Hemophagocytic lymphohistiocytosis in very young infants

We report three cases of hemophagocytic lymphohistiocytosis (HLH) in infants within the first 6 weeks of life. Diagnosis of HLH was made early after symptoms started. All three cases were successfully treated with dexamethasone and none relapsed, indicating that not all cases of HLH in very young infants are familial.     

Hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis: a case report

Leishmania-associated hemophagocytic lymphohistiocytosis is a rare clinicopathological entity. This condition is often difficult to diagnose, so treatment is often delayed. This report describes the case of a 5-year-old boy who was admitted with fever of 1 month's duration, hepatosplenomegaly, and pancytopenia. Serum testing showed elevated transaminase levels, hypertriglyceridemia, hyperferritinemia, and normal fibrinogen level. Hemophagocytic lymphohistiocytosis was diagnosed on bone marrow examination. The patient was tested for various infectious agents. He was negative for all except Leishmania, which was detected by indirect fluorescent antibody testing. Treatment with amphotericin B resulted in a dramatic resolution of all signs and symptoms within 1 week.     

Hemophagocytic lymphohistiocytosis triggered by Gaucher disease in a preterm neonate

Objective: To present the diagnostic workup in an extremely low birth weight infant patient with signs of both sepsis and hemophagocytosis. Participants: A preterm infant presented with clinical and laboratory signs of early-onset sepsis including hepatosplenomegaly, thrombocytopenia, direct hyperbilirubinemia, and elevated liver enzymes. Methods: Despite extensive septic workup, no underlying infection was detected. Additional hyperferritinemia and other elevated inflammatory parameters raised the suspicion of a primary or secondary hemophagocytic lymphohistiocytosis (HLH). Results: However, further metabolic analysis yielded a positive result for Gaucher disease (GD) type 2, a rare, but possible trigger of HLH. Conclusions: Our case shows that GD may lead to the picture of a secondary HLH and that a metabolic workup should always be performed in patients in whom primary HLH has been excluded.     

Hemophagocytic lymphohistiocytosis caused by systemic herpes simplex virus type 1 infection: Successful treatment with dexamethasone palmitate

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition resulting from an uncontrolled and ineffective immune response. Here, we report a case of HLH caused by disseminated herpes simplex virus (HSV)‐1 infection. The patient was initially treated with prednisolone and high‐dose acyclovir. Although liver enzymes, coagulation abnormalities, and inflammatory markers were remarkably improved, the platelet count remained low. Prednisolone was therefore switched to dexamethasone palmitate. Thereafter, the platelet count normalized. Inflammatory markers normalized 30 days after admission and serum HSV‐DNA became undetectable on day 41. The patient was discharged on day 91 and no developmental delay was evident at 7 months of age. These findings suggest that dexamethasone palmitate is effective for neonatal HLH.     

噬血细胞性淋巴组织细胞增生症47例

目的探讨噬血细胞性淋巴组织细胞增生症(HLH)的临床特点及预后,初步评价早期化疗疗效。方法除诊断所需检测项目外,患儿均常规行细胞及体液免疫功能检测、头部CT或MRI检测,并定期监测上述指标以评估疗效。患者化疗前均常规送检脑脊液生化及常规分类及爱泼斯坦病毒(EBV)、巨细胞病毒(CMV)、单纯疱疹病毒(HSV)、柯萨奇病毒(Cox-V)、埃可病毒(ECHOV)抗体检测。结果1.HLH48例患儿接受化疗,1例死亡,余47例均临床有效,8例因治疗过程中再次出现活动性病变放弃治疗,1例于化疗1.5年后病情再次恶化。25例进入停药观察期,其中3例复发。3年预期生存率为78%。2.疗效差12例中11例(92%)为EBV相关HLH。3.在所有监测指标中脾脏大小变化及铁蛋白可早期反映疾病转归,MRI对脑实质受累的检出率明显高于CT,二者具有非常显著差异(P=0.006)。结论1.化疗过程中应定期监测脾脏大小及血清铁蛋白。2.HLH患者确诊后应常规行头颅MRI检查,并在治疗不同阶段予以监测。3.EBV感染是预后不良因素之一,前期化疗疗效不满意的EBV-HLH应尽早接受干细胞移植。4.适时化疗可明显改善HLH患儿预后。     

Hemophagocytic lymphohistiocytosis associated with necrotizing enterocolitis in premature newborns

Hemophagocytic lymphohistiocytosis (HLH) is a systemic disease resulting from the excessive release of inflammatory cytokines by macrophages under prolonged antigenic stimulation. If untreated, it leads to multiorgan failure and death. Necrotizing enterocolitis (NEC) has not previously been associated with HLH. Here we report four preterm infants who were diagnosed with HLH associated with NEC. Two patients received chemotherapy and one survived. The other two infants succumbed to multiorgan failure. These results suggest that NEC may be a common clinical manifestation of HLH in premature neonates.     

Familial hemophagocytic lymphohistiocytosis and viral infections

A retrospective study was performed in 32 children with hemophagocytic lymphohistiocytosis, 16 of whom had affected siblings. Altogether 22 of these children, of whom the majority (13/22) were familial cases, had clinical or laboratory signs of infection. Laboratory analysis demonstrated Epstein-Barr virus in five children, cytomegalovirus in three and human parvovirus in two. Two siblings with onset of familial hemophagocytic lymphohistiocytosis within one month of each other, both of whom demonstrated serological indications of a recent human parvoviral infection at onset, are described. It is concluded that a viral infection cannot serve as the sole criterion for distinguishing a virus-associated hemophagocytic syndrome as an entity separate from familial hemophagocytic lymphohistiocytosis. Instead, it is suggested that viral infections may elicit a bout of the familial hemophagocytic lymphohistiocytosis disorder in genetically predisposed individuals.     

Hemophagocytic lymphohistiocytosis following dengue hemorrhagic fever in Hb H/Hb Constant Spring patient

Infection‐associated hemophagocytic syndrome (IAHS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), has been found following several types of infections and can be fatal. We report herein a case of IAHS following dengue infection in a 14‐year‐old patient with underlying α‐thalassemia syndrome (non‐deletional Hb H/Hb Constant Spring disease). He developed prolonged fever, thrombocytopenia, and progressive splenomegaly. Further investigations indicated hyperferritinemia, and increased reactive histiocytes with hemophagocytic activity in the bone marrow. He responded promptly to dexamethasone and i.v. immune globulin. Physicians should be aware of this condition, especially in countries where both dengue hemorrhagic fever and thalassemia are prevalent. The fatal outcome of IAHS can be prevented with prompt appropriate treatment.     

Hemophagocytic lymphohistiocytosis in systemic mastocytosis treated with allogeneic bone marrow transplant: A case report

Systemic mastocytosis is a rare entity in pediatrics, usually associated with mutations in the c‐KIT gene. We describe a Caucasian female who presented with severe systemic mastocytosis with food allergies requiring prolonged total parenteral nutrition. Her course was further complicated by the onset of hemophagocytic lymphohistiocytosis, which responded poorly to conventional chemotherapy. She underwent an allogeneic hematopoietic stem cell transplant that resulted in resolution of all symptoms related to systemic mastocytosis and hemophagocytic lymphohistiocytosis. She is now disease‐free and without any complications two years after the transplant.     

Familial hemophagocytic lymphohistiocytosis in two brothers with X-linked agammaglobulinemia

Hemophagocytic lymphohistiocytosis (HLH) is often familial and is associated with high mortality. Primary (familial) HLH is known to occur in children with mutations in perforin, Munc13-4, or syntaxin 11. We describe a case series of two brothers who developed HLH in the setting of X-linked agammaglobulinemia (XLA, Bruton's disease) and adenovirus infection. Further studies revealed absence of Bruton's tyrosine kinase (BTK) protein expression and a novel BTK mutation.     

Hemophagocytic lymphohistiocytosis secondary to Varicella zoster infection in a child with Henoch–Schönlein purpura

Hemophagocytic lymphohistiocytosis (HLH) is a fatal, hyper‐inflammatory syndrome that is characterized by untimely activation of macrophages, and manifests as cytopenia, organ dysfunction, and coagulopathy. Secondary HLH can be associated with infection, drugs, malignancy, and transplantation, and is mostly triggered by infection. Herein, we report the case of a patient with Henoch–Schönlein purpura (HSP) who developed severe HLH secondary to Varicella zoster infection.     

病毒感染相关噬血细胞淋巴组织细胞增生症的研究进展

噬血细胞淋巴组织细胞增生症是以发热、脾肿大、血细胞减少、高铁蛋白血症、高甘油三脂血症和低纤维蛋白原血症等为临床表现的一种综合征,包括原发性和继发性两大类型.继发性噬血细胞淋巴组织增生症由很多因素引起,其中病毒感染较为常见,尤其是EB病毒感染.该文就几种常见病毒感染相关噬血细胞淋巴组织细胞增生症的临床特征作一概述.     

EB病毒相关噬血细胞性淋巴组织细胞增生症患儿的EB病毒感染特征

目的 了解儿童EB病毒(EBV)相关噬血细胞性淋巴组织细胞增生症(EBV-HLH)患儿的EBV血清学抗体及病毒复制水平等特征.方法 对67例EBV-HLH患儿和60例原发性EBV感染所致的传染性单核细胞增多症(EBV-IM)患儿的临床资料进行分析,EBV特异性抗体和血清EBV DNA载量分别采用间接免疫荧光法和荧光定量PCR测定.结果 EBV-HLH患儿EBV特异性抗体结果:EBV-CA-IgM、EBV-CA-IgG、EBV-EA-IgG和EBV-NA-IgG的阳性率分别为28.8％、100.0％、51.5％和78.8％,EBV-VCA-IgG高亲和力为78.9％,低亲和力为12.1％;血清学抗体结果显示,71.2％的患儿为EBV再激活感染,其余为急性原发EBV感染;45.5％的EBV-HLH患儿可在血清中检测到EBV DNA,其拷贝数中位数为1.976×103 copies·L-1.EBV-IM患儿的EBV-CA-IgM、EBV-CA-IgG、EBV-EA-IgG和EBV-NA-IgG阳性率分别为100.0％、100.0％、58.3％和26.7％,EBV-VCA-IgG高亲和力为18.3％,低亲和力为81.7％,EBV DNA阳性率为10.0％,DNA拷贝数均值为8.495 copies·1-1.IM患儿均为EBV原发感染状态.结论 EBV-HLH可发生在EBV原发感染或既往EBV感染再激活时期,但多数患儿由既往EBV感染再激活所致.EBV-HLH患儿血清中EBV复制水平显著高于EBV-IM患儿.     

Hemophagocytic syndrome in a 4-month-old infant with biotinidase deficiency

Hemophagocytic syndromes such as hemophagocytic lymphohistiocytosis (HLH) are life-threatening hyperinflammatory conditions caused by inherited or acquired immune disorders. Awareness of the clinical symptoms and diagnostic criteria for hemophagocytic syndromes is crucial to start timely life-saving therapy. We present a case of a 4-month-old boy presenting with HLH. However, the patient was subsequently diagnosed with biotinidase deficiency and was successfully treated with biotin-replacement therapy, upon which the hemophagocytic syndrome ceased. Subsequent laboratory evaluations revealed normal lymphocyte cytotoxicity and no mutations in genes associated with familial HLH were found. Biotinidase deficiency should be considered as a differential diagnosis of patients fulfilling HLH criteria.     

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目的探讨儿童EB病毒感染相关噬血细胞淋巴组织细胞增生症(Epstein-Barr virus associated hemophagocytic lymphohistiocytosis,EBV-HLH)的主要死因及相关危险因素。方法回顾性分析首都医科大学附属北京儿童医院2003年6月至2010年10月收治的103例EBV-HLH患儿临床资料,并对其转归进行随访。采用单因素及多因素分析方法进行统计学分析。结果本组失访13例。随访成功的90例患儿中,存活32例,死亡58例,病死率为64.4%。其中未进行化疗的36例患儿病死率高达87.8%,其中33例在诊断后2个月内死亡;接受化疗患儿(化疗组)的病死率为44.9%。化疗组8例诊断后早期死亡病例,其中7例发生重症感染;6例发生严重的凝血功能障碍;7例发生脏器功能衰竭。14例晚期死亡病例中,9例患儿在化疗后病情持续不缓解并最终死亡;4例在停药后出现复发而死亡。单因素分析显示死亡组较存活组患儿的纤维蛋白原水平更低,而乳酸脱氢酶更高(P1=0.033、P2=0.005,均<0.05);Logistics回归分析显示,发病-诊断时间大于4周、未进行化疗及低纤维蛋白原均为与EBV-HLH患儿死亡相关的危险因素,其死亡危险度分别为3.436、11.09和1.866。结论儿童EBV-HLH预后差、病死率高。重症感染、凝血功能障碍及脏器功能衰竭是早期死亡主要原因;持续疾病活动及复发为晚期死亡的主要原因。发病-诊断时间大于4周、未进行化疗及低纤维蛋白原水平为与EBV-HLH死亡相关的危险因素。