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

Abstract

Background: Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy.Objective: On the basis of preventing the accumulation of toxic metabolites while replenishing essential end-products, we studied the efficacy of topical lovastatin/cholesterol in different variants of porokeratosis.Methods: A series of 5 patients with disseminated superficial actinic porokeratosis (DSAP,n=1), porokeratosis palmaris et plantaris disseminata (PPPD,n=2) and linear porokeratosis (LP,n=2) were enrolled. Patients were genotyped prior to initiation of therapy and then applied topical lovastatin/cholesterol twice daily to a unilateral defined treatment area for up to 3 months. Response was evaluated and patients were photographed every visit.Results: Three patients had MVD mutations and 2 patients had PMVK mutations. Treatment with topical lovastatin/cholesterol (but not cholesterol alone) resulted in near complete clearance of DSAP lesions after 4 weeks of therapy, and moderate improvement of lesions in PPPD and LP. There were no adverse events.Limitations: Case series design with a small number of patients. Conclusion:Topical cholesterol/lovastatin is a safe and effective therapy for porokeratosis that underscores the utility of a pathogenesis-based therapies which replace deficient end-products and prevent accumulation of potentially toxic precursors.

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Clinical course of porokeratosis ptychotropica over 7 years in an otherwise healthy child

“…However, mounting evidence suggests that many patients with porokeratosis may harbor postzygotic mosaic somatic mutations in enzymes of the mevalonate biosynthetic pathway . If this is true, treatment with inhibitors of HMG‐CoA reductase or other preceding steps in the mevalonate biosynthetic pathway may represent a future therapeutic approach …”

The Efficacy of Cholesterol-Based Carriers in Drug Delivery

“…All the patients showed tolerance to the therapy with no reported irritation, redness or allergic contact dermatitis at the treatment sites. The results showed that topical cholesterol/lovastatin is effective in treating porokeratosis [ 131 ].…”