Pachyonychia congenita: A case report of a successful treatment with rosuvastatin in a patient with a KRT6A mutation F. Abdollahimajd,1 F. Rajabi,1,5 M. Shahidi-Dadras,1 S. Saket,2 L. Youssefian,3 H. Vahidnezhad,3,4 and J. Uitto3,5 1Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA 4Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran 5Corresponding authors British Journal of Dermatology. DOI: 10.111/bjd.xxxxx

Lead Researcher Dr. Fahimeh Abdollahimajd

Introduction What’s already known? Pachyonychia congenita (PC) is a rare autosomal dominant disorder characterized by nail dystrophy and painful palmoplantar keratoderma. PC results from mutations in specific keratin genes (KRT6A, KRT6B, KRT6C, KRT16, and KRT17). The disease has a major impact on quality of life since it causes pain and disfigurement. Currently, there is no gold standard treatment for the disease, and keratolytics, emollients, retinoids and steroids have been used for treatment but with limited benefits.

Case report An 8-year old female presented to our clinic with painful plantar hyperkeratosis and thickened nails with a progressive course since early infancy. Nail abnormalities were the first features that became apparent at the age of 12 months, followed by plantar hyperkeratosis that gradually worsened and caused her considerable pain upon walking. She was initially treated with oral acitretin 10 mg/day for 10 months, which exacerbated her pain necessitating discontinuation of the drug, and treatment with emollients and keratolytics only.

Case report Examination revealed focal yellow hyperkeratotic plaques and deep fissures that were more prominent on the heels and metatarsal areas. Fingernails had a wedge shaped hypertrophy at the distal end with a mild brown discoloration. The child also had follicular hyperkeratotic papules over her extremities and white plaques on the buccal mucosa. These clinical features were consistent with PC.

Case report The patient was found to have a de novo heterozygous mutation in KRT6A; NM_005554: c.1381G>A, NP_005545: p.Glu461Lys. This sequence variant was absent in 119,654 alleles (ExAC) in the control population and previously reported as a pathogenic mutation. Simvastatin is known to reduce transcription of the KRT6A gene therefore we hypothesized that statins could be beneficial in the treatment of our patients. The best statin available for use in paediatric patients is rosuvastatin

Case report We started treatment with oral rosuvastatin, 5 mg per day. The patient was evaluated for drug side effects every month. After six months, she reported a marked decrease in pain and reduction in blister formation. The plantar lesions showed partial improvement with fewer scales and fissures. On ultrasound examination, the maximum thickness on her left callus was 1.18 cm, representing a 23.4% decrease.

Before treatment After treatment

Before treatment After treatment

Discussion Since painful palmoplantar keratoderma is the most debilitating manifestation of PC, treatment options mainly focus on these lesions. The most effective treatment so far is mechanical debridement of the calluses. Topical regimens, such as keratolytics, emollients, retinoids, and steroids are used but have limited benefits (Goldberg et al. 2014).

Discussion Oral retinoids reduce hyperkeratosis by suppressing keratin production but they are ineffective in pain reduction (Gruber et al. 2012). It has been suggested that compactin, a precursor of statins, can decrease the transcription of keratin 6A gene (Zhao et al. 2011). Based on their study and the fact that the best statin available for use in pediatric patients is rosuvastatin, we started a low dose regimen of rosuvastatin for our patient.

Conclusions What does this study add? A PC patient with a KRT6A mutation was treated with rosuvastatin with significant improvement in plantar hyperkeratosis and pain. Statins could be a promising treatment for PC with long-term safety but further studies are needed.

Research Team F. Abdollahimajd F. Rajabi M. Shahidi-Dadras S. Saket L. Youssefian H. Vahidnezhad J. Uitto

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