Safety and efficacy of topical simvastatin plus cholesterol cream versus topical simvastatin cream alone for porokeratosis ptychotropica: A randomized, single-blind, split-body, placebo-controlled, investigator-initiated trial

Zhiming Chen; Yihe Liu; Hui Yu; Jing Li; Xin Huang; Ruiyu Xiang; Ran Mo; Hao Chen; Yong Yang

doi:10.1016/j.jaad.2025.04.082

Safety and efficacy of topical simvastatin plus cholesterol cream versus topical simvastatin cream alone for porokeratosis ptychotropica: A randomized, single-blind, split-body, placebo-controlled, investigator-initiated trial

J Am Acad Dermatol. 2025 May 20:S0190-9622(25)02180-2. doi: 10.1016/j.jaad.2025.04.082. Online ahead of print.

Authors

Zhiming Chen¹, Yihe Liu², Hui Yu³, Jing Li⁴, Xin Huang², Ruiyu Xiang², Ran Mo², Hao Chen⁵, Yong Yang⁶

Affiliations

¹ Genetic Skin Disease Center, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China. Electronic address: zmchen@pumcderm.cams.cn.
² Genetic Skin Disease Center, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.
³ Medicinal Preparation Center, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.
⁴ Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.
⁵ Department of Dermatopathology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China. Electronic address: ch76ch@163.com.
⁶ Genetic Skin Disease Center, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China. Electronic address: yyang@pumcderm.cams.cn.

PMID: 40403974
DOI: 10.1016/j.jaad.2025.04.082

Abstract

Background: Porokeratosis ptychotropica (PP) is a severe inherited skin disorder resistant to traditional treatments. Topical statins are being explored as a potential alternative.

Objective: To evaluate the efficacy and safety of topical simvastatin and simvastatin/cholesterol in treating PP.

Methods: In this single-blind, split-body, placebo-controlled trial, PP patients were 1:1 randomized to apply either 2% simvastatin or 2% simvastatin/cholesterol cream on 1 randomized side of the buttocks twice daily for 8 weeks. If blinded evaluation determined that the treatment side showed superior efficacy over placebo at week 8, both sides would continue treatment for 40 more weeks.

Results: Of 24 participants screened, 18 were enrolled and underwent randomization. One patient withdrew from each group before preliminary assessment. After 8 weeks, 8 of 8 patients in the 2% simvastatin group and 7 of 8 patients in the 2% simvastatin/2% cholesterol group showed better efficacy than placebo. By week 48, severity index and pruritus scores continued to improve, and no difference was seen between the 2 groups. No treatment-related adverse events were observed.

Limitations: This trial had a relatively small sample size.

Conclusion: Both topical simvastatin and simvastatin/cholesterol were well tolerated and effective in relieving the erythema, thickness, scaling, and pruritus of PP with relatively long-term use.

Keywords: cholesterol; mevalonate pathway; placebo-controlled; porokeratosis; porokeratosis ptychotropica; simvastatin; split-body; statins; topical therapy.