Faculty Bibliography

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. Multiple therapies were approved to treat AD in children and adolescents since publication of the AAD's 2014 AD guidelines. OBJECTIVE:To provide evidence-based recommendations on the use of topical therapies, phototherapy, and systemic therapies for AD in children and adolescents. METHODS:A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS:The workgroup developed 27 evidence-based recommendations on the medical management of pediatric AD. LIMITATIONS:This analysis is based on the best available evidence at the time it was conducted. Most randomized controlled trials of therapies for AD are of short duration limiting long-term efficacy and safety conclusions. CONCLUSIONS:We make strong recommendations for the use of moisturizers, topical calcineurin inhibitors, topical corticosteroids, crisaborole ointment, roflumilast cream, ruxolitinib cream, tapinarof cream, dupilumab, tralokinumab, lebrikizumab, nemolizumab with concomitant topical therapy, upadacitinib, abrocitinib, and baricitinib in the treatment of pediatric AD. We make conditional recommendations in favor of bathing, bleach baths, wet dressings, phototherapy, methotrexate, mycophenolate mofetil, azathioprine, and cyclosporine. We conditionally recommend against the use of topical antimicrobials, PUVA phototherapy, and strongly recommend against systemic corticosteroids.

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.

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.

INTRODUCTION/BACKGROUND:A matching-adjusted indirect comparison (MAIC) was performed comparing the efficacy of delgocitinib and dupilumab in patients with atopic hand eczema (AHE), one aetiological subtype of chronic hand eczema (CHE). METHODS:DELTA 1/2 were phase 3 trials in which adults with moderate to severe CHE received delgocitinib cream 20 mg/g or cream vehicle twice daily for 16 weeks. LIBERTY-AD-HAFT was a phase 3 trial in which patients with moderate to severe AD with hand or foot involvement received subcutaneous dupilumab or placebo every 2 weeks for 16 weeks. An anchored MAIC was conducted using individual patient data (IPD) from DELTA 1/2 and aggregate published data from LIBERTY-AD-HAFT, with vehicle and placebo as the common anchor. IPD from patients with AHE as the primary subtype in DELTA 1/2 were weighted to match age, race, sex and baseline Hand Eczema Severity Index (HECSI) score in LIBERTY-AD-HAFT. RESULTS:LIBERTY-AD-HAFT included 133 patients (dupilumab, n = 67, placebo, n = 66) while DELTA 1/2 included 345 patients with AHE; the effective sample size after weighted matching was 201 (delgocitinib, n = 128, cream vehicle, n = 73). Anchor-adjusted odds ratios comparing delgocitinib versus dupilumab at week 16 were 1.1 (95% CI: 0.3, 3.4; p = 0.890) for Investigator's Global Assessment for Chronic Hand Eczema / Hand and Foot Investigator's Global Assessment score 0/1, 1.2 (95% CI: 0.4, 3.2; p = 0.773) for HECSI 75 and 1.3 (95% CI: 0.4, 4.9; p = 0.661) for HECSI 90 while response difference for HECSI percent improvement was 11.7% (95% CI: -9.2%, 32.7%; p = 0.273). CONCLUSIONS:Topical delgocitinib and dupilumab in patients with AHE had comparable efficacy, with all results being numerically in favour of delgocitinib, although not statistically significant. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT04871711, NCT04872101, NCT04417894.

Contact dermatitis (CD) is a common and burdensome condition divided into irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Treatment relies on accurate diagnosis and identification of the trigger, as definitive treatment is irritant/allergen avoidance. However, avoidance is not always possible, such as if the patient is reacting to a necessary medical device, if the trigger is integral to the patient's occupation, or if avoidance is practically untenable. In these cases, treatment is particularly challenging, especially as the literature on treatments in this clinical scenario is limited. Additionally, CD has a complex pathophysiology that varies according to trigger type, leading to variable treatment efficacy. This article reviews the current literature on treatments for CD with a focus on treatments when trigger avoidance is not feasible.

IMPORTANCE/UNASSIGNED:Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. OBJECTIVE/UNASSIGNED:To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. EVIDENCE REVIEW/UNASSIGNED:A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. FINDINGS/UNASSIGNED:The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.