Background: Porokeratosis comprises a group of clinically diverse keratinization disorders unified by the cornoid lamella and increasingly understood through alterations in the mevalonate/cholesterol biosynthesis pathway, including germline variants, somatic second‐hit events, clonal mosaicism, and emerging epigenetic mechanisms. These biological insights support investigation of pathogenesis‐directed topical statin‐based therapy, with or without cholesterol supplementation. Aim: This systematic review evaluated the reported clinical improvement, safety, and comparative evidence of topical cholesterol/statin combination therapy versus topical statin monotherapy for porokeratosis. Methods: PubMed, Scopus, Web of Science, and Cochrane Library were searched through January 2026. Two independent reviewers screened studies and extracted data on study design, porokeratosis subtype, treatment formulation, clinical outcomes, and adverse events. Because the evidence base consisted largely of small uncontrolled reports with heterogeneous outcome definitions, quantitative summaries were considered exploratory and were interpreted cautiously. Results: Thirteen studies including 89 patients were included. Most studies were case reports or case series, with limited controlled evidence. Published uncontrolled reports generally described clinical improvement after topical cholesterol/statin therapy, including improvement in erythema and lesion morphology; however, these findings are subject to substantial selection, reporting, and publication bias. Safety data suggested that adverse events were usually mild and local, including application‐site discomfort, transient pruritus, erythema, dryness, or eczematous reactions. In the available controlled studies comparing combination therapy with topical statin monotherapy, no statistically significant difference was detected in clinical improvement or severity‐score change, although confidence intervals were wide and the analyses were underpowered. Conclusion: Topical cholesterol/statin therapy remains a biologically plausible and clinically promising approach for porokeratosis, but larger standardized randomized trials are required to define its comparative effectiveness, optimal formulation, and long‐term safety.

Background/Objectives: To systematically evaluate and compare the clinical efficacy and safety of non-cryotherapy modalities versus standard liquid nitrogen cryotherapy for the treatment of plantar warts, while exploring the influence of specific cryotherapy procedural parameters and intervention-related subgroup characteristics on treatment outcomes. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted according to PRISMA guidelines. We searched four major databases from inception until 1 July 2026. The primary outcome was complete clearance. Secondary outcomes included partial clearance, recurrence, and treatment-related adverse events. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Results: Thirty-one RCTs involving 2313 patients were included. No statistically significant difference was detected between non-cryotherapy modalities and cryotherapy in complete clearance rates (RR = 1.09, 95% CI: 0.98–1.20; p = 0.10; I² = 0.00%) or recurrence outcomes (RR = 0.90, 95% CI: 0.56–1.44; p = 0.66). Partial clearance significantly favored cryotherapy (RR = 0.65, 95% CI: 0.44–0.95; p = 0.03), particularly in subgroup analyses using two freeze–thaw cycles and treatment intervals of every two weeks. Regarding safety, topical therapies demonstrated significantly lower erythema rates than cryotherapy, while no statistically significant differences were observed in blistering, scarring, or secondary bacterial infection. Conclusions: No statistically significant difference was detected between non-cryotherapy modalities and cryotherapy regarding complete clearance or recurrence of plantar warts. Cryotherapy may offer better partial clearance under optimized treatment parameters, whereas topical therapies may be better tolerated in selected patients.