11例黑热病相关噬血细胞综合征的临床特点分析

目的:分析黑热病相关噬血细胞综合征患者的临床特征,讨论此类患者的诊断和治疗。方法:收集并分析2018年10月—2021年12月确诊的11例黑热病相关噬血细胞综合征患者的临床资料。结果:11例患者中,10例来自黑热病流行地区,6例初诊时血清球蛋白升高,9例行噬血细胞综合征细胞因子谱检测到IL-10异常增高,2例合并EB病毒感染,1例合并干燥综合征。经8周治疗后,通过噬血细胞综合征疗效评估,6例达完全缓解(其中3例使用了芦可替尼治疗),5例达部分缓解;所有患者均未检测到利什曼原虫;血小板计数、铁蛋白、纤维蛋白原三项指标治疗后均明显改善,与治疗前比较差异有统计学意义(P<0.05)。结论:临床医生接诊来自黑热病流行地区的噬血细胞综合征患者需警惕黑热病可能。分子生物学筛查对黑热病相关噬血细胞综合征的诊断有重要意义,早期联合芦可替尼治疗或可提高黑热病相关噬血细胞综合征的疗效,血小板、铁蛋白、纤维蛋白原可作为重要的疗效评估指标。     

肝功能异常为主要临床表现的噬血细胞综合征10例临床分析

目的通过对10例以肝功能异常为主要临床表现的噬血细胞综合征病例进行分析,探讨本病的临床特点,提高对本病的认识。方法对10例患者的病史、临床表现和实验室检查结果进行综合分析。结果噬血细胞综合征（HPS）可表现为严重的肝功能损害,其特点为胆红素明显升高,以直接胆红素升高为主,以及ALT、AST及GGT升高。结论不明原因肝功能异常并伴有发热和血细胞减少的患者应警惕HPS,早期诊断和治疗。     

噬血细胞综合征30例临床分析

目的:探讨噬血细胞综合征(HPS)的临床特点、诊断、治疗以及预后的危险因素。方法:对我院30例HPS患者的病因、临床表现、实验室检查指标、治疗方案及临床转归进行回顾性分析。结果:30例HPS病因以感染最多见(30%),其中EB病毒感染达20%,然而病因不明者也高达56.7%。HPS临床表现为持续高热(100%)、脾肿大(93.3%)、全血细胞减少(83.3%)、乳酸脱氢酶(100%)及血清铁蛋白(100%)升高。肝功能损害(90%)及心肌酶谱(60%)升高也较为常见。30例经治HPS患者30d、100d、1年的生存率分别为36.7%、23.3%、10.0%。其中7例给予包含VP16的化疗方案,30d、100d、1年的生存率分别为85.1%、71.4%、42.9%。结论:HPS可由多种病因所致,EB病毒最为常见,临床表现多样。发热、血清铁蛋白、乳酸脱氢酶升高在诊断中的灵敏度较高。包含VP16的化疗方案是有效的治疗方案。     

成人斯蒂尔病与巨噬细胞活化综合征关联性的临床分析

目的 探讨成人斯蒂尔病(AOSD)与巨噬细胞活化综合征(MAS)的关系.方法 选择AOSD组为78例资料完整的AOSD;MAS组是从26例有组织学证据的噬血细胞综合征的随访治疗中确定11例为风湿免疫疾病相关的噬血细胞综合征.对以上患者的临床表现和实验室资料进行分析.结果 在AOSD组78例中,有9例(占12%)在使用治疗之前可以诊断为MAS,但无噬血组织学依据.在11例有噬血现象的MAS中,AOSD 6例,脂膜炎2例,系统性红斑狼疮、皮肌炎、系统性血管炎各1例.脾脏肿大、白细胞减低、贫血、血小板下降、高甘油三酯是AOSD出现MAS的相关临床指标.结论 AOSD继发MAS的现象比较常见,严重者可以有组织学的噬血表现.AOSD出现脾脏增大、血细胞降低时,需要作MAS的相关检查,包括骨髓检查以及甘油三酯、纤维蛋白原、自然杀伤(NK)细胞活性等,以便及时诊断MAS.     

自身免疫病相关性噬血细胞性淋巴组织细胞增多症16例临床特征

目的探讨自身免疫病相关性噬血细胞性淋巴组织细胞增多症(autoimmune associated hemophagocytic lymphohistiocytosis,AAHLH)患者的临床特点。方法收集并整理16例AAHLH患者的基础疾病、并发感染情况、临床、实验室检查、治疗及预后情况。结果基础疾病:系统性红斑狼疮(systemic lupus erythematosus,SLE)7例,类风湿关节炎(rheumatoid arthritis,RA)1例,SLE并发RA 1例,原发性干燥综合征(primary Sjogren's syndrome,pSS)1例,皮肌炎(dermatomyositis,DM)1例,未分化结缔组织病(undifferentiated connective tissue disease,UCTD)5例。部分患者同时并发感染,包括病毒感染4例,细菌感染3例,混合感染7例,感染部位以肺部为主。临床表现:高热(100%)、肝肿大(18.8%)、脾肿大(68.8%)、淋巴结肿大(75%)、皮疹(62.5%)、关节炎(68.8%),并发弥漫性血管内凝血(disseminated intravascular coagulation,DIC) 3例(18.8%)。实验室检查:血细胞减少(100%)、肝功能异常(87.5%)、高甘油三脂血症(100%)、低纤维蛋白原血症(43.8%)、铁蛋白500μg/L(100%)、可溶性CD25 (sCD25)≥2 400 U/ml(75%)、NK细胞活性降低(100%)。骨髓检查有成熟的单核巨噬细胞吞噬血细胞现象占56.3%。经过积极抗感染、治疗原发病以及经人免疫球蛋白、糖皮质激素、免疫抑制剂治疗,存活12例,病情恶化自动出院3例后死亡,在院死亡1例。结论 AAHLH临床表现多样,容易并发感染,病死率高。sCD25水平高可能是AAHLH预后的不良因素。     

儿童噬血细胞综合征26例实验室检查分析

目的探讨儿童噬血细胞综合征的临床特点。方法回顾性分析26例感染相关性噬血细胞综合征病的临床及实验室资料。结果感染相关性17例(65.38%),非感染相关性3例(11.54%),原因不明6例(23.08%)。全组病例临床主要特点为持续高热(100.0%)、肝肿大(84.62%)、脾肿大(92.31%);外周血白细胞计数减少(76.92%)、血小板减少(88.46%)、血红蛋白减少(80.77%);骨髓涂片找到噬血细胞(100.0%)。结论儿童感染相关性噬血细胞综合征临床以持续高热、肝肿脾大为主要表现,实验室检查白细胞计数、血红蛋白及血小板中两系或三系减少、低纤维蛋白血症、高脂血症、肝功能、心功能异常及血清铁蛋白升高,骨髓找到噬血细胞等为主要特点。     

获得性噬血细胞综合征合并多脏器功能障碍综合征病例分析

目的：探讨获得性噬血细胞综合征（HPS）合并多脏器功能障碍综合征的临床特点,提高对本病的认识。方法：对10例HPS患者的临床病历资料进行综合分析。结果：10例患者均符合HLH-2004获得性HPS的诊断标准,同时伴有3-6个脏器功能障碍,SOFA评分4～12分,平均8．8±2．2分。10例均伴有NK细胞活性减低和sCD25水平升高,经治疗后存活4例,死亡6例。结论：对发热原因不明、多脏器功能障碍的患者,若血细胞减少、肝脾肿大、血清铁蛋白升高,并发NK细胞活性减低和sCD25水平升高,应警惕噬血细胞综合征。早期诊断和及时治疗能够改善预后。     

不同病因伴发严重噬血细胞综合征9例诊疗体会

目的:探讨噬血细胞综合征(HPS)的临床表现、实验室特点、治疗及预后。方法:回顾性分析9例HPS患者的临床资料。结果:9例HPS患者中有1例为原发HPS,1例感染相关HPS,4例恶性淋巴瘤相关HPS,1例EB病毒HPS,2例病因不明。临床上均有不同程度发热,血细胞不同程度下降,凝血功能异常及铁蛋白升高,其中淋巴结肿大5例,脾大5例。8例治疗患者初期评估有效,目前3例已死亡。结论:HPS临床表现多样,疾病快速进展,须提高对该疾病认识,尽早启动治疗方案,改善预后。     

自身免疫性溶血为首发表现的同时性胰腺癌和弥漫大B细胞淋巴瘤合并噬血细胞综合征1例

自身免疫性溶血性贫血和噬血细胞综合征常继发于病毒感染、血液系统恶性肿瘤及自身免疫病, 特别是与B-淋巴瘤相关性噬血细胞综合征相比, T/NK-淋巴瘤相关性噬血细胞综合征发病率高、EB病毒颗粒检出率高, 实体肿瘤合并自身免疫性溶血性贫血和噬血细胞综合征的报道也罕见。本文报道一例老年男性, 入院时表现为自身免疫性溶血性贫血, 给予糖皮质激素治疗, 病情仍迅速进展, 经病理证实同时患有小B淋巴细胞白血病和胰体部腺癌, 并因反复黑便行肠镜及免疫组织化学(IHC)检查确诊为横结肠脾区EB病毒阳性弥漫大B细胞淋巴瘤, 最终因消化道出血抢救无效。     

慢性淋巴细胞白血病并发自身免疫性血细胞减少症7例

目的:报道7例慢性淋巴细胞白血病(CLL)并发自身免疫性血细胞减少症,提高对CLL并发自身免疫性血细胞减少症的认识。方法:回顾性分析2000-2007年就诊于中国医学科学院血液病医院的7例CLL并发自身免疫性血细胞减少症患者的症状和体征、实验室检查、治疗及转归,并复习相关文献。结果:6例患者诊断为自身免疫性溶血性贫血(AIHA),1例患者为Evans综合征。3例患者在诊断CLL的同时发现有溶血发作,另4例患者在CLL诊断后中位20.5个月出现溶血。5例患者用瘤可宁加激素的方案治疗,1例患者单用激素治疗,1例患者用单克隆抗体及联合化疗方案治疗。治疗有效6例,无效1例。3例在随访中溶血复发,再次治疗仍有效。1例患者对治疗反应不佳,需输血维持。随访至2008年4月,除1例患者失访外,其余6例患者全部存活。结论:自身免疫性血细胞减少症是CLL较常见的并发症。尽管激素加烷化剂的常规治疗疗效较好,但复发率较高。并发自身免疫性血细胞减少症无明显预后意义。     

Hemophagocytic syndrome in elderly patients with underlying autoimmune diseases

In patients with autoimmune disease-associated hemophagocytic syndrome (AAHS), the clinical features may differ from hemophagocytic syndrome (HPS) of other etiologies, and new criteria for AAHS have been proposed. Since bone marrow (BM) circumstances are changed according to aging, here we reviewed retrospectively our cases with AAHS in elderly patients, including two systemic lupus erythematosus (SLE), three Evans syndrome, one rheumatoid arthritis (RA), one Hashimoto thyroiditis, and one autoimmune pancreatitis. Although only two SLE patients were diagnosed as HPS by the classical criteria, the remaining patients except one RA met the criteria for AAHS. Seven patients except one SLE patient showed good response to therapy and demonstrated positive autoantibodies to blood cells, lower serum ferritin levels, and increased erythroblastic islands in the BM. We consider the diagnosis of AAHS should be carefully made when macrophages phagocytosing blood cells are observed in BM smear without hyperferritinemia in elderly patients with autoimmune diseases.     

Autoimmune-associated hemophagocytic syndrome

Hemophagocytic syndrome (HPS) is a clinicopathological condition characterized by the activation of histiocytes with prominent hemophagocytosis in bone marrow and other reticuloendothelial systems. The occurrence of HPS is usually associated with underlying disorders such as infection and lymphoma. Recently, we described patients with autoimmune disease who developed HPS. In these cases there was no evidence of underlying infection and malignancy, and the occurrences of HPS were associated with active autoimmune disease. Based on these observations, we described autoimmune-associated hemophagocytic syndrome (AAHS). This disease entity is becoming better known, and case reports presenting features compatible with clinical AAHS are increasing. Here, we review the clinical aspects, mechanisms, diagnosis, and treatment of AAHS according to our data and that in the literature.     

继发性嗜血细胞综合征15例临床分析

目的 探讨自身免疫病相关性与非自身免疫病相关性嗜血细胞综合征(HPS)两者的临床特征、治疗及预后.方法 回顾性收集15例2008年1月至2010年6月我院风湿科及血液科住院的继发性嗜血细胞综合征患者,分析临床及实验室特征、治疗以及预后的关系.并比较自身免疫病相关性嗜血细胞综合征(A组)与非自身免疫病相关性嗜血细胞综合征(B组)之间的异同点.采用Fisher精确概率法、t检验和秩和检验.结果 2组均表现出发热、出血、黄疸、肝脾肿大,A组特异性表现出关节痛、皮疹、自身抗体阳性,而B组中黄疸更常见(38%和100%,P=0.018).但比较2组实验室指标及预后差异均无统计学意义(P>0.05).激素联合免疫抑制剂和丙种球蛋白治疗预后更好(P<0.05).结论除黄疸外,自身免疫病相关性HPS与其他继发性HPS的临床表现及实验室指标无明显差异,激素联合免疫抑制剂及丙种球蛋白治疗有效.

Abstract：

Objecfive To investigate the clinical characteristics,treatment and prognosis of autoimmune diseases associated and non-autoimmune diseases associated hemophagocytic syndrome.Methotis Clinical records of 15 cases witll secondary hemophagocytic syndrome'were collected and the relations with treatment and prognosis was analyze.The similarities and differences between autoimmune disease associated bemophagocytic syndrome (group A)and non-autoimmune disease associated hemophagocytic syndrome (group B)were compared.Fisher exact test,t test and Willcoxen test were used for statistical analysis.Results Both groups had fever,bleeding,jaundice,hepatosplenomegaly,and arthralgia,skin rash and positive of autoantibodies in group A were discovered specifically.But in group B,the patients with icterus were mo common(38% vs 100%,p=0.018).There was no significant difference in their laboratory data and prognosis when compared between the two groups(P>0.05).The patients who received corticosteroids and IVIG and/or immunosuppressive agents had better prognosis(P<0.05).Conclusion Except for icterus there is no significant difference in clinical features and laboratory data among autoimmune disease associated hemophagocytic syndrome and other secondary hemophagocytic syndrome.And the therapy with corticosteroids combined with IVIG and/or immunosupprcssive agents is effective.     

Low glycosylated ferritin, a good marker for the diagnosis of hemophagocytic syndrome

OBJECTIVE: A very low percentage of glycosylated ferritin (<20%) has only been reported in association with adult-onset Still's disease (AOSD), a disease classically associated with hemophagocytic syndrome. We undertook this study to determine whether hemophagocytic syndrome outside the context of AOSD is also associated with a very low percentage of glycosylated ferritin. METHODS: From October 2006 to September 2007, the serum level of glycosylated ferritin was determined in all consecutive patients seen in 3 departments and for whom the diagnosis of hemophagocytic syndrome was suspected. The level of glycosylated ferritin in these patients was compared with that in age- and sex-matched controls with a marked inflammatory syndrome not associated with hemophagocytic syndrome. We assessed the value of glycosylated ferritin as a marker for the diagnosis of hemophagocytic syndrome. RESULTS: Forty-two patients were included in the study (14 with confirmed hemophagocytic syndrome, 7 with suspected but unconfirmed hemophagocytic syndrome, and 21 controls). The median level (interquartile range [IQR]) of total serum ferritin was significantly higher in patients with confirmed hemophagocytic syndrome (3,344 microg/liter [2,074-7,334]) than in patients with suspected but unconfirmed hemophagocytic syndrome (555 microg/liter [464-1,420]) (P = 0.02) or in controls (451 microg/liter [126-929]) (P < 0.001). The median (IQR) percentage of glycosylated ferritin was significantly lower in patients with confirmed hemophagocytic syndrome (10% [3-14]) than in patients with suspected but unconfirmed hemophagocytic syndrome (40% [36-47]) (P < 0.001) or in controls (36% [26-49]) (P < 0.001). The diagnostic performance of glycosylated ferritin tended to be higher than that of total serum ferritin for the diagnosis of hemophagocytic syndrome (area under the receiver operating characteristic curve [95% confidence interval] 0.97 [0.92-1.00] versus 0.79 [0.59-1.00]; P = 0.10). CONCLUSION: These results suggest that glycosylated ferritin may be a helpful marker for the diagnosis of hemophagocytic syndrome.     

系统性红斑狼疮合并淋巴瘤临床特征

目的探讨系统性红斑狼疮(SLE)合并恶性淋巴瘤(ML)的临床特点。方法回顾1998年1月至2012年2月北京协和医院收治的9例SLE合并ML患者的临床资料,分析其临床表现、实验室检查指标、淋巴瘤病理分型、治疗及预后。结果 SLE合并ML患者共9例,占同期SLE入院患者的0.18%;其中女性患者7例,男性患者2例;SLE平均发病年龄43.1岁(24～57岁),SLE平均确诊年龄为44.7岁(29～57岁),淋巴瘤平均确诊年龄为48.7岁(39～63岁),SLE发病到合并淋巴瘤病程均数为3.8年(1～15年)。淋巴瘤病理类型以非霍奇金淋巴瘤(NHL)为主,共7例,占77.8%(7/9),且淋巴瘤结外受累多见,共7例,占77.8%(7/9)。淋巴瘤在消化系统、呼吸系统、骨髓等部位均可发生,其中胃肠道受累3例,支气管和肺受累2例,骨髓受累2例。SLE合并ML患者中100%出现关节痛、淋巴结肿大及发热。实验室检查结果发现9例患者中6例补体减低,9例乳酸脱氢酶升高,5例红细胞沉降率(ESR)升高大于100mm/h。SLE合并ML的患者6例对化疗敏感,4例死亡,2例死因均为淋巴瘤消化道受累;2例诊断淋巴瘤放弃治疗后死亡。结论当SLE患者出现不明原因持续发热、淋巴结肿大、ESR持续大于100mm/h,乳酸脱氢酶持续偏高者需警惕SLE合并淋巴瘤的可能。当SLE合并淋巴瘤时结外受累多见,SLE合并ML多数对化疗敏感,但消化道受累时预后差。     

成人still''s病59例临床分析

目的探讨成人斯蒂尔氏病(AOSD)的临床特点、伴随症状和误诊原因,以提高对本病的认识和诊断水平.方法回顾性分析59例经临床和实验室确诊的成人斯蒂尔氏病患者的临床表现和实验室检查结果.结果59例患者中发热100%、皮疹78%、关节炎和关节疼痛74%、WBC升高95%、ESR增快91%.有32例患者测定血清铁蛋白,26例升高(81%),病情好转后均明显下降(P<0.01).结论发热、皮疹和关节/关节疼痛是AOSD的主要临床特点,若有WBC升高则诊断AOSD的敏感性和特异性明显增高,血清铁蛋白可作为疾病活动的指标.     

成人嗜血细胞综合征的临床分析

目的：探讨成人嗜血细胞综合征（HPS）的临床特点。方法：回顾性分析11例成人HPS患者的临床资料。结果：11例均有发热,同时表现为肝脾肿大、血细胞减少、肝功能损害和凝血功能异常等。4例病因分别为扁桃体炎、急性肾炎、干燥综合征、克罗恩病,其他7例病因不明。经治疗原发病及激素等对症治疗后,5例好转,6例死亡。结论：成人HPS病情进展迅速,易引起多脏器功能衰竭和弥散性血管内凝血（DIC）,要早诊断、早治疗。