Journal of the American Academy of Dermatology
Phosphodiesterase 4 inhibitors
Section snippets
PDE4 activity is increased in AD and associated with proinflammatory cytokines
Alterations in nucleotide metabolism in atopic disease were first described in 1968 by Szentivanyia et al.16 Elevated phosphodiesterase (PDE) activity in a variety of inflammatory cells involved in AD has been described in adults with AD17, 18, 19, 20 and the cord blood of children born to atopic parents.21 Intracellular cyclic adenosine monophosphate (cAMP) levels depend on the relative rate of cAMP production and degradation. PDE 4 (PDE4) degrades cAMP, a negative regulator of the production
Clinical studies of PDE4 inhibitors
During the past 2 decades, several oral and topical PDE4 inhibitors have been studied and approved for the treatment of a variety of inflammatory disorders, including AD, asthma, chronic obstructive pulmonary disease, psoriasis and psoriatic arthritis, and rheumatoid arthritis.43
Oral PDE4 inhibitors are minimally immunosuppressive, in contrast to other systemically administered medications for inflammatory skin disease, but they have a narrow therapeutic window, with nausea, vomiting, abdominal
Conclusions
There is a need for additional topical treatments for AD. PDE4 activity is increased in inflammatory cells of patients with AD, leading to degradation of intracellular cAMP, with subsequent increased production of proinflammatory cytokines. PDE4 inhibitors are a promising targeted treatment option for children and adults with mild-to-moderate AD. Future studies will be needed explore the efficacy and safety of PDE4 compounds beyond crisaborole and in pediatric patients younger than 2 years.
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Cited by (0)
Publication of this article was supported by Leo Pharma, Bayer, and Sanofi/Regeneron.
Funding sources: Supported by Bayer, LEO Pharma, and Sanofi.
Disclosure: Dr Paller has received funds for serving as an investigator for Anacor and as a consultant for Pfizer. Dr Zebda disclosed no conflicts of interest.