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. 2020 Jan;82(1):123-131.
doi: 10.1016/j.jaad.2019.08.043. Epub 2019 Aug 23.

Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy

Lihi Atzmony  1 , Young H Lim  2 , Claire Hamilton  3 , Jonathan S Leventhal  3 , Annette Wagner  4 , Amy S Paller  4 , Keith A Choate  5
Affiliations

Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy

Lihi Atzmony et al. J Am Acad Dermatol. 2020 Jan.

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.

Keywords: cholesterol; disseminated superficial actinic porokeratosis; genetic skin diseases; genetics; linear porokeratosis; medical dermatology; mevalonate pathway; pediatric dermatology; porokeratosis; statins; therapy; topical therapy.

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Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1:
Figure 1:. The Mevalonate pathway.
The mevalonate pathway is an essential metabolic pathway that uses acetyl-CoA to produce sterols and isoprenoid metabolites that are essential for a broad range of metabolic processes. Genes previously found to be involved in porokeratosis are in bold. Asterisk marks genes in which mutations were found in the present study. Dashed arrows indicate multiple processes.
Figure 2:
Figure 2:. Disseminated superficial actinic porokeratosis.
Clinical improvement of treated skin of FP100–1 with topical application of lovastatin/cholesterol. The patient shaved his arms prior to week 4 of therapy.
Figure 3:
Figure 3:. Porokeratosis palmaris et plantaris disseminata.
Clinical improvement with topical application of cholesterol/lovastatin.
Figure 4:
Figure 4:. Linear porokeratosis.
Clinical improvement with topical application of cholesterol/lovastatin.
See this image and copyright information in PMC

Comment in

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