Expression Profile and Clinical Significance of Cytokines and Chemokines in Patients with Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival.@*METHODS@#Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated.@*RESULTS@#Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05).@*CONCLUSION@#IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.

Comparative Analysis of Primary and Reactivated EB Virus Infection Associated Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To compare the clinical characteristics of children with hemophagocytic lymphocytosis (HLH) associated with primary Epstein-Barr virus (EBV) infection and EBV reactivation, and explore the effects of different EBV infection status on the clinical indexes and prognosis of HLH.@*METHODS@#The clinical data of 51 children with EBV associated HLH treated in Henan Children's Hospital from June 2016 to June 2021 were collected. According to the detection results of plasma EBV antibody spectrum, they were divided into EBV primary infection-associated HLH group (18 cases) and EBV reactivation-associated HLH group (33 cases). The clinical features, laboratory indexes and prognosis of the two groups were analyzed and compared.@*RESULTS@#There were no significant differences in age, gender, hepatomegaly, splenomegaly, lymphadenopathy, neutrophil count in peripheral blood, hemoglobin content, platelet count, plasma EBV-DNA load, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, albumin, fibrinogen, triglyceride, ferritin, hemophagocytosis in bone marrow, NK cell activity and sCD25 between the two groups(P>0.05). The central nervous system involvement and CD4/CD8 in EBV reactivation-associated HLH group were significantly higher than those in primary infection-associated HLH group, but the total bilirubin was significantly lower than that in primary infection-associated HLH group (P<0.05). After treatment according to HLH-2004 protocol, the remission rate, 5-year OS rate and 5-year EFS rate of patients in EBV reactivation-associated HLH group were significantly lower than those in EBV primary infection-associated HLH group (P<0.05).@*CONCLUSION@#EBV reactivation-associated HLH is more likely to cause central nervous system involvement and the prognosis is worser than EBV primary infection-associated HLH, which requires intensive treatment.

Clinical Analysis of Acute Myeloid Leukemia Patients with Hemophagocytic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features of acute myeloid leukemia patients with hemophagocytic syndrome.@*METHODS@#The clinical data of 2 patients with acute myeloid leukemia complicated with hemophagocytic syndrome were collected, and the clinical characteristics and treatment outcomes were analyzed.@*RESULTS@#There were two patients with acute myeloid leukemia, including 1 male and 1 female，aged for 67 and 40 years old，respectively. Hemophagocytic syndrome occurred in one patient after induction therapy for acute myeloid leukemia and one patient after consolidation therapy. Both of the patients with hemophagocytic syndrome showed fever, hemocytopenia, high ferritin, high titer sCD25 levels and hemophagocytes in bone marrow. After achieved anti-infection, glucocorticoid, human immunoglobulin and etoposide regimens treatment, hemophagocytic syndrome was controlled in both of the two patients. One patient failed to induce acute myeloid leukemia and one patient achieved complete remission.@*CONCLUSION@#Acute myeloid leukemia complicated with hemophagocytic syndrome is rare. Early identification, early anti-infection combined with HLH94 regimen can control hemophagocytosis and improve prognosis.

Hemophagocytic lymphohistiocytosis presenting as acute coronary syndrome

Acquired Hemophagocytic Lymphohistiocytosis is a rare and deadly syndrome resulting from an overactive immune system, with uncontrolled activation of macrophages and lymphocytes, hypercytokinemia, and systemic inflammatory response. A 75-year-old male presented with typical anginal pain and was diagnosed with the acute coronary syndrome, which required a percutaneous transluminal coronary angioplasty. Instead of resolving the symptoms, the patient began to exhibit pyrexia and worsening altered sensorium with progressing renal failure, anemia, thrombocytopenia and respiratory failure. This constellation of symptoms caused the patient to require mechanical ventilation and hemodialysis. Upon laboratory analysis, hyperferritinemia provided an indication to the diagnosis of acquired hemophagocytic lymphohistiocytosis. After the initiation of dexamethasone, the patient made a significant recovery and was discharged from the hospital.

Linfohistiocitosis hemofagocítica, un síndrome potencialmente fatal. Presentación de tres casos / Hemophagocytic lymphohistiocytosis, a potentially fatal syndrome. Presentation of three cases

Introducción: La evidencia actual sobre el síndrome de linfohistiocitosis hemofagocítica se basa en series de casos y, por tanto, las decisiones clínicas se fundamentan en el criterio de expertos. En Cuba son escasos los informes publicados, lo cual valida los esfuerzos que incrementen la comprensión de esta entidad en nuestro medio. Objetivo: Describir tres casos de síndrome de linfohistiocitosis hemofagocítica secundaria, una complicación extremadamente infrecuente y poco sospechada. Casos clínicos: De los tres pacientes estudiados, dos presentaron linfoma como enfermedad subyacente. A uno de ellos se le diagnosticó un linfoma no Hodgkin de células T anaplásico en la necropsia; mientras el otro paciente fue diagnosticado y tratado precozmente por linfoma no Hodgkin de células grandes B, el cual evolucionó satisfactoriamente. El tercer paciente presentó endocarditis de valva tricúspide y alcanzó la remisión luego de tratamiento antibiótico, inmunomodulador y quirúrgico. Conclusiones: Los casos presentados destacan la complejidad del síndrome de linfohistiocitosis hemofagocítica y refuerzan la necesidad crítica de su diagnóstico y tratamiento oportuno en nuestro medio(AU)

Introduction: The current evidence about hemophagocytic lymphohistiocytosis syndrome is based on case series and, therefore, clinical decisions are based on expert criteria. In Cuba, there are few published reports, which validates the efforts that may increase understanding of this entity in our environment. Objective: To describe three cases of secondary hemophagocytic lymphohistiocytosis syndrome, an extremely rare and little suspected complication. Clinical cases: Of the three patients studied, two presented lymphoma as subjacent disease. One of them was diagnosed with anaplastic T-cell non-Hodgkin lymphoma at autopsy. The other was diagnosed and treated early for large B-cell non-Hodgkin lymphoma, and evolved satisfactorily. The third patient presented tricuspid valve endocarditis and achieved remission after antibiotic, immunomodulatory and surgical treatment. Conclusions: The cases presented highlight the complexity of hemophagocytic lymphohistiocytosis syndrome and reinforce the critical need for diagnosis and timely treatment of this condition in our setting(AU)

Hemophagocytic lymphohistiocytosis associated with H1N1 virus infection and visceral leishmaniasis in a 4.5-month-old infant / Linfohistiocitose hemofagocítica associada pela infecção do vírus H1N1 e leishmaniose visceral em um bebê de 4,5 meses de vida

We present a case of a 4.5-month-old boy from Turkey with hemophagocytic lymphohistiocytosis (HLH) associated with H1N1 virus and Leishmania spp. coinfection. Because visceral leishmaniasis can mimic hematologic disorders like HLH, it is important to rule out this clinical condition before starting immunosuppressive therapy. In our case, treatment with liposomal amphotericin B resulted in a dramatic resolution of clinical and laboratory abnormalities.

É relatado um caso de um menino de 4,5 meses de idade, da Turquia, com linfohistiocitose hemofagocítica (HLH) associado à coinfecção com o vírus H1N1 e leishmaniose visceral. Como a leishmaniose visceral pode imitar doenças hematológicas como HLH, é importante afastar essa condição clínica antes de iniciar a terapia imunossupressora. No caso relatado, o tratamento com anfotericina B lipossomal resultou em uma resolução dramática das anomalias clínicas e laboratoriais.

Rare case of hemophagocytic lymphohistiocytosis: a case report

A two-month old infant was admitted to our hospital with history of fever and cough. He was active and playful with normal systemic examination. He was started on antibiotics because the C-reactive protein [CRP] was high. Over the next few days he deteriorated with persisting fever, altered sensorium and hepatomegaly. Inspite of using third line antibiotics, the CRP kept increasing and the child showed no signs of improvement. A possibility of Hemophagocytic Lymphohistiocytosis [HLH] was considered. Ferritin was high and so the child was referred to a tertiary centre for further treatment. Bone marrow biopsy confirmed the diagnosis of HLH. HLH is a clinical syndrome of hyper inflammation, and uncontrolled and ineffective immune response. It could be primary where genetic mutations have been demonstrated or secondary to infection, malignancy or metabolic condition. Criteria have been laid done for the diagnosis of HLH. This condition should be considered when there is continued deterioration in spite of maximal supportive care

Fever of unknown origin in a patient of systemic onset juvenile idiopathic arthritis.

Hemophagocytic lymphohistiocytosis is a potentially fatal condition characterized by pathologic immune activation, which can complicate infections, childhood systemic rheumatologic diseases and malignancies. Here we report a case of reactive hemophagocytic lymphohistiocytosis [macrophage activation syndrome] complicating systemic onset juvenile idiopathic arthritis, which was treated successfully with dexamethasone and cyclosporine. Reactive hemophagocytic lymphohistiocytosis or macrophage activation syndrome should be considered in patients of juvenile idiopathic arthritis with prolonged fever of unknown origin and cytopenias. Early diagnosis with high index of suspicion and prompt, aggressive treatment are needed for successful outcomes.

Síndrome hemofagocítico secundario en el recién nacido / Secondary hemophagocytosis syndrome in the newborn

El síndrome hemofagocítico secundario o reactivo es una entidad poco frecuente, de etiología multifactorial, que clínicamente se manifiesta como un cuadro grave y de alta letalidad. Se caracteriza por activación benigna de los macrófagos, asociada a infecciones virales, bacterianas, fúngicas o parasitarias, a inmunodeficiencias y a neoplasias. Se presenta el caso clínico de un neonato varón, de 17 días de vida, que presentó fiebre, manifestaciones catarrales y digestivas. Evolucionó clínicamente con ictericia, hepatoesplenomegalia, trombocitopenia y anemia. Se diagnosticó un citomegalovirus en la orina. Egresó vivo a los 68 días de vida, con regresión del cuadro clínico

The secondary or reactive hemophagocytosis syndrome is an uncommon entity clinically manifested by a severe clinical picture and a high mortality rate. It is characterized by a macrophages benign activation, associated with viral, bacterial, fungoid or parasitic infections and immunodeficiencies and neoplams. This is the clinical case of a 17 days male neonate with fever, suffering from cold and digestive manifestations who clinically evolving with jaundice, hepatosplenomegaly and anemia. A cytomegalovirus was diagnosed in urine. Was discharged being alive at 68 days with a regression of clinical picture

A Case of Hemophagocytic Syndrome in an Ulcerative Colitis Patient / 대한소화기학회지

A case of hemophagocytic syndrome associated with ulcerative colitis is very rare. A 32-year-old man visited the hospital complaining of fever and severe abdominal pain for 7 days. He was diagnosed to have ulcerative colitis 2 years ago and had been treated with sulfasalazine. Three months ago, he had abdominal pain, weight loss, and hematochezia, so prednisolone and mercaptopurine were added to the treatment. On admission, the physical examination showed splenomegaly. Peripheral blood counts revealed pancytopenia, and bone marrow aspirate smears showed many histiocytes with active hemophagocytosis. There was no evidence of viral and bacterial infections and other neoplasms, which were commonly associated with hemophagocytic syndrome. He was successfully treated with high dose steroid. We report this case along with a review of the related literatures.

A case of hemophagocytic syndrome complicated by acute viral hepatitis A infection / 대한간학회지

Hemophagocytic syndrome (HPS) is a rare but serious condition that is histopathologically characterized by activation of macrophage or histiocytes with hemophagocytosis in bone marrow and reticuloendothelial systems. Clinically it presents with high fever, hepatosplenomegaly, pancytopenia, liver dysfunction, and hyperferritinemia. Hepatitis A virus is a very rare cause of secondary HPS. We report a case of a 22-year-old woman infected by hepatitis A virus who was consequently complicated with HPS. She presented typical clinical features of acute hepatitis A, and showed clinical and biochemical improvements. However, HPS developed as a complication of acute hepatitis A and the patient died of intraperitoneal bleeding caused by hepatic decompensation and disseminated intravascular coagulation.

Hemophagocytic Syndrome in a Patient with Acute Tubulointerstitial Nephritis Secondary to Hepatitis A Virus Infection

Hepatitis A virus (HAV) infection is generally a self-limited disease, but the infection in adults can be serious, to be often complicated by acute kidney injury (AKI) and rarely by virus-associated hemophagocytic syndrome (VAHS). Our patient, a 48-yr-old man, was diagnosed with HAV infection complicated by dialysis-dependent AKI. His kidney biopsy showed acute tubulointerstitial nephritis with massive infiltration of activated macrophages and T cells, and he progressively demonstrated features of VAHS. With hemodialysis and steroid treatment, he was successfully recovered.

Reactive haemophagocytic lymphohistiocytosis.

We present a series of five cases diagnosed and treated as reactive haemophagocytic lymphohistiocytosis (HLH) in three tertiary referral centers of Kolkata, within a time frame of 3 months. The initial presentations were very variable, the most prominent clinical feature being - acute renal failure in the first patient, convulsions in the second, encephalopathy the third, marked cervical lymphadenopathy in the fourth and polyserositis in the fifth. All had a history of prolonged fever preceding admission and hepatosplenomegaly on examination. Investigations revealed multi-organ involvement with pancytopenia;- haemophagocytosis was eventually diagnosed by bone marrow examination. These cases highlight the diagnostic challenge posed by infection associated haemophagocytosis and the need for maintaining a high index of suspicion to promptly diagnose and treat this potentially life threatening condition.

Reactive hemophagocytic syndrome.

We describe two cases of Reactive Hemophagocytic syndrome (RHS) occurring in rheumatic diseases in childhood. Patient 1, an adolescent girl with systemic onset Juvenile idopathic arthritis (JRA) presented like severe sepsis with shock, hepatic dysfunction and coagulopathy. Patient 2 presented with cardiac tamponade, she was later detected to have systemic lupus erythematosus (SLE). Her bone marrow aspirate revealed prominent hemophagocytosis. Both cases improved with pulse methylprednisolone therapy.

An unusual cause of ascites: hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis is character-ized by fever, hepatosplenomegaly, cytopenia, hyper-triglyceridemia, hypofibrinogenemia, and hemophago-cytosis. Ascites is not mentioned as a symptom of hemophagocytic syndrome. We report a one month-old girl suffering from familial erythrophagocytic lympho-histiocytosis, who presented with ascites.

A Case of Therapy-Related Acute Monocytic Leukemia following Low-dose of Etoposide Treatment for Hemophagocytic Lymphohistiocytosis / 대한진단검사의학회지

We report a case of therapy-related acute myeloid leukemia after low-dosed topoisomerase II inhibitor (etoposide) treatment for hemophagocytic lymphohistiocytosis (HLH). A 62-yr-old female patient had previously been treated with a HLH-94 protocol containing a low-dose of etoposide (total dose of 300 mg/m2). Thirty-one months later, the patient was admitted to the hematology department with general weakness and upper respiratory infection symptoms. Peripheral blood smear and bone marrow study revealed acute monocytic leukemia. There was no evidence of myelodysplastic syndrome, and a cytogenetic study showed no chromosomal abnormalities.

A Case of Hemophagocytic Syndrome with Terminal Ileal Ulcerations / 대한소화기학회지

Reactive hemophagocytic syndrome or hemophagocytic lymphohistiocytosis, is characterized by the proliferation of benign histiocytes showing phagocytosis of blood cells in hematopoietic organs including bone marrow, spleen, or lymph nodes, accompanied by fever, hepatosplenomegaly, hepatic dysfunction, pancytopenia, and hypertriglyceridemia. The pathogenesis of reactive hemophagocytic syndrome is unknown. It is often associated with infection, malignant neoplasm, autoimmune disease, drugs and various immunodeficiencies. The prognosis of this syndrome is poor and the causes of death are hemorrhage, infection, or multiorgan failure. We experienced a case of hemophagocytic syndrome with terminal ileal ulcers, not associated with other causes. Thus, we report this case with a review of literatures.