Efficacy of Botulinum Toxin A for the Management of Melasma: A Split-Face, Randomized Control Study

A型肉毒毒素治疗黄褐斑的疗效：一项半侧面部、随机对照研究

Background: Melasma management remains challenging due to its multifactorial nature pathogenesis and recurrent nature. Previous studies showed positive effects of botulinum toxin A (BoNT-A) for treating and preventing ultraviolet-induced hyperpigmentation.

Objective: To evaluate the effectiveness of adjunctive incoBoNT-A injection combined with triple combination cream (TCC, 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide) for treating and preventing melasma recurrence compared to topical therapy alone.

Methods: A split-face study was conducted in 30 female patients with melasma. One side of the face was randomly applied TCC to the melasma-affected areas for 12 weeks (monotherapy), while the contralateral side received TCC and intradermal incoBoNT-A at baseline and week 12 (combination therapy side). Evaluations were performed at baseline and 2, 4, 8, 12, 16, 20, and 24 weeks. Clinical improvement and melanin index were assessed using the MASI score on the malar area (MASIm), and Colorimeter respectively. Patient satisfaction was also evaluated.

Results: Twenty-eight subjects completed the study. The combination therapy side showed significant MASIm decrease at week 2 (p = 0.0032), while the monotherapy side showed no significant change. At 4 weeks, a greater reduction of MASIm was observed in the combination therapy side (MASIm 14.5 and 11.54, 20.41% reduction) when compared to the monotherapy side (MASIm 11.68 and 11.79, 0.93% worsening). At week 12, worsening of melasma was observed on both sides during the summer period. At week 24 (3 months after discontinuing TCC), MASIm was 14.79 on the monotherapy side (worsen 21.03% from baseline) and 9.14 on the combined technique (36.97% improvement, p = 0.0003). Patients' satisfaction was higher for the combination therapy when compared to the monotherapy at the end of the study (8.92 vs. 7.04, p < 0.0001). No serious adverse events occurred.

Conclusion: Intradermal incoBoNT-A injection combined with TCC demonstrated superior efficacy in melasma treatment and recurrence prevention compared to TCC monotherapy.

背景：黄褐斑的治疗极具挑战性，这与其发病机制的多因素性及易复发特性有关。既往研究表明，A型肉毒毒素（BoNT-A）在治疗和预防紫外线诱导的色素沉着方面具有积极作用。

目的：评估在“三联疗法”药膏（TCC，含4%氢醌、0.05%维A酸和0.01%氟轻松）的基础上，联合注射A型肉毒毒素（incoBoNT-A）治疗黄褐斑及预防其复发的有效性，并与单纯外用药物治疗进行对比。

方法：本研究采用半脸对照设计，纳入30名患有黄褐斑的女性患者。面部一侧（单药治疗侧）在黄褐斑区域外涂TCC，持续12周；另一侧（联合治疗侧）在基线和第12周时，除外涂TCC外，还接受了皮内注射incoBoNT-A。分别在基线及第2、4、8、12、16、20和24周进行评估。通过颧骨区域的黄褐斑面积及严重程度指数（MASIm）评估临床改善情况，并使用比色仪测量黑色素指数。同时评估了患者的满意度。

结果：共有28名受试者完成了研究。联合治疗侧在第2周时MASIm评分显著下降（p = 0.0032），而单药治疗侧未见显著变化。在第4周时，联合治疗侧的MASIm评分降幅更为明显（从14.5降至11.54，降幅为20.41%），而单药治疗侧则无明显改善（从11.68变为11.79，反而加重了0.93%）。在第12周（夏季期间），观察到两侧的黄褐斑均出现了加重。在第24周（停止TCC治疗3个月后），单药治疗组的MASI评分（MASIm）为14.79（较基线恶化21.03%），而联合治疗组为9.14（改善36.97%，p = 0.0003）。研究结束时，患者对联合治疗的满意度高于单药治疗（8.92分 vs. 7.04分，p < 0.0001）。未发生严重不良事件。

结论：与单纯TCC治疗相比，皮内注射incoBoNT-A联合TCC在黄褐斑治疗及预防复发方面展现出更优的疗效。

Chaijaras S, Boonpethkaew S, Chirasuthat S, Sakpuwadol N, Yongpisarn T, Anansiripun P, Vachiramon V. Efficacy of Botulinum Toxin A for the Management of Melasma: A Split-Face, Randomized Control Study. J Cosmet Dermatol. 2025 Aug;24(8):e70376.

202508-肉毒联合三联乳膏治疗黄褐斑.pdf