Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan;14(1):45-57.
doi: 10.1007/s13555-023-01081-0. Epub 2024 Jan 6.

Cutaneous Components Leading to Pruritus, Pain, and Neurosensitivity in Atopic Dermatitis: A Narrative Review

Sonja Ständer  1 , Thomas Luger  2 , Brian Kim  3 , Ethan Lerner  4 , Martin Metz  5   6 , Roni Adiri  7 , Juliana M Canosa  8 , Amy Cha  9 , Gil Yosipovitch  9   10
Affiliations
Review

Cutaneous Components Leading to Pruritus, Pain, and Neurosensitivity in Atopic Dermatitis: A Narrative Review

Sonja Ständer et al. Dermatol Ther (Heidelb). 2024 Jan.

Abstract

Atopic dermatitis (AD) is a chronic, relapsing immunoinflammatory skin condition characterized by sensations such as pruritis, pain, and neuronal hypersensitivity. The mechanisms underlying these sensations are multifactorial and involve complex crosstalk among several cutaneous components. This review explores the role these components play in the pathophysiology of atopic dermatitis. In the skin intercellular spaces, sensory nerves interact with keratinocytes and immune cells via myriad mediators and receptors. These interactions generate action potentials that transmit pruritis and pain signals from the peripheral nervous system to the brain. Keratinocytes, the most abundant cell type in the epidermis, are key effector cells, triggering crosstalk with immune cells and sensory neurons to elicit pruritis, pain, and inflammation. Filaggrin expression by keratinocytes is reduced in atopic dermatitis, causing a weakened skin barrier and elevated skin pH. Fibroblasts are the main cell type in the dermis and, in atopic dermatitis, appear to reduce keratinocyte differentiation, further weakening the skin barrier. Fibroblasts and mast cells promote inflammation while dermal dendritic cells appear to attenuate inflammation. Inflammatory cytokines and chemokines play a major role in AD pathogenesis. Type 2 immune responses typically generate pruritis, and the type 1 and type 3 responses generate pain. Type 2 responses and increased skin pH contribute to barrier dysfunction and promote dysbiosis of the skin microbiome, causing the proliferation of Staphyloccocus aureus. In conclusion, understanding the dynamic interactions between cutaneous components in AD could drive the development of therapies to improve the quality of life for patients with AD.

Keywords: Alloknesis; Chronic itch; Hyperknesis; Keratinocyte; Neuroimmunology; Neuronal sensitization; Sensory biology; Skin pain; Skin physiology.

PubMed Disclaimer

Conflict of interest statement

Roni Adiri, Juliana M. Canosa, and Amy Cha are employees and shareholders of Pfizer Inc. Ethan Lerner is a member of the Scientific Advisory Board for Escient Pharmaceuticals Inc. Martin Metz has received honoraria as a speaker and/or advisor for Pfizer Inc., AbbVie, Amgen, AstraZeneca, argenx, Bayer, Beiersdorf, Celldex, Escient, Galderma, GSK, Jasper, Novartis, Pharvaris, Sanofi-Aventis, Teva, ThirdHarmonicBio, and Vifor. Sonja Ständer was a speaker, consultant, and/or investigator and/or has received research funding from Pfizer Inc., AbbVie, Almirall, Beiersdorf, BMS, Clexio, Eli Lilly and Company, FomF, Galderma, German Research Foundation, Integrity CE, Kiniksa, LEO Pharma, L'Oréal, MEDahead, Moroscience, NACCME, Novartis, Omnicuris, P.G. Unna Academy, Sanofi, TouchIME, UCB, Vifor, and WebMD. Gil Yosipovitch has been a consultant and an advisor for Pfizer Inc., Arcutis, Bellus, Eli Lilly, Galderma, Kiniksa, LEO Pharma, Novartis, Pierre Fabre, Sanofi-Regeneron, Trevi Therapeutics, and a principal investigator for Pfizer Inc., Eli Lilly, Escient, Galderma, Kiniksa, LEO Pharma, Novartis, Pierre Fabre, and Sanofi-Regeneron. Thomas Luger has participated on advisory boards for Pfizer Inc., AbbVie, Amgen, Argenx, Celgene, Ceres Pharma, Eli Lilly, Galderma, Janssen, La Roche-Posay, LEO Pharma, Menlo Therapeutics, Mylan/Meda, Novartis, Pierre Fabre, PIQUR Therapeutics, Sandoz, Sanofi, and Symrise; acted as an investigator for Pfizer Inc., AbbVie, Celgene, Eli Lilly, Janssen, LEO Pharma, Menlo Therapeutics, Novartis, and Sandoz; participated as a speaker for Pfizer Inc., AbbVie, Galderma, Janssen, La Roche-Posay, Merck Sharp & Dohme, Mylan, Novartis, and Sanofi; and has received funding from Pfizer Inc., AbbVie, Celgene, Jansen-Cilag, Merck Sharp & Dohme, Mylan/Meda, Novartis, and Wolfe Laboratories. Brian Kim is a consultant and advisor for Pfizer Inc., AbbVie, Boehringer Ingelheim, Cara Therapeutics, Kiniksa, Menlo Therapeutics, and Sanofi-Regeneron; has received research grants from Cara Therapeutics, Celgene, and LEO Pharma; and is founder and stockholder in Nuogen Pharma. Brian Kim is currently affiliated with the Mark Lebwohl Center for Neuroinflammation and Sensation, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Figures

Fig. 1
Fig. 1
The skin is a laminated structure composed of several components that contribute to pruritis, pain, and neurosensitization in atopic dermatitis: the neurosensory component (nociceptors and pruriceptors), resident cell component (keratinocytes, Langerhans cells, Merkel cells, fibroblasts, mast cells), immune/infiltrating cell component (macrophages and lymphocytes), and the skin microbiome
See this image and copyright information in PMC

References

    1. Boguniewicz M, Fonacier L, Guttman-Yassky E, Ong PY, Silverberg J, Farrar JR. Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018;120:10–22.e2. doi: 10.1016/j.anai.2017.10.039. - DOI - PubMed
    1. Ständer S. Atopic dermatitis. N Engl J Med. 2021;384:1136–1143. doi: 10.1056/NEJMra2023911. - DOI - PubMed
    1. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396:345–360. doi: 10.1016/S0140-6736(20)31286-1. - DOI - PubMed
    1. Bylund S, Kobyletzki LB, Svalstedt M, Svensson Å. Prevalence and incidence of atopic dermatitis: a systematic review. Acta Derm Venereol. 2020;100:adv00160. doi: 10.2340/00015555-3510. - DOI - PMC - PubMed
    1. Murota H, Koike Y, Morisaki H, Matsumoto M, Takenaka M. Exacerbating factors and disease burden in patients with atopic dermatitis. Allergol Int. 2022;71:25–30. doi: 10.1016/j.alit.2021.10.002. - DOI - PubMed