Although patients with refractory melasma have been treated using various methods, there is still no precise definition or summary of the therapies. To define refractory melasma and conduct a review of the treatments, we searched for relevant publications in PubMed, Web of Science, and the Cochrane Library, and a total of 35 references were obtained. Refractory melasma can be roughly defined as an ineffective treatment for melasma, including topical bleaching agents, chemical peels, laser therapy, microdermabrasion for more than six months, or chemical peels treated more than six times. Meanwhile, physicians should be careful when treating patients with darker skin and dermal or mixed types of melasma since these individuals do not respond well to treatment. Lasers combined with other methods, especially different types of lasers or topical agents, are considered more effective than monotherapy. Oral tranexamic acid (TXA) is a prospective cure for refractory melasma. Other methods include a combination of chemical peels, microneedling, or injections with additional therapies. In conclusion, we were able to provide a rough definition of refractory melasma and list the available therapies. According to the literature, the most prevalent treatment is laser combination therapy. However, laser treatment should be considered only after topical agents and chemical peeling have failed. Considering its side effects, efficacy, and safety, oral TXA may be a better option, but more research is needed to make a firm conclusion. Moreover, maintenance therapy is required after treatment.

尽管顽固性黄褐斑患者已采用多种方法进行治疗，但治疗方法仍没有准确的定义或总结。为了定义难治性黄褐斑并对治疗方法进行回顾，我们在 PubMed、Web of Science 和 Cochrane 图书馆中检索了相关出版物，总共获得了 35 篇参考文献。难治性黄褐斑可以粗略地定义为对黄褐斑治疗无效，包括局部漂白剂、化学换肤、激光治疗、微晶磨皮治疗超过六个月，或化学换肤治疗六次以上。同时，医生在治疗深色皮肤和真皮或混合型黄褐斑患者时应小心，因为这些人对治疗的反应不佳。激光与其他方法相结合，特别是不同类型的激光或外用制剂，被认为比单一疗法更有效。口服氨甲环酸（TXA）是治疗难治性黄褐斑的一种有前景的药物。其他方法包括化学换肤、微针或注射与其他疗法的组合。总之，我们能够提供难治性黄褐斑的粗略定义并列出可用的治疗方法。根据文献，最流行的治疗方法是激光联合疗法。然而，只有在局部药物和化学换肤失败后才应考虑激光治疗。考虑到其副作用、疗效和安全性，口服TXA可能是更好的选择，但需要更多的研究才能得出明确的结论。而且治疗后还需要维持治疗。