Intralesional corticosteroid injection is a standard treatment for keloid and hypertrophic scars, and a 2021 meta-analysis of randomized trials (Liu and Zhang) reported that adding botulinum toxin type A improved pain, scar scores, thickness, itching, and satisfaction. Later syntheses have sharpened rather than settled the question: a 2024 meta-analysis of 11 trials confirmed better effective rate and symptom scores but found no significant effect on scar thickness, and 2025–2026 network meta-analyses show botulinum toxin type A has strong treatment response but unproven recurrence reduction, while both call for well-designed head-to-head trials with standardized endpoints and longer follow-up. The unresolved problem is whether corticosteroid combined with botulinum toxin type A is durably superior to corticosteroid alone — with follow-up beyond the toxin's 2–6 month effective duration — and what the effective dose, injection interval, and safety profile of the combination are.

Background

Keloids and hypertrophic scars are benign fibroproliferative overgrowths of dermal collagen that form after skin injury: hypertrophic scars stay within the original wound boundaries and may regress, whereas keloids extend beyond the wound edges and recur after excision. Both cause pain, itching, disfigurement, and psychological distress, and there is no unified standard treatment. Intralesional corticosteroid injection — most commonly triamcinolone acetonide injected directly into the scar — is a first-line therapy that suppresses inflammation and collagen synthesis, but its efficacy is incomplete and injections carry adverse effects such as skin atrophy, hypopigmentation, and telangiectasia (visible small dilated blood vessels). Botulinum toxin type A (BTX-A), the toxin that blocks acetylcholine release at neuromuscular junctions and is better known for treating dystonia and wrinkles, has been proposed as an adjunct on the rationale that reducing local muscular tension and fibroblast activity (including effects on transforming growth factor beta signaling) limits scar formation. Since BTX-A acts for only about 2–6 months per injection, any benefit it adds must be judged against the need for repeat injections. Efficacy is typically measured with subjective or semi-objective instruments: the Vancouver Scar Scale (VSS, a composite score of scar thickness, vascularity, pliability, and pigmentation), a Visual Analog Scale (VAS) for pain or itching, direct scar-thickness measurement, effective rate (the proportion of patients meeting a predefined improvement criterion), and patient satisfaction. Liu and Zhang (2021) pooled the randomized comparisons available at the time — a small, geographically concentrated evidence base of seven trials, mostly from China, India, and Iran, using heterogeneous drug doses, injection intervals, and schedules, and following patients for roughly 6 months — and concluded that corticosteroid plus BTX-A was superior to corticosteroid alone on all pooled endpoints. That conclusion, and the limitations it rests on, define the still-open clinical question: what the combination truly adds over corticosteroid alone, for how long, and at what regimen and safety cost.

Problem Statement

Determine, from the best available evidence — the existing randomized comparisons together with any further trials identified by systematic literature search — whether intralesional corticosteroid combined with botulinum toxin type A is durably superior to intralesional corticosteroid alone in the treatment of keloid and hypertrophic scars when patients are followed beyond the roughly 6-month horizon of the existing trials — beyond the toxin's 2–6 month effective duration per injection — resolving the now-contested scar-thickness endpoint and quantifying effects on symptom scores, scar quality, effective rate, and recurrence, and establish, for the combination, its safety and complication profile relative to corticosteroid monotherapy and which dose and injection-interval regimen is effective, questions that the existing heterogeneous, geographically concentrated trial base (predominantly in China, India, and Iran) leaves open. For each of these questions, where fewer than two comparable randomized comparisons report the endpoint, the evidence does not determine it.

References

  1. Liu XG, Zhang D (2021). Evaluation of Efficacy of Corticosteroid and Corticosteroid Combined with Botulinum Toxin Type A in the Treatment of Keloid and Hypertrophic Scars: A Meta-Analysis. Aesthetic Plastic Surgery 45(6):3037-3044. DOI: 10.1007/s00266-021-02426-w. https://doi.org/10.1007/s00266-021-02426-w
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