口服阿维A对106例儿童身高和骨骼发育影响的回顾性分析

Effect of oral acitretin on the height and bone development of children:a retrospective analysis of 106 cases

目的分析口服阿维A对患儿身高和骨骼发育的影响。方法回顾性分析2007年3月至2021年1月于北京儿童医院皮肤科口服阿维A疗程≥1个月的106例患儿的临床资料和影像学资料。主要观察指标为身高和接近成年终身高,多因素logistic回归分析患儿身材矮小的影响因素,对已达接近成年终身高者采用非劣效性检验分析身高与遗传靶身高的接近程度。次要观察指标为骨龄、骨骺闭合情况,Wilcoxon符号秩检验分析患儿基线与末次随访时骨龄与时序年龄差值的差异和骨骺早闭情况。结果106例患儿中,男62例,女44例,84例为脓疱型银屑病,10例为寻常型银屑病,11例为毛发红糠疹,1例为颜面播散性粟粒型狼疮,阿维A治疗剂量<1 mg·kg^(-1)·d^(-1),疗程1~90个月;0~18岁患儿96例,91例(94.8%)身材正常,5例(5.2%)身材矮小;83例阿维A单药治疗的患儿中,81例(97.6%)身材正常,2例(2.4%)身材矮小。二元logistic回归分析结果示,阿维A联合糖皮质激素治疗致身材矮小的风险比阿维A单药治疗增加76.57倍(OR=77.57,95%CI 2.20~2738.82,P=0.017),而病种、性别、发病年龄和阿维A初始治疗年龄、疗程、平均日剂量对身材矮小的影响均无统计学意义(P值分别为0.988、0.214、0.087、0.078、0.066、0.350)。13例已达接近成年终身高者均身材正常,非劣效性检验示接近成年终身高均不劣于遗传靶身高(Satterthwaite=0.23,P=0.030)。比较45例患儿基线与末次随访时骨龄与时序年龄差值,两时间点差异无统计学意义(Z=-0.85,P=0.250),且治疗前后均未出现骨骺早闭。结论本研究初步显示口服阿维A治疗(剂量<1 mg·kg^(-1)·d^(-1),疗程<90个月)对患儿身高和骨骼发育可能无明显影响。

Objective To evaluate the effect of oral acitretin on the height and bone development of children.MethodsClinical and imaging data were collected from 106 children receiving oral acitretin for at least 1 month in Department of Dermatology,Beijing Children's Hospital from March 2007 to January 2021,and retrospectively analyzed.The main outcome measures were height and near-adult height.Multivariate logistic regression analysis was carried out to investigate relevant factors for short stature in children,and non-inferiority test was used to analyze the proximity of the actual height to target height of children who had reached near-adult height.The secondary outcome measures were bone age and epiphyseal closure.Wilcoxon signed-rank test was used to analyze differences in the value of bone age minus chronological age between the baseline and last follow-up,and the premature closure of epiphysis was also evaluated.ResultsAmong the 106 children,62 were males and 44 were females;84 were diagnosed with pustular psoriasis,10 with psoriasis vulgaris,11 with pityriasis rubra pilaris,and 1 with lupus miliaris disseminatus faciei.These children received oral acitretin at doses of<1 mg·kg^(-1)·d^(-1) for 1-90 months.Among the 96 children aged under 18 years,91(94.8%)were of normal stature,and 5(5.2%)were short in stature;among the 83 children receiving acitretin monotherapy,81(97.6%)were of normal stature,and 2(2.4%)of short stature.Binary logistic regression analysis showed that the risk of short stature caused by acitretin combined with glucocorticoid therapy was 76.57 times higher than that of acitretin monotherapy(0R=77.57,95%CI:2.20-2738.82,P=0.017),while the type of disease,gender,age at onset,age at initial treatment with acitretin,course of treatment,and average daily dose of acitretin did not significantly affect the stature of children(P=0.988,0.214,0.087,0.078,0.066,0.350,respectively).At the last follow-up visit,13 children who had reached near-adult height were of normal stature,and the non-inferiority test showed that their near-adult height was not inferior to the target height(Satterthwaite=0.23,P=0.030).Bone age was evaluated in 45 children at baseline and last follow-up visit,there was no significant difference in the value of bone age minus chronological age between the baseline and last follow-up(Z=-0.85,P=0.250),and no patients experienced premature closure of epiphysis before and after the treatment.Conclusion This study preliminarily revealed that oral acitretin at doses of<1 mg·kg^(-1)·d^(-1) for less than 90 months might not significantly affect the height and bone development of children.