INTRODUCTION
Porokeratosis is a group of disorders characterized by inherited or acquired dysregulation of skin keratinization.1 Lesions classically present as annular plaques with raised, hyperkeratotic borders and an area of central atrophy.2 While several clinical subtypes vary in morphology, distribution, and clinical course, all reliably exhibit the presence of cornoid lamella on histopathology.1,2 The global incidence of porokeratosis is unknown, but a 2023 Swedish study estimated a national disease incidence of 1.2/100,000 person-years and prevalence of 24.2/100,000.3 Additionally, the exact mechanism of pathogenesis remains unknown.1,3
Observational studies have linked porokeratosis to ultraviolet radiation, with a higher incidence in areas of high sun exposure.1 Also, acquired cases have been linked to immunosuppression, particularly in those with solid organ and bone marrow transplants, where the incidence can be as high as 10%.1 Moreover, cases of porokeratosis have been seen in relation to specific drugs and infections, and are associated with autoimmune and systemic diseases.1,4 Porokeratosis may also be a genetic disorder, given significant numbers of familial cases are inherited as an autosomal dominant condition with variable penetrance and recently described mutations in the mevalonate pathway.1,3,4
Observational studies have linked porokeratosis to ultraviolet radiation, with a higher incidence in areas of high sun exposure.1 Also, acquired cases have been linked to immunosuppression, particularly in those with solid organ and bone marrow transplants, where the incidence can be as high as 10%.1 Moreover, cases of porokeratosis have been seen in relation to specific drugs and infections, and are associated with autoimmune and systemic diseases.1,4 Porokeratosis may also be a genetic disorder, given significant numbers of familial cases are inherited as an autosomal dominant condition with variable penetrance and recently described mutations in the mevalonate pathway.1,3,4
Porokeratosis is considered a premalignant lesion, with malignant transformation seen in 7.5% to 11% of cases across all subtypes.4 Histologically, the parakeratotic cells of the cornoid lamella possess similarities to the cells seen in squamous cell carcinoma, including abnormal DNA ploidy.4 Given this transformation risk, treatment of porokeratosis remains an active area of discovery.
Current treatment modalities include several topical therapies, systemic therapies, and destructive therapies.1 The recent link of genomic variations in the mevalonate pathway has sparked interest in a pathogenesis-directed therapy with topical cholesterol and topical statin therapy.5-8 The mevalonate pathway is essential for the production of cholesterol, an integral component of the extracellular lipid matrix in the stratum corneum, which maintains the skin's barrier function.5
