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Journal of the American Academy of Dermatology
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le lundi 4 novembre 2019
Doi : 10.1016/j.jaad.2019.08.043
accepted : 20 August 2019
Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy
 

Lihi Atzmony, MD a, b, c, Young H. Lim, BS a, b, d, Claire Hamilton, MD, PhD a, Jonathan S. Leventhal, MD a, Annette Wagner, MD e, f, Amy S. Paller, MD e, f, Keith A. Choate, MD, PhD a, b, d,
a Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut 
b Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 
c Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 
d Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 
e Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 
f Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois 

Reprint requests: Keith A. Choate, MD, PhD, Departments of Dermatology, Genetics, and Pathology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520.Departments of Dermatology, Genetics, and PathologyYale University School of Medicine333 Cedar StNew HavenCT06520
Abstract
Background

Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy. We hypothesized that topical therapy that aims to replenish cholesterol, an essential mevalonate pathway end-product, and block the accumulation of mevalonate pathway toxic metabolites could alleviate porokeratosis.

Objective

To study the efficacy of topical cholesterol/lovastatin in different variants of porokeratosis.

Methods

We enrolled a series of 5 porokeratosis patients,1 with disseminated superficial actinic porokeratosis, 2 with porokeratosis palmaris et plantaris disseminata, and 2 with linear porokeratosis. Patients were genotyped before initiation of therapy. Patients then applied topical cholesterol/lovastatin twice daily to a unilaterally defined treatment area for up to 3 months. The response was evaluated and patients photographed at every visit.

Results

Three patients had MVD mutations, and 2 patients had PMVK mutations. Treatment with topical cholesterol/lovastatin (but not cholesterol alone) resulted in near complete clearance of disseminated superficial actinic porokeratosis lesions after 4 weeks of therapy and moderate improvement of porokeratosis palmaris et plantaris disseminata lesions and linear porokeratosis lesions. There were no adverse events.

Limitations

Case series design with a small number of patients.

Conclusion

Topical cholesterol/lovastatin is an effective and well-tolerated therapy for porokeratosis that underscores the utility of a pathogenesis-based therapy that replaces deficient end products and prevents accumulation of potentially toxic precursors.

The full text of this article is available in PDF format.

Key words : cholesterol, disseminated superficial actinic porokeratosis, genetics, genetic skin diseases, linear porokeratosis, medical dermatology, mevalonate pathway, pediatric dermatology, porokeratosis, statins, therapy, topical therapy

Abbreviations used : CHILD, DSAP, LP, PPPD



 Funding sources: Supported in part by the National Institutes of Health (R01 AR071491 to Dr Choate) and the Yale Center for Mendelian Genomics (U54 HG006504). Dr Atzmony was supported by Davidoff Foundation.
 Conflicts of interest: None disclosed.



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