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The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition
Author(s) -
GuttmanYassky Emma,
Hanifin Jon M.,
Boguniewicz Mark,
Wollenberg Andreas,
Bissonnette Robert,
Purohit Vivek,
Kilty Iain,
Tallman Anna M.,
Zielinski Michael A.
Publication year - 2019
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13808
Subject(s) - medicine , atopic dermatitis , dupilumab , pathophysiology , calcineurin , adverse effect , rosacea , acne , dermatology , phosphodiesterase , thymic stromal lymphopoietin , immunology , pharmacology , biochemistry , chemistry , transplantation , enzyme
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 ( TCS s) and topical calcineurin inhibitors ( TCI s). Several limitations are associated with these agents. TCS s can cause a wide range of adverse effects, including skin atrophy, telangiectasia, rosacea and acne. TCI s 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 ( PDE 4) 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 PDE 4 inhibitors are in clinical development for use in the treatment of AD , including crisaborole, which recently became the first topical PDE 4 inhibitor approved for treatment of mild to moderate AD . This review will further describe the pathophysiology of AD , explain the possible role of PDE 4 in AD and review PDE 4 inhibitors currently approved or being investigated for use in AD .