Oral Statin Therapy in KRT16- and KRT17-Associated Palmoplantar Epidermal Differentiation Disorder (Pachyonychia Congenita)

Palmoplantar epidermal differentiation disorder associated with pachyonychia congenita (pEDD-PC) is a rare autosomal dominant skin disorder caused by pathogenic variants in keratin genes, including KRT6A, KRT6B, KRT6C, KRT16, and KRT17. While statins have been reported to alleviate symptoms in KRT6A-pEDD-PC, their efficacy in other subtypes remains unclear. We report six adult patients, including four with KRT17 variants and two with KRT16 variants, who underwent off-label oral statin therapy. Statins were administered for at least 6 months following dose stabilization. Although the treatment was well tolerated in most cases, no significant clinical improvement in plantar calluses or pain was observed. All patients discontinued therapy due to insufficient efficacy. Our findings indicate that oral statin therapy may offer limited benefit in KRT16/KRT17-pEDD-PC and suggest the potential importance of early intervention and genotype-specific therapeutic strategies.