Adelaide Ann Hebert

Dermatologists play a central role in the diagnosis and medical management of vascular anomalies. Currently, vascular anomalies are categorized into vascular tumors and vascular malformations. The latest designations for the numerous types of vascular lesions are delineated in the International Society for the Study of Vascular Anomalies website ( www.issva.org ). The arenas for the therapy for hemangiomas, the most common vascular tumor, have been studied extensively and have been recognized as standard of care by the Society for Pediatric Dermatology, the American Academy of Dermatology and the American Academy of Pediatrics. Options for hemangioma treatment include systemic beta‐blockers such as propranolol, atenolol, and nadolol, and the topical beta‐blocker timolol. Vascular malformations and overgrowth syndromes encompass a separate set of treatment regimens. Recent pharmacological and technological advances in the medical management of vascular anomalies have decreased the need for surgery in many patients while also leading to improved outcomes and quality of life. This review will guide the dermatologist through the current medical treatment landscape for vascular malformations.

1. Atopic dermatitis is a common skin condition that is characterized by itchiness, dryness, and inflammatory patches. Atopic dermatitis (AD) is one of the most prevalent skin conditions in childre...

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

Two 4‐week, phase 2, open‐label, maximal usage pharmacokinetic (PK) and safety studies of once‐daily roflumilast cream 0.3% (a potent phosphodiesterase 4 inhibitor) were conducted in children aged 2–5 years and 6–11 years with psoriasis. Evidence of systemic exposure to roflumilast and its active N‐oxide metabolite was seen in most patients following daily application, consistent with previous studies. Under maximal use conditions, once‐daily roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis in children aged 2–11 years, consistent with phase 3 results in adults and adolescents. Trial Registration: Clinicaltrials.gov listing: 215: NCT04655313; 216: NCT04746911.

Purpose: Provide insights into the incidence, pre-sentation and management of follicular events and contact dermatitis in patients with plaque psoriasis or atopic dermatitis (AD) treated with tapinarof cream 1%. Materials and methods: Key clinical trial publications for tapinarof were reviewed and augmented with the authors' opinions based on real-world clinical experience. Results: In the PSOARING and ADORING trials, discontinuation rates due to follicular events and contact dermatitis were low and most patients did not require dose modifications or treatment interruptions. In our experience, which includes the use of tapinarof in combination with other agents, tapinarof is generally well tolerated and if events of folliculitis or contact dermatitis occur, patients can be advised to temporarily discontinue application on affected sites until the event resolves, continuing application to other affected areas and body regions. Education on the correct application of tapinarof is important in the management of psoriasis and AD. Conclusions: Tapinarof is a novel topical treatment option for adults with plaque psoriasis and patients with AD, with no restrictions regarding application sites and duration of use. Follicular events and contact dermatitis associated with tapinarof treatment are generally mild and self-limiting and rarely interfere with therapy. Clinicaltrials.gov numbers: NCT05014568, NCT05032859, NCT05142774, NCT03956355, NCT03983980, NCT04053387.

Background Tapinarof cream 1% is an aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration to treat atopic dermatitis (AD) in patients down to age 2 years. Objective The aim of this study was to evaluate the safety and pharmacokinetics of tapinarof cream 1% once daily (QD) in adolescents and children with extensive AD under maximal usage conditions. Methods Patients with a validated Investigator Global Assessment scale for Atopic Dermatitis™ (vIGA-AD™) score ≥ 3 and body surface area (BSA) involvement ≥ 25% (ages 12–17 years) or ≥ 35% (ages 2–11 years) were enrolled into three age cohorts (2–6, 7–11, and 12–17 years) and received tapinarof cream 1% QD for 4 weeks. Results Overall, 36 patients (12 per cohort) were enrolled; mean BSA affected was 42.8% (range 26.0–90.0) and mean Eczema Area and Severity Index (EASI) score was 23.8. At baseline, 28 patients (77.8%) had a vIGA-AD™ score of 3 (moderate). No-to-minimal tapinarof systemic exposure was observed (25% of post-treatment plasma samples were below the quantifiable limit of a highly sensitive assay [< 50 pg/mL]). Mean maximum plasma concentration (C_max) was 2.44 ng/mL, and median time to C_max was 2.9 h. Eight patients (22.2%) reported treatment-emergent adverse events (TEAEs), which were mild or moderate; only one patient discontinued due to two unrelated TEAEs. One case of mild folliculitis and no contact dermatitis occurred. Tapinarof was well tolerated, including on sensitive skin and extensor/flexural surfaces. Conclusion Tapinarof cream exhibits highly favorable safety and pharmacokinetics in adolescents and children down to age 2 years with extensive AD. Trial Registration ClinicalTrials.gov: NCT05186805.