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Atopic dermatitis (AD) is a complex and heterogeneous skin disease for which achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role in AD, aiming to advance our understanding of the diverse molecular profiles implicated. Although traditionally characterized as a T H 2-driven disease, extensive research has recently revealed the involvement of T H 1, T H 17, and T H 22 immune pathways as well as the interplay of pivotal immune molecules, such as OX40, OX40 ligand (OX40L), thymic stromal lymphopoietin, and IL-33. This review explores the mechanistic effects of treatments for AD, focusing on mAbs and Janus kinase inhibitors. It describes how these treatments modulate immune pathways and examines their impact on key inflammatory and barrier biomarkers., Competing Interests: Disclosure statement Disclosure of potential conflict of interest: E. Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from AbbVie, Almirall, AnaptysBio, Boehringer-Ingelheim, Celgene, Dermavant, DS Biopharma, Eli Lilly, Innovaderm, Janssen, Kiniska, KyowaKirin, Novan, Pfizer, Regeneron, Ralexar, Glenmark, Galderma, Asana, Innovaderm, Leo Pharma, Sienna Biopharm, Union Therapeutics, and UCB; and is a consultant for Sanofi Aventis, Regeneron, Cara Therapeutics, Celgene, Concert, Amgen, Boehringer-Ingelheim, DBV, Dermira, DS Biopharma, EMD Serono, Escalier, Flx Bio, Galderma, Glenmark, Incyte, Kyowa Kirin, Novartis, Pfizer, Leo Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, Sienna Biopharm, and Union Therapeutics. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Vitiligo is a dermatological autoimmune condition characterized by areas of progressive skin depigmentation. Vitiligo lesions are cosmetically disfiguring and associated with significant psychological conditions such as depression and anxiety and comorbidities such as thyroid disease and diabetes. All races, ethnicities, ages, and regions of the world are impacted by vitiligo, with a global prevalence of about 0.5-2%. Currently, there is no published information available on the prevalence of vitiligo in Puerto Rico. Our study's aim was to estimate the prevalence of vitiligo among patients attending the specialized clinic of dermatology at UPR School of Medicine in Puerto Rico and describe the distribution of cases by age and sex., Methods: We performed a descriptive study to evaluate the patients attending the University of Puerto Rico School of Medicine Clinics from January 2017 to May 2022. Using ICD-10 code L80 and medical records, we identified 581 patients with vitiligo and their respective demographic data distributed by sex and age., Results: Of the 581 vitiligo patients, 350 (60.2%) were women, and 231 (39.8%) were men. The median age in the vitiligo population was 33.5 years. Out of the studied sample, 30.2% were under the age of 18. Overall, there was an estimated prevalence of 5.2%., Conclusion: We report a vitiligo prevalence of 5.2% in a specialized clinic in Puerto Rico, suggesting further studies are necessary to discover possible underlying factors contributing to this increased prevalence.

Introduction: Atopic Dermatitis (AD) is the most common inflammatory skin disease with a complex and multifactorial pathogenesis. The use of proteomics in understanding AD has yielded the discovery of novel biomarkers and may further expand therapeutic options., Areas Covered: This review summarizes the most recent proteomic studies and the methodologies used in AD. It describes novel biomarkers that may monitor disease course and therapeutic response. The review also highlights skin and blood biomarkers characterizing different AD phenotypes and differentiates AD from other inflammatory skin disorders. A literature search was conducted by querying Scopus, Google Scholar, Pubmed/Medline, and Clinicaltrials.gov up to June 2023., Expert Opinion: The integration of proteomics into research efforts in atopic dermatitis has broadened our understanding of the molecular profile of AD through the discovery of new biomarkers. In addition, proteomics may contribute to the development of targeted treatments ultimately improving personalized medicine. An increasing number of studies are utilizing proteomics to explore this heterogeneous disease.

Atopic dermatitis (AD) is a heterogeneous immune-mediated skin disorder affecting people of all ages and ethnicities. Despite the development of targeted therapeutics such as biologics and Janus kinase inhibitors, attaining complete clinical efficacy remains difficult. This therapeutic challenge may be attributed to the complex pathogenesis of AD. Although the T H 2 axis has been extensively studied, recent advancements have started to reveal the involvement of additional immune pathways including T H 1, T H 17, and T H 22. Understanding the interplay of these immune axes may contribute to a more personalized therapeutic approach based on patients' molecular profile, with the prospect of improving clinical outcome. This review will discuss studies exploring the molecular profile of AD in both skin and blood across age, ethnicity/race, disease chronicity, IgE levels, filaggrin mutation status, and AD association with other atopic conditions. Moreover, it will explore the potential of personalized treatment strategies based on a patient's distinct immune signature., Competing Interests: Disclosures Dr Guttman-Yassky has served as a consultant to AbbVie, Almirall, Amgen, Aslan Pharmaceuticals, AstraZeneca, Biolojic Design, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Connect Pharma, DBV Technologies, Eli Lilly, EMD Serono, Evidera, Galderma, Gate Bio, Genentech, Incyte, Inmagene, Janssen Biotech, Kyowa Kirin, Leo Pharma, Merck, Pfizer, Q32 Bio, RAPT, Regeneron, Sanofi, SATO, Siolta, Target, UCB, and Ventyx; and has had research grants paid to her institution from the following: Boehringer-Ingelheim, Leo Pharma, Pfizer, Cara Therapeutics, UCB, Kyowa Kirin, RAPT, Amgen, GlaxoSmithKline, Incyte, Sanofi, Bristol-Myers Squibb, Aslan, Regeneron, Anaptysbio, Concert, and Janssen. All other authors disclose no conflict of interest., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Pruritus is the most common and burdensome symptom of atopic dermatitis (AD). Pruritus-targeted treatments in AD are lacking, particularly for patients with milder skin disease., Objective: We sought to evaluate the impact of the selective κ-opioid receptor agonist difelikefalin (DFK) on pruritus intensity and pruritus- and immune-related biomarkers in subjects with moderate to severe AD-related pruritus., Methods: A phase 2 clinical trial investigated the efficacy and safety of oral DFK 0.25, 0.5, and 1.0 mg in subjects with moderate to severe AD-related pruritus. A biomarker substudy evaluated the effects of DFK on the expression of pruritus, T H 2-associated genes, and skin barrier-related genes., Results: In the clinical trial (N = 401), all DFK doses reduced itch versus placebo; however, the results were not statistically significant at week 12. In a subgroup of subjects in the trial with mild to moderate skin inflammation and moderate to severe itch (itch-dominant AD phenotype), DFK reduced itch at week 12 versus placebo. In the biomarker substudy, DFK downregulated the expression of key pruritus-related genes (eg, IL-31 and TRPV1) and the AD phenotype (eg, CCL17). Gene set variation analysis confirmed that DFK, but not placebo, downregulated pruritus-related genes and T H 2 pathways. DFK improved skin barrier integrity markers and upregulated the expression of claudins and lipid metabolism-associated genes (eg, SEC14L6, ELOVL3, CYP1A2, and AKR1D1)., Conclusions: DFK treatment reduced itch in subjects with moderate to severe AD-related pruritus, particularly those with an "itch-dominant" AD phenotype, and had an impact on the expression of pruritus, T H 2-associated genes, and skin barrier-related genes. DFK is a promising therapy for AD-related pruritus; further clinical studies are warranted., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted-therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD., Methods: We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT-PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile., Results: Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL-36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p-value < .05). In contrast, higher Th1-(IFN-γ, IL-2, IL-15, CCL5) upregulation and Th1-skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro-inflammatory and cardiovascular-risk markers. Th1-related products showed significant correlations between their skin and blood expressions only in AOAD subjects., Conclusion: Age-of-onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient-reported disease severity and quality of life (QoL)., Methods: A cross-sectional analysis was conducted using a September 2021 data cut from the TARGET-DERM AD study, a real-world, longitudinal cohort of children, adolescents, and adults with AD enrolled at 44 academic and community dermatology and allergy sites in the US. Clinical AD severity was measured using vIGA-AD while disease severity and QoL were assessed by the Patient Oriented Eczema Measure (POEM) and (Children’s) Dermatology Life Quality Index (C/DLQI), respectively. Patient characteristics, clinical- and patient reported-outcomes were assessed by stratified POEM and C/DLQI categories using descriptive statistics. Associations with vIGA-AD were evaluated using unadjusted and adjusted ordinal logistic regression and linear regression models., Results: The analysis cohort (n=1,888) primarily consisted of adults (57%), females (56%), and patients with private insurance (63%). Unadjusted analyses suggest that clinical AD severity was associated with age, with more adolescents and adults having moderate/severe vIGA-AD than pediatric patients. Clinical AD severity was also associated with disease severity, with greater POEM scores observed at greater vIGA-AD severity levels (r = 0.496 and 0.45 for adults and pediatrics, respectively). Clinical AD severity and QoL were positively correlated, with greater CDLQI/DLQI scores at greater vIGA-AD severity levels (r = 0.458 and 0.334 for DLQI and CDLQI, respectively). After adjusting for demographics and other risk factors, vIGA-AD continued to show significant associations with POEM and DLQI/CDLQI. Compared to patients with clear/almost clear disease, adults and pediatrics with moderate-to-severe AD were 8.19 and 5.78 times as likely to be in a more severe POEM category, respectively. Similarly, compared to patients with clear/almost clear disease, adults and pediatrics with moderate/severe AD were 6.69 and 3.74 times as likely to be in a more severe DLQI/CDLQI category. Adjusted linear regression analyses of DLQI in adults showed significant differences by vIGA-AD level, with mild AD and moderate/severe AD associated with a 2.26-point and 5.42-point greater DLQI relative to clear/almost clear AD., Conclusions: In this real-world study of patients with AD, greater clinician-reported disease severity is positively correlated with higher patient-reported disease severity and lower QoL. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7473 Access Supplementary Material here Citation: Guttman-Yassky E, Bar J, Rothenberg Lausell C, et al. Do atopic dermatitis patient-reported outcomes correlate with validated investigator global assessment? Insights from TARGET-AD registry. J Drugs Dermatol. 2023;22(4):344-355. doi:10.36849/JDD.7473.