探讨儿童系统性红斑狼疮(cSLE)患儿甲状腺相关抗体检测对发现甲状腺损伤及自身免疫性甲状腺炎(AITD)的临床意义。

选择2017年1月至2021年8月，在首都儿科研究所附属儿童医院风湿免疫科住院治疗的50例初发cSLE患儿为研究对象，并纳入cSLE组。同时选取在本院体检中心进行体检的50例健康儿童纳入对照组。回顾性分析2组受试儿的一般临床资料和甲状腺相关抗体阳性率，并对cSLE组患儿的临床特征、甲状腺相关抗体阳性率、甲状腺损伤情况、治疗和随访情况进行分析。采用电化学发光法检测促甲状腺素受体抗体(TRAb)、甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TPOAb)。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求，与所有受试儿监护人签署临床研究知情同意书。

①2组受试儿性别构成比、年龄等一般临床资料比较，差异均无统计学意义(P>0.05)。②cSLE组50例患儿中，年龄为4~15岁[(11.0±2.5)岁]，均无甲状腺疾病家族史。所有患儿首诊时系统性红斑狼疮(SLE)病情活动评分(SLEDAI-2k)均>5分，仅1例以甲状腺损伤表现起病。50例cSLE患儿中TRAb、TgAb和TPOAb呈阳性分别为6例(12.0%)、18例(36.0%)、20例(40.0%)。对cSLE不同病情活动度患儿的甲状腺相关抗体阳性率比较，差异均无统计学意义(P>0.05)。③cSLE组患儿的3种甲状腺相关抗体阳性率均高于对照组，2组比较，差异均有统计学意义(P<0.05)。④cSLE组50例患儿中，13例(26.0%，13/50)诊断为AITD，包括12例(24.0%，12/50)桥本甲状腺炎(HT)和1例(1/50，2.0%)毒性弥漫性甲状腺肿(GD)；2例(2/50，4.0%)诊断为甲状腺功能减退症(亚临床型)；9例(9/50，18.0%)患儿虽然甲状腺相关抗体呈阳性，但是无甲状腺疾病症状，并且甲状腺功能及超声检查结果均正常；其余26例无甲状腺损伤。⑤50例患儿均使用糖皮质激素联合免疫抑制剂治疗，于治疗6~18个月后cSLE病情缓解(SLEDAI-2k评分<5分)。对13例cSLE合并AITD的患儿，部分给予补充左甲状腺素或口服甲巯咪唑治疗，随访6~48个月时症状消失，甲状腺功能恢复正常，甲状腺相关抗体转阴，甚至停药。对2例cSLE合并甲状腺功能减退症而甲状腺相关抗体呈阴性的患儿，给予口服左甲状腺素治疗后，随着其原发病的缓解，甲状腺素片减量，随访期间甲状腺相关抗体未转阳。

cSLE患儿发生甲状腺损伤较常见，多为AITD，其中又以HT为主，但是多数甲状腺损伤表现隐匿。因此，对于cSLE患儿，特别是活动期患儿，无论其是否为重度疾病活动度，除检测甲状腺功能外，均应该常规检测甲状腺相关抗体，早期发现甲状腺损伤。一旦发现甲状腺损伤，应以积极控制原发病为主，对症予左甲状腺素或甲巯咪唑等治疗，随着患儿cSLE疾病的缓解，其甲状腺相关抗体可转阴，甲状腺功能可恢复。

To investigate the clinical significance of the prevalence of thyroid-related antibodies in childhood systemic lupus erythematosus (cSLE) patients for the detection of thyroid injury and autoimmune thyroiditis (AITD).

Fifty children with first-onset cSLE who were hospitalized at the Department of Rheumatology and Immunology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2017 to August 2021 were selected into this study and included in cSLE group. Another fifty healthy children who underwent physical examination at same hospital were also selected and included in control group. The general clinical data and positive rate of thyroid-related antibodies of 2 groups were retrospectively analyzed. Moreover, the clinical characteristics, positive rate of thyroid-related antibodies, thyroid injury, treatment and follow-up of patients in cSLE group were retrospectively analyzed. Thyrotropin receptor antibody (TRAb), thyroglobulin antibody (TgAb), and thyroid peroxidase antibody (TPOAb) were detected by electrochemiluminescence method. The procedure followed in this study was in line with the requirements of the Helsinki Declaration of the World Medical Association revised in 2013. Informed consent for clinical research was obtatin from each patient′s guardians.

① There were no significant differences in general clinical data such as gender ratio and age between two groups (P>0.05). ② Among 50 children in cSLE group, the age ranged from 4 to 15 years old [(11.0±2.5) years old], and all the 50 children had negatime family history of thyroid diseases. At the first visit, Systemic Lupus Erythematosus Disease Activing Index (SLEDAI-2k) of all children were higher than 5, and only one patient presented with thyroid injury. TRAb, TgAb and TPOAb were positive in 6 cases (12.0%), 18 cases (36.0%) and 20 cases (40.0%) of 50 children with cSLE, respectively. There were no significant differences in the positive rates of thyroid-related antibodies among cSLE children with different disease activities (P>0.05). ③ The positive rates of three thyroid-related antibodies in cSLE group were higher than those in control group, and the differences between two groups were statistically significant (P<0.05). ④ Among 50 children in cSLE group, 13 case (26.0%, 13/50) were diagnosed as AITD, including 12 cases (24.0%, 12/50) were Hashimoto′s thyroiditis (HT) and 1 case (1/50, 2.0%) was Graves disease (GD); 2 cases (2/50, 4.0%) were diagnosed as hypothyroidism (subclinical type); 9 cases (9/50, 18.0%) had no symptoms of thyroid diseases, and their thyroid function and ultrasonic examination results were normal, although thyroid-related antibodies were positive. The remaining 26 cases had no thyroid injury. ⑤After treatment with glucocorticoids and immunosuppressants, cSLE in 50 children was relieved from 6 months to 18 months after treatment (SLEDAI-2k score <5). Among them, 13 cases with cSLE complicated with AITD were given levothyroxine or methimazole orally. After 6 to 48 months of follow-up, the symptoms disappeared, the thyroid function returned to normal, and the thyroid-related antibodies turned negative or even medication discontinuation. Two cases with cSLE complicated with hypothyroidism and negative thyroid-related antibodies were given oral levothyroxine. With the remission of the primary disease, thyroxine tablets could be reduced, and the thyroid-related antibodies did not turn positive.

Thyroid injury is more common in children with cSLE, most of whom have AITD, with HT predominating, but most thyroid injuries are insidious. Therefore, for children with newly diagnosed cSLE, especially those with active SLE, thyroid autoantibodies should be routinely detected in addition to thyroid function, regardless of whether SLE is severely active or not. Once thyroid injury is found, cSLE should be actively controlled, and thyroxine or methimazole should be taken as symptomatic treatment. With the remission of cSLE, thyroid-related antibodies can turn negative and thyroid function can be restored.