Stopping pachyonychia congenita plantar pain with a statin?

Theocharopoulos, Ioannis; O’Toole, Edel A.

doi:10.1111/bjd.18254

Cited by 5 publications

(2 citation statements)

References 4 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 However, use of statins PC has been disputed since then, due to lack of clinical trials and sufficient evidence related to mechanism of action of statins in PC. 8 We prescribed oral simvastatin in our patient, and after 16 weeks of treatment, considerable improvement was noted in palmoplantar keratoderma, plantar pain and quality of life, which was in agreement to the previous report.…”

Section: Discussionsupporting

confidence: 92%

Scrutinising the role of simvastatin in a patient of Pachyonychia Congenita with KRT6A gene mutation

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

Scrutinising the role of simvastatin in a patient of Pachyonychia Congenita with KRT6A gene mutation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, these results have not been confirmed in a placebo-controlled randomized controlled trial. 52,53 Risks and benefits need to be balanced. 54 Plantar injections with botulinum toxin type A have showed reduced keratoderma and plantar pain in PC-K6a and PC-K16, thought to be initiated through inhibition of sweating, and subsequent reduced epidermal damage, blistering, and pain.…”

Section: Future Management Optionsmentioning

confidence: 99%

Pachyonychia Congenita: Clinical Features and Future Treatments

Mccarthy,

De brito,

O’toole

2023

Keio J. Med.

View full text Add to dashboard Cite

Pachyonychia congenita (PC) is a rare, autosomal dominant inherited disorder of keratinization that is characterized by a triad of focal palmoplantar keratoderma, plantar pain, and hypertrophic nail dystrophy. It can be debilitating, causing significantly impaired mobility. PC is diagnosed clinically alongside identification of a heterozygous pathogenic mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. Each keratin gene mutation is associated with a distinct clinical phenotype, with variable age of onset and additional features, which has allowed classification by genotype. Additional features include pilosebaceous cysts, follicular hyperkeratosis, natal teeth, oral leukokeratosis, hidradenitis suppurativa, itching, and neurovascular structures. Although classed as rare, the prevalence of PC is likely to be underestimated. There is no cure or specific treatment for PC at present. Current treatments are limited to conservative measures to reduce plantar friction and trauma, mechanical debridement, topical treatments, and treatments for associated features or complications, most commonly infection. However, through active research in collaboration with PC Project, a patient-advocacy group, and the International PC Research Registry, a global registry of PC patients, there are now many new potential therapeutic options on the horizon. This review summarizes the clinical features associated with PC and highlights the current and future treatment of its manifestations.

show abstract