A20单倍剂量不足合并系统性红斑狼疮1例并文献复习

Haploinsufficiency of A20 complicated with systemic lupus erythematosus:a case report and literature review

目的总结1例A20单倍剂量不足(HA20)合并系统性红斑狼疮(SLE)患儿的临床特点。方法选择2019年6月于西安市儿童医院治疗的1例HA20合并SLE患儿(患儿1)为研究对象。采用回顾性分析法,对患儿1的临床病例资料进行分析,并检索国内外数据库中关于HA20合并SLE患者的研究文献,总结该病患者的临床特点。本研究遵循的程序经西安市儿童医院伦理委员会批准(审批文号:20230048)。监护人对患儿1的诊治知情同意。结果①患儿1为女性,5岁6个月龄,以脓疱疮、发热、关节痛为主要表现,伴口腔溃疡,肝、脾、淋巴结大及身材矮小。其既往有肝、脾大及血小板减少症状。患儿1实验室检查结果显示,蛋白尿、自身免疫性溶血性贫血、血清补体成分(C)3降低,抗核抗体(1∶1000)、抗Sm抗体均呈阳性;肾脏穿刺组织病理检查结果为轻度系膜增生型狼疮性肾炎Ⅱ型(LN-Ⅱ);基因检测结果显示TNFAIP3基因c.547(exon4)C>T杂合变异,为致病性变异,来源于其父亲。对患儿1相继采取激素、环孢素、环磷酰胺、吗替麦考酚酯治疗,期间在激素减量后再次出现皮疹、血清C3下降及尿蛋白量增加,截至发稿患儿1无皮疹等表现,血清C3轻度降低,尿蛋白呈阴性。患儿1最终被诊断为HA20、SLE及LN-Ⅱ。②文献复习结果:文献检索到关于HA20合并SLE患者(患者2~15)研究文献,对这14例该病患者,加上患儿1,共计15例的分析结果显示:男性患者为2例、女性为13例,发病年龄为2个月至29岁;合并肾脏损害者为12例,仅2例合并生殖器溃疡。这15例的治疗方案为,12例采取激素治疗,10例联合生物制剂治疗。经治疗后,多数患者症状可控制,但是部分患儿病情反复。结论HA20合并SLE患者的临床发病率低,临床表现不典型。对于发病年龄早、治疗效果差的SLE患儿,建议进行基因检测,这有利于该病患者的早期诊断及治疗。

Objective To summarize the clinical characteristics of patient with haploinsufficiency of A20(HA20)complicated with systemic lupus erythematosus(SLE).Methods A case of HA20 complicated with SLE(patient 1)was treated in Xi′an Children′s Hospital in June 2019 was selected in the study.The clinical case data of patient 1 were analyzed retrospectively,and the relevant literature of patients with HA20 complicated with SLE in domestic and foreign databases were retrieved in order to summarize the clinical characteristics of the disease.This study was approved by the Ethics Committee of Xi′an Children′s Hospital(Approval No.20230048).The guardians were informed consent of the diagnosis and treatment of patient 1.Results①The patient 1 was a girl,5 and a half years old,the main manifestations were pustulosis,fever and joint pain,accompanied by oral ulcer,enlarged liver,spleen and lymph nodes,and short stature.She had a history of hepatosplenomegaly and thrombocytopenia.Her laboratory examinations results showed proteinuria,autoimmune hemolytic anemia,decreased of serum complement(C)3,positive antinuclear antibody(1∶1000),and positive antism antibody.Renal puncture pathological examination showed mild mesangial proliferative lupus nephritis typeⅡ(LN-Ⅱ).Gene detection showed that the heterozygous variation of TNFAIP3 gene c.547(exon4)C>T,which was a pathogenic mutation and came from her father.She was treated with hormone,cyclosporine,cyclophosphamide and mycophenolate mofetil successively.During the treatment,after hormone reduction,rash occurred again,serum C3 decreased and urine protein increased.Up till now,she has no rash and other manifestations,serum C3 decreased slightly and urine protein is negative.She was final diagnosed with HA20,SLE and LN-Ⅱ.②Literature review results:There were 14 HA20 complicated with SLE patients retrieved(patients 2-15),the analysis of 15 cases including patient 1 showed that:there were 2 males and 13 females,and the age of onset ranges from 2 months to 29 years old,and 12 patients had the damage of kidney,only 2 patients had genital ulcer.The treatments of these 15 cases was as follows,12 patients were treated with hormone and 10 patients were treated combined with biological agents.After the treatments,the symptoms of most patients could be controlled,and some patients had repeated symptoms.Conclusions The incidence rate of HA20 complicated with SLE is low,and its clinical manifestations are not typical.For SLE children with early onset and poor treatment effect,gene detection is conducive to early diagnosis and treatment for patient of the disease.