 [1.7] years; 148 [59.0%] male). Of 250 patients with data available on concurrent allergic conditions, most had comorbid type 2 diseases (asthma, 134 [53.6%]; food allergies, 60.8%; allergic rhinitis, 65.6%). A total of 240 patients (95.6%) completed the study. Dupilumab achieved both coprimary end points at week 16. The proportion of patients with EASI-75 improvement from baseline increased (every 2 weeks, 41.5%; every 4 weeks, 38.1%; placebo, 8.2%) with differences vs placebo of 33.2% (95% CI, 21.1%-45.4%) for every 2 weeks and 29.9% (95% CI, 17.9%-41.8%) for every 4 weeks (P < .001). Efficacy of the every-2-week regimen was generally superior to the every-4-week regimen. Patients in the dupilumab arms had higher percentage values of conjunctivitis (every 2 weeks, 9.8%; every 4 weeks, 10.8%; placebo, 4.7%) and injection-site reactions (every 2 weeks, 8.5%; every 4 weeks, 6.0%; placebo, 3.5%), and lower nonherpetic skin infections (every 2 weeks, 9.8%; every 4 weeks, 9.6%; placebo, 18.8%). CONCLUSIONS AND RELEVANCE In this study, dupilumab significantly improved AD signs, symptoms, and quality of life in adolescents with moderate to severe AD, with an acceptable safety profile. Placebo-corrected efficacy and safety of dupilumab were similar in adolescents and adults. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03054428

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Etanercept significantly reduced disease severity in children and adolescents with moderate-to-severe plaque psoriasis. (ClinicalTrials.gov number, NCT00078819 [ClinicalTrials.gov].).

Background: Children with severe atopic dermatitis (AD) have limited treatment options.Objective: We report the efficacy and safety of dupilumab 1 topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies.Methods: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight \30 kg; 200 mg q2w, baseline weight $30 kg), or placebo; with concomitant medium-potency TCS.Results: Both the q4w and q2w dupilumab 1 TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo 1 TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved $75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved $4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children \30 kg and 200 mg q2w in children $30 kg.

Hemangioma of infancy is a condition that may be associated with significant morbidity. While evidence most supports the use of corticosteroids, there is no well-defined or Federal Drug Administration (FDA)-approved systemic therapy for hemangioma of infancy. All currently used treatments have significant risks. Dramatic improvement of complicated hemangioma of infancy to propranolol was recently reported, but details for initiating therapy, monitoring, and potential risks were not included. We present two infants treated with propranolol, who suffered complications and propose a treatment protocol to minimize potential adverse events.

Harlequin ichthyosis (HI) is the most severe phenotype of the autosomal recessive congenital ichthyoses. HI is caused by mutations in the lipid transporter adenosine triphosphate binding cassette A 12 (ABCA12). Neonates are born with a distinct clinical appearance, encased in a dense, platelike keratotic scale separated by deep erythematous fissures. Facial features are distorted by severe ectropion, eclabium, flattened nose, and rudimentary ears. Skin barrier function is markedly impaired, which can lead to hypernatremic dehydration, impaired thermoregulation, increased metabolic demands, and increased risk of respiratory dysfunction and infection. Historically, infants with HI did not survive beyond the neonatal period; however, recent advances in neonatal intensive care and coordinated multidisciplinary management have greatly improved survival. In this review, the authors combine the growing HI literature with their collective experiences to provide a comprehensive review of the management of neonates with HI.

Therapeutic options for superficial infantile hemangiomas (IH) are limited. Recently, timolol maleate gel, a topical nonselective beta-blocker, has been reported as a potentially effective treatment for superficial IH. This study is an extension of a previously published pilot study designed to further investigate the efficacy and safety and to identify predictors of good response of topical 0.5% or 0.1% timolol maleate gel-forming solution. This was a retrospective cohort study including patients enrolled from five centers. Patients were included if they were treated with timolol maleate 0.1% or 0.5% gel-forming solution and had photographic documentation of the IH and at least one follow-up visit. Patients with concomitant active treatment using other IH treatments were excluded. The primary endpoint was change in the appearance of IH as evaluated using a visual analog scale (VAS). Data from 73 subjects were available for final analysis. Timolol maleate gel-forming solution 0.5% was used in 85% (62/73) of patients, the remainder being treated with 0.1%. The median age at treatment initiation was 4.27 months (interquartile range [IQR] 2.63-7.21 mos), and patients were treated for a mean of 3.4 ± 2.7 months. All patients except one improved, with a mean improvement of 45 ± 29.5%. Predictors of better response were superficial type of hemangioma (p = 0.01), 0.5% timolol concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04). Sleeping disturbance was noted in one patient. This study further demonstrates the efficacy and tolerability of topical timolol maleate and gradual improvement with longer treatment in patients with superficial IH.

Topical calcineurin inhibitors (TCIs), commercially available since 2000–2001, are the first and only topical medications approved for chronic treatment of atopic dermatitis (AD) in pediatric patients and remain a welcomed alternative to topical corticosteroids. In January 2006, the US Food and Drug Administration (FDA) issued a boxed warning requirement based on a theoretical risk of malignancy (including lymphoma) with TCI use. However, in the years since, analyses of epidemiologic and clinical data have failed to demonstrate a causal relationship between TCI use and malignancy or lymphoma risk, especially for pimecrolimus cream. In fact, the observed number of malignancies and lymphomas observed both in post-marketing surveillance and reported to the FDA using its adverse events reporting system is much lower among TCI-exposed patients than the expected number for the general population. Furthermore, among children enrolled in post-marketing pediatric registry studies for both tacrolimus and pimecrolimus followed for up to 5.5 years [10,724 patient-years (PY)] or 6.5 years (16,219 PY), respectively, the observed number of malignancies and lymphomas is very low and similar to the number expected for a sample of similar size in the general population. In addition to reporting these comparative malignancy and lymphoma data, this article provides a historical overview of the boxed warning requirement and critically evaluates the preclinical, clinical, and epidemiological evidence that has thus far failed to substantiate a relationship between TCI use and malignancy. The authors also provide practical clinical advice for optimizing AD management and patient care in the context of the boxed warning.