Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?

Nicholas K. Mollanazar, Peter K. Smith, Gil Yosipovitch

Research output: Contribution to journalReview articlepeer-review

109 Scopus citations

Abstract

For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options.

Original languageEnglish (US)
Pages (from-to)263-292
Number of pages30
JournalClinical Reviews in Allergy and Immunology
Volume51
Issue number3
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Keywords

  • Alternative itch therapies
  • Atopic dermatitis
  • Barrier disruption
  • Chronic pruritus
  • Immunomodulators
  • Neural hypersensitization
  • Neuropeptides
  • Nonhistaminergic itch
  • Patient education
  • Pruritus receptor unit

ASJC Scopus subject areas

  • Immunology and Allergy

Fingerprint Dive into the research topics of 'Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?'. Together they form a unique fingerprint.

Cite this