Pt BD Sharma Postgraduate Institute of Medical Sciences, Rohtak, India.
Australas J Dermatol. 2022 May;63(2):e145-e149. doi: 10.1111/ajd.13835. Epub 2022 Apr 16.
A 25-year-old male patient presented with palmoplantar keratoderma, dystrophic nails, severe plantar pain and oral leukokeratosis since birth. On genetic analysis, a heterozygous KRT6A gene missense mutation (c.1381G > A, p.Glu461Lys in exon 7) was identified by next-generation sequencing technology, consistent with pachyonychia congenita 6a. Oral simvastatin 40 mg was started once daily, and after 16 weeks of therapy, excellent improvement was noted in palmoplantar keratoderma and plantar pain. The maximum thickness of his foot callosity reduced by 4 mm on ultrasonography, and the Dermatology Life Quality Index score dropped significantly by eight points. These benefits may be attributed to inhibition of KRT6A gene expression, modulation of autophagy and mitophagy and Keap1-Nrf2 signalling activation; the latter two mechanisms of statins previously undiscussed in the context of pachyonychia congenita. Simvastatin and other statins are pathogenesis-targeted, disease-modifying therapy in pachyonychia congenita, therefore qualifying as a promising treatment avenue and warranting further clinical trials.
一位 25 岁男性患者自出生起即出现手掌足底角化过度、甲营养不良、严重足底疼痛和口腔角化过度。基因分析显示，通过下一代测序技术发现杂合 KRT6A 基因突变（c.1381G>A，exon7 中的 p.Glu461Lys），与先天性厚甲症 6a 一致。开始每日口服辛伐他汀 40mg，16 周治疗后，手掌足底角化过度和足底疼痛显著改善。足部胼胝的最大厚度在超声检查中减少了 4mm，皮肤病生活质量指数评分显著下降了 8 分。这些益处可能归因于 KRT6A 基因表达的抑制、自噬和线粒体自噬的调节以及 Keap1-Nrf2 信号通路的激活；他汀类药物在先天性厚甲症中的后两种机制以前没有讨论过。辛伐他汀和其他他汀类药物是先天性厚甲症的靶向发病机制、疾病修饰治疗，因此是一种有前途的治疗途径，值得进一步临床试验。
