Various anomalies and diseases such as corneal opacities, spastic paralysis, epilepsy, oligophrenia, colonic adenocarcinoma, and gastroduodenal ulcers have been reported infrequently in association with KPPP8,10,26-34; however, none were observed in our case.
As previously mentioned, KPPP is transmitted as an autosomal-dominant trait. The causative gene, however, has not been identified. Linkage to keratin gene clusters 12q and 17q has been excluded by Kelsell et al.27 Various authors propose that the defect may lie in another gene involved in epithelial development and/or regulation in keratin expression (ie, genes responsible for structural proteins that are integral to keratin filament assembly and function).7,8,10
Unlike diffuse and focal PPKs, the association of punctate PPKs with malignancies is not well established. To date, only 3 reports of inherited punctate PPK and malignancy have been published. Bennion and Patterson33 reported a small kindred of 8 affected individuals; 2 developed adenocarcinoma of the colon and 1 developed adenocarcinoma of the pancreas. Interestingly, none of the family members without punctate keratoses developed cancer of any type. Ena et al34 reported a family with 8 affected members, one of whom developed adenocarcinoma of the colon at 53 years of age. The statistical significance in these 2 studies is questionable due to the small number of subjects involved. Stevens et al30 reported a larger kindred of more than 320 individuals spanning 4 generations. In this study, 10 of 43 adults with punctate PPK developed malignancies, including Hodgkin disease and renal, breast, pancreatic, and colon adenocarcinomas. Of the remaining 277 unaffected individuals, 6 developed malignancies.
Discovery of the causative gene(s) would serve at least 2 purposes: (1) it would provide insights into the possible association of punctate PPK and malignancy and (2) it may lead to an improved classification of the heterogeneous group of punctate PPKs.
Historically, KPPP was treated with mechanical debridement and topical keratolytics, which only provided temporary control. More recently, systemic retinoids have been used with improved results; however, relapse is reported with cessation of treatment. Baran and Juhlin35 treated a patient with a disabling case of KPPP with etretinate 75 mg daily and observed significant clinical improvement after 3 weeks. The patient remained free from the hyperkeratoses with a maintenance dose of 50 mg daily; however, the lesions recurred when the dose was further decreased to 25 mg daily. Hesse et al36 also treated a disabling case with acitretin, the active metabolite of etretinate, and observed similar success. Treatment with acitretin 30 mg daily resulted in significant, but incomplete, regression of the lesions after one month. Relapse occurred upon cessation of treatment; however, adequate control was maintained with 10 to 20 mg daily.
We chose to treat our patient with a trial of tazarotene 0.1% gel to minimize potential adverse reactions present with long-term use of oral retinoids. After 3 months of daily application of tazarotene, the hyperkeratotic lesions significantly diminished in size, and more importantly to the patient, the pain over the pressure areas resolved. Given our positive experience with tazarotene, topical retinoids may be a practical alternative for mild cases of KPPP. Long-term use is likely required for optimal control given the high relapse occurrence observed with cessation of oral retinoids.
Conclusion
In conclusion, we presented a case of KPPP in a patient with a strong family history supporting the autosomal-dominant inheritance pattern. The causative gene has not yet been identified, but its discovery would provide more insight into the possible association with malignancy and also may lead to an improved classification of the punctate PPKs. Punctate PPK has an extensive differential diagnosis and, if unrecognized, may be confused with common entities such as verrucae, leading to unnecessary frustration from multiple ineffective treatments. Multisystem conditions such as Darier disease and Cowden disease also must be considered when evaluating a patient with palmoplantar punctate keratoses. A full cutaneous examination, family history, and histologic evaluation are important components in making an accurate diagnosis. Treatment options include mechanical debridement, topical keratolytics, and topical and systemic retinoids. Maintenance therapy is required with all forms of treatment to prevent relapse.