Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
J Am Acad Dermatol. 2020 Jan;82(1):123-131. doi: 10.1016/j.jaad.2019.08.043. Epub 2019 Aug 23.
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.
To study the efficacy of topical cholesterol/lovastatin in different variants of porokeratosis.
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.
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.
Case series design with a small number of patients.
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.
角层松解角化病与甲羟戊酸途径基因突变有关。治疗选择很少，且往往疗效有限。我们假设旨在补充胆固醇（甲羟戊酸途径的重要终产物）并阻断甲羟戊酸途径有毒代谢物积累的局部治疗可能缓解角层松解角化病。
研究局部胆固醇/洛伐他汀治疗不同角层松解角化病变异型的疗效。
我们招募了一系列 5 名角层松解角化病患者，其中 1 名患有播散性浅表光化性角层松解角化病，2 名患有掌跖播散性角层松解角化病，2 名患有线性角层松解角化病。患者在开始治疗前进行基因分型。然后，患者将局部胆固醇/洛伐他汀每天应用于单侧定义的治疗区域，持续长达 3 个月。每次就诊时都评估反应并拍摄患者照片。
3 名患者存在 MVD 突变，2 名患者存在 PMVK 突变。局部应用胆固醇/洛伐他汀（而非胆固醇单独应用）治疗 4 周后，播散性浅表光化性角层松解角化病病变几乎完全清除，掌跖播散性角层松解角化病和线性角层松解角化病病变有中度改善。没有不良反应。
病例系列设计，患者数量较少。
局部胆固醇/洛伐他汀是一种有效且耐受性良好的角层松解角化病治疗方法，强调了基于发病机制的治疗方法的实用性，该方法可替代缺乏的终产物并防止潜在有毒前体的积累。
