Study On The Efficacy And Safety Of CO₂ Fractional Laser-Assisted Delivery Of Eucalyptol In The Treatment Of Vitiligo

BackgroundVitiligo is the most common depigmented skin disease,with a global prevalence of about 0.5%-2%^[1].Vitiligo seriously affects the physical and mental health and quality of life of patients,and brings great psychological burden and social burden to patients.At present,the etiology of vitiligo is not yet clear.Regarding the pathogenesis of vitiligo,there are several theories including oxidative stress hypothesis,autoimmune hypothesis and genetic hypothesis^[1].Oxidative stress hypothesis and autoimmune hypothesis are mainly two viewpoints in the pathogenesis of vitiligo.The oxidative stress hypothesis holds that reactive oxygen species can damage the structure and function of melanocytes and cause melanin synthesis disorder,which is the initiating factor of vitiligo^[2].The autoimmune hypothesis suggests that melanocytes are mainly damaged by CD8⁺T cells and cause dysfunction^[1,3].The treatment of vitiligo is still a huge challenge for the world’s dermatology community.In recent years,both domestic and abroad have emphasized that repair of oxidative stress injury is an important aspect of vitiligo treatment.More and more antioxidants have been used to treat vitiligo and found that they can regulate multiple signaling pathways to protect melanocytes from oxidative stress damage^[4].Studies have found that topical antioxidants（e.g.peroxiredoxin/superoxide dismutase）have promise clinical efficacy which is comparable to that of topical glucocorticoids in the treatment of vitiligo^[5].Eucalyptol（also named 1,8-cineole,Cin）is a single compound with a wide range of biological activities.It has strong antioxidant^[6,7],anti-inflammatory and analgesic effects.It has been widely used in respiratory and nervous system diseases.A variety of antioxidant mechanisms have been confirmed.Laser-assisted delivery is a new approach to promote percutaneous drug absorption.And it is in the treatment of vitiligo because it can promote the penetration and absorption of drugs,and the curative effect is better than that of single laser or drug treatment^[8].ObjectiveTo evaluate the efficacy and safety of CO₂ fractional laser（hereinafter:CO₂laser）-assisted delivery of eucalyptol in the treatment of vitiligo,and to explore whether eucalyptol can be used as an alternative or adjuvant therapy for patients with mild to moderate vitiligo and those who cannot tolerate the adverse reactions of traditional treatment,so as to provide theoretical and practical basis for expanding the application of eucalyptol in the treatment of skin diseases.MethodVitiligo patients skin lesions with loss of pigmentation or hypopigmentation were selected as objects.On the basis of CO₂ fractional laser treatment,different concentrations of eucalyptol emulsion/spirit agent were topically applied.Through self-control before and after treatment and comparison with matrix group,the VASI score,VASI improvement rate,efficacy classification and efficacy satisfaction were used as indicators to explore the clinical efficacy and safety of CO₂ fractional laser-assisted delivery of different concentrations and different dosage forms of eucalyptol in the treatment of vitiligo.Results1.The VASI score of the CO₂ laser+eucalyptol group at the 20th week（W20）was lower than that of at the beginning（W0）（0.0605vs.0.0369）,and the difference was statistically significant（P<0.05）.The proportion of VASI50 at W20 was 36.71%,the effective rate was 69.62%,and the curative effect satisfaction was 4.165±2.539;The median VASI scores of W0,W4,W8,W12,W16 and W20 weeks in the CO₂ laser+eucalyptol group were 0.0605,0.0459,0.0433,0.0401,0.0373 and 0.0369,respectively,and the difference was statistically significant（P<0.05）.The VASI score of the eucalyptol group at W20 was lower than that at W0（0.0367 vs.0.0147）,and the difference was statistically significant（P<0.05）.There was no significant difference in VASI improvement rate,effective rate and efficacy satisfaction between CO₂ laser+eucalyptol group and CO₂ laser+matrix group,and between CO₂ laser+eucalyptol group and eucalyptol group（all P>0.05）.2.There was no significant difference in VASI improvement rate,effective rate and efficacy satisfaction between facial and neck lesions and non-facial and neck lesions,and lesions with a course of less than 1 year and lesions with a course of more than 1 year,and advanced lesions and stable lesions（all P>0.05）at the W20post-treatment for group of CO₂ laser+eucalyptol.3.At W20 of treatment,there was no significant difference in VASI improvement rate,effective rate and satisfaction between CO₂ laser+5%eucalyptol emulsion group and CO₂ laser+2.5%eucalyptol emulsion group,CO₂ laser+5%eucalyptol emulsion group and CO₂ laser+2.5%eucalyptol spirit group（all P>0.05）.4.The incidence of pruritus was 3.38%and the incidence of desquamation was1.27%in the treatment of vitiligo with CO₂ laser+eucalyptol.There was no local adverse reaction in the single eucalyptol preparation group.There was no significant difference in liver and renal function（ALT,AST,Cr,BUN）levels at 0,12 and 20weeks of post-treatment（P>0.05）.Conclusion1.CO₂ fractional laser-assisted delivery of eucalyptol in the treatment of vitiligo has good clinical efficacy,and the efficacy is positively correlated with the treatment time..2.The clinical efficacy of different concentrations and different dosage forms of eucalyptol for external use is not related to whether vitiligo is exposed,whether the course of disease is more than 1 year,and whether vitiligo is stable,but it needs to expand the sample size to continue in-depth study.3.CO₂ fractional laser-assisted delivery of eucalyptol has good safety in the treatment of vitiligo.The incidence of local adverse reactions is low and mild,and no systemic adverse reactions occur.