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.

In-person validation of the Ichthyosis Scoring System.

BACKGROUND: Ichthyoses are a heterogeneous group of skin disorders characterized by scaling and erythema. Recognizing the variability of scale and erythema by region and ichthyosis subtype, we developed the Ichthyosis Scoring System (ISS) to quantify severity. We previously found ISS to have high inter- and intrarater reliability in evaluating photographic images. To confirm ISS clinical utility, we examined its performance at the 2022 Foundation for Ichthyosis and Related Skin Types conference. METHODS: Sixty-five participants were evaluated by 3 of 9 medical professionals trained to score ichthyosis scale and erythema using ISS. Intrarater and interrater intraclass correlation coefficients (ICC) were analyzed using one-way and two-way random effects models, respectively. RESULTS: Intrarater reliability was excellent (ICC = 0.931, 95% CI, 0.921-0.940) for scale and good (ICC = 0.876, 95% CI, 0.853-0.899) for erythema scoring. Compared to photo validation with excellent intrarater reliability ratings for both scale (ICC = 0.956, 95% CI, 0.925-0.974) and erythema (ICC = 0.913, 95% CI, 0.855-0.949), ISS demonstrated equivalent reliability for live use. Overall interrater reliability for 10 body sites showed excellent (ICC >0.9) and good (ICC >0.75) agreement and consistency for both scale and erythema. Palms were an exception, demonstrating moderate (ICC >0.5) interrater agreement and consistency for erythema evaluation. CONCLUSIONS: ISS is a reliable measure of global and regional ichthyosis severity during in-person evaluations. Ease-of-use, accessibility, and content validity in both live and photographic evaluation endorse ISS as a standard for ichthyosis severity analysis.

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.

The Many Faces of Pediatric Acne: A Practical Algorithm for Treatment, Maintenance Therapy, and Skincare Recommendations for Pediatric Acne Patients.

BACKGROUND: Pediatric acne is a common, complex, multifactorial inflammatory skin disease with various expressions in childhood that can be categorized by age, severity, and pubertal status. METHODS: The Faces of Pediatric Acne Project (FoPAP) aims to improve patient outcomes. The FoPAP group developed an algorithm that follows a consensus paper and a clinical case series on pediatric acne by applying the selected literature and drawing from the clinical knowledge and experience of each group member. RESULTS: The algorithm addresses neonatal, infantile, mid-childhood, preadolescent, and adolescent acne and starts with education on acne, general measures for prevention, treatment, maintenance, and ongoing skin care. Evaluation of pediatric acne requires a directed medical history and physical examination. For mid-childhood acne patients, a workup is warranted, and endocrine-associated abnormalities necessitate referral to a pediatric dermatologist. The second section of the algorithm identifies the type of pediatric acne, followed by the third section on acne treatment using a prescription or nonprescription treatment and skincare options. After successfully controlling the disease, maintenance treatment with topical agents and skincare using gentle cleansers and moisturizers containing lipids such as ceramides is important. CONCLUSIONS: The pediatric acne algorithm offers a comprehensive approach to treating and maintaining pediatric acne. In addition, it may support healthcare providers to bring more attention to pediatric acne patients and improve outcomes. Schachner LA, Andriessen A, Latanya Benjamin L, et al. The many faces of pediatric acne: a practical algorithm for treatment, maintenance therapy, and skincare recommendations for pediatric acne patients. J Drugs Dermatol. 2023;22(6):539-545. doi:10.36849/JDD.7440 .

The Many Faces of Pediatric Acne: How to Tailor Nonprescription Acne Treatment and Skincare Using Cleansers and Moisturizers.

BACKGROUND: Acne vulgaris (acne) is a common, complex, multifactorial disorder. Various expressions of acne in childhood can be categorized by age, severity, and pubertal status. OBJECTIVE: To improve pediatric acne patients’ outcomes, various expressions of pediatric acne to educate and tailor nonprescription acne treatment and skincare using cleansers and moisturizers were defined and discussed. METHODS: An expert panel of pediatric dermatologists and dermatologists reviewed and discussed nonprescription acne treatment and skincare literature. The results from the literature searches were used together with the panel’s expert opinion and experience to adopt various expressions of pediatric acne and prevention, treatment, and maintenance of the condition using nonprescription acne treatment and skincare. RESULTS: The panel agreed on sixteen acne patient profiles addressing various age categories of pediatric acne: neonatal acne: birth to ≤ 8 weeks; infantile acne: 8 weeks to ≤1 year; mid-childhood acne: 1 year to <7 years; preadolescent acne: ≥7 to 12 years; adolescent acne: ≥12 to 19 years or after menarche for girls. Nonprescription acne treatment and skincare products containing lipids such as ceramides play an important role in monotherapy, adjunctive, and maintenance treatment; however, their role in pediatric acne is not well defined and requires more studies. CONCLUSION: Pediatric acne deserves more attention from healthcare providers treating children regarding differential diagnosis, treatment, and maintenance using nonprescription acne treatment and skincare. J Drugs Dermatol. 2022;21(6):602-612. doi:10.36849/JDD.6872.

Development and Initial Validation of a Novel System to Assess Ichthyosis Severity.

IMPORTANCE: A comprehensive, user-friendly system to assess global ichthyosis disease burden is imperative to improving the care of patients with ichthyosis, identifying appropriate participants for clinical trials, and quantifying treatment outcomes. To our knowledge, there is currently no validated scale to objectively and systematically measure ichthyosis severity across the entire body. OBJECTIVE: To create and evaluate a comprehensive and user-friendly instrument to measure total body ichthyosis severity in adults and children. DESIGN, SETTING, PARTICIPANTS: In this qualitative study, ichthyosis experts participated in the content development of the Ichthyosis Scoring System (ISS). The body was divided into 10 regions, and Likert scales (0-4) were created to quantify scale and erythema, with extensive descriptors and photographic standards. An 83-image teaching set was created from photographs of participants with ichthyosis. Two cohorts of dermatologists (11 total) independently scored all test photographs twice to evaluate interrater and intrarater reliabilities. Participants were enrolled worldwide from referral centers and patient advocacy groups. Participants of all ages, races, and ethnicities were included in the creation of ISS, and dermatologists with varying experience and areas of expertise participated as raters to evaluate the ISS. The study was conducted from 2019 to 2021, and the data were analyzed in 2021. MAIN OUTCOMES AND MEASURES: Intraclass correlation coefficients determined overall reliabilities. RESULTS: Across both cohorts of 11 dermatologists in total, the intraclass correlation coefficients for total, scale and erythema scores were greater than 0.90 (95% CI, 0.77-0.97), greater than 0.91 (95% CI, 0.79-0.98), and greater than 0.88 (95% CI, 0.72-0.97), respectively. Most body sites exhibited moderate to good interrater reliabilities for scale and erythema. Intrarater reliabilities were good to excellent. CONCLUSIONS AND RELEVANCE: The results of this qualitative study demonstrate reproducibility and suggest that the ISS is a reliable system to measure global ichthyosis severity in adults and children.

The Importance of Skincare for Neonates and Infants: An Algorithm.

BACKGROUND: The skin of neonates and infants undergoes a maturation process from birth and is susceptible to barrier disruption. The current algorithm follows a US-based consensus paper on skincare approaches using gentle cleansers and moisturizers in neonatal and healthy infant skin. This summary provides clinical information for pediatric dermatologists, dermatologists, and pediatric healthcare providers treating neonates and infants. METHODS: The project used a modified Delphi process comprising virtual discussions followed by an online follow-up replacing the use of a questionnaire. During the virtual meeting, the systematic literature review results and a draft algorithm addressing over-the-counter skincare for neonates and infants with healthy skin were discussed and adopted using evidence coupled with the expert opinion and experience of the panel. RESULTS: The algorithm addresses three clinical signs: xerosis, erythema, and erosion/bulla. A growing body of evidence recognizes the benefits of ongoing daily use of non-alkaline cleansers and ceramides containing moisturizers to reduce inflammation and maintain a healthy skin barrier function. Diaper rash is common in infants presenting as erythema or, in more severe cases, skin erosion. Skin protection with a barrier cream and frequent diaper changes using disposable diapers resolves most cases; however, if the rash continuous despite appropriate care, rule out a candida infection. CONCLUSION: The current algorithm focuses on neonatal and infant healthy skin that can benefit from skincare. When applied from birth onwards, gentle cleansers and moisturizers containing barrier lipids help maintain the protective skin barrier. J Drugs Dermatol. 2021;20(11):1195-1205. doi:10.36849/JDD.6219.

Photodocumentation in skin of color.

Photodocumentation is an important tool utilized across medical specialties and plays an especially pivotal role in dermatology given the visual nature of the field. Although it has been well-established that dermatologic diseases manifest differently in dark skin compared to light skin, there is under-representation of images of dark skin in dermatology textbooks and other educational resources. It is essential for dermatologists to work toward increasing the availability of images of dermatologic disease in dark skin by improving their own ability to successfully photograph dark-skinned patients. In this article, we describe our nuanced approach to photographing skin of color in regards to the ideal background type, lighting, and camera settings.

Diversity in pediatric dermatology: A report from the Pediatric Dermatology Research Alliance and a call to action.

BACKGROUND/OBJECTIVES: The Pediatric Dermatology Research Alliance (PeDRA) connects pediatric dermatologists, trainees, basic scientists, allied health professionals, and patient advocates to improve the lives of children with skin disease through research. As a training pipeline for future pediatric dermatologists and steward of research in the field, PeDRA has a responsibility to examine its history and take actionable steps to diversify its membership, grant recipients, study leads, research priorities, and leadership. METHODS: In 2020, PeDRA formed an Equity, Diversity, and Inclusion Task Force to address this need. In an effort to assess PeDRA's past and plan for PeDRA's future, a review of PeDRA's membership, leadership, grant awardees, and research topics was conducted. RESULTS/CONCLUSIONS: Results demonstrated gaps in PeDRA's current operational efforts to diversify the pediatric dermatology workforce and identified areas for improvement. Recommendations are proposed as a call to action for the community.

Training in pediatric skin of color: Suggested curricular guidelines of the pediatric dermatology research alliance special interest group in pediatric skin of color.

BACKGROUND: Deficiencies in the skills necessary to diagnose and manage patients with skin of color may contribute to health disparities. The Pediatric Dermatology Research Alliance Special Interest Group in Pediatric Skin of Color (PSOCG) convened to generate a curriculum of topics required for basic pediatric skin of color (PSOC) education for medical students and residents in dermatology to improve the quality of education in PSOC. METHODS: A survey was distributed to the PSOCG members to assess expert opinion regarding critical topics for inclusion in a basic PSOC syllabus. Video conference and two rounds of survey were used to rank topics for inclusion and to highlight the underlying need for inclusion. RESULTS: Group members composed of academic pediatric dermatologists with teaching responsibilities including skin of color topics for dermatology residents and medical students. Learning objectives were developed for an educational lecture on basic science, and clinical conditions affecting PSOC were grouped by age-infantile, pediatric, and adolescent skin conditions affecting the PSOC population were identified for inclusion with rank score based on specific parameters including greater frequency in skin of color, nuances in skin of color, and need for medical workup. CONCLUSIONS: Increased focus on PSOC education is needed to improve quality of care for children of color through enhanced knowledge. Inflammatory, genetic, and particularly primary pigmentary disorders should be the focus of a broad curriculum in pediatric skin of color education for medical trainees. Objectives should include improved diagnosis, treatment, and ability to educate patients and their families regarding the nature of their conditions.

Do Antimicrobial Resistance Patterns Matter? An Algorithm for the Treatment of Patients With Impetigo.

BACKGROUND: Impetigo, a highly contagious bacterial skin infection commonly occurring in young children, but adults may also be affected. The superficial skin infection is mainly caused by Staphylococcus aureus (S. aureus) and less frequently by Streptococcus pyogenes (S. pyogenes). Antimicrobial resistance has become a worldwide concern and needs to be addressed when selecting treatment for impetigo patients. An evidence-based impetigo treatment algorithm was developed to address the treatment of impetigo for pediatric and adult populations. METHODS: An international panel of pediatric dermatologists, dermatologists, pediatricians, and pediatric infectious disease specialists employed a modified Delphi technique to develop the impetigo treatment algorithm. Treatment recommendations were evidence-based, taking into account antimicrobial stewardship and the increasing resistance to oral and topical antibiotics. RESULTS: The algorithm includes education and prevention of impetigo, diagnosis and classification, treatment measures, and follow-up and distinguishes between localized and widespread or epidemic outbreaks of impetigo. The panel adopted the definition of localized impetigo of fewer than ten lesions and smaller than 36 cm2 area affected in patients of two months and up with no compromised immune status. Resistance to oral and topical antibiotics prescribed for the treatment of impetigo such as mupirocin, retapamulin, fusidic acid, have been widely reported. CONCLUSIONS: When prescribing antibiotics, it is essential to know the local trends in antibiotic resistance. Ozenoxacin cream 1% is highly effective against S. pyogenes and S. aureus, including methycyllin-susceptible and resistant strains (MRSA), and may be a suitable option for localized impetigo.J Drugs Dermatol. 2021;20(2):134-142. doi:10.36849/JDD.5475 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

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.

Atopic Dermatitis and the Role of the Skin Microbiome in Choosing Prevention, Treatment, and Maintenance Options.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition characterized by disturbed barrier function, skin inflammation, and cutaneous dysbiosis. Clinically, it manifests as chronic-recurrent xerosis, pruritus, and erythematous lesions. Its pathophysiology is complex, making the selection of appropriate treatment options a task. AIM: To share insights gained from a literature review and discussions with experts in dermatology on key factors related to the prevention, treatment, and management of AD in relation to the skin microbiome. METHODS: Results from an expert panel were summarized and discussed to provide updated recommendations for the treatment and maintenance of AD. RESULTS: Evidence supports a strategy for managing inflammatory skin diseases with a selenium-rich post-biotic thermal water and biomass containing moisturizer. The moisturizer helps to restore homeostasis of the skin, re-populate a diverse microbiome, encourage the growth of commensal bacteria, and improve barrier function and symptoms of AD. CONCLUSIONS: Normalization of skin microbiome diversity using a topical moisturizer containing post-biotic aqua and biomass may offer a valuable option for the treatment and maintenance of inflammatory skin diseases. Clinicians should discuss the benefits of this treatment in the context of a full AD management program that covers prevention, active treatment, and maintenance. J Drugs Dermatol. 2020;19(10):935-940. doi:10.36849/JDD.2020.5393.

A Consensus About the Importance of Ceramide Containing Skincare for Normal and Sensitive Skin Conditions in Neonates and Infants.

Background: Neonates and infants are susceptible to skin barrier disruption as their skin anatomically and functionally is still developing. The process of skin acidification plays a vital role in barrier maturation and the activation of enzymes involved in the extracellular processing of stratum corneum lipids. The current consensus paper explores challenges, and current treatment approaches in neonatal and infant normal and sensitive skin and the role of ceramides containing moisturizers. Methods: For this purpose, an expert panel of pediatric dermatologists and dermatologists discussed information from systematic literature searches, coupled with expert opinion and experience of the panel, to adopt eight statements. The consensus process consisted of a modified Delphi technique. Results: During the first years after birth, the neonatal and infant skin is more permeable to topical agents and, therefore, requires particular caution with topical skincare regimens. Mildly acidic or pH-neutral cleansers have benefits for neonates and infants. Skincare for neonates and infants should be safe, effective, and fragrance free as well as sensitizing agent-free. Additionally, the skincare should be pleasant to use, containing ingredients that benefit the lipid and water content of the SC, such as those products containing ceramides. Conclusion: Taking into consideration the maturation process of neonatal and infant skin, the application of moisturizers and cleansers containing barrier lipids may help maintain the protective skin barrier and soothe with long-term moisturizing benefits. J Drugs Dermatol. 2020;19(8) 769-776: doi:10.36849/JDD.2020.5252 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Consensus on Neonatal Through Preadolescent Acne.

BACKGROUND: Acne vulgaris is the most common dermatological disorder. Pediatric acne may be a manifestation of the underlying pathology and can occur in the first weeks, months, or years of life. Acne in childhood can be categorized by age and pubertal status. OBJECTIVE: An expert panel of pediatric dermatologists and dermatologists developed a consensus paper on neonatal through preadolescent acne, providing information on differential diagnosis, prevention, treatment, and maintenance of the condition. METHODS: A systematic literature review explored present clinical guidelines, treatment options, and therapeutic approaches addressing neonatal through preadolescent acne. The information from the literature searches was used together with the panel’s expert opinion and experience to adopt consensus statements following established standards. RESULTS: The panel members reached unanimous consensus on seven statements addressing the various age categories of pediatric acne: neonatal acne: birth to ≤ 8 weeks; infantile acne: 8 weeks to ≤1 year; mid-childhood acne: 1 year to <7 years; preadolescent acne: ≥7 to 12 years; adolescent acne: ≥12 to 19 years or after menarche for girls. Health care providers treating children need to pay more attention to pediatric acne and should monitor the risk of endocrine-associated abnormalities, especially in mild-childhood acne. When prescribing acne treatment, newer medications approved for use in children older than nine years of age may offer a suitable option. CONCLUSION: The differential diagnosis of pediatric acne, as well as its treatment and maintenance, requires much more attention and consideration from health care providers treating children. J Drugs Dermatol. 2020;19(6):592-600. doi:10.36849/JDD.2020.5065.

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.

Treatment of complex periorbital venolymphatic malformation in a neonate with a combination therapy of sirolimus and prednisolone.

Venolymphatic malformations (VLMs) are vascular anomalies consisting of both veins and lymph vessels. A 2-week-old newborn presented with large VLMs on the left forehead, temple, preauricular area, and orbit. Patient was at imminent risk for permanent vision loss due to a localized mass effect. Surgical excision or debulking was contraindicated due to its complexity and proximity to the left eye, and the patient failed to respond to the sildenafil treatment and sclerotherapy. Patient was subsequently started on oral sirolimus 0.8 mg/m(2) twice daily in combination with prednisolone 2 mg/kg daily. The patient had an excellent therapeutic outcome for 7 months with complete preservation of vision before treatment was discontinued. However, 2 months after the medical treatments were discontinued, her VLM rebounded. She responded to the combination therapy again after a failed treatment with the mTOR inhibitor alone. This case demonstrates that the sirolimus and prednisolone combination therapy could be beneficial for treatment of complex VLM intractable to other treatments.

A randomized, controlled trial of oral propranolol in infantile hemangioma.

BACKGROUND: Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. METHODS: We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. RESULTS: Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. CONCLUSIONS: This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).