Introduction Tralokinumab is approved for moderate-to-severe AD in patients aged ≥ 12 years. Here, we present the first data for tralokinumab in children 6 - <12 years with moderate-to-severe AD, with the primary objective of establishing the PK profile and secondary objective of assessing safety to confirm dosing in children. Methods Interim analysis of the ongoing TRAPEDS 1 (NCT05388760) trial included the initial (Week [W] 0-16) and open-label (W16-68) treatment periods. Patients were randomized 1:1 to low-dose (150mg Q4W if 17 - <40kg [n=10], 150mg Q2W if ≥40kg [n=3]) or high-dose (150mg Q2W if 17 - <40kg [n=11], 300mg Q2W if ≥40kg [adult dosing; n=4]) tralokinumab for W0-16. For W16-68, all patients received open-label tralokinumab 150mg Q2W plus optional TCS or TCI. Results Baseline age and weight were similar between groups. At W16, systemic exposure of tralokinumab in the low-dose group was approximately half that of the high-dose group (geometric mean serum concentration: 47.15μg/mL vs 105.02μg/mL), with levels of 80-87μg/mL for W16-68. A similar safety profile was observed between groups; almost all AEs were mild or moderate in severity with 2 serious AEs deemed unrelated to drug and no anti-drug antibodies were detected. Conclusion These results showed that tralokinumab had a PK profile consistent with previous observations in adults treated with 300mg Q2W and was largely well-tolerated with no safety concerns in children 6 - <12 years with moderate-to-severe AD.

Reactive infectious mucocutaneous eruption (RIME) is a condition characterized by mucositis often accompanied by varying skin lesions, prodromal cough, fever, and malaise. Here we present two cases of otherwise healthy children with Mycoplasma-induced RIME who developed acute unilateral facial swelling due to parotitis. The parotitis in both cases was thought to result from obstruction of the parotid duct and resolved with management of RIME, local compresses, and massage. Parotitis as a complication of oral mucositis is an important clinical finding that should be recognized and managed promptly with standard RIME treatment and supportive care.

Recent publications reporting increased cutaneous T-cell lymphoma (CTCL) risk with dupilumab in atopic dermatitis (AD) have sparked debate, amplified by media coverage linking dupilumab to lymphoma. These concerns have reached pediatric populations, where we observe increasing parental hesitancy about initiating dupilumab for their children. This hesitancy is particularly acute given that dupilumab was only approved for infants aged 6 months and older in 2022-the first cohort now approaching 3-4 years of exposure. Parents understandably question the long-term effects of decades of IL-4/IL-13 blockade initiated during critical immune development periods. The diagnostic overlap between AD and mycosis fungoides (the most common CTCL) complicates assessment. We examine evidence regarding dupilumab safety and CTCL risk specifically in pediatric patients, incorporating recently presented long-term open-label extension data, and provide recommendations for monitoring, distinguishing AD from CTCL, and counseling families navigating this complex topic.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that requires a complex management strategy, which often involves multiple and diverse topicals and systemic treatment regimens. While topical steroids and more recently calcineurin inhibitors have been the mainstay therapy for mild-to-moderate disease, recent advances in the understanding of AD pathogenesis have led to the development of different new targets, rapidly widening our therapeutic armamentarium. This review summarizes their efficacy and safety data. We also review topical optimization strategies, including the recently published topical volume calculator, to maximize long-term disease control, especially when using multiple agents at the same time.

Dystrophic epidermolysis bullosa (DEB) and junctional EB (JEB) are severe, bullous genodermatoses induced by mutations of genes encoding structural skin proteins that disrupt epidermal adhesion. Until recently, treatment was limited to symptomatic care. Since 2022, three therapies - birch triterpenes gel (Filsuvez), beremagene geperpavec-svdt (B-VEC, Vyjuvek), and prademagene zamikeracel (pz-cel, Zevaskyn) - have received regulatory approval, representing the first specific interventions for epidermolysis bullosa. Herein, we provide an overview on their mechanisms of action, efficacy, safety, and clinical implications.

Chronic hand eczema (CHE) is an inflammatory skin disease localized to the hands and wrists that lasts for more than 3 months or relapses at least twice per year. The diagnosis, treatment, and management of CHE presents clinical challenges owing to its multifactorial etiology, heterogeneous presentation, and the absence of a standardized classification system. In the USA there are no specific International Classification of Disease-10 (ICD-10) diagnostic codes, which makes tracking the diagnosis and resultant treatments difficult. Topical delgocitinib is currently the only Food and Drug Administration approved medication for CHE, for patients who have not responded adequately to, or are unable to use, topical corticosteroids. This article provides an overview of the diagnostic and therapeutic considerations of CHE, while presenting practical recommendations to help improve management of the disease within the USA. Diagnostic assessments focusing on detailed patient history and physical examination are proposed, followed by a multi-step approach to treatment. The importance of both clinician, and patient, reported outcome measures are emphasized, to encompass not only disease presentation and severity, but also the impact on patient quality of life.

BACKGROUND:While many adults diagnosed with atopic dermatitis (AD) achieve disease control with standard treatments, a subset of patients remains refractory to optimal management. In these cases, misdiagnosis or the presence of concomitant conditions may be contributing to treatment failure. OBJECTIVE:To provide evidence-informed guidance for the diagnostic workup of presumed adult AD unresponsive to optimized treatment. METHODS:An expert multidisciplinary workgroup applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for issuing guidance on approaching suspected AD refractory to treatment by reviewing the indirect evidence, assessing the balance of benefits and harms, and reaching consensus. RESULTS:The workgroup developed a Good Practice Statement on the diagnostic workup of adults with presumed AD unresponsive to therapy. LIMITATIONS:This guidance is based on indirect evidence and expert consensus, as direct empirical data on diagnostic workup strategies for treatment-resistant AD are lacking. Applicability may vary depending on access to dermatologic and allergy specialist care. CONCLUSION:The Good Practice Statement supports consideration of diagnostic reassessment in cases of presumed AD in adults not responding to optimized treatment.

BackgroundAtopic dermatitis (AD) is a chronic inflammatory disease significantly impacting patients' quality of life (QoL). While multiple outcome measures exist, a critical gap remains in establishing treatment goals that meaningfully connect improvements in clinician-reported outcome measures (ClinROMs) with patient-reported outcome measures (PROMs).ObjectiveTo determine the Eczema Area and Severity Index (EASI) threshold that best corresponds with clinically meaningful and optimal treatment responses in PROMs, linking ClinROMs and PROMs.MethodsLIBERTY AD CHRONOS, a randomized controlled trial, included adult patients treated with dupilumab 300 mg every 2 weeks plus topical corticosteroids. In this post-hoc analysis of the trial, repeated-measures regression analysis was used to quantify the relationship between EASI and improvements in PROMs.ResultsMost clinically meaningful responses in PROMs were associated with 50-75% EASI improvement from baseline with the greatest impact on achieving clinically meaningful and optimal PROM responses when transitioning from EASI-50 to EASI-75 and minimal additional benefit when transitioning from EASI-75 to EASI-90 and EASI-90 to EASI-100. Two PROM composite end points, encompassing treatment responses in symptoms and QoL, confirmed these findings.ConclusionsThis analysis bridges clinician-reported EASI with PROMs, demonstrating that EASI-75 aligns closely with clinically meaningful and optimal treatment responses from the patient perspective, providing a treatment goal that is both meaningful to patients and visually quantifiable for physicians in moderate-to-severe AD [Graphical abstract available online].Clinicaltrials.gov IdentifierNCT02260986 (registered October 06, 2014).

This is a summary of the original article “Apremilast improves skin outcomes in pediatric plaque psoriasis of shorter disease duration: 52-week results from the SPROUT phase 3 trial”. Enrolled patients were aged 6–17 years with moderate to severe plaque psoriasis (PsO) inadequately controlled by, or inappropriate for, topical therapy (NCT03701763). Patients were randomized to apremilast or placebo for 16 weeks, after which all patients transitioned to apremilast through 52 weeks. The efficacy of apremilast was assessed by disease duration at baseline (shorter, < 2 years; medium, ≥ 2 to < 5 years; longer, ≥ 5 years). In this post hoc analysis, patients had generally similar baseline characteristics across disease durations. At week 16, patients receiving apremilast vs placebo experienced numerically greater improvements in most skin clearance outcomes across all disease durations, particularly in patients with disease duration < 2 years. Through week 52, patients experienced numerical improvements across all disease durations, with the most pronounced efficacy in patients with disease duration < 5 years. These findings suggest early intervention with a systemic therapy such as apremilast in pediatric patients with moderate to severe PsO may mitigate disease burden.

BACKGROUND:INTEGUMENT-PED/NCT04845620, a 4-week, phase 3 trial, demonstrated efficacy and safety of roflumilast cream 0.05% in children aged 2-5 years with mild-to-moderate atopic dermatitis (AD). A phase 3 open-label extension trial (INTEGUMENT-OLE [NCT04804605]) investigated long-term outcomes continuing roflumilast cream for ≤ 56 weeks. METHODS:Caregivers of eligible patients from INTEGUMENT-PED applied roflumilast cream 0.05% once-daily in INTEGUMENT-OLE. Patients achieving Validated Investigator Global Assessment for AD (vIGA-AD) clear (0) at/after week 4 of INTEGUMENT-OLE switched to twice-weekly (BIW) application. Evaluation of safety (adverse events [AEs] and application-site tolerability) was the primary objective. Efficacy endpoints assessed from INTEGUMENT-PED baseline included vIGA-AD success (clear/almost clear [0/1] plus ≥ 2-point improvement), vIGA-AD 0/1, ≥ 75% improvement in Eczema Area and Severity Index, and Worst Itch-Numeric Rating Scale success (≥ 4-point improvement in patients with baseline score ≥ 4). Duration of vIGA-AD 0/1 and sign/symptom control ("disease control") with BIW application was determined. RESULTS:Among 562 patients, 14 (2.5%) had treatment-related AEs reported. Roflumilast was well tolerated; application-site pain AEs were reported for four (0.7%) patients. At treatment-week 56, AD signs/symptoms continued to improve (63.1% of patients achieved vIGA-AD 0/1). Of 170 (30.2%) patients who switched to BIW application, the median Kaplan-Meier duration of "disease control" was 238 days. CONCLUSIONS:Roflumilast cream 0.05% demonstrated a favorable long-term safety profile and durable efficacy for up to 56 weeks of treatment in children aged 2-5 years with AD, and "disease control" was maintained with BIW application. These results are consistent with previous studies, including patients aged ≥ 6 years from INTEGUMENT-OLE. TRIAL REGISTRATION:Clinicaltrials.gov identifier: NCT04845620.

Atopic dermatitis (AD) has the highest incidence in 3-6-month-olds. Common topical prescription treatments (eg, corticosteroids, calcineurin inhibitors, and a phosphodiesterase 4 inhibitor [PDE4i; crisaborole]) have limited efficacy, adverse event (AE) concerns, and/or use restrictions. Roflumilast (ROF) cream is a highly potent PDE4i formulated without potentially irritating ingredients. Efficacy and safety of ROF cream 0.15% and 0.05% for the treatment of mild-to-moderate AD in ≥6-year-olds and 2-5-year-olds, respectively, have been demonstrated in phase 3 clinical trials. The phase 2, open-label, INTEGUMENT-INFANT/ NCT06998056 study is evaluating ROF cream 0.05% in infants aged 3 months to <2 years with AD (mild/moderate [2/3] Validated Investigator Global Assessment for AD [vIGA-AD]; ≥ 3% body surface area affected). Caregivers will apply ROF once daily for 4 weeks. Safety assessments include treatment-emergent adverse events and application-site tolerability. Efficacy assessments include vIGA-AD, Scalp-IGA, Eczema Area and Severity Index, Body Surface Area-Scalp and -Total, Worst Scratch/Itch-Numeric Rating Scale, Dynamic Pruritus Scale, and quality-of-life and family impact measures. Approximately 100 patients will be enrolled in the United States, Canada, and the Dominican Republic begining in June 2025. Outcomes from INTEGUMENT-INFANT will provide important data on the potential use of ROF cream 0.05% in infants aged 3 months to <2 years with mild to-moderate AD.

Icotrokinra, a first-in-class targeted oral peptide, precisely blocks the interleukin (IL)-23 receptor and inhibits IL-23 pathway signaling. In phase 3 studies (ICONIC-LEAD, ICONIC-TOTAL, ICONIC-ADVANCE 1 and 2), icotrokinra provided superior skin clearance versus placebo and deucravacitinib in adults and adolescents with moderate-to-severe psoriasis and psoriasis affecting high-impact sites. This analysis evaluates icotrokinra safety through 1 year using pooled data from these four studies. Icotrokinra-randomized participants received 200-mg pills once daily, and placebo-randomized participants crossed over to icotrokinra at week 16; participants randomized to deucravacitinib 6 mg (ICONIC-ADVANCE 1 and 2 only) switched to icotrokinra at week 24. Pooled safety data are summarized for the placebo-controlled period (week 0–16, all studies), active-controlled period (week 0–24, ICONIC-ADVANCE 1 and 2), and through week 52 (all studies). During the placebo-controlled period across all studies, 568 participants received placebo and 1296 received icotrokinra. From week 0 to 24 in the ICONIC-ADVANCE studies, 632 participants received icotrokinra and 634 received deucravacitinib. Through week 52, 2400 icotrokinra-treated participants contributed 1840 participant-years [PY] of follow-up. Through week 16, in the icotrokinra and placebo groups, respectively, exposure-adjusted incidence rates/100 PY of adverse events (AEs; 232 and 269), serious AEs (5.2 and 6.6), infections (91 and 104), and AEs leading to discontinuation (6.6 and 10.0) were comparable between groups. Through week 24, in the ICONIC-ADVANCE studies, rates/100 PY with icotrokinra versus deucravacitinib were as follows: AEs, 204 vs 265; serious AEs, 6.4 vs 7.2; infections, 81 vs 119; AEs leading to discontinuation, 5.7 vs 6.8. Through week 52, event rates/100 PY in icotrokinra-treated participants were as follows: AEs, 167; serious AEs, 4.6; infections, 76; AEs leading to discontinuation, 3.0. In this analysis of 2400 icotrokinra-treated participants with psoriasis followed through 1 year, icotrokinra demonstrated favorable safety; event rates through week 16 were similar to placebo and remained consistent through week 52. NCT06095115, NCT06095102, NCT06143878, NCT06220604. Infographic available for this article.

Neonatal ichthyoses/epidermal differentiation disorders (EDDs) encompass a spectrum of rare genetic scaling disorders, with manifestations that may be limited to the skin and its appendages or involve other organs. Despite the critical need for early intervention and tailored care, there are currently no standardized management guidelines for neonates with EDDs. This project addresses this gap by developing consensus guidelines to improve clinical management and patient outcomes. A group of experts was assembled to review and generate statements related to the management of neonates with hereditary EDDs. Generated statements were reviewed by pediatric dermatologists, neonatologists, caregivers of children with EDDs, and other specialists. A modified Delphi method, with consensus defined as at least 70% of respondents rating a statement as strongly agree or agree, was implemented. Statements with 30% or greater disagreement were rejected, although statements could be revised for the next review. The accepted statements address 11 areas of focus: making the diagnosis, preparing the environment, bathing and moisturization, lines and monitoring, feeding and nutritional support, pain and itch management, surveillance for infections and their management, the multidisciplinary team, family considerations during hospitalization and at discharge, considerations for neonates with keratinopathies/epidermolytic EDD, considerations for neonates with ABCA12-nEDD/harlequin ichthyosis.

Background: Atopic dermatitis (AD) may impact children’s growth, especially those treated with topical corticosteroids and immunosuppressants. Analysis of height, weight and body mass index (BMI) of children with AD compared to the general population could characterize the impact of AD on growth. Methods: Overall, 1329 children (aged <12 years) with moderate-to-severe AD were enrolled in PEDISTAD (NCT03687359); an ongoing, international, observational study. This analysis assesses the percentage of patients above 50th percentile and mean percentiles for height, weight and BMI at baseline against the CDC Learning Management System reference healthy population, by age in months. Results: Compared with age-specific population norms, in the PEDISTAD study, at baseline 50% of males were above 50th percentile for weight but only 38% were above for height. In females these figures were 51% and 52% respectively. In patients aged 5 to 12 years only 28% of males and 47% of females were above 50th percentile for height. For BMI, 69% of males and 71% of females were above 50th percentile. Overall, average across all age specific percentiles for height, weight and BMI were 46th, 51st and 58th for male; and 50th, 50th and 59th for females in this population. Conclusion: Findings suggest that moderate-to-severe AD has a negative impact on growth in children (<12 years), potentially due to sleep deprivation or long-term exposure to topical/systemic glucocorticoids and immunosuppressants.

BACKGROUND:Moderate and severe atopic dermatitis (AD) may affect bone growth and mineral density in children. OBJECTIVE:To investigate stature, height gain, and biomarker of mineralization bone alkaline phosphatase (BALP) level over time in children with AD treated with dupilumab. METHODS:Children aged 6 to 11 years with severe AD received dupilumab or placebo in a phase 3 trial for 16 weeks, followed by dupilumab in an open-label trial to week 52. Endpoints included baseline height percentile distribution, proportion of patients achieving ≥5-percentile height increase at weeks 16 and 52, and BALP level to week 52. RESULTS:Children with severe AD were overrepresented in lower height percentiles at baseline. Among dupilumab-treated children below the 40th height percentile at baseline, 31.3% achieved ≥5-percentile height increase (vs 15.5% with placebo, P < .05) at week 16, and 50.7% at week 52. BALP level, while within normal range throughout, was significantly higher with dupilumab vs placebo at week 16, with further increase to week 52. At week 52, patients who transitioned to dupilumab at week 16 attained height and BALP improvements comparable with patients receiving dupilumab throughout. LIMITATIONS:One-year duration. CONCLUSION:Dupilumab treatment in children with AD was associated with height and BALP level improvements.

As atopic dermatitis signs and symptoms wax and wane, assessing severity scores over time best captures sustained response to treatment. We report that the majority of pediatric patients (6 months to 17 years) had sustained improvements in skin lesions (Eczema Area and Severity Index ≤ 7), itch (SCORING Atopic Dermatitis pruritus Visual Analog Scale [SCORAD Pruritus VAS < 4]), and sleep loss (SCORAD sleep loss VAS < 4) over one year of treatment with dupilumab.

Background Pediatric atopic dermatitis (AD) is a common, chronic inflammatory skin disorder that significantly impacts the quality of life of affected children and their families. In addition to skin-related symptoms, AD in pediatric patients may be associated with a range of comorbid conditions. Objective To provide evidence-based recommendations on primary prevention of AD and to appraise evidence of the association between AD and comorbidities among pediatric patients. Methods A multidisciplinary workgroup conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. Results The workgroup developed 14 evidence-based recommendations on primary prevention of AD and 29 statements on the association between pediatric AD and comorbid conditions. Limitations This analysis is based on the best available evidence at the time it was conducted. This guideline does not make recommendations for screening or management of comorbidities in children with AD. Conclusions We make a conditional recommendation for moisturizing skin care to reduce the occurrence of AD and conditional recommendations against early food introduction, human milk consumption, and probiotic or vitamin D supplementation for the primary prevention of AD. Clinicians should be aware of comorbidities associated with pediatric AD, but further research is needed to optimize screening and/or management of comorbidities.