INTRODUCTION
Melasma is an acquired skin disease characterized by symmetric patches of hyperpigmentation on sun-exposed areas such as the cheeks, forehead, chin, nose, and upper lips. Histological features may include epidermal and dermal pigmentation, solar elastosis, increased vascularization, and mastocytosis.1
Although the true incidence of melasma is unknown, melasma has been reported to affect 1% to 50% of the population globally.2 Melasma is more prevalent in female patients of Asian, Latin American, Middle Eastern, and African descent due to multifactorial causes including increased skin pigmentation, alterations in hormone levels, family history, and sun exposure.3-6 Melasma has a tremendous societal and psychosocial impact as patients with melasma report dramatically lower self-esteem, depression, and social isolation.7,8
Therapy for melasma remains a clinical challenge and topical agents are the mainstay. First-line topical treatment options for melasma are hydroquinone (HQ) and triple combination (TC) therapies, which include HQ, a retinoid, and a steroid. Second-line treatments include chemical peels and laser therapies.9 There have been concerns about the long-term safety and efficacy of HQ. Topical HQ is associated with ochronosis, a bluish-gray discoloration of the skin.9 In response, HQ has been banned in the European Union as a cosmetic additive, but is available as a prescription medication.9
Recently, there has been tremendous scientific and general public interest in novel, safe, and effective topical agents to improve melasma. To determine the safety and efficacy of newer topical agents for melasma, we performed a systematic review of randomized controlled trials (RCTs) on topical agents for the treatment of melasma and provided evidence-based recommendations for clinical use and further research.
Although the true incidence of melasma is unknown, melasma has been reported to affect 1% to 50% of the population globally.2 Melasma is more prevalent in female patients of Asian, Latin American, Middle Eastern, and African descent due to multifactorial causes including increased skin pigmentation, alterations in hormone levels, family history, and sun exposure.3-6 Melasma has a tremendous societal and psychosocial impact as patients with melasma report dramatically lower self-esteem, depression, and social isolation.7,8
Therapy for melasma remains a clinical challenge and topical agents are the mainstay. First-line topical treatment options for melasma are hydroquinone (HQ) and triple combination (TC) therapies, which include HQ, a retinoid, and a steroid. Second-line treatments include chemical peels and laser therapies.9 There have been concerns about the long-term safety and efficacy of HQ. Topical HQ is associated with ochronosis, a bluish-gray discoloration of the skin.9 In response, HQ has been banned in the European Union as a cosmetic additive, but is available as a prescription medication.9
Recently, there has been tremendous scientific and general public interest in novel, safe, and effective topical agents to improve melasma. To determine the safety and efficacy of newer topical agents for melasma, we performed a systematic review of randomized controlled trials (RCTs) on topical agents for the treatment of melasma and provided evidence-based recommendations for clinical use and further research.
METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol, we performed a systematic search for novel and currently used topical treatments for melasma on March 4th, 2019 (Figure 1). Included articles were RCTs using topical treatments for melasma published within the
