Phenotypic and Endotypic Determinants of Atopic Dermatitis Severity From the Atopic Dermatitis Research Network (ADRN) Registry

Eric L. Simpson; Anna De Benedetto; Mark Boguniewicz; Peck Y. Ong; Stephanie Lussier; Miguel Villarreal; Lynda C. Schneider; Amy S. Paller; Emma Guttman-Yassky; Jon M. Hanifin; Jonathan M. Spergel; Kathleen C. Barnes; Gloria David; Briahnna Austin; Donald Y.M. Leung; Lisa A. Beck

doi:10.1016/j.jaip.2023.04.052

Phenotypic and Endotypic Determinants of Atopic Dermatitis Severity From the Atopic Dermatitis Research Network (ADRN) Registry

Eric L. Simpson, Anna De Benedetto, Mark Boguniewicz, Peck Y. Ong, Stephanie Lussier, Miguel Villarreal, Lynda C. Schneider, Amy S. Paller, Emma Guttman-Yassky, Jon M. Hanifin, Jonathan M. Spergel, Kathleen C. Barnes, Gloria David, Briahnna Austin, Donald Y.M. Leung, Lisa A. Beck^*

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype. Objective: This study aimed to identify historical and clinical features and biomarkers associated with AD severity. Methods: A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity. Results: Participants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001). Conclusions: In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.

Original language	English (US)
Pages (from-to)	2504-2515
Number of pages	12
Journal	Journal of Allergy and Clinical Immunology: In Practice
Volume	11
Issue number	8
DOIs	https://doi.org/10.1016/j.jaip.2023.04.052
State	Published - Aug 2023

Funding

Conflicts of interest: A. De Benedetto is a consultant for dMed Biopharmaceutical Co, Ltd and has received grant or clinical trial support from Dermira , Kiniksa , Novartis , and Pfizer . E. L. Simpson is a consultant for AbbVie, Amgen, Arena Pharmaceuticals, Aslan Pharma, Boston Consulting Group, Collective Acumen, LLC (CA), Dermira, Eli Lilly, Evidera, Excerpta Medica, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin Pharmaceutical Development, Leo Pharm, Medscape LLC, Merck, Pfizer, Physicians World LLC, Regeneron, Roivant, Sanofi-Genzyme, Trevi therapeutics, Valeant, and WebMD; and an investigator for AbbVie, Amgen, Arcutis, Aslan, Castle Biosciences, Corevita, Dermavant, Dermira, Eli Lilly, Incyte, Kyowa Hakko Kirin, Leo Pharmaceuticals, Merck, Novartis, Pfizer, Regeneron, Sanofi, TARGET-DERM, Tioga, and Vanda. M. Boguniewicz is an investigator for Regeneron and Incyte, and a consultant for Regeneron, Sanofi-Genzyme, Abbvie, Leo, Lilly, Pfizer, and Janssen. P. Y. Ong is a consultant for Incyte, Abbvie, and Janssen, and an investigator for Regeneron, Sanofi Genzyme, Leo, and Incyte. L. C. Schneider is an investigator for Regeneron (dupilumab) and DBV Technologies (Viaskin peanut patch), has received grants from Genentech and Pfizer , and serves on advisory boards for FARE, Ukko, Amagma, DBV Technologies, Alladapt, Immunotherapeutics, Leo Pharmaceuticals, and Biothea Therapeutics. A. S. Paller is an investigator for AbbVie, AnaptysBio, Dermavant, Eli Lilly, Incyte, and Janssen; consultant with honorarium for Abbvie, Acrotech, Almirall, Arcutis, Azitra, BiomX, Boeringer Ingelheim, Botanix, Bristol Myers Squibb, Catawba, Eli Lilly, Gilead, Incyte, Janssen, Leo, Novartis, Pfizer, RAPT, Regeneron, Sanofi/Genzyme, Seanergy, and Union; and serves on the data safety monitoring board for AbbVie, Bausch, and Galderma. E. Guttman-Yassky is an employee of Mount Sinai; has received research funds (grants paid to the institution) from Abbvie , Almirall , Amgen , AnaptysBio, Asana Biosciences, AstraZeneca , Boehringer-Ingelheim, Celgene , Dermavant, DS Biopharma, Eli Lilly, Galderma , Glenmark/Ichnos Sciences, Innovaderm, Janssen, Kiniksa , Kyowa Kirin , Leo Pharma, Novan, Novartis , Pfizer , Ralexar, Regeneron Pharmaceuticals , Inc, Sienna Biopharma, UCB, and Union Therapeutics/Antibiotx; and is a consultant for Abbvie , Aditum Bio, Almirall, Alpine, Amgen , Arena, Asana Biosciences, AstraZeneca , Bluefin Biomedicine, Boehringer-Ingelheim, Boston Pharmaceuticals, Botanix, Bristol-Meyers Squibb, Cara Therapeutics, Celgene , Clinical Outcome Solutions, DBV, Dermavant, Dermira , Douglas Pharmaceutical, DS Biopharma, Eli Lilly, EMD Serono, Evelo Bioscience, Evidera, FIDE, Galderma , GSK, Haus Bioceuticals, Ichnos Sciences, Incyte, Kyowa Kirin , Larrk Bio, Leo Pharma, Medicxi, Medscape, Neuralstem, Noble Insights, Novan, Novartis , Okava Pharmaceuticals, Pandion Therapeutics, Pfizer , Principia Biopharma, RAPT Therapeutics, Realm, Regeneron Pharmaceuticals , Inc, Sanofi , SATO Pharmaceutical, Sienna Biopharma, Seanegy Dermatology, Seelos Therapeutics, Serpin Pharma, Siolta Therapeutics, Sonoma Biotherapeutics, Sun Pharma , Target PharmaSolutions and Union Therapeutics, Vanda Pharmaceuticals , Ventyx Biosciences, and Vimalan. J. M. Spergel has received grant support from Regeneron , Sanofi , Novartis , FARE, and NIH; and has consultant agreement with Regeneron , Sanofi , Novartis , and Leo Pharma. K. C. Barnes receives royalties from UpToDate. D.Y.M. Leung is a consultant for AbbVie Pharma, Amagma Therapeutics, Incyte, Boehringer Ingelheim, Evomune, Genentech, Leo, Sanofi-Genzyme, and Zoetis. L. A. Beck is a consultant for Allakos, Arena Pharmaceuticals, DermTech, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Numab Therapeutics, Pfizer, RAPT Therapeutics, Regeneron, Ribon Therapeutics, Sanofi/Genzyme, Sanofi-Aventis, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics, and Xencor; is a DMC member for Novartis; and is an investigator for Abbvie, AstraZeneca, DermTech, Kiniksa, Pfizer, Regeneron, Ribon Therapeutics, and Sanofi. The rest of the authors declare that they have no relevant conflicts of interest. This work was supported by the National Institutes of Health (NIAID Funding Mechanism: HHSN272201000020C [DYML], HHSN272201000017C, UL1TR002369, U01AI152011, and U19AI117673 [LAB]).

Keywords

Allergen sensitization
Atopic dermatitis
Biomarkers
Comorbidity
Disease severity
Endotype
Infection
Rajka-Langeland score
Registry
Staphylococcus aureus

ASJC Scopus subject areas

Immunology and Allergy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jaip.2023.04.052

Cite this

Simpson, E. L., De Benedetto, A., Boguniewicz, M., Ong, P. Y., Lussier, S., Villarreal, M., Schneider, L. C., Paller, A. S., Guttman-Yassky, E., Hanifin, J. M., Spergel, J. M., Barnes, K. C., David, G., Austin, B., Leung, D. Y. M., & Beck, L. A. (2023). Phenotypic and Endotypic Determinants of Atopic Dermatitis Severity From the Atopic Dermatitis Research Network (ADRN) Registry. Journal of Allergy and Clinical Immunology: In Practice, 11(8), 2504-2515. https://doi.org/10.1016/j.jaip.2023.04.052

@article{03656628c2a7477a854b711e19caf58d,

title = "Phenotypic and Endotypic Determinants of Atopic Dermatitis Severity From the Atopic Dermatitis Research Network (ADRN) Registry",

abstract = "Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype. Objective: This study aimed to identify historical and clinical features and biomarkers associated with AD severity. Methods: A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity. Results: Participants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001). Conclusions: In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.",

keywords = "Allergen sensitization, Atopic dermatitis, Biomarkers, Comorbidity, Disease severity, Endotype, Infection, Rajka-Langeland score, Registry, Staphylococcus aureus",

author = "Simpson, {Eric L.} and {De Benedetto}, Anna and Mark Boguniewicz and Ong, {Peck Y.} and Stephanie Lussier and Miguel Villarreal and Schneider, {Lynda C.} and Paller, {Amy S.} and Emma Guttman-Yassky and Hanifin, {Jon M.} and Spergel, {Jonathan M.} and Barnes, {Kathleen C.} and Gloria David and Briahnna Austin and Leung, {Donald Y.M.} and Beck, {Lisa A.}",

note = "Publisher Copyright: {\textcopyright} 2023 American Academy of Allergy, Asthma & Immunology",

year = "2023",

month = aug,

doi = "10.1016/j.jaip.2023.04.052",

language = "English (US)",

volume = "11",

pages = "2504--2515",

journal = "Journal of Allergy and Clinical Immunology: In Practice",

issn = "2213-2198",

publisher = "American Academy of Allergy, Asthma and Immunology",

number = "8",

}

Simpson, EL, De Benedetto, A, Boguniewicz, M, Ong, PY, Lussier, S, Villarreal, M, Schneider, LC, Paller, AS, Guttman-Yassky, E, Hanifin, JM, Spergel, JM, Barnes, KC, David, G, Austin, B, Leung, DYM & Beck, LA 2023, 'Phenotypic and Endotypic Determinants of Atopic Dermatitis Severity From the Atopic Dermatitis Research Network (ADRN) Registry', Journal of Allergy and Clinical Immunology: In Practice, vol. 11, no. 8, pp. 2504-2515. https://doi.org/10.1016/j.jaip.2023.04.052

TY - JOUR

T1 - Phenotypic and Endotypic Determinants of Atopic Dermatitis Severity From the Atopic Dermatitis Research Network (ADRN) Registry

AU - Simpson, Eric L.

AU - De Benedetto, Anna

AU - Boguniewicz, Mark

AU - Ong, Peck Y.

AU - Lussier, Stephanie

AU - Villarreal, Miguel

AU - Schneider, Lynda C.

AU - Paller, Amy S.

AU - Guttman-Yassky, Emma

AU - Hanifin, Jon M.

AU - Spergel, Jonathan M.

AU - Barnes, Kathleen C.

AU - David, Gloria

AU - Austin, Briahnna

AU - Leung, Donald Y.M.

AU - Beck, Lisa A.

PY - 2023/8

Y1 - 2023/8

N2 - Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype. Objective: This study aimed to identify historical and clinical features and biomarkers associated with AD severity. Methods: A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity. Results: Participants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001). Conclusions: In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.

AB - Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype. Objective: This study aimed to identify historical and clinical features and biomarkers associated with AD severity. Methods: A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity. Results: Participants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001). Conclusions: In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.

KW - Allergen sensitization

KW - Atopic dermatitis

KW - Biomarkers

KW - Comorbidity

KW - Disease severity

KW - Endotype

KW - Infection

KW - Rajka-Langeland score

KW - Registry

KW - Staphylococcus aureus

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SN - 2213-2198

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JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

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Phenotypic and Endotypic Determinants of Atopic Dermatitis Severity From the Atopic Dermatitis Research Network (ADRN) Registry

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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