Dermatology · Medical Literature
Assessment and Comparison of Efficacy and Safety of Monotherapy With Topical 50% Urea Cream and Combination Therapy With Topical 50% Urea Cream and Carboxytherapy in Treatment of Recalcitrant Common Wart: A Randomized, Single-Blinded, 2-Split Clinical Trial.
Abstract
The treatment of common warts can occasionally be a challenge in recalcitrant cases, either recurrent ones or non-responders to treatment. In the current study, the efficacy and safety of monotherapy with topical 50% urea cream and combination therapy with topical 50% urea cream and carboxytherapy were assessed and compared in the treatment of recalcitrant common wart. Twenty subjects with recalcitrant common warts in the extremities (excluding the plantar surface) were selected. For the lesions of one side of the body, topical 50% urea cream was used 2 times a day (group A), while for the other side, combination of topical 50% urea cream and carboxytherapy was administered (group B). Carboxytherapy was done weekly, and both treatments were continued until complete resolution. The lesion count and size were assessed until 2 weeks after the fifth session of carboxytherapy. Recurrence rate was evaluated 6 months after complete resolution. Regarding the lesion count, no statistically significant difference was seen between the 2 groups. In group B, decrease of lesion size was significantly greater than that in group A. The time for complete resolution was significantly shorter in the group B. No significant adverse event was reported in either treatment group. No recurrence of lesions was reported 6 months after complete resolution in either group. Our findings demonstrated that both monotherapy with topical 50% urea cream and combination therapy with topical 50% urea cream and carboxytherapy were effective in the treatment of recalcitrant recurrent common warts, although the effectiveness of combination therapy was statistically more.
Clinical relevance
In adults with recalcitrant common warts of the extremities (excluding plantar surfaces), does the combination of topical 50% urea cream plus weekly carboxytherapy produce superior efficacy and a comparable safety profile compared with topical 50% urea cream monotherapy? __SNAPSHOT__ {"studyDesign":"Randomized, single-blinded, 2-split (split-body/intra-individual) clinical trial","setting":"Not reported (authorship affiliations suggest an academic dermatology center in Iran, based on prior publications by this group)","sampleSize":"n=20 subjects; each subject served as their own control (lesions on one body side assigned to Group A, contralateral side to Group B)","population":"Adults with recalcitrant common warts located on the extremities, explicitly excluding the plantar surface; 'recalcitrant' defined as recurrent or non-responder to prior treatment","intervention":"Group B: Topical 50% urea cream applied twice daily PLUS weekly intralesional/subcutaneous carboxytherapy (CO₂ injection), continued until complete lesion resolution","comparator":"Group A (intra-individual control): Topical 50% urea cream applied twice daily as monotherapy, continued until complete lesion resolution","primaryOutcome":"Not formally designated as a single primary endpoint in the abstract; outcomes assessed included lesion count change, lesion size change, time to complete resolution, and recurrence rate at 6 months after complete resolution","followUp":"Active treatment monitored through 2 weeks after the fifth carboxytherapy session; recurrence surveillance at 6 months post-complete resolution","fundingSource":"Not reported"}
Key findings
Three efficacy domains were assessed. (1) Lesion count: No statistically significant between-group difference was observed—the abstract does not report the direction of effect, p-value, or absolute/relative counts for either group. (2) Lesion size reduction: Reduction in lesion size was statistically significantly greater in the combination arm (Group B) than in the urea monotherapy arm (Group A); specific effect sizes, confidence intervals, and p-values are not reported in the abstract. (3) Time to complete resolution: Complete resolution occurred significantly faster in Group B than in Group A; specific absolute time values, hazard ratios, and p-values are not reported in the abstract. NNT and NNH cannot be calculated from available data. Safety and recurrence data beyond the 6-month recurrence assessment are not detailed in the abstract; adverse event rates and recurrence frequencies are not reported herein.
Practice implications
Based solely on the abstract, the addition of weekly carboxytherapy to topical 50% urea cream appeared to accelerate lesion size reduction and time to complete resolution in recalcitrant common warts compared with urea cream alone, whereas the effect on total lesion count was not statistically different between arms. The study did NOT establish: superiority on lesion count, long-term recurrence benefit with quantified rates, generalizability to plantar warts or mucosal warts, efficacy in immunocompromised patients (who were not specified as included), or the magnitude of any effect (no absolute numbers, CIs, or p-values are provided in the abstract). The split-body design controls for inter-individual variability, which is methodologically appropriate for this population, but the intra-individual crossover of inflammatory responses between body sides cannot be excluded. Clinical importance of the observed differences in lesion size and resolution time cannot be judged without the underlying quantitative data. Whether these findings are sufficient to change prescribing or procedural practice cannot be determined from the abstract alone. IMPORTANT CAVEAT: This summary is based exclusively on the published abstract (PMID 42541394); full-text data including complete statistical results, adverse event tables, and protocol details were not available for review. __LIMITATIONS__ 1. Very small sample size (n=20 subjects), substantially limiting statistical power, precision of effect estimates, and generalizability. 2. Single-blinded design: patients were presumably aware of treatment allocation, introducing performance and reporting bias; assessor blinding status is not specified in the abstract. 3. No formal pre-specified primary endpoint is declared in the abstract, raising concern for outcome selection or multiplicity of testing. 4. No quantitative statistics (p-values, confidence intervals, effect sizes, absolute counts or dimensions) are provided in the abstract, precluding independent assessment of clinical magnitude. 5. Exclusion of plantar warts—the most treatment-refractory anatomical subtype—limits applicability to a common and clinically important subset. 6. Recurrence data (6-month rate) are referenced but not quantified in the abstract. 7. Potential anatomical asymmetry between body sides (dominant vs. non-dominant extremity) and potential contralateral inflammatory cross-effects are inherent risks of a split-body design that may not have been fully controlled. 8. Funding source is unreported, preventing assessment of conflicts of interest. 9. Setting is not explicitly reported, limiting assessment of external validity to broader healthcare systems. 10. This review is limited to the abstract; full-text analysis may reveal additional methodological strengths or weaknesses not captured here. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ In this small (n=20), single-blinded, split-body RCT, adding weekly carboxytherapy to topical 50% urea cream significantly accelerated lesion size reduction and time to complete resolution in recalcitrant common warts of the extremities compared with urea monotherapy, without a significant difference in lesion count reduction. The evidence base is preliminary and quantitatively incomplete as reported in the abstract; clinicians should await full-text publication with complete statistical data and, ideally, replication in larger blinded trials before routinely adopting carboxytherapy as an add-on for this indication.