Abstract: 【Abstract】 Objective To compare the clinical data and peripheral blood levels of CXC chemokine ligand （CXCL） 9 and CXCL10 between patients with progressive non-segmental vitiligo who were sensitive to systemic glucocorticoid treatment and those who were resistant, and to clarify key clinical factors influencing the sensitivity to systemic glucocorticoid treatment. Methods From May 2021 to May 2023, a cohort of patients with progressive non-segmental vitiligo receiving systemic glucocorticoid treatment was established in Huashan Hospital, Fudan University. Clinical data and peripheral blood samples were prospectively collected from all enrolled patients. Standard treatment, i.e., intramuscular injections of 1 ml of compound betamethasone once a month, was administered. After 3-month treatment, the improvement of patients′ skin lesions was estimated, and the vitiligo area and severity index （VASI） score and the Vitiligo European Task Force assessment tool （VETFa） were used to evaluate the efficacy. Patients with VASI changes ≥ 0 and VETFa progression scores ≤ 0 point were included in the glucocorticoid-sensitive group （i.e., the patients′ condition was stable or improved）, otherwise those with VASI changes < 0 and VETFa progression scores of 1 point were included in the glucocorticoid-resistant group. Associations of lesion locations, specific clinical markers （trichrome lesions, confetti-like depigmentation, and Koebner phenomenon）, previous medication history, family history of vitiligo, etc. with the response to systemic glucocorticoid treatment were analyzed. At baseline and after 3-month treatment, peripheral blood samples were collected from the patients, and enzyme-linked immunosorbent assay was performed to detect the plasma levels of CXCL9 and CXCL10. Statistical analysis was carried out by using the chi-square test, Fisher′s exact test, binary logistic regression analysis, Mann-Whitney U test, and Wilcoxon signed-rank test. Results A total of 142 patients with vitiligo were enrolled, and 127 completed 3-month treatment, including 77 males and 50 females. Their age at diagnosis was 18 to 65 （36.6 ± 11.4） years, and the disease duration ranged from 2 months to 58 （13.5 ± 10.7） years; 25 （19.7%） had a family history of vitiligo; the percentage of lesion area to total body surface area before treatment ranged from 1% to 70% （11.5% ± 12.7%）, and the VASI score was 1% to 70% （10.8% ± 11.6%）. Multivariate logistic regression analysis showed that the absence of specific clinical markers （odds ratio ［OR］ = 6.900, 95% confidence interval ［CI］: 1.228, 38.757, P = 0.028）, carrying a single specific clinical marker （OR = 2.579, 95% CI: 1.012, 6.574, P = 0.047）, having a history of topical glucocorticoid treatment （OR = 2.643, 95% CI: 1.019, 6.850, P = 0.041）, the absence of family history of vitiligo （OR = 5.090, 95% CI: 1.070, 24.215 , P = 0.030）, and lesions on the proximal extremities （OR = 3.767, 95% CI: 1.315, 10.793, P = 0.037） were risk factors for the resistance to systemic glucocorticoid treatment in the patients with vitiligo. After 3-month treatment, the glucocorticoid-sensitive group showed a significant decrease in plasma CXCL10 levels compared with those before treatment （W = 571.00, P < 0.001）, while there was no significant difference between the pre- and post-treatment CXCL10 levels in the glucocorticoid-resistant group （W = 48.00, P = 0.524）. Additionally, no significant difference was observed in changes of the plasma CXCL9 level before and after treatment between the glucocorticoid-sensitive and glucocorticoid-resistant groups （P > 0.05）. Conclusions Carrying no or a single specific clinical marker, having a history of topical glucocorticoid treatment, the absence of family history of vitiligo, and lesions on the proximal extremities appeared to be risk factors for the resistance to systemic glucocorticoid treatment in patients with progressive non-segmental vitiligo. Changes in CXCL10 levels after treatment may be used as an important evaluation indicator for determining whether patients with progressive vitiligo were resistant to systemic glucocorticoid treatment.

Key words: Vitiligo, Glucocorticoids, Chemokine CXCL10, Systemic treatment, Influencing factors