Childhood systemic lupus erythematosus with histiocytic necrotizing lymphadenitis as the first clinical manifestation: three cases report and literature review

doi:10.3877/cma.j.issn.1673-5250.2023.06.012

Objective

To investigate clinical features and prognosis of childhood systemic lupus erythematosus (cSLE) with histiocytic necrotizing lymphadenitis (HNL) as the first clinical manifestation.

Methods

From January 2013 to January 2023, 3 cases of cSLE with HNL as the first clinical manifestation (children 1-3) were selected in the study. The clinical data of these 3 cases were analyzed by retrospective analysis. Then, with " histiocytic necrotizing lymphadenitis" " systemic lupus erythematosus" " children" as Chinese and English keywords, the relevant pieces of literature were searched in CNKI, Wanfang Database and PubMed, and every piece of literature was reviewed. This study was approved by the Ethics Committee of the General Hospital of Ningxia Medical University (Approval No. KYLL-2023-0011), and the guardians gave informed consent to the diagnosis and treatment of children.

Results

Among these 3 children, Child 1 was boy and child 2, were girl. The course of the disease was 11 d-1 month at the time of diagnosis. The chief complaint was fever with lymphadenopathy (diameter>2 cm). The white blood cell count (WBC) decreased, with lymphocytes accounting for the majority. Pathological examination results of lymph node biopsy were HNL. All three children showed high titer of antinuclear antibody (ANA) and double-stranded DNA (ds-DNA) was positive. Child 1 showed elevated WBC, hematuria, butterfly erythema on the face and decreased level of complement 3 (C3), and systemic lupus erythematosus (SLE) activity score was 16. Child 2 combined central neuropathy, hematuria and arthritis, and SLE activity score was 19. Child 3 showed hematuria, butterfly erythema on the face, decreased level of C3, and SLE activity score was 12. ②According to the literature retrieval strategy set in this study, the literature review results were as follows. three pieces of relevant Chinese literature were retrieved, including all of children were about the cSLE disease with HNL as the first manifestation. One case (child 4) was diagnosed with HNL and SLE simultaneously, while the other two cases (child 5-6) gradually developed into SLE six months after being diagnosed with HNL.

Conclusions

Lymph nodes may be one of the multiple organs arrested involved in SLE, and children with cSLE who present with HNL as the first manifestation may have relatively mild organ damage and a better prognosis.

Key words: Histiocytic necrotizing lymphadenitis, Lupus erythematosus, systemic, Signs and symptoms, Sjogren′s syndrome, Autoantibodies, Immunosuppressive agents, Child

图1 1例以HNL为首发的cSLE患儿的颈部淋巴结组织病理学检查结果[图1A：蓝色箭头示CD3^＋(T淋巴细胞)(免疫组织化学法，低倍)；图1B：蓝色箭头示CD20^＋(B淋巴细胞)(免疫组织化学法，高倍);图1C：蓝色箭头示组织细胞标志物CD68^＋(坏死区)染色呈棕色，提示组织细胞阳性(免疫组织化学法，高倍)；图1D：蓝色箭头示淋巴组织原有结构消失，淋巴组织增生，淋巴滤泡形成，组织细胞吞噬核碎屑现象(HE染色，高倍)；图1E：蓝色箭头显示斑驳状是由于巨噬细胞吞噬现象，又被称为"星空现象"(HE染色，高倍)] 注：HNL为组织细胞坏死性淋巴结炎，cSLE为儿童系统性红斑狼疮，HE为苏木精-伊红

表1 3例cSLE患儿(患儿1～3)的SLE疾病活动性评分(分)

评估项目	具体表现	最高分	患儿1	患儿2	患儿3
狼疮性头痛	严重持续性头痛，麻醉性止痛药无效	8	0	8	0
关节炎	≥2个关节痛和炎性体征(压痛、肿胀、积液)	4	0	4	0
血尿	红细胞>5个/HP，除外结石、感染和其他原因	4	4	4	4
新发皮疹	新出现或复发的炎症性皮疹	2	2	0	2
补体水平低	C3、C4水平均低于正常值	2	2	0	2
抗ds-DNA抗体水平升高	>25%(Farr法)或高于检测范围	2	2	2	2
发热	体温>38 ℃，除外感染因素	1	1	1	1
WBC降低	<3.0×10⁹/L，排除药物所致	1	1	0	1
合计		24	16(重度)	19(重度)	12(中度)

表1 3例cSLE患儿(患儿1～3)的SLE疾病活动性评分(分)

评估项目	具体表现	最高分	患儿1	患儿2	患儿3
狼疮性头痛	严重持续性头痛，麻醉性止痛药无效	8	0	8	0
关节炎	≥2个关节痛和炎性体征(压痛、肿胀、积液)	4	0	4	0
血尿	红细胞>5个/HP，除外结石、感染和其他原因	4	4	4	4
新发皮疹	新出现或复发的炎症性皮疹	2	2	0	2
补体水平低	C3、C4水平均低于正常值	2	2	0	2
抗ds-DNA抗体水平升高	>25%(Farr法)或高于检测范围	2	2	2	2
发热	体温>38 ℃，除外感染因素	1	1	1	1
WBC降低	<3.0×10⁹/L，排除药物所致	1	1	0	1
合计		24	16(重度)	19(重度)	12(中度)

表2 6例cSLE患儿(患儿1～6)的临床特征比较

患儿编号	性别	年龄(岁)	主诉	特殊病情	特殊体征	淋巴结	脏器损伤
患儿1(本研究)	男	11	发热伴颈部肿物11 d	既往无特殊	颜面部逐渐出现皮疹	颌下淋巴结大，最大为2.1 cm×0.8 cm；有压痛	血液系统、肝、肾、神经系统
患儿2(本研究)	女	11	间断发热伴淋巴疼痛37 d，手指肿痛4 d	母亲30岁时患类风湿性关节炎	无	颈部淋巴结大，最大为3.1 cm×4.1 cm；有压痛	肾、神经系统
患儿3(本研究)	女	12	间断发热16 d	既往无特殊	双侧面颊部皮肤见暗红色斑片状陈旧性皮疹	颈部淋巴结大，最大为2.0 cm×0.7 cm；有压痛	血液系统、肝、神经系统、呼吸系统
患儿4^[7]	女	14	发热2^＋周	既往无特殊	无	左侧颈部淋巴结最大约为1.42 cm×0.9 cm；有压痛	血液与呼吸系统、肾
患儿5^[8]	女	12	发热4 d	确诊为HNL后采用地塞米松治疗，半年后复发，伴脱发、口腔溃疡、光过敏	颧部蝶形红斑，光照后加重	颈部、颌下、腋窝可扪及散在黄豆大小淋巴结	血液系统、肾、肝
患儿6^[9]	男	14	右侧颈部淋巴结无痛性增大伴发热及皮疹8^＋个月，口干3个月	在当地医院经淋巴结活检确诊为HNL，给予地塞米松治疗	面部蝶形红斑，双耳、躯干皮肤红斑，四肢皮肤瘀斑，口腔溃疡和脱发。散瞳后双侧视网膜可见数个白色棉絮样斑	右侧颈部触及2个2 cm×1 cm淋巴结	血液系统、肝、肾
患儿编号	WBC(×10⁹/L)	Hb(g/L)	PLT(×10⁹/L)	ds-DNA	ANA	C3(g/L)	ESR(mm/h)	CRP(mg/L)	24 h尿蛋白定量(mg)	SLE疾病活动性评分(分)
患儿1(本研究)	1.38	114	151	39.62	1∶320	0.29	35	1.4	444.00	16
患儿2(本研究)	3.24	110	230	32.17	1∶320	1.55	120	45.9	160.00	19
患儿3(本研究)	1.21	115	193	98.55	1∶1 000	0.36	22	10.0	277.00	12
患儿4^[7]	2.44	128	168	阳性	1∶1 000	正常	82	正常	267.58	8
患儿5^[8]	1.92	正常	正常	阳性	阳性	未查	125	正常	358.31	12
患儿6^[9]	1.30	113	60	－	1∶160	下降	34	2.06	725.40	16

表2 6例cSLE患儿(患儿1～6)的临床特征比较

患儿编号	性别	年龄(岁)	主诉	特殊病情	特殊体征	淋巴结	脏器损伤
患儿1(本研究)	男	11	发热伴颈部肿物11 d	既往无特殊	颜面部逐渐出现皮疹	颌下淋巴结大，最大为2.1 cm×0.8 cm；有压痛	血液系统、肝、肾、神经系统
患儿2(本研究)	女	11	间断发热伴淋巴疼痛37 d，手指肿痛4 d	母亲30岁时患类风湿性关节炎	无	颈部淋巴结大，最大为3.1 cm×4.1 cm；有压痛	肾、神经系统
患儿3(本研究)	女	12	间断发热16 d	既往无特殊	双侧面颊部皮肤见暗红色斑片状陈旧性皮疹	颈部淋巴结大，最大为2.0 cm×0.7 cm；有压痛	血液系统、肝、神经系统、呼吸系统
患儿4^[7]	女	14	发热2^＋周	既往无特殊	无	左侧颈部淋巴结最大约为1.42 cm×0.9 cm；有压痛	血液与呼吸系统、肾
患儿5^[8]	女	12	发热4 d	确诊为HNL后采用地塞米松治疗，半年后复发，伴脱发、口腔溃疡、光过敏	颧部蝶形红斑，光照后加重	颈部、颌下、腋窝可扪及散在黄豆大小淋巴结	血液系统、肾、肝
患儿6^[9]	男	14	右侧颈部淋巴结无痛性增大伴发热及皮疹8^＋个月，口干3个月	在当地医院经淋巴结活检确诊为HNL，给予地塞米松治疗	面部蝶形红斑，双耳、躯干皮肤红斑，四肢皮肤瘀斑，口腔溃疡和脱发。散瞳后双侧视网膜可见数个白色棉絮样斑	右侧颈部触及2个2 cm×1 cm淋巴结	血液系统、肝、肾
患儿编号	WBC(×10⁹/L)	Hb(g/L)	PLT(×10⁹/L)	ds-DNA	ANA	C3(g/L)	ESR(mm/h)	CRP(mg/L)	24 h尿蛋白定量(mg)	SLE疾病活动性评分(分)
患儿1(本研究)	1.38	114	151	39.62	1∶320	0.29	35	1.4	444.00	16
患儿2(本研究)	3.24	110	230	32.17	1∶320	1.55	120	45.9	160.00	19
患儿3(本研究)	1.21	115	193	98.55	1∶1 000	0.36	22	10.0	277.00	12
患儿4^[7]	2.44	128	168	阳性	1∶1 000	正常	82	正常	267.58	8
患儿5^[8]	1.92	正常	正常	阳性	阳性	未查	125	正常	358.31	12
患儿6^[9]	1.30	113	60	－	1∶160	下降	34	2.06	725.40	16

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