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

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

卷:82

Article

Atzmony, Lihi^1,2,3  Lim, Young H.^1,2,4  Hamilton, Claire¹  Leventhal, Jonathan S.¹  Wagner, Annette^5,6  Paller, Amy S.^5,6  Choate, Keith A.^1,2,4 

[1] Yale Univ, Sch Med, Dept Dermatol, 333 Cedar St, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA

[3] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[4] Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06520 USA

[5] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA

[6] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA

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

DOI  :  10.1016/j.jaad.2019.08.043

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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