肝豆状核变性并发红斑狼疮4例及文献复习

Lupus erythematosus in Wilson's disease:four cases and literature review

目的分析肝豆状核变性(Wilson's disease,WD)并发红斑狼疮患者的临床特点。方法收集北京协和医院2013年1月至2020年1月WD并发红斑狼疮患者的临床资料,回顾性分析及总结临床表现、实验室检查、诊治及转归并复习相关文献。结果WD并发红斑狼疮患者4例,其中2例为青霉胺诱导的药物性红斑狼疮(drug induced lupus erythematosus,DILE),分别在青霉胺治疗后2年和5年后出现;2例为系统性红斑狼疮(systematic lupus erythematosus,SLE)与WD同时诊断。仅1例为男性,年龄13~20岁。WD方面,3例患者表现为肝酶升高,1例表现为锥体外系症状。红斑狼疮方面,4例患者均表现为多系统受累,包括肾脏、血液、神经、皮肤关节等,3例有补体下降,4例均发现抗核抗体(ANA),2例发现抗双链DNA(dsDNA)抗体,2例存在抗磷脂抗体谱(APLA)。2例DILE均将青霉胺更换为硫酸锌口服,1例SLE并发WD加用硫酸锌口服,另1例则加用二巯基丙磺酸钠静脉治疗序贯硫酸锌口服;3例加用激素治疗,1例联合霉酚酸酯(MMF)。随访3个月~2年,4例患者病情均好转。结论WD可并发红斑狼疮。SLE患者出现无法解释的肝损伤、锥体外系症状突出、MRI提示双侧基底节区异常信号以及K-F环是WD诊断最重要的线索,治疗上慎用青霉胺。青霉胺致DILE的患者皮肤、关节、浆膜腔受累以及乏力等系统性症状更为多见,多伴ANA、抗ds-DNA等自身抗体阳性,治疗上应停用青霉胺,必要时可应用糖皮质激素,预后总体较好。

Objective To analyze the clinical features,treatment,and outcome of Wilson's disease(WD)coexisting with lupus erythematosus.Methods Four patients of WD coexisting with lupus erythematosus were retrospectively enrolled in Peking Union Medical College Hospital from January 2013 to January 2020.Their clinical records were analyzed and recent literature was reviewed.Results Among the four cases,2 were drug induced lupus erythematosus(DILE),which appeared 2 years and 5 years after penicillamine treatment for WD respectively.Two were systemic lupus erythematosus(SLE)diagnosed with WD simultaneously.Only 1 patient was male and their ages ranged between 13 and 20 years old.Three patients presented with elevated liver enzymes and 1 presented with extrapyramidal symptoms as WD manifestations.All patients presented with multi-organ involvement as lupus manifestations,including abnormalities of kidneys,nervous system,hematologic system,skin and joints.Three patients had hypocomplementemia and all patients had positive ANA.Two had anti-dsDNA antibodies and 2 had APLA.Penicillamine was changed into oral zinc sulfate in the 2 DILE cases.Oral zinc sulfate was the initial treatment in 1 WD case complicated with SLE while sodium dimercaptopropane sulfonate was started as initial therapy in the other case.Three patients were treated with corticosteroid.1 case was also treated with mycophenolate mofetil.Follow-up ranged from 3 months to 2 years and all cases showed improvement.Conclusions WD can coexist with SLE or DILE.Unexplained liver damage despite stable SLE,prominent extrapyramidal symptoms,abnormal signals of bilateral basal ganglia on MRI,and K-F rings are the most important diagnostic clues towards WD.Penicillamine should be avoided in such circumstances.Compared with SLE,rashes,arthritis,serositis and constitutional symptoms are more common in DILE.ANA and anti-dsDNA antibodies are usually positive.Penicillamine should be stopped and glucocorticoids may be needed to treat DILE.Overall prognoses are optimal.