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嗜血细胞性淋巴组织细胞增生症(hemophagocytosis hemophagocytic,HLH)是严重潜在危及生命的系统性炎症性疾病, 分为原发性(家族性)和反应性嗜血细胞综合征(reactive hemophagocytic syndrome, RHS), 后者常继发于感染、肿瘤、自身免疫病和药物[1]。在自身免疫疾病[系统性红斑狼疮(Systemic lupus erythematosus, SLE)、成人Still病(adult-onset Still disease, AOSD)和皮肌炎(dermatomyositis, DM)]均可合并RHS,也称巨噬细胞活化综合征[2]; 继发于肿瘤者主要与血液病相关,常见于非霍奇金淋巴瘤。RHS的基础疾病各异,但发病主要涉及以下因素[3]:CD8+T细胞分泌细胞因子活化组织细胞,促进其吞噬功能,使得单核细胞释放细胞因子,再刺激T细胞,形成放大的恶性循环,即"细胞因子瀑布效应",产生以下临床表现, 特征为发热、血细胞减少、肝脾淋巴结肿大,出凝血障碍以及高铁蛋白血症,原发病活动、复发或免疫抑制剂应用招致感染发生均可诱发RHS,然而,因疾病起病急骤,进展较快,加上临床医生对该病的认识不足,死亡率高。本文就22例RHS病人的临床特征包括实验室检查和治疗方案及预后作一总结。
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入组的22例病人中,自身免疫相关的RHS 17例,原发病依次为AOSD 13例,SLE引起的RHS 1例,肠系膜脂膜炎1例,皮肌炎1例,抗中性粒细胞胞质抗体(anti-neutrophil cytoplasmic antibodies, ANCA)相关性血管炎1例; 其他为淋巴瘤导致的RHS 5例。主要临床特征:高热发生率95.5%,肝脾、淋巴结肿大发生率81.8%,血液系统受累、贫血发生率72.7%,PLT减少50.0%,而PLT<50×109/L发生率为31.8%,SF>2 000 μg/L发生率95.4%(见表 1)。
观察项目 n 发生率/% 观察项目 n 发生率/% 高热 21 95.5 AST增高 17 77.3 肝脾淋巴结肿大 18 81.8 ALB减少 20 90.9 WBC减低 8 36.4 TBIL增高 8 36.3 贫血 16 72.7 LDH增高 21 95.4 PLT减少 11 50.0 TG增高 16 72.7 CRP增高 18 81.8 Fbg减低 18 81.8 ESR降低 14 63.6 SF>2 000 μg/L 21 95.4 ALT增高 17 77.3 表 1 RHS病人观察项目发生情况
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22例病人RHS发生时WBC计数(19.5±8.1) ×109/L,HB(95.2±14.4)g/L,ALB(26.1±4.4)g/L,TG(3.2±2.1)mmol/L,Fbg(1.5±0.7)g/L。经骨髓细胞学见到嗜血现象11例,但嗜血病人与非嗜血病人实验室检查各项指标阳性率差异均无统计学意义(P>0.05)(见表 2)。
分组 n WBC/
(<4.0×109/L)HB/
(<100 g/L)PLT/
(<100×109/L)CRP/
(>10 mg/L)ESR/
(>20 mm/h)ALT/
(>64 U/L)AST/
(>64 U/L)ALB/
(<35 g/L)TBIL/
(>18 μmol/L)LDH/
(>310 U/L)TG/
(>1.8 mmol/L)Fbg/
(<2.0/L)SF/
(>275 μg/L)嗜血组 11 7(63.6) 8(72.7) 6(54.5) 7(63.6) 5(45.5) 9(81.8) 9(81.8) 10(90.9) 6(54.5) 11(100.0) 8(72.7) 10(90.9) 11(100) 非嗜血组 11 2(18.2) 7(63.6) 6(54.5) 11(100.0) 3(27.3) 8(72.7) 8(72.7) 11(100.0) 5(45.5) 11(100.0) 7(63.6) 8(72.7) 10(90.9) 合计 22 9(40.9) 15(68.2) 12(54.5) 18(81.8) 8(36.4) 17(77.3) 17(77.3) 21(95.5) 11(50.0) 22(100.0) 15(68.2) 18(81.8) 21(95.4) χ2 — 4.73 0.21 0.06 2.33 0.78 0.26 0.26 1.05 0.12 — 0.21 1.22 1.05 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 表 2 RHS病人嗜血组与非嗜血组的实验室检查比较[n;阳性率(%)]
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22例中,全部加用糖皮质激素,19例加用环孢素A(CsA),12例启用静脉注射人免疫球蛋白(IVIG),50%病人经治疗后缓解出院,病死10例,其中AOSD 5例,淋巴瘤1例,皮肌炎1例,ANCA相关性血管炎1例,SLE 1例,肠系膜脂膜炎1例。病死原因主要是呼吸衰竭(7例)和心力衰竭(3例),其余为消化道出血、颅内出血,还有1例为脾切除术后大咯血而死亡,最后1例为淋巴瘤自动出院失访。死亡的病例中有3例治疗过程中发生相关感染。
反应性嗜血细胞综合征临床特征分析
Analysis of the clinical characteristics of reactive hemophagocytic syndrome
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摘要:
目的总结反应性嗜血细胞综合征(RHS)的临床特征、实验室资料、治疗及预后。 方法分析22例诊断为RHS病人的临床特点、实验室检查和治疗方案。同时以骨髓细胞学证实发生嗜血细胞与否分组, 比较2组之间的异同情况。 结果主要临床特征为高热发生率95.5%, 肝脾、淋巴结肿大发生率81.8%,血液系统受累、贫血发生率72.7%,血小板减少50.0%,RHS发生时WBC(19.5±8.1)×109/L,血红蛋白(95.2±14.4)g/L,白蛋白(26.1±4.4)g/L,三酰甘油(3.2±2.1)mmol/L,纤维蛋白原(1.5±0.7)g/L。经骨髓细胞学明确见到嗜血现象11例,嗜血组和非嗜血组病人实验室检查各项指标阳性率差异均无统计学意义(P>0.05)。50.0%(11/22)病人经治疗后缓解出院(其中1例失访),病死10例,其中成人Still病5例,淋巴瘤1例,皮肌炎1例,抗中性粒细胞胞质抗体相关性血管炎1例,系统性红斑狼疮1例,肠系膜脂膜炎1例。呼吸衰竭是主要死因。 结论风湿性疾病导致的RHS以成人still病多见,其他RHS最常见的为淋巴瘤,该病预后差, 死亡发生率较高,呼吸衰竭为主要死因。抓住实验室相关指标的动态变化有助于RHS的早期识别。激素联合环磷酰胺可控制疾病的进程。 -
关键词:
- 反应性嗜血细胞综合征 /
- 巨噬细胞活化综合征 /
- 成人Still病 /
- 非霍其金淋巴瘤
Abstract:ObjectiveTo analyze the clinical presentation, laboratory data, treatment and prognosis of reactive hyemophagocytic syndrome(RHS). MethodsThe clinical presentation, laboratory test, treatment protocols in 22 cases with RHS were retrospectively analyzed.The patients were divided into two groups according to the bone marrow hemocytology, and the difference between two groups was compared. ResultsAmong 22 patients, the incidence rates of hyperpyrexia, lymphadenectasis, blood system involovement rate, anemia and thrombocytopenia were 95.5%, 81.8%, 72.7% and 50.0%, respectively.The levels of WBC, HB, ALB, TG and fibrinogen(Fbg) in RHS patients were(19.5±8.1)×109/L, (95.2±14.4)g/L, (26.1±4.4)g/L, (3.2±2.1)mmol/L and(1.5 ±0.7)g/L, respectively.The bone marrow cytology Results showed the hemophagocytic phenomenon in 11 cases were indentified, and the difference of the positive indicators of examination between two groups were not statistically significant(P>0.05).The 50% patients alleviated after treatment, and discharged.Ten cases(one case lose to follow-up) died, which included adult Still disease in 5 cases, lymphoma in 1 case, dermatomyositis in 1 case, vasculitis related to anti-neutrophil cytoplasmic antibody in 1 case, systemic lupus erythematosus in 1 case and mesenteric lipid membrane inflammation in 1 case, and the respiratory failure was the death cause. ConclusionsThe adult still disease in RHS caused by rheumatic disease is often found, the lymphoma is more, poor prognosis and high death rate, and the main death cause of which is respiratory failure.The related indicator test can help to early diagnose the RHS.Hormones combined with cyclophosphamide can control the progression of disease. -
表 1 RHS病人观察项目发生情况
观察项目 n 发生率/% 观察项目 n 发生率/% 高热 21 95.5 AST增高 17 77.3 肝脾淋巴结肿大 18 81.8 ALB减少 20 90.9 WBC减低 8 36.4 TBIL增高 8 36.3 贫血 16 72.7 LDH增高 21 95.4 PLT减少 11 50.0 TG增高 16 72.7 CRP增高 18 81.8 Fbg减低 18 81.8 ESR降低 14 63.6 SF>2 000 μg/L 21 95.4 ALT增高 17 77.3 表 2 RHS病人嗜血组与非嗜血组的实验室检查比较[n;阳性率(%)]
分组 n WBC/
(<4.0×109/L)HB/
(<100 g/L)PLT/
(<100×109/L)CRP/
(>10 mg/L)ESR/
(>20 mm/h)ALT/
(>64 U/L)AST/
(>64 U/L)ALB/
(<35 g/L)TBIL/
(>18 μmol/L)LDH/
(>310 U/L)TG/
(>1.8 mmol/L)Fbg/
(<2.0/L)SF/
(>275 μg/L)嗜血组 11 7(63.6) 8(72.7) 6(54.5) 7(63.6) 5(45.5) 9(81.8) 9(81.8) 10(90.9) 6(54.5) 11(100.0) 8(72.7) 10(90.9) 11(100) 非嗜血组 11 2(18.2) 7(63.6) 6(54.5) 11(100.0) 3(27.3) 8(72.7) 8(72.7) 11(100.0) 5(45.5) 11(100.0) 7(63.6) 8(72.7) 10(90.9) 合计 22 9(40.9) 15(68.2) 12(54.5) 18(81.8) 8(36.4) 17(77.3) 17(77.3) 21(95.5) 11(50.0) 22(100.0) 15(68.2) 18(81.8) 21(95.4) χ2 — 4.73 0.21 0.06 2.33 0.78 0.26 0.26 1.05 0.12 — 0.21 1.22 1.05 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 -
[1] RAMOS-CASALS M, BRITO-ZERON P, LOPEZ-GUILLERMO A, et al.Adult haemophagocytic syndrome[J].Lancet, 2014, 383(9927):1503. doi: 10.1016/S0140-6736(13)61048-X [2] KUMAKURA S, MURAKAWA Y.Clinical characteristics and treatment outcomes of autoimmune-associated hemophagocytic syndrome in adults[J].Arthritis Rheumatol, 2014, 66(8):2297. doi: 10.1002/art.v66.8 [3] GUPTA S, WEITZMAN S.Primary and secondary hemophagocytic lymphohistiocytosis:clinical features, pathogenesis and therapy[J].Expert Rev Clin Immunol, 2010, 6(1):137. doi: 10.1586/eci.09.58 [4] TZANNOU I, BALTA AM, BAKIRI M.Hemophagocytic syndrome associated with hematologic malignancies[J].Hospital Chronicles, 2011, 6(3):110. [5] CHANDRAKASAN S, FILIPOVICH AH.Hemophagocytic lymphohistiocytosis:advances in pathophysiology, diagnosis, and treatment[J].J Pediatr, 2013, 163(5):1253. doi: 10.1016/j.jpeds.2013.06.053 [6] BAE CB, JUNG JY, KIM HA, et al.Reactive hemophagocytic syndrome in adult-onset Still disease:clinical features, predictive factors, and prognosis in 21 patients[J].Medicine(Baltimore), 2015, 94(4):e451. [7] 赵东宝.挑战成人巨噬细胞活化综合征[J].中华风湿病学杂志, 2012, 16(7):433. doi: 10.3760/cma.j.issn.1007-7480.2012.07.001 [8] JIA J, SONG Y, LIN N, et al.Clinical features and survival of extranodal natural killer/T cell lymphoma with and without hemophagocytic syndrome[J].Ann hematol, 2016, 95(12):2023. doi: 10.1007/s00277-016-2805-9 [9] RAVELLI A, MINOIA F, DAV S, et al.2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis:a European league against rheumatism/American college of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative[J].Arthritis Rheumatol, 2016, 68(3):566. doi: 10.1002/art.39332 [10] SCHULERT GS, GROM AA.Pathogenesis of macrophage activation syndrome and potential for cytokine-directed therapies[J].Annu Rev Med, 2015, 66:145. doi: 10.1146/annurev-med-061813-012806 [11] GROM AA, HORNE A, DE BENEDETTI F.Macrophage activation syndrome in the era of biologic therapy[J].Nat Rev Rheumatol, 2016, 12(5):259. [12] MARIA ATJ, QUELLEC AL, JORGENSEN C, et al.Adult onset Still's disease (AOSD) in the era of biologic therapies:dichotomous view for cytokine and clinical expressions[J].Autoimmunity Reviews, 2014, 13(11):1149. doi: 10.1016/j.autrev.2014.08.032 [13] EMILE JF, ABLA O, FRAITAG S, et al.Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages[J].Blood, 2016, 127(22):2672. doi: 10.1182/blood-2016-01-690636 [14] WEAVER LK, BEHRENS EM.Hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome and hemophagocytic lymphohistiocytosis[J].Curr Opin Rheumatol, 2014, 26(5):562. doi: 10.1097/BOR.0000000000000093