The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition

Emma Guttman-Yassky, Jon M. Hanifin, Mark Boguniewicz, Andreas Wollenberg, Robert Bissonnette, Vivek Purohit, Iain Kilty, Anna M. Tallman, Michael A. Zielinski

Research output: Contribution to journalReview article

12 Scopus citations

Abstract

Atopic dermatitis (AD) is a highly prevalent, chronic inflammatory skin disease that affects children and adults. The pathophysiology of AD is complex and involves skin barrier and immune dysfunction. Many immune cytokine pathways are amplified in AD, including T helper (Th) 2, Th22, Th17 and Th1. Current treatment guidelines recommend topical medications as initial therapy; however, until recently, only two drug classes were available: topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). Several limitations are associated with these agents. TCSs can cause a wide range of adverse effects, including skin atrophy, telangiectasia, rosacea and acne. TCIs can cause burning and stinging, and the prescribing information lists a boxed warning for a theoretical risk of malignancy. Novel medications with new mechanisms of action are necessary to provide better long-term control of AD. Phosphodiesterase 4 (PDE4) regulates cyclic adenosine monophosphate in cells and has been shown to be involved in the pathophysiology of AD, making it an attractive therapeutic target. Several PDE4 inhibitors are in clinical development for use in the treatment of AD, including crisaborole, which recently became the first topical PDE4 inhibitor approved for treatment of mild to moderate AD. This review will further describe the pathophysiology of AD, explain the possible role of PDE4 in AD and review PDE4 inhibitors currently approved or being investigated for use in AD.

Original languageEnglish (US)
Pages (from-to)3-10
Number of pages8
JournalExperimental Dermatology
Volume28
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • calcineurin inhibitor
  • corticosteroids
  • crisaborole
  • cytokines
  • eczema

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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    Guttman-Yassky, E., Hanifin, J. M., Boguniewicz, M., Wollenberg, A., Bissonnette, R., Purohit, V., Kilty, I., Tallman, A. M., & Zielinski, M. A. (2019). The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition. Experimental Dermatology, 28(1), 3-10. https://doi.org/10.1111/exd.13808