Search

Background: Patients with atopic dermatitis (AD) have systemic biomarker dysregulation that differs by age group; however, the proteomic characteristics of these age-based changes are unknown., Objective: To profile blood proteins of patients with AD across different age groups versus age-appropriate controls., Methods: Using the Olink high-throughput proteomic platform, we profiled 375 serum proteins of 20 infants (age, 0-5 years), 39 children (age, 6-11 years), 21 adolescents (age, 12-17 years), and 20 adults (age, ≥18 years) with moderate-to-severe AD and 83 age-appropriate controls., Results: Each group presented a distinct systemic proteomic signature. Th2-related proteins were increased in infant AD and further intensified with age through adolescence and adulthood (interleukin 4/CCL13/CCL17). In contrast, Th1 axis down-regulation was detected in infants with AD and gradually reversed to increased Th1 products (interferon γ/CXCL9/CXCL10/CCL2) in patients with AD from childhood to adulthood. Despite their short disease duration, infants already had evidence of systemic inflammation, with significant upregulation of innate immunity (interleukin 17C/ interleukin-1RN), T-cell activation/migration (CCL19), Th2 (CCL13/CCL17), and Th17 (PI3) proteins. Adults with AD present unique upregulation of cardiovascular proteins related to coagulation and diabetes., Limitations: Cross-sectional observational study with a single time point., Conclusion: Systemic immune signatures of AD are age-specific beyond the shared Th2 immune activation. These data advocate for precision medicine approaches based on age-specific AD profiles., Competing Interests: Conflicts of interest Dr Guttman-Yassky is an employee of Mount Sinai; has received research funds (grants paid to the institution) from AbbVie, Celgene, Eli Lilly, Janssen, Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB; and is a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. Dr Krueger has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. Dr Paller has received research funds (grants paid to the institution) from AbbVie, AnaptysBio, Eli Lilly, Incyte, Janssen, KrystalBio, Regeneron, and UCB and is a consultant for AbbVie, Abeona, Acrotech, Almirall, Amgen, Amryt, Arcutis, Arena, Azitra, BioCryst, BiomX, Bridgebio, Bristol Myers Squibb, Castle Biosciences, Catawba, Eli Lilly, Exicure, Galderma, Kamari, Leo, Novan, Novartis, OM Pharma, Pfizer, Pierre Fabre, RAPT, Regeneron, Sanofi/Genzyme, Seanergy, and UCB. Dr Rangel has received research funds (grants paid to the institution) from AbbVie, DermTech, and Galderma. Drs Del Duca, Renert-Yuval, Pavel, Wu, Lefferdink, Fang, and Facheris and authors Mikhaylov, Sheth, Blumstein, and Estrada have no conflicts of interest to disclose., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest None disclosed.

Competing Interests: Conflicts of interest Dr Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi-Genzyme. Dr Paller has been an investigator for Regeneron and is a consultant for Regeneron and Sanofi-Genzyme. Authors Rangel, Sheth, and Blumstein have no conflicts of interest.

Background: The distribution of pediatric-onset morphea and site-based likelihood for extracutaneous complications has not been well characterized., Objective: To characterize the lesional distribution of pediatric-onset morphea and to determine the sites with the highest association of extracutaneous manifestations., Methods: A retrospective cross-sectional study was performed. Using clinical photographs, morphea lesions were mapped onto body diagrams using customized software., Results: A total of 823 patients with 2522 lesions were included. Lesions were more frequent on the superior (vs inferior) anterior aspect of the head and extensor (vs flexor) extremities. Linear morphea lesions were more likely on the head and neck, whereas plaque and generalized morphea lesions were more likely on the trunk. Musculoskeletal complications were more likely with lesions on the extensor (vs flexor) extremity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.4), whereas neurologic manifestations were more likely with lesions on the anterior (vs posterior) (OR, 2.8; 95% CI, 1.7-4.6) and superior (vs inferior) aspect of the head (OR, 2.3; 95% CI, 1.6-3.4)., Limitations: Retrospective nature and the inclusion of only patients with clinical photographs., Conclusion: The distribution of pediatric-onset morphea is not random and varies with body site and within individual body sites. The risk stratification of extracutaneous manifestations by body site may inform decisions about screening for extracutaneous manifestations, although prospective studies are needed., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Accurately documenting pediatric atopic dermatitis (AD) severity is important, but research tools, such as Eczema Area and Severity Index (EASI), are too time consuming for clinical settings. Product of the Physician Global Assessment and affected percentage of body surface area (PGA×BSA) is a new, rapid measure of psoriasis severity., Objective: To evaluate an Investigator Global Assessment and body surface area product (IGA×BSA) as an easy-to-use severity measure for pediatric AD., Methods: Patient-reported and objective disease severity measures were collected from 195 caretaker/child dyads (child age range, 5-17 years) with almost clear (Validated Investigator Global Assessment for AD [vIGA] of 1) to severe (vIGA of 4) AD. Data were assessed with Spearman coefficients and plots. Severity strata were proposed by using an anchoring approach based on the EASI., Results: IGA×BSA correlates better with the EASI than IGA alone (r = 0.924 vs r = 0.757, P < .001). Bland-Altman plot indicates high and consistent agreement between IGA×BSA and the EASI. Suggested severity strata for IGA×BSA are 0-30, mild; 30.1-130, moderate; and 130.1-400, severe (κ = 0.760)., Limitations: The patient cohort was predominantly from the midwestern United States., Conclusions: IGA×BSA (using the vIGA) is a simple measure that correlates well with the EASI in patients with mild to severe pediatric AD. Future work is needed to affirm reliability across IGA scales and responsiveness to change., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD., Objective: To analyze blood inflammatory proteins of early pediatric AD., Methods: Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD., Results: In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11)., Limitations: Different baseline expression levels in healthy pediatric vs adult samples., Conclusions: Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers., (Copyright © 2019. Published by Elsevier Inc.)