A mother and daughter presented to the dermatology clinic with similar hyperkeratotic papules on the palms, soles, and extremities along with cystic nodules in the groin. The daughter was a 13-year-old girl with a history of asthma and multiple laryngeal papillomas with multiple skin lesions on her upper and lower extremities that were treated as common warts with cryotherapy for several years. The mother of the patient noted that papules initially appeared on the patient’s palms and soles around 2 years of age and underwent periods of growth and regression. Additionally notable was a history of odontohypophosphatasia with early tooth loss beginning at age 6 with complete loss of deciduous teeth by age 10 along with current loosening of permanent teeth. To date, she has not had conjunctival lesions but does have a history of myopia.
Physical examination found hyperkeratotic crusted papules and plaques on the palms, soles, and legs along with scattered hyperpigmented macules and patches in areas of previous lesions (Fig 1, A , B , and D ). Additionally, involving the bilateral upper thighs and inguinal creases were pink-to-brown cystic nodules consistent with HS (Hurley stage 1). Keratoderma was present on her palms and soles bilaterally (Fig 1, C ). Shave biopsy of a lesion on her left ankle found histology consistent with a KA (Fig 1, E ), and the lesion was negative for high-risk human papillomavirus infection. She underwent whole genome sequencing which found a significant pathologic mutation in the NLRP1 gene on chromosome 17p13 with a c.197 C>T (p.A66V) variant. Of note, this genetic change was also identified in the patient’s mother, maternal aunt, and maternal grandmother. Further workup included an interleukin (IL)-1 level, which was within normal limits.
To address the KA lesions, she was started on tretinoin 0.05% cream and oral niacinamide (500 mg twice a day) supplementation. Furthermore, to treat the HS, she was given clindamycin 1% topical solution and Hibiclens 4% topical solution. At 6-month follow-up, she had minimal improvement with either condition so her topical retinoid was switched to tazarotene and her HS was more aggressively managed with intralesional triamcinolone injections and oral doxycycline with the consideration to start isotretinoin in the near future. To date, squamous cell carcinoma has not been diagnosed.
The mother was a 45-year-old woman who presented with multiple self-healing lesions on her lower legs and feet that started during childhood. She also had history of odontohypophosphatasia with early loss of her deciduous teeth along with lack of classic ocular findings. Physical examination found multiple hyperkeratotic firm papules on the legs (Fig 2, A ). Involving the groin were small cystic red-to-brown papules consistent with HS (Hurley stage 1). Yellow keratoderma was present on the pressure points of the palms and soles bilaterally (Fig 2, B ). Biopsy of 2 characteristic lesions on the left and right legs were consistent with invasive squamous cell carcinoma. After both lesions were excised, the patient was started on acitretin (10 mg/d) along with oral niacinamide (500 mg twice a day) supplementation. At 4-month follow-up, the KA and HS lesions completely resolved. The treatment regimen was well tolerated by the patient and subsequently continued. Unfortunately, breast cancer was recently diagnosed in this patient.