טיפול מוכוון פתוגנזה משפר אנומליות עוריות בפורוקרטוזיס- מחקר גישוש

Background: Porokeratosis is a heterogenous group of keratinization disorders associated with mevalonate pathway gene mutations. Treatments options for the disease are few and often ineffective.
Aim: On the basis of the possible pathogenic role of pathway end-product deficiency (cholesterol) and accumulation of toxic precursors, we studied the efficacy of topical lovastatin/cholesterol in different variants of porokeratosis.
Methods: We recruited one patient with disseminated superficial actinic porokeratosis (DSAP), 2 patients with porokeratosis palmaris et plantaris disseminate (PPPD) and 2 patients with linear porokeratosis (LP). Patients were genotyped prior to initiation of therapy and applied topical lovastatin/cholesterol twice daily for a duration of up to a year with the rest of the untreated affected skin serving as a control. Response was evaluated using clinical photographs every visit.
Results: Three patients had germline MVD mutations and 2 patients had germline PMVK mutations. Topical lovastatin/cholesterol (but not cholesterol alone) almost cleared lesions after 4 weeks of therapy in DSAP and partially improved lesions in PPPD and LP. There were no adverse events.
Conclusions: Topical cholesterol/lovastatin is an effective and safe therapy for porokeratosis that validates the utility of pathogenesis-based therapy that replaces deficient end products and prevents accumulation of potentially toxic metabolites.