Use of botulinum toxin for the treatment of keloid scars: scoping review

MONTEIRO, EDUARDO LAFAYETTE; QUEIROZ, KARINE LORENA SOUSA; AZEVEDO, THIAGO ALEXANDRE MACEDO DE

doi:10.5935/2177-1235.2024RBCP0841-EN

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Review Article • Rev. Bras. Cir. Plást. 39 (1) • 2024 • https://doi.org/10.5935/2177-1235.2024RBCP0841-EN copy

Use of botulinum toxin for the treatment of keloid scars: scoping review

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction:

Visible scars can cause problems, whether aesthetic, psychological, functional, or social, mainly of great extension and volume, such as keloids. The discovery of new treatments for keloids is not easy, given the presence of some methodological and ethical obstacles, and it is an area that is little explored. Botulinum toxin has been presented as a therapeutic alternative in national and international studies, requiring a compilation and highlighting of the main studies that can support clinical practice. Thus, the objective was to present a scoping review on the therapeutic use of botulinum toxin for the treatment of keloid scars. Method: The review was carried out using the PICO strategy and using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. It was carried out in the PubMed/Medline, Virtual Health Library, and SciELO databases, considering studies from 2016 to September 2021. Results: Overall, 34 articles related to the topic were found. After filtering and selection, the review was constructed with the support of 5 articles. The studies varied between cohorts, case reports, randomized clinical trials, and case-control. It was possible to observe as main results of the short-term action of botulinum toxin in reducing keloids, greater effectiveness in reducing symptoms, and possibilities of clinical use for different populations and clinical manifestations. Conclusion: The mechanism of action of botulinum toxin can facilitate the treatment of keloids and reduce symptoms, requiring more robust studies to define effective scar management protocols.

Keywords:
Keloid; Therapeutic Human experimentation; Botulinum toxins; type A; Reconstructive surgical procedures; Evidence-based practice

Reference	Title	Study type
Cardoso et al. (2016)²2 Cardoso AS, Teixeira DA, Oliveira BV, Carneiro PP, Junqueira RF. Botulinum toxin application in the secondary intention healing. Surg Cosmet Dermatol 2016;8(2):163-6.	Application of botulinum toxin in secondary intention healing	Case report
Pruksapong et al. (2017)⁹9 Pruksapong C, Yingtaweesittikul S, Burusapat C. Efficacy of Botulinum Toxin A in Preventing Recurrence Keloids: Double Blinded Randomized Controlled Trial Study: Intraindividual Subject. J Med Assoc Thai. 2017;100(3):280-6.	Efficacy of Botulinum Toxin A in Preventing Recurrence of Keloids: Double Blinded Randomized Controlled Trial Study: Intraindividual Subject	Randomized Clinical Trial
Zhou et al. (2017)¹⁰10 Zhou M, Wang L, Jiang R, Zhu M, Chen F. Evaluation on efficacy and adverse reactions of combined therapy with botulinum toxin type A in treatment of keloid. J Jilin Un (Medicine Ed.). 2017;6:386-90.	Evaluation on efficacy and adverse reactions of combined therapy with botulinum toxin type A in treatment of keloid	Case-control
Rasaii et al. (2019)¹¹11 Rasaii S, Sohrabian N, Gianfaldoni S, Hadibarhaghtalab M, Pazyar N, Bakhshaeekia A, et al. Intralesional triamcinolone alone or in combination with botulinium toxin A is ineffective for the treatment of formed keloid scar: A double blind controlled pilot study. Dermatol Ther. 2019;32(2):e12781.	Intralesional triamcinolone alone or in combination with botulinium toxin A is ineffective for the treatment of formed keloid scar: A double blind controlled pilot study	Cohort
Pires et al. (2020)¹²12 Pires M, Soudo A, Costa MJ. Toxina Botulínica Tipo A no Tratamento das Cicatrizes Hipertróficas por Queimadura em Idade Pediátrica: Caso Clínico. Rev Soc Port Med Fís Reab. 2020;32(3):126-9.	Botulinum toxin type A in the treatment of hypertrophic burn scars in pediatric age: Clinical Case	Case report

Reference	Method	Clinical criteria
Cardoso et al. (2016)²2 Cardoso AS, Teixeira DA, Oliveira BV, Carneiro PP, Junqueira RF. Botulinum toxin application in the secondary intention healing. Surg Cosmet Dermatol 2016;8(2):163-6.	N=1 Age = 36 years Botulinum toxin application type A	Scar resulting from Mohs micrographic surgery in the supralabial region; Operative scar measuring 3 x 1.6cm; Application in the immediate postoperative period
Pruksapong et al. (2017)⁹9 Pruksapong C, Yingtaweesittikul S, Burusapat C. Efficacy of Botulinum Toxin A in Preventing Recurrence Keloids: Double Blinded Randomized Controlled Trial Study: Intraindividual Subject. J Med Assoc Thai. 2017;100(3):280-6.	N=25 patients, 50 keloids Average age = 26 years Control group = injection of corticosteroid therapy Study group = toxin botulinum type A	Present two scars keloids; Not being pregnant or breastfeeding; Scars larger than 10cm; not be allergic to toxin, lidocaine; Do not present undesirable medical conditions and use anticoagulant drugs or antiplatelet agents
Zhou et al. (2017)¹⁰10 Zhou M, Wang L, Jiang R, Zhu M, Chen F. Evaluation on efficacy and adverse reactions of combined therapy with botulinum toxin type A in treatment of keloid. J Jilin Un (Medicine Ed.). 2017;6:386-90.	N=58 Control group = injection of betamethasone and topical hyaluronic acid Study group = toxin combined type A botulinum with injection of betamethasone and topical hyaluronic acid	Present scars keloids; No restrictions on the pharmacological components of the study
Rasaii et al. (2019)¹¹11 Rasaii S, Sohrabian N, Gianfaldoni S, Hadibarhaghtalab M, Pazyar N, Bakhshaeekia A, et al. Intralesional triamcinolone alone or in combination with botulinium toxin A is ineffective for the treatment of formed keloid scar: A double blind controlled pilot study. Dermatol Ther. 2019;32(2):e12781.	N=23 Average age = 23 years Control group = intralesional triamcinolone acetonide plus placebo Study Group = botulinum toxin type A combined with saline solution	Present two scars keloids; Do not be pregnant or breastfeeding; Absence of neuromuscular junction disease or use of neuromuscular junction blockers
Pires et al. (2020)¹²12 Pires M, Soudo A, Costa MJ. Toxina Botulínica Tipo A no Tratamento das Cicatrizes Hipertróficas por Queimadura em Idade Pediátrica: Caso Clínico. Rev Soc Port Med Fís Reab. 2020;32(3):126-9.	N=1 Age = 12 years Application of botulinum toxin type A with prior topical analgesia with lidocaine + prilocaine 25 mg/g cream	Scars resulting from 2^nd and 3^rd burns on the face, scalp, ear pinna, neck, anterior side of the chest, and upper limbs; Application to the right axillary scar and radial border of the first finger of the right hand; Application 5 months post-burn

Reference	Treatment	Results	Conclusions
Cardoso et al. (2016)²2 Cardoso AS, Teixeira DA, Oliveira BV, Carneiro PP, Junqueira RF. Botulinum toxin application in the secondary intention healing. Surg Cosmet Dermatol 2016;8(2):163-6.	8 units of BTA in the surgical wound, with healing by secondary intention.	Complete wound healing in 18 days with formation of slightly erythematous scar tissue on the upper lip, with slight extension to the supralabial region, maintained in the late postoperative period, favoring aesthetics and functionality.	The molecular properties of BTA suggest that its action is best at the beginning of healing, when the fibroblasts are still in the proliferative phase and have intense apoptotic activity, requiring further studies on this process in secondary healing.
Pruksapong et al. (2017)⁹9 Pruksapong C, Yingtaweesittikul S, Burusapat C. Efficacy of Botulinum Toxin A in Preventing Recurrence Keloids: Double Blinded Randomized Controlled Trial Study: Intraindividual Subject. J Med Assoc Thai. 2017;100(3):280-6.	Control group = Injection of triamcinolone acetonide (10mg/cc) seven days after stitch removal, repeated in the first, second, and third months. Study group = intradermal BTA, with a dose of 1.5 units / 1cm length (Botox® 50 units of toxin with 0.9% NSS for injection 2.5cc, concentration 2 units per 0.1cc) seven days after stitch removal (one dose).	In the first and third months, the outcome in the toxin group was more favorable than in the control group, while the outcome in the control group was more favorable than in the toxin group in the sixth month of follow-up.	The use of BTA is significantly better at preventing keloids from recurring when compared to corticosteroid therapy after one and three months. However, corticosteroid therapy offers significantly better results at 6-month follow-up.
Zhou et al. (2017)¹⁰10 Zhou M, Wang L, Jiang R, Zhu M, Chen F. Evaluation on efficacy and adverse reactions of combined therapy with botulinum toxin type A in treatment of keloid. J Jilin Un (Medicine Ed.). 2017;6:386-90.	Control group = Betamethasone and topical hyaluronic acid injection. Study group = botulinum toxin type A combined with betamethasone and topical hyaluronic acid injection. Both groups of patients were locally injected with betamethasone once every 4 weeks, 3 consecutive times, and topical hyaluronic acid was used daily. Patients in the combined treatment group were injected with botulinum toxin type A into the periphery of the skin lesion after the first injection of betamethasone.	The aesthetics of the skin lesions in the study group improved better after 3 applications. Pain and itch scores in the control group decreased during 1 month of treatment but gradually increased at 2 and 3 months; in contrast, in patients in the study gradually decreased within 3 months of treatment, this difference being statistically significant. Over the course of 3 months of treatment, the thickness of skin lesions in the study group gradually decreased, but the reduction in the control group was not significant. The pain, itching symptoms, and skin thickness of patients in the control group increased 2 weeks after each injection, while the combination treatment group did not experience recurrence. The incidence of adverse reactions in the control group was 26.7% and in the study group it was 25.0%, with no significant difference between the two groups.	BTA combined with local injection of betamethasone and topical hyaluronic acid for the treatment of keloids is more effective than local injection of betamethasone and topical hyaluronic acid alone, and there is no significant difference in the incidence of adverse reactions, being favorable for clinical application.

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[1] Conflicts of interest: none.