Efficacy and Safety of Cryotherapy Combined With Intralesional Steroid for Keloid and Hypertrophic Scar: A Systematic Review and Meta‐Analysis

OBJECTIVE: Intralesional steroid injection is the first-line therapy for scars. Emerging evidence indicates that combining intralesional steroid injection with cryotherapy yields promising therapeutic outcomes for scar management. However, a consensus on the efficacy and safety of this combined regimen has not yet been reached. Consequently, the present meta-analysis aimed to assess the efficacy and safety of this combination compared with control groups. METHODS: A full-scale literature retrieval was performed across a range of databases to identify eligible randomized controlled trials (RCTs) and prospective non-randomized studies that evaluated the efficacy and safety of cryotherapy plus intralesional steroid injection against control treatments for keloids or hypertrophic scars. Key outcome data, including the mean percentage change in scar improvement, the excellent clinical response rate (defined as ≥ 75% reduction in scar volume), and the incidence of adverse events, were extracted. Meta-analyses were performed using a fixed- or random-effects model based on the heterogeneity assessment results. RESULTS: Thirteen studies involving 1012 cases were included in this meta-analysis. The pooled results exhibited that cryotherapy combined with intralesional steroid injection yielded a significantly higher efficacy rate than various control interventions (including intralesional steroid monotherapy, cryotherapy alone, bleomycin/verapamil treatment, laser plus steroid, and surgical excision plus radiotherapy) (risk ratio [RR] = 1.19, 95% confidence interval (CI): 1.03-1.36; p = 0.01). However, no statistically significant differences were detected between the experimental and control groups in either the mean percentage change in scar improvement (standard mean difference (SMD) = 0.14, 95% CI: -0.39 to 0.68; p = 0.60) or the overall incidence of adverse events (RR = 1.35, 95% CI: 0.99-1.83; p = 0.06). CONCLUSIONS: Cryotherapy combined with intralesional steroid injection is a viable alternative to other first-line treatments for keloids and hypertrophic scars. Clinical recommendations should be made cautiously based on specific patient and scar conditions. Further well-designed, large-scale RCTs are required to validate the long-term efficacy and safety of this combined regimen.