Background: Botulinum toxin type A (BTA) has a wide range of clinical applications, and its use in improving aesthetics is one of them. The aim of this study was to better assess the efficacy and safety of BTA in patients with facial scars. Summary: We extracted the data of the visual analog scale (VAS) score, Vancouver scar scale (VSS) score, scar width, observer scar assessment scale (OSAS), patient scar assessment scale (PSAS), and/or drug-related adverse events. Five studies provided the data of VAS score, and the results showed that the VAS score in the BTA group was significantly higher than that in the control group. Three randomized controlled trials (RCTs) reported the VSS score. A statistically significant difference exists between the BTA group and the control group. Three RCTs reported the scar width after BTA treatment. A more favorable change was found in the BTA group with scar width even without statistical significance. Data about the OSAS and PSAS scores were available in two trials. There was no significant difference in OSAS and PSAS scores between the BTA group and the control group. Only three studies recorded three slight adverse events. There were no reports of severe complications. In conclusions, this study demonstrated that BTA has the potential to improve facial scars with an acceptable safety profile.

Facial scars caused by either trauma or surgical intervention can be cosmetically disfiguring. Besides, it causes contracture, itching, or tingling that puts patients under physical pain and emotional stress [1, 2]. Additionally, the presence of facial scars may profoundly affect the daily routines and psychosocial well-being of patients [1-3]. Despite the advancements of surgical techniques, radiation, laser, and pressure therapy to treat facial scars, the outcomes are largely unsatisfactory [4-6].

Botulinum toxin type A (BTA) is widely used to correct wrinkles caused by muscular hyperactivity [7, 8], and it is approved as a form of treatment for glabellar rhytides [9], primary axillary hyperhidrosis [10-12], blepharospasm [13, 14], cervical dystonia [15-17], and strabismus [18, 19]. Recently, there has been increasing interest in injecting BTA into fresh wounds to reduce the occurrence of scars by relaxing the adjacent muscles and minimizing the wound tension. Several randomized controlled trials (RCTs) have evaluated the effects of BTA on facial scar formation [20-22]. Hu et al. [22] reported that injecting BTA immediately after surgical wound closure at a distance of 5 mm on either side of the wound appeared to produce a better and narrower facial wound. Another study conducted by Kim et al. [23] also found similar results for BTA treatment of forehead wounds, where injecting BTA after the wound closure at multiple points around the sutured site within a 0.5 cm distance improved scar properties in various aspects. In 2013, Ziade et al. [20] evaluated whether BTA injection in facial muscles involved in scar widening within 72 h after surgery decreased scarring. They found there were no statistically significant differences in many assessment scores, including the visual analog scale (VAS) score, observer scar assessment scale (OSAS), and Vancouver scar scale (VSS) score between the BTA group and the control group [20]. Practical guidelines have been developed to prevent hypertrophic scars and keloid, and it is advised to apply the guidelines in dermatological practice when applying BTA [24, 25]. However, it cannot be determined whether BTA injection still confers benefits in patients with facial scars. Individuals’ trials were not significantly powered to evaluate the efficacy and safety of BTA across various subgroups. Therefore, for the first time, we conducted this meta-analysis to better assess the efficacy and safety of BTA in patients with facial scars by pooling available interventional evidence.

Search Strategy

The studies were retrieved in the following databases: MEDLINE (from 1950 to April 2021), Embase (from 1950 to April 2021), and Cochrane Central Register of Controlled Trials (CENTRAL, from 1950 to April 2021) with related keywords of “botulinum,” “botulin,” “Botox,” “toxin,” “randomized controlled trials (RCTs),” “randomized study,” “forehead scars,” and “facial scars.” The relevant reference lists from identified trials and review articles were also searched. We restricted the search to those published in the English language. This study was conducted according to PRISMA (online suppl. Table 1; for all online suppl. material, see www.karger.com/doi/10.1159/000522396) [26].

Study Selection, Inclusion, and Exclusion Criteria

RCTs regarding comparison of therapeutic effects of BTA in patients with facial scars were adopted. The inclusion criteria of studies were defined as follows: (1) a comparison of BTA and the placebo; (2) studies aiming at facial scars; (3) included studies have at least one reported outcome or more, including the VAS score, VSS score, scar width, OSAS, patient scar assessment scale (PSAS), and/or drug-related adverse events; and (4) the study design was an RCT, and the sample size was larger than 10. Exclusion criteria were as follows: (1) non-RCT, reviews, case reports, or experimental studies; (2) no relevant statistical information; (3) not BTA treatment; (4) no control group; and (5) duplicate publication.

Data Extraction and Quality of Evidence

First, the retrieved abstracts and full-text articles of relevant studies were screened by two authors. Subsequently, they extracted the relevant information using a standard data extraction form, which included the treatment dosage, injection time, patient age, wound location, scar length, follow-up, number of patients, and adverse events. A third reviewer checked and confirmed the accuracy of the above data. The risk of bias of trials was assessed using the Cochrane Collaboration’s tool [27].

Statistical Analysis

We calculated the mean difference (MD) with 95% confidence interval (95% CI) for continuous variables. The random-effects model was applied to these analyses. Heterogeneity among studies was evaluated using an I2 statistic. The results were considered significant with 2-sided p < 0.05. We used Review Manager 5.1 software to perform meta-analysis.

Overall, the literature search yielded 213 articles. Ultimately, after reviewing the full texts of 30 records, 7 studies relevant to BTA injection in 210 patients with facial scars were included (Fig. 1), with the sample size ranging from 14 to 45 patients in a single study [20-23, 28-30]. The studies were conducted between 2006 and 2021. The mean age ranged from 12 to 60 years, and the mean scar length ranged from 27 to 67 mm. In five studies, the wound was located on the forehead, and in two studies, the patients had face wounds. Five studies compared BTA with saline, and two studies compared BTA with a blank control. The dosage of BTA ranged from 15 U to 50 U. In two studies, BTA was injected in the entire forehead area, one in half of the forehead, two at a 5 mm distance from the sutured site, and one at 1–3 cm around the wound edges. Three studies reported BTA was injected immediately after wound closure, two studies reported within 3–5 days after surgery, and one study reported accordingly 10 days before surgery. Four studies of facial scars were post-traumatic; in two studies, the scars were caused by surgery; and one study included a complex wound that involved neoplasm, trauma, radiation, and secondary healing. The period of follow-up was from 6 months to 27 months. Baseline characteristics of included studies were shown in Table 1.

Table 1.

Characteristics of included studies

Characteristics of included studies
Characteristics of included studies
Fig. 1.

Process for identifying studies eligible for the meta-analysis.

Fig. 1.

Process for identifying studies eligible for the meta-analysis.

Close modal

Quality Assessment

The inherent risk of bias of trials was performed by the Cochrane risk of bias tool, including sequence generation, allocation concealment, performance bias, detection bias, incomplete outcome data, selective reporting, and other possible sources of bias. The summary of the risk of bias is presented in Figure 2.

Fig. 2.

Risk of bias graph (a) and risk of bias summary (b).

Fig. 2.

Risk of bias graph (a) and risk of bias summary (b).

Close modal

VAS Score

The VAS score is a widely used scale to evaluate the cosmetic outcomes of the skin, which ranges from worst (0 point) to the best (10 points). Five studies with 140 patients provided the data of the VAS score. According to the results, the VAS score in the BTA group was significantly higher than that in the control group (MD 1.25, 95% CI 0.88–1.62, p < 0.0001) with low heterogeneity (I2 = 20%, p = 0.29, Fig. 3).

Fig. 3.

Effect of BTA on the VAS score in patients with facial scars.

Fig. 3.

Effect of BTA on the VAS score in patients with facial scars.

Close modal

VSS Score

The VSS score is a tool specially designed for scar assessment, which includes four aspects: scar height (0–4 points), vascularity (0–3 points), pigmentation (0–3 points), and pliability (0–5 points). The higher scores indicate more severe scarring. The VSS score was reported in three RCTs. The results showed a statistically significant difference between the BTA group and the control group (MD = −1.49, 95% CI −2.30 to 0.68, p = 0.0003). It suggested that BTA injection had better scar quality than did the control group (Fig. 4).

Fig. 4.

Effect of BTA on the VSS score in patients with facial scars.

Fig. 4.

Effect of BTA on the VSS score in patients with facial scars.

Close modal

Scar Width

The scar width reflects the extension and proliferation of the scar after the wound has healed. Three RCTs reported scar width after BTA treatment. There was a more favorable change in the BTA group with scar width even without statistical significance (MD = −0.39, 95% CI −0.81 to 0.03, p = 0.07, Fig. 5).

Fig. 5.

Effect of BTA on the scar width in patients with facial scars.

Fig. 5.

Effect of BTA on the scar width in patients with facial scars.

Close modal

Observer Scar Assessment Scale

The OSAS reflects the observer’s opinions about the appearance of scars. Two trials reported data about the OSAS score. Accordingly, there was no significant difference in the OSAS between the BTA group and the control group (MD −1.30, 95% CI −3.18 to 0.58, p = 0.18, Fig. 6).

Fig. 6.

Effect of BTA on the OSAS in patients with facial scars.

Fig. 6.

Effect of BTA on the OSAS in patients with facial scars.

Close modal

Patient Scar Assessment Scale

The PSAS reflects the patients’ opinions about the appearance of scars. Two studies provided the data of the PSAS in 69 patients. Accordingly, BTA injection did not exhibit a significant difference in the PSAS score compared with the control group (MD 0.06, 95% CI −0.76 to 0.89, p = 0.88), which was shown in Figure 7.

Fig. 7.

Effect of BTA on the PSAS in patients with facial scars.

Fig. 7.

Effect of BTA on the PSAS in patients with facial scars.

Close modal

Adverse Events

Two studies reported two adverse events after the injections of BTA, including mild eyelid ptosis and an asymmetrical smile in the BTA group. One study reported an adverse event in the control group with a mild headache. There were no reports of any severe complications (Table 2).

Table 2.

Adverse events of included studies

Adverse events of included studies
Adverse events of included studies

To the best of our knowledge, this is the first meta-analysis to evaluate the efficacy and safety of BTA injection therapy in the treatment of facial scars. Seven studies with 210 patients were included. According to the results, it was confirmed that compared to the control group, the addition of BTA had superior efficacy in treating facial scars, which significantly improved the VAS score, VSS score, and reduced scar width. The overall differences in the PSAS and OSAS between the two groups were not statistically significant. In addition, there were not any obvious adverse events observed in BTA-treated patients. Accordingly, the results indicate that BTA is an effective and safe treatment for facial scars.

Visible facial scars can have a significant psychological impact on patients and give a negative impression to others, thereby reducing a person’s social role. Numerous studies discuss how to treat scars after formation rather than preventing them. Early positive management could likely improve cosmetic appearance and yield benefits. In 2018, an RCT conducted by Lee et al. [30] showed that patients with facial scars who received an injection of BTA within the first 5 days of surgery had significant improvement of cosmesis of facial wounds. In 2021, Lin et al. [21] followed up with 40 patients with forehead scars and demonstrated that injecting BTA immediately after wound closure could minimize facial scarring. In this study, the results showed that the VAS and VSS scores favor the BTA group. Besides, the scar width was also significantly improved in the BTA-treated group.

On the contrary, there were no significant differences in the PSAS and OSAS between the two groups, and the results were similar to Ziade et al. [20] in 2013. Traditionally, observer and patient scar assessments are used to evaluate complex wounds similar to burn scars. In recent times, BTA has been gradually used in preventing postoperative scars and improving scar quality with demonstrated improved outcomes [31-33]. Numerous studies have revealed that the tension acting on the wound edges is a critical reason for the formation of scars. The wound tension force activates local fibroblast cells to induce collagen expression and transforming growth factor-β1 expression [34]. Notably, the damaged skin releases inflammatory cell infiltration and reactive oxidative species that contribute to undesirable scars [35]. Jeong et al. [36] reported that BTA significantly reduced the α-smooth muscle actin expression and inhibited fibroblast-to-myofibroblast differentiation in hypertrophic scars. In a prospective randomized experimental study on a rat surgical wound model, the BTA-treated group exhibited less infiltration of inflammatory cells, less fibrosis, and a lower transforming growth factor-β1 expression than the control group [37]. It is possible to regulate scar formation by controlling these factors. Injecting BTA could induce temporary muscular paralysis to minimize tension on wound edges. Then again, BTA plays a role in smooth muscle relaxation on wound edges.

There is no consensus in the literature regarding the dosage and injection time of BTA to prevent facial scars. In the related studies, the BTA dosage was from 15 U to 50 U. The BTA injection time varied from 10 days before surgery to 5 days after surgery. Generally, BTA works within 3–14 days after injection. Therefore, it is believed that BTA can be injected before the surgery or immediately after wound closure. Additional clinical trials are required to standardize the indications, the technique, and the timing of the injection.

Safety is a vital concern of BTA therapy in patients with facial scars. Only three studies recorded three slight adverse events, two of which occurred in the BTA group and the other occurred in the control group. None of the studies reported any severe adverse events. Based on the results, BTA had favorable safety when used to treat facial scars.

The strength of this meta-analysis is its rigorous methodology. However, there are some limitations to the study. First, the positive results of VAS and VSS scores in the BTA group should be interpreted with caution because there were certain differences in the injection site, time, dose of BTA, and the type of facial scars among various studies. The authors did not perform subgroup analysis of VAS and VSS scores because of the small number of included studies. Second, scant outcomes prevented the authors from undertaking subgroup analysis to study the effective dose of BTA and when to commence treatment. Third, this analysis is not registered under PROSPERO. Fourth, the remodeling phase of wound healing could extend beyond 6 months. However, most studies have only 6 months of follow-up. Fifth, few studies addressed scar outcomes from a hypertrophic scar versus attenuated scar perspective. Therefore, high-quality RCTs with a longer follow-up period are needed to elucidate the efficacy and safety of BTA therapy in patients with facial scars.

This study demonstrated that BTA has the potential to improve facial scars with an acceptable safety profile. Additional high-quality RCTs with standardized injection processes, longer follow-up periods, and adequate sample sizes are required to verify if BTA is effective and safe to be injected into fresh wounds as early as possible.

We thank all the authors whose publications could be included in our meta-analysis.

Ethical approval was not required for this study in accordance with local/national guidelines.

The authors declare that they have no competing interests.

This article did not receive any funding.

Xiaobing Li designed the study. Wendi Wang and Guangjing Liu searched and collected the data. Wendi Wang analyzed the results. Wendi Wang drafted the manuscript.

All data generated or analyzed during this study are included in this article.

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