成人继发性噬血细胞综合征临床特征及误诊分析

目的分析成人继发性噬血细胞综合征(HLH)的临床特点及误诊原因,总结防范误诊措施。方法回顾性分析2019年1月—2021年1月收治6例误诊成人继发性HLH的临床资料。结果本组误诊率为54.5%。6例早期表现为发热、乏力,5例炎症指标升高,2例咽痛、咳嗽、关节肌肉酸痛。误诊为肺部感染3例,上呼吸道感染2例,膀胱炎1例。误诊时间4 d~1个月。1例行骨髓穿刺后确诊白血病继发HLH,3例行淋巴结活组织病理检查后确诊淋巴瘤继发HLH,1例完善细胞学和病原学检查后确诊系统性红斑狼疮合并EB病毒感染继发HLH,1例完善布鲁菌病血清凝集试验后确诊布鲁菌病继发HLH。确诊后应用糖皮质激素联合依托泊苷治疗4例,未在本院治疗2例。随访6个月,正在治疗2例,病情相对稳定;另外死亡4例,主要原因为多器官衰竭和(或)弥散性血管内凝血。结论成人继发性HLH早期缺乏特异性临床表现,常继发于感染、肿瘤、风湿免疫性疾病,易误诊。唯有加强对其早期临床表现的认识,提高对相关检查结果的敏感性,才能减少误诊误治。     

GATA2 mutation underlies hemophagocytic lymphohistiocytosis in an adult with primary cytomegalovirus infection

We report a case of a 27-year old woman with persistent fever and pancytopenia who had multiple episodes of a hemophagocytic lymphohistiocytosis (HLH) like condition. The criterion for HLH was satisfied; primary cytomegalovirus (CMV) infection was identified as the cause. Further examination revealed a GATA binding protein 2 mutation. Reports of GATAs deficiency presenting with HLH after primary CMV infection is very limited. As early recognition and diagnosis will improve patients' outcomes, internists and infectious disease specialists should be aware of this disease.     

Malaria-associated secondary hemophagocytic lymphohistiocytosis: A case report

BACKGROUNDMalaria-associated secondary hemophagocytic lymphohistiocytosis (HLH) is rare. Moreover, the literature on malaria-associated HLH is sparse, and there are no similar cases reported in China.CASE SUMMARYWe report the case of a 29-year-old woman with unexplained intermittent fever who was admitted to our hospital due to an unclear diagnosis. The patient concealed her history of travel to Nigeria before onset. We made a diagnosis of malaria-associated secondary HLH. The treatment strategy for this patient included treatment of the inciting factor (artemether for 9 d followed by artemisinin for 5 d), the use of immunosuppressants (steroids, intravenous immunoglobulin) and supportive care. The patient was discharged in normal physical condition after 25 d of intensive care. No relapses were documented on follow-up at six months and 1 year. CONCLUSIONEarly diagnosis of the primary disease along with timely intervention and a multidisciplinary approach can help patients achieve a satisfactory outcome.     

Aggressive natural killer cell leukemia with skin manifestation associated with hemophagocytic lymphohistiocytosis: A case report

BACKGROUNDAggressive natural killer cell leukemia (ANKL) is a rare natural killer cell neoplasm characterized by systemic infiltration of Epstein–Barr virus and rapidly progressive clinical course. ANKL can be accompanied with hemophagocytic lymphohistiocytosis (HLH). Here, we report a case of ANKL with rare skin lesions as an earlier manifestation, accompanied with HLH, and review the literature in terms of etiology, clinical manifestation, diagnosis and treatment.CASE SUMMARYA 30-year-old woman from Northwest China presented with the clinical characteristics of jaundice, fever, erythema, splenomegaly, progressive hemocytopenia, liver failure, quantities of abnormal cells in bone marrow, and associated HLH. The immunophenotypes of abnormal cells were positive for CD2, cCD3, CD7, CD56, CD38 and negative for sCD3, CD8 and CD117. The diagnosis of ANKL complicated with HLH was confirmed. Following the initial diagnosis and supplementary treatment, the patient received chemotherapy with VDLP regimen (vincristine, daunorubicin, L-asparaginase and prednisone). However, the patient had severe adverse reactions and complication such as severe hematochezia, neutropenia, and multiple organ dysfunction syndrome, and died a few days later. CONCLUSIONThis is the first reported case of ANKL with rare skin lesions as an earlier manifestation and associated with HLH.     

The knocked-out erythrocyte sedimentation rate: periodontal abscess

INTRODUCTION: The erythrocyte sedimentation rate (ESR) is a common but nonspecific test that is often used as an indicator of active disease. Infection of dental origin may be responsible for a number of cases in unresolved elevated ESR and fever etiology. Dental sepsis is the one of the potential causes of persistent fever that can escape detection. CLINICAL PICTURE: An 18-year-old female patient was admitted to the emergency room with complaints of headache, fever, nausea, and vomiting for the past four days. Erythrocyte sedimentation rate was 110 mm/h. She was started empirically on antibiotic treatment as no etiology was found. Four days later, while searching for the etiology of the fever, the patient experienced an acute pain in association with localizing symptoms in two decayed teeth. Oral examination revealed abscess formation in both teeth. TREATMENT: Teeth were extracted and ESR was decreased to 95 mm/h on the day of the second extraction and to 60, 35, and 10 mm/h taken weekly. OUTCOME: During the follow-up, she was in good health with no fever seen 3 months after treatment and her ESR was 15 mm/h. CONCLUSION: Dental infection should be considered as an unusual but very treatable cause of pyrexia of unknown origin.     

Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment?

ABSTRACT: INTRODUCTION: Hyperferritinemia is associated with increased mortality in pediatric sepsis multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patient with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH. METHODS: Multi-center cohort study of children in Turkish Pediatric Intensive Care units with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS treated with less immunosuppression (plasma exchange and intravenous immunoglobulin or methyl prednisolone) or with the primary HLH protocol (plasma exchange and dexamethasone or cyclosporine A and/or etoposide). The primary outcome assessed was hospital survival. RESULTS: 23 children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS were enrolled (median ferritin = 6341 g/dL, median number of organ failures = 5). Univariate and multivariate analyses demonstrated that use of plasma exchange and methyl prednisolone or intravenous immunoglobulin (n=17, survival 100%) was associated with improved survival compared to plasma exchange and dexamethasone and/or cyclosporine and/or etoposide (n = 6, survival 50%) (P = 0.002). CONCLUSIONS: Children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS can be successfully treated with plasma exchange, intravenous immunoglobulin, and methylprednisone. Randomized trials are required to evaluate if the HLH-94 protocol is helpful or harmful compared to this less immune suppressive and cytotoxic approach in this specific population.     

Hemophagocytic lymphohistiocytosis secondary to composite lymphoma: Two case reports

BACKGROUNDHemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disease caused by inherited pathogenic mutations and acquired dysregulations of the immune system. Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphomas that occur in a single patient. Here, we report two cases of HLH secondary to composite lymphoma with mixed lineage features of T- and B-cell marker expression both in the bone marrow and lymph nodes in adult patients.CASE SUMMARYTwo patients were diagnosed with HLH based on the occurrence of fever, pancytopenia, lymphadenopathy, splenomegaly, hemophagocytosis and hyperferritinemia. Immunohistochemical staining of the axillary lymph node and bone marrow in case 1 showed typical features of combined B-cell and T-cell lymphoma. In addition, a lymph node gene study revealed rearrangement of the T-cell receptor chain and the immunoglobulin gene. Morphology and immunohistochemistry studies of a lymph node biopsy in case 2 showed typical features of T cell lymphoma, but immunophenotyping by flow cytometry analysis of bone marrow aspirate showed B cell lymphoma involvement. The patients were treated with high-dose methylprednisolone combined with etoposide to control aggressive HLH progression. The patients also received immunochemotherapy with the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen immediately after diagnosis. Both patients presented with highly aggressive lymphoma, and died of severe infection or uncontrolled HLH.CONCLUSIONWe present two rare cases with overwhelming hemophagocytosis along with composite T- and B-cell lymphoma, which posed a diagnostic dilemma. HLH caused by composite lymphoma was characterized by poor clinical outcomes.     

PD-1 blockader-associated atypical hemophagocytic lymphohistiocytosis: A cautionary case report

Hemophagocytic lymphohistiocytosis (HLH) is a fatal immune hyperactivity syndrome with high mortality. It seriously endangers human health. HLH associated with immune checkpoint inhibitors is rare, and no particular diagnostic guidelines or treatment regimens exist. A 36-year-old patient with metastatic right atrial angiosarcoma was treated with programmed cell death-1 (PD-1) blockader toripalimab and pazopanib, a vascular endothelial growth factor receptor blockader. However, the patient presented to our center with HLH, and he accepted combination therapy of therapeutic plasma exchange (TPE) and immunotherapy. The patient improved quickly, after only one TPE procedure. Finally, he was discharged after completing two TPE procedures. We summarize a case of PD-1 blocker associated atypical HLH that was successfully treated with TPE. Further evidence is needed to elucidate whether TPE has therapeutic potential for immunotherapy associated HLH.     

Successful rescue of acute liver failure and hemophagocytic lymphohistiocytosis following varicella infection: A case report and review of literature

Herein we report a case of acute liver failure (ALF) and hemophagocytic lymphohistiocytosis (HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosuppression with dexamethasone and etoposide. A previously healthy 16-year-old boy presented with generalized rash, fever, severe abdominal pain, and abnormal liver function within 4 d. Chickenpox was suspected, and acyclovir and intravenous immunoglobulin were started on admission. However, the patient’s condition deteriorated overnight with soaring transaminases, severe coagulopathy and encephalopathy. On the fourth day of admission, pancytopenia emerged, accompanied by hypofibrinogenemia and hyperferritinemia. The patient was diagnosed with ALF. He also met the diagnostic criteria of HLH according to the HLH-2004 guideline. Polymerase chain reaction (PCR) amplifications of varicella-zoster virus (VZV) were positive, confirming that VZV was a causative trigger for ALF and HLH. In view of the devastating immune activation in HLH, immunosuppression therapy with dexamethasone and etoposide was administered, in addition to high dose acyclovir. The patient’s symptoms improved dramatically and he finally made a full recovery. To our knowledge, this is only the second report of a successful rescue of ALF associated with HLH, without resorting to liver transplantation. The first case was reported in a neonate infected by herpes simplex virus-1. However, survival data in older children and adults are lacking, most of whom died or underwent liver transplantation. Our report emphasizes the clinical vigilance for the possible presence of HLH, and the necessity of extensive investigation for underlying etiologies in patients presenting with indeterminate ALF. Early initiation of specific therapy targeting the underlying etiology, and watchful immunosuppression such as dexamethasone and etoposide, together with supportive therapy, are of crucial importance in this life-threatening disorder.     

MRSA感染相关噬血细胞性淋巴组织细胞增多症两例附文献复习

目的 探讨耐甲氧西林金黄色葡萄球菌感染（MRSA）相：相关噬血细胞性淋巴组织细胞增多症（HLH）临床特征、治疗和预后.方法 通过两例典型病例深入分析MRSA感染相关HLH的临床表现、治疗方案和疾病转归以及结合该领域最新进展和文献进行讨论.结果 两例HLH患者均经病原学（细菌培养）检查确诊为MRSA感染,经过积极抗感染联合适当免疫抑制治疗,均好转出院.结论 MRSA感染为噬血细胞性淋巴组织细胞增多症罕见病因之一,由于病因明确,经过抗感染治疗联合免疫抑制治疗后预后优于其他原因导致的HLH.     

Neonatal hemophagocytic lymphohistiocytosis associated with a vertical transmission of coxsackievirus B1

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy with the background of hypercytokinemia. Early diagnosis and etoposide therapy are not established for affected newborns. An afebrile infant suffered from apnea 4 days after birth, showing leukocytosis, thrombocytopenia, coagulopathy, and cerebrospinal fluid pleocytosis. Serum levels of ferritin and sIL-2R were high. Bone marrow studies revealed activated/hemophagocytosing macrophages. Coxsackievirus B1 (CB1) was isolated from the throat and stool. Serum anti-CB1 antibody titers were elevated in the patient (4 → 16; 6 → 43 days after birth) and mother (128; 10 days after delivery). Normal expressions of perforin and CD107a precluded inherited HLH. The vertically transmitted CB1-HLH was successfully treated without administration of corticosteroid, cyclosporine, or etoposide. Serum cytokine levels showed dominant expression of monokines (IL-1β/6/8, and TNF-α) but not IFN-γ, which is the central player of inherited HLH. The cytokine profile might represent a unique pathophysiology of enterovirus-driven neonatal HLH.     

A case of isoniazid-resistant miliary tuberculosis in which tuberculous meningitis paradoxically developed despite systemic improvement

A 63-year-old man with chronic myelomonocytic leukemia was admitted to our hospital with miliary tuberculosis. He received anti-tuberculosis drugs: isoniazid (INH), rifampicin (RFP), ethambutol (EB), and pyrazinamide (PZA). His condition clearly and immediately improved after the therapy, but he experienced a high fever of about 38°C every day from 1 month after the initiation of the therapy. Drug-induced fever and tumor fever were suspected as causes, but the etiology could not be determined. The tuberculosis was identified as an INH-resistant strain, so INH was stopped and levofloxacin (LVFX) was introduced, with streptomycin (SM), in addition to RFP, EB, and PZA. At 2 months after the initiation of the therapy (about one week after the change in the anti-tuberculosis drug regimen), his spinal fluid was examined, given his complaints of headache and vomiting. The spinal fluid analysis revealed invasion of lymphocytic inflammatory cells and high adenosine deaminase activity; the patient was thus diagnosed with tuberculous meningitis. His condition gradually improved after the changing of the anti-tuberculosis drugs. Thus, to summarize, the tuberculous meningitis had worsened paradoxically despite his systemic improvement, although it was successfully treated by the addition of LVFX and SM. We must keep in mind that a potential cause of fever during anti-tuberculosis therapy may be INH-resistant tuberculous meningitis.     

Successful multidrug treatment of a pediatric patient with severe Churg-Strauss syndrome refractory to prednisolone

Churg-Strauss syndrome (CSS), which is characterized by systemic small-vessel vasculitis of unknown etiology, is associated with a history of asthma. Although reports of CSS occurring in children are limited, effective treatment of pediatric patients with severe CSS remains challenging. A 10-year-old Japanese boy with a 6-month history of asthma treated with a leukotriene modifier, pranlukast, developed high fever, pleural infiltration, and pericarditis that were associated with marked hypereosinophilia (10,350 eosinophils/μl). Owing to his persistent high fever, mononeuritis multiplex, and severe abdominal pain that was refractory to prednisolone, his general condition progressively deteriorated thereafter. Although intravenous high-dose immunoglobulin administration was transiently effective for mononeuritis multiplex, the recurrent high fever and severe abdominal pain remained refractory. An endoscopic study revealed ulcerative lesions of the total colon. In this context, we treated the patient with an aggressive multidrug immunosuppressive regimen consisting of a high-dose methylprednisolone pulse plus short-course intravenous cyclophosphamide pulse therapy, followed by oral tacrolimus combined with prednisolone. After the rescue multidrug treatment, his severe clinical signs dramatically subsided within a short time, and the concomitantly administered prednisolone was successfully tapered without flare. At present, 12 months after the presentation, he is free from CSS signs or therapy-related toxicity except for an occasional mild asthma attack. Although further close observation should be needed to draw a long-term outcome in this patient, we believe that aggressive multidrug immunosuppressive treatment should be considered as an alternative rescue treatment in selected patients with severe CSS, even with pediatric-onset disease, that is refractory to prednisolone.     

血栓性血小板减少性紫癜12例临床分析

目的探讨血栓性血小板减少性紫癜的病因、临床特点和治疗效果。方法对我院1993.-2005.6收治的血栓性血小板减少性紫癜(TTP)患者12例进行回顾性分析。结果本组12例患者中,原发性TTP5例,继发性TTP7例;7例继发性TTP中,感染所致2例,自身免疫性疾病伴感染1例,术后1例,宫内死胎1例,肝移植及骨髓移植术后各1例。原发性TTP中1例起病缓、病程达半年呈慢性型,其余4例及继发性均以急性暴发型起病。临床表现为微血管病性溶血性贫血(12/12)、血小板减少(12/12)、神经精神障碍(12/12)、肾脏损害(11/12)、发热(11/12),全部患者均有血清乳酸脱氢酶(LDH)明显升高。7例继发性TTP中4例血浆置换(PE)和病因治疗为主,均治愈,3例未行PE,均死亡;5例原发性TTP中2例行PE,1例治愈,1例死亡,3例未行PE,均死亡。结论本组12例TTP中以继发性TTP多见,多为急性暴发型起病;突出临床表现为微血管病性溶血性贫血、血小板减少、神经精神障碍、肾脏损害、发热,LDH明显升高;死亡率仍高。治疗上应强调PE的重要性;继发性TTP,若病因能有效控制,预后较原发者好。     

Lung adenocarcinoma and sequential antineutrophil cytoplasmic antibody-associated vasculitis: a case report

The relationship between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and lung cancer remains unclear. A 66-year-old man presented with pulmonary nodules. Histological examination of a specimen from computed tomography-guided percutaneous transthoracic biopsy revealed adenocarcinoma. The patient was treated using cryoablation and systemic chemotherapy. Sixteen months later, the patient presented with fever, nasal inflammation, recurrent lung lesions, elevated serum creatinine levels, and high levels of ANCA. Histological examination of a specimen from ultrasound-guided percutaneous renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. The patient responded to treatment, but granulomatosis with polyangiitis recurred and he later died. This case highlights the possibility of sequential AAV with lung cancer. Although this is relatively rare, further research is needed to better understand the association or pathophysiological link between lung cancer and AAV.     

Splenectomy for an adult patient with refractory secondary hemophagocytic lymphohistiocytosis

Treatment regimens of secondary hemophagocytic lymphohistiocytosis (sHLH) are complicated and individualized. CHOP regimen is well known for the treatment of adult sHLH, but it was not so effective for the 56-year-old male patient in our study. Splenomegaly, one of clinical manifestations of HLH, has urged us to investigate the role of splenectomy in HLH patients. Splenectomy is not only beneficial to confirm the underlying diseases, but also beneficial for the treatment of HLH. Here, we present a case diagnosed as sHLH who has recovered from HLH following comprehensive treatment based on splenectomy. The therapeutic value of splenectomy in sHLH needs further study.     

Hemophagocytic syndrome in children with acute monoblastic leukemia—another cause of fever of unknown origin

Purpose

Intensification of antileukemic treatment and progress in supportive management have improved the survival rates of children with acute myeloid leukemia (AML). However, morbidity and early mortality in these patients are still very high, especially in children with acute monoblastic leukemia (AML FAB M5). Inflammatory syndromes complicating the management of these children after application of cytosine arabinoside and due to hyperleukocytosis at initial presentation have been reported. Hemophagocytic lymphohistiocytosis (HLH) has been described as a serious and life-threatening acute complication during treatment of different oncologic entities; however, data on HLH in children with AML FAB M5 are extremely rare.

Methods

A retrospective study of all children with AML FAB M5 treated at our institution between 1993 and 2013 was performed to describe the clinical characteristics of patients who developed an inflammatory syndrome with HLH during oncologic treatment.

Results

Three of 10 children developed an inflammatory syndrome with fever, elevation of C-reactive protein, hyperferritinemia, elevation of soluble interleukin-2, and hemophagocytosis during prolonged aplasia following the first cycle of chemotherapy not responding to broad-spectrum antibiotics. No infectious agents could be identified; the initial symptoms occurred 17, 18, and 28 days after diagnosis of AML, respectively. The children immediately responded to dexamethasone; however, the same syndrome was observed again after the second cycle of chemotherapy and, in one patient, also after the third cycle.

Conclusions

Treating physicians should be aware of an inflammatory syndrome resembling HLH in children with monoblastic leukemia since this problem might extremely complicate management and supportive care of these children. The co-incidence of monoblastic leukemia with HLH might be explained by cytokines released from the monoblastic leukemic cells themselves.     

Reactive hemophagocytic syndrome associated with thrombotic thrombocytopenic purpura during therapeutic plasma exchange.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, cytopenia, splenomegaly, and lymphohistiocytic proliferation with hemophagocytosis. Sporadic, familial, and reactive HLH varieties exist. The latter, also termed the reactive hemophagocytic syndrome (RHS), has been associated with a variety of infectious and noninfectious etiologies. Activation of monocytes in RHS is due to stimulation by high levels of activating cytokines. RHS has not been associated previously with thrombotic thrombocytopenic purpura (TTP). TTP is a multisystem disorder characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, renal impairment, and fever. We report on a 33 year old male patient with a classic picture of TTP who initially responded to therapeutic plasma exchange but then became refractory to treatment and developed RHS. It is likely that a specific pathophysiology involving the activation of neutrophils during TPE is present for the development of cytokine-induced hemophagocytosis during TTP treatment. The consequent development of RHS possibly caused early TTP relapse.     

What intensivists need to know about hemophagocytic syndrome: an underrecognized cause of death in adult intensive care units

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a rare and frequently fatal disorder caused by an uncontrollable and ineffective systemic immune response. Patients initially present with fever, cytopenia, and hepatosplenomegaly, and subsequently develop multiorgan failure (MOF). Hemophagocytosis can be found on biopsy specimen but is not required. Acquired forms of HLH can occur in apparently healthy adults, while children present more often with an inherited form of the disease. Since HLH often presents with sepsis-like symptoms and organ dysfunction, patients are usually treated for presumed sepsis, which inevitably leads to delayed diagnosis and treatment. Intensivists need to have a low threshold for suspecting this disorder when previously healthy individuals present with a fulminant sepsis-like syndrome, which are unresponsive to conventional treatment. We present 3 patients with HLH who were admitted to our adult medical intensive care unit (MICU) over a 2-year period with fatal outcomes and emphasize the diagnostic importance of markedly elevated serum ferritin levels and the need for tissue biopsy in making an accurate diagnosis in a timely manner.     

The choice of the intravenous fluid influences the tolerance of acute normovolemic anemia in anesthetized domestic pigs

Introduction

Hyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH.

Methods

We conducted a multi-center cohort study of children in Turkish Pediatric Intensive Care units with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS treated with less immunosuppression (plasma exchange and intravenous immunoglobulin or methyl prednisolone) or with the primary HLH protocol (plasma exchange and dexamethasone or cyclosporine A and/or etoposide). The primary outcome assessed was hospital survival.

Results

Twenty-three children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS were enrolled (median ferritin = 6341 ??g/dL, median number of organ failures = 5). Univariate and multivariate analyses demonstrated that use of plasma exchange and methyl prednisolone or intravenous immunoglobulin (n = 17, survival 100%) was associated with improved survival compared to plasma exchange and dexamethasone and/or cyclosporine and/or etoposide (n = 6, survival 50%) (P = 0.002).

Conclusions

Children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS can be successfully treated with plasma exchange, intravenous immunoglobulin, and methylprednisone. Randomized trials are required to evaluate if the HLH-94 protocol is helpful or harmful compared to this less immune suppressive and cytotoxic approach in this specific population.