Topical Statins in the Treatment of Porokeratosis: A Systematic Review

Abstract Porokeratosis (PK) is a chronic disorder of keratinization associated with significant morbidity and no spontaneous resolution. Currently, there are no US Food and Drug Administration (FDA)–approved therapies. However, the off-label use of topical statins—targeting the mevalonate pathway—has shown promise as a novel therapeutic strategy. This systematic review aims to evaluate the efficacy and safety of topical statins in the treatment of PK. We conducted a systematic review of PubMed, Semantic Scholar, and Cochrane databases from January 1, 2015, to February 15, 2025, identifying clinical studies evaluating topical statin therapy (atorvastatin, fluvastatin, lovastatin, rosuvastatin, or simvastatin) in patients with any subtype of PK. Twenty-four studies encompassing 95 patients met the inclusion criteria. Most publications (88%) were case reports. The majority (79%) received compounded topical lovastatin 2% or simvastatin 2% typically in combination with cholesterol 2%. Clinical improvement—defined as partial resolution of symptoms or reduction in lesion size—was observed in 92% of patients, with onset of response reported as early as 4 weeks. Adverse events were reported in 15% of patients, primarily mild, localized dermatologic reactions. Two patients discontinued treatment due to side effects. Topical statins appear to provide preliminary evidence of some clinical benefits in PK by inhibiting the mevalonate pathway, supporting a promising and plausible mechanism-based approach. However, the use of off-label compounded formulations introduces variability in efficacy and safety due to lack of quality control. The absence of FDA-approved therapies for PK represents an ongoing unmet therapeutic need warranting further investigation in prospective, controlled studies. Together, these preliminary case reports indicating clinical benefit encourage the development of an FDA-approved, GMP quality topical statin formulation that is carefully evaluated in rigorous, well-designed clinical trials that demonstrate safety and substantial evidence of effectiveness.