以弥漫性肺泡出血综合征为首发表现的儿童ANCA相关性血管炎临床分析

doi:10.12372/jcp.2026.25e0280

摘要/Abstract

摘要：

目的探讨以弥漫性肺泡出血综合征（DAHS）为首发表现的儿童抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）的临床特征、治疗及转归。方法回顾性分析医院2010年1月至2023年12月收治的以DAHS为首发表现并最终确诊为AAV的6例患儿的临床资料。结果 6例患儿中女4例、男2例，DAHS起病中位年龄5.4（4~7.6）岁，AAV诊断中位年龄7.2（6.3~10.6）岁，DAHS起病至诊断AAV的时间间隔为6个月~3年。首次诊断DAHS时，6例患儿ANCA检测均为阴性。6例患儿均存在不同程度的贫血，均为抗髓过氧化物酶抗体、核周型ANCA阳性的显微镜下多血管炎。胸部影像学主要表现为肺弥漫性浸润，表现为片絮影、斑片影及磨玻璃影，痰液、胃液、支气管肺泡灌洗液或肺活检找到含铁血黄素巨噬细胞。6例患儿均存在不同程度的肾脏受累，所有患儿均予糖皮质激素联合免疫抑制剂或生物制剂治疗，2例患儿接受血浆置换，1例予腹膜透析治疗。随访24~84个月，6例患儿肺部病灶均较前明显吸收、减少，未再出现咯血、痰中带血，症状明显好转，其中1例进展为慢性肾脏病5期，予规律腹膜透析，病情稳定。结论 DAHS是AAV的一种严重并发症，首发表现为DAHS时可能缺乏AAV的其他特征性表现，造成诊断困难。临床医师应对此类情况提高警惕，尽早明确诊断，积极予激素联合免疫抑制剂或生物制剂治疗可有效改善预后。

关键词: 弥漫性肺泡出血综合征, ANCA相关性血管炎, 儿童

Abstract:

Objective To investigate the clinical features, treatment and prognosis of pediatric ANCA-associated vasculitis (AAV) presenting initially with diffuse alveolar hemorrhage syndrome (DAHS). Methods A retrospective analysis was conducted on the clinical data of 6 children, admitted to the hospital from January 2010 to December 2023, who presented with DAHS as the initial manifestation and were eventually diagnosed with AAV. Results Among the 6 children, 4 were female and 2 were male. The median age at DAHS onset was 5.4 ( 4-7.6) years, while the median age at AAV diagnosis was 7.2 (6.3-10.6) years. The interval between DAHS onset and AAV diagnosis ranged from 6 months to 3 years. At the initial diagnosis of DAHS, ANCA testing was negative in all 6 children. All children exhibited varying degrees of anemia and were diagnosed as MPO/p-ANCA-positive microscopic polyangiitis (MPA). Chest imaging primarily showed diffuse pulmonary infiltrations, manifesting as patchy, flocculent, and ground-glass opacities. Hemosiderin-laden macrophages were found in sputum, gastric fluid, bronchoalveolar lavage fluid, or lung biopsy specimens. All 6 children had varying degrees of renal involvement. Treatment for all patients involved glucocorticoids combined with immunosuppressants or biologics. Two children underwent plasma exchange, and one received peritoneal dialysis. During a follow-up period of 24 to 84 months, pulmonary lesions in all 6 children showed significant absorption and reduction compared to previous imaging. No recurrence of hemoptysis or blood-streaked sputum was observed, and symptoms markedly improved. One patient progressed to chronic kidney disease stage 5, receiving regular peritoneal dialysis with stable condition. Conclusions DAHS is a severe complication of AAV. When presenting as the initial manifestation, DAHS may lack other characteristic features of AAV, leading to diagnostic challenges. Clinicians should maintain a high index of suspicion for such presentations. Early definitive diagnosis and aggressive treatment with glucocorticoids combined with immunosuppressants or biologics can effectively improve prognosis.

Key words: diffuse alveolar hemorrhage syndrome, ANCA-associated vasculitis, child

中图分类号:

张少丽, 康平, 田明, 杨建伟, 孙红启, 杨俊梅, 张利明. 以弥漫性肺泡出血综合征为首发表现的儿童ANCA相关性血管炎临床分析[J]. 临床儿科杂志, 2026, 44(3): 229-235.

ZHANG Shaoli, KANG Ping, TIAN Ming, YANG Jianwei, SUN Hongqi, YANG Junmei, ZHANG Liming. Clinical analysis of ANCA-associated vasculitis presenting with diffuse alveolar hemorrhage syndrome as the initial manifestation[J]. Journal of Clinical Pediatrics, 2026, 44(3): 229-235.

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参考文献 22

[1]	Bhushan A, Choi D, Maresh G, et al. Risk factors and outcomes of immune and non-immune causes of diffuse alveolar hemorrhage: a tertiary-care academic single-center experience[J]. Rheumatol Int, 2022, 42(3): 485-492. doi: 10.1007/s00296-021-04842-2
[2]	Sun XJ, Li ZY, Chen M. Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis[J]. Rheumatol Immunol Res, 2023, 4(1): 11-21. doi: 10.2478/rir-2023-0003
[3]	Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised international Chapel Hill Consensus Conference nomenclature of vasculitides[J]. Arthritis Rheum, 2013, 65(1): 1-11. doi: 10.1002/art.v65.1
[4]	Lara AR, Schwarz MI. Diffuse alveolar hemorrhage[J]. Chest, 2010, 137(5): 1164-1171. doi: 10.1378/chest.08-2084 pmid: 20442117
[5]	Cohen SP, Eisner M, Fussner LA, et al. Diffuse alveolar hemorrhage in pediatrics: Etiologies and outcomes[J]. Pediatr Pulmonol, 2024, 59(12): 3364-3370. doi: 10.1002/ppul.v59.12
[6]	Nakashima K, Nishimura N, Yanagihara T, et al. A fatal case of diffuse alveolar hemorrhage complicated by rheumatoid arthritis[J]. Respir Med Case Rep, 2021, 32: 101363.
[7]	田云凤, 郭晓琴, 赵星, 等. 儿童狼疮肾炎伴弥漫性肺泡出血一例[J]. 中华风湿病学杂志, 2021, 25(4): 254-256.
	Tian YF, Guo XQ, Zhao X, et al. Lupus nephritis with diffuse alveolar hemorrhage in a child[J]. Zhonghua Fengshibingxue Zazhi, 2021, 25(4): 254-256.
[8]	肖景玉, 林发全. 以弥漫性肺泡出血为首发症状的幼年特发性关节炎1例报告并文献复习[J]. 医学理论与实践, 2022, 35(20): 3524-3525.
	Xiao JY, Lin FQ. Juvenile idiopathic arthritis presenting with diffuse alveolar hemorrhage: a case report and literature review[J]. Yixue Lilun Yu Shijian, 2022, 35(20): 3524-3525.
[9]	Cody E, Hooper DK. Kidney transplantation in pediatric patients with rheumatologic disorders[J]. Curr Opin Pediatr, 2022, 34(2): 234-240. doi: 10.1097/MOP.0000000000001100
[10]	Jariwala M, Laxer RM. Childhood GPA, EGPA, and MPA[J]. Clin Immunol, 2020, 211: 108325. doi: 10.1016/j.clim.2019.108325
[11]	Watts RA, Mahr A, Mohammad AJ, et al. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis[J]. Nephrol Dial Transplant, 2015, 30 (Suppl 1): i14-i22. doi: 10.1093/ndt/gfv022
[12]	刘京祺, 李永珍, 帅兰军, 等. 儿童抗中性粒细胞胞质抗体相关性血管炎临床特征分析[J]. 中国当代儿科杂志, 2024, 26(8): 823-828.
	Liu JQ, Li YZ, Shuai LJ, et al. Clinical characteristics of children with anti-neutrophil cytoplasmic antibodyassociated vasculitis[J]. Zhongguo Dangdai Erke Zazhi, 2024, 26(8): 823-828.
[13]	马晨曦, 刘久煜, 朱一辉, 等. 儿童共患ANCA相关性血管炎肾损害双胞胎一对报告[J]. 临床儿科杂志, 2025, 43(8): 615-620.
	Ma CX, Liu JY, Zhu YH, et al. Two cases of renal damage in twin children with co-morbid ANCA-associated vasculitis[J]. Linchuang Erke Zazhi, 2025, 43(8): 615-620.
	赵三龙, 吴红梅, 赵非, 等. 儿童抗中性粒细胞胞质抗体相关性血管炎13例临床分析[J]. 中华肾脏病杂志, 2022, 38(8): 664-671.
	Zhao SL, Wu HM, Zhao F, et al. Clinical analysis of antineutrophil cytoplasmic antibody-associated vasculitis in 13 children[J]. Zhonghua Shenzangbing Zazhi, 2022, 38(8): 664-671.
[14]	Thompson GE, Specks U. Update on the management of respiratory manifestations of the antineutrophil cytoplasmic antibodies-associated vasculitides[J]. Clin Chest Med, 2019, 40(3): 573-582. doi: S0272-5231(19)30040-1 pmid: 31376892
[15]	Da Silva RC, Adhikari P. Granulomatosis with polyangiitis presenting with diffuse alveolar hemorrhage: a systematic review[J]. Cureus, 2022, 14(10): e29909.
[16]	邬秋蓉, 吴茜, 彭元洪. ANCA相关性血管炎合并弥漫性肺泡出血1例[J]. 风湿病与关节炎, 2024, 13(1): 43-46.
	Wu QR, Wu Q, Peng YH. A case of ANCA-associated vasculitis with diffuse alveolar hemorrhage[J]. Fengshibing Yu Guanjieyan, 2024, 13(1): 43-46.
[17]	中华医学会儿科学分会肾脏学组, 中华儿科杂志编辑委员会. 中国儿童抗中性粒细胞胞质抗体相关性肾炎诊断与治疗临床实践指南(2023版)[J]. 中华儿科杂志, 2023, 61(9): 773-785.
	The Subspecialty Group of Nephrology, the Society of Pediatrics, Chinese Medical Association; the Editorial Board, Chinese Journal of Pediatrics. Evidence-based guideline for diagnosis and treatment of pediatric anti-neutrophil cytoplasmic antibody associated glomerulonephritis (2023)[J]. Zhonghua Erke Zazhi, 2023, 61(9): 773-785.
[18]	陈旻, 于峰, 张颖, 等. 426例抗中性粒细胞胞浆抗体相关性小血管炎患者多系统临床表现和肾脏病理分析[J]. 中华内科杂志, 2005, 44(11): 828-831.
	Chen M, Yu F, Zhang Y, et al. An analysis of multi-system involvement and renal pathology of anti-neutrophil cytoplasmic autoantibodies-related vasculitis[J]. Zhonghua Neike Zazhi, 2005, 44(11): 828-831.
[19]	West S, Arulkumaran N, Ind PW, et al. Diffuse alveolar haemorrhage in ANCA-associated vasculitis[J]. Intern Med, 2013, 52(1): 5-13. doi: 10.2169/internalmedicine.52.8863
[20]	Smith RM, Jones RB, Specks U, et al. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial[J]. Ann Rheum Dis, 2023, 82(7): 937-944. doi: 10.1136/ard-2022-223559 pmid: 36958796
[21]	Li X, Ma C, Xu J, et al. Analysis of risk factors associated with diffuse alveolar haemorrhage in patients with ANCA-associated vasculitis and construction of a risk prediction model using line graph[J]. Clin Exp Rheumatol, 2024, 42(4): 864-871. doi: 10.55563/clinexprheumatol/7m21vr pmid: 38634373
[22]	Kidney Disease: Improving Global Outcomes (KDIGO) ANCA Vasculitis Work Group. KDIGO 2024 clinical practice guideline for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis[J]. Kidney Int, 2024, 105(3S): S71-S116. doi: 10.1016/j.kint.2023.10.008 pmid: 38388102

患儿	性别	起病年龄/AAV诊断年龄	首发表现	确诊前诊断	肺外表现
例1	女	5岁10个月/7岁	咳嗽、发热、面色苍白、咯血	IPH	血尿、蛋白尿、库欣面容
例2	女	4岁1个月/7岁1个月	咳嗽、气促、面色苍白、咯血	HA	血尿、蛋白尿、肾功能损害、关节痛
例3	女	5岁9个月/9岁	面色苍白、咯血	IPH	少尿、蛋白尿、心脏受累
例4	女	14岁/15岁6个月	咳嗽、乏力、气促、心慌	DAHS	血尿、蛋白尿、肾功能损害、心脏受累
例5	男	3岁7个月/4岁2个月	咳嗽、发热、乏力、气促	IPH	血尿、蛋白尿、水肿、泡沫尿
例6	男	5岁/7岁2个月	乏力、面色苍白、咯血	重度贫血、IPH	血尿、蛋白尿、肾功能损害、耳受累

患儿	Hb /g·L^-1	PRO	BLD	BUN /mmol·L^-1	Scr /μmol·L^-1	LDH /U·L^-1	eGFR /mL·min^-1·1.73 m^-2	ANA	核周型ANCA	MPO /RU·mL^-1	24h UP /g·24h^-1
例1	104	±	+	5.6	67.4	825	216.2	1∶100	+	71.9	0.052
例2	58	++	++	19.3	243.1	384	83.1	1∶100	+	115.2	1.375
例3	98	-	-	4.8	58.6	465	145.2	-	+	45.1	0.063
例4	110	+	+	11.5	92.7	373	98.5	1∶100	+	101	0.652
例5	63	+	+	6.4	47.2	1 212	112.4	-	+	53.4	0.203
例6	45	++	+++	37.5	487.3	313.2	14.7	1∶320	+	120	2.365

患儿	治疗方案			随访时间 /月	eGFR /mL·min^-1·1.73 m^-2	转归
患儿	AAV诊断前	诱导缓解	维持治疗	随访时间 /月	eGFR /mL·min^-1·1.73 m^-2	转归
例1	GC 10个月效果欠佳，+AZA减量复发	MP+MMF	Pre+AZA+RTX	84	208.9	完全缓解、肺部病灶吸收
例2	GC 15个月效果欠佳，+MTX仍有肺出血	MP+CYC+IVIg+PE	Pre+MMF+RTX	62	124.8	完全缓解、肺部病灶吸收
例3	GC 20个月效果欠佳，+AZA 3个月仍有肺出血，GC+CYC+IVIg减量复发	MP+MMF+RTX	Pre+AZA	59	166.3	完全缓解、肺部病灶吸收
例4	GC 8个月效果欠佳，+MMF 6个月复发	MP+CYC+IVIg	Pre+AZA+RTX	54	130.1	完全缓解、肺部病灶吸收
例5	GC 3个月效果欠佳，+MTX、HCQ仍有肺出血，GC+CYC减量复发	MP+CYC	Pre+MMF+RTX	24	213.6	完全缓解、肺部病灶吸收
例6	GC 4个月效果欠佳，+AZA 20个月复发	MP+CYC+IVIg+PE	Pre+MMF+RTX	48	9.7	部分缓解，CKD 5期，PD