Abstract: 【Abstract】 Objective To analyze factors influencing the melasma severity, and to evaluate the efficacy of different treatment modalities. Methods A retrospective analysis was conducted on clinical data from patients diagnosed with melasma at the Pigmentary Disorders Specialty Clinic in the Department of Dermatology, Huashan Hospital, Fudan University from July 2018 to December 2023. Patients' Fitzpatrick skin types, lesion color, locations and subtypes were evaluated by dermatologists, the melasma area and severity index （MASI）scores were calculated, and ΔMASI scores （baseline MASI scores - post-treatment MASI scores） were used for efficacy evaluation. The t test and one-way analysis of variance were used to analyze factors influencing the severity of melasma, the paired t test was used to analyze the differences in MASI scores before and after treatment, and a multivariate linear regression model was established to analyze factors influencing the efficacy in the treatment of melasma. Results A total of 254 patients （including 249 females, 98.0%） with melasma were included, with ages of 40.8 ± 6.1 years. The Fitzpatrick skin type was Ⅲ in 213 （83.9%） patients, and Ⅳ in 41 （16.1%） patients; 180 （70.9%） patients lacked the habit of using sunscreens regularly. According to the location of pigment deposition?, 166 cases （65.4%） were classified as epidermal type, and 88 （34.6%） as mixed type. Pigmented lesions were located on the cheek （174 cases, 68.5%）, midface （26 cases, 10.2%）, or lower jaw （54 cases, 21.3%）, with periorbital involvement observed in 127 cases （50.0%）. Before treatment, baseline MASI scores were significantly higher in the skin type Ⅳ group （19.75 ± 5.08） than in the skin type Ⅲ group （14.47 ± 4.18, P < 0.001）, in the non-sunscreen users （16.45 ± 4.61） than in the sunscreen users （12.59 ± 3.91, P < 0.001）, in the epidermal type group （15.99 ± 4.82） than in the mixed type group （14.07 ± 4.35, P < 0.001）, in the mandibular type group （18.37 ± 5.14） than in the midfacial type group （14.23 ± 3.46, P < 0.001） and malar type group （14.54 ± 4.40, P < 0.001）, as well as in the patients with periorbital involvement （16.54 ± 4.90） than in those without （14.10 ± 4.26, P < 0.001）. According to the main treatment regimens, the patients were divided into the topical 2% hydroquinone group （109 cases, topically treated with 2% hydroquinone cream nightly）, topical non-hydroquinone skin-lightening agents group （36 cases, topically treated with non-hydroquinone skin-lightening or exfoliating agents）, oral tranexamic acid group （50 cases, treated with oral tranexamic acid 250 mg twice daily）, and alpha hydroxy acid （AHA） chemical peeling group （30 cases, receiving AHA chemical peeling treatment monthly with the AHA concentration escalating from 20% to 50%）. After treatment, MASI scores were significantly reduced from baseline in all the 4 groups （all P < 0.001）, and the ΔMASI values significantly differed among the topical 2% hydroquinone group, topical non-hydroquinone skin-lightening agents group, oral tranexamic acid group, and AHA chemical peeling group （1.65 ± 2.19, 1.40 ± 2.16, 4.58 ± 3.09, 3.39 ± 3.61, respectively, F = 17.40, P < 0.001）. The oral tranexamic acid group and AHA chemical peeling group showed significantly superior efficacy compared to the topical 2% hydroquinone group and topical non-hydroquinone skin-lightening agents group （all P < 0.05）, while there was no significant difference in the efficacy between the oral tranexamic acid group and the AHA chemical peeling group （P > 0.05）. After adjustment for potential confounders in the multivariate linear regression model, the oral tranexamic acid group （β = 2.64） and AHA chemical peeling group （β = 1.55） still showed significantly superior efficacy compared to the topical 2% hydroquinone group （both P < 0.05）; the skin type Ⅳ group exhibited significantly superior efficacy compared to the skin type Ⅲ group （β = 1.87, P < 0.001）. Conclusions Dark skin color, lack of sun protection habits, epidermal melasma, and mandibular-type melasma, and periorbital involvement were associated factors for the severity of melasma. Oral tranexamic acid and AHA chemical peeling appeared to exhibit superior efficacy compared to topical 2% hydroquinone cream and topical non-hydroquinone skin-lightening agents.

Key words: Chloasma, Clinical types, Severity of illness index, Influencing factors, Therapy, Tranexamic acid, Chemexfoliation, Treatment outcome, Melasma area and severity index