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Article in Chinese | WPRIM | ID: wpr-880176


OBJECTIVE@#To investigate the changes in function of CD8@*METHODS@#Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8@*RESULTS@#The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8@*CONCLUSION@#The exhausted CD8

CD8-Positive T-Lymphocytes , Hepatitis A Virus Cellular Receptor 2 , Humans , Interferon-gamma , Lymphocyte Count , Lymphohistiocytosis, Hemophagocytic
Article in Chinese | WPRIM | ID: wpr-880064


OBJECTIVE@#To investigate the difference in the therapeutic effect of plasma exchange and continuous renal replacement therapy (PE+CRRT) combined with chemotherapy in the treatment of children with severe Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and non-EBV-HLH.@*METHODS@#The clinical data of 21 cases of all children with severe HLH treated by PE+CRRT combined with chemotherapy from January 2017 to January 2020 were collected and retrospectively analyzed. According to the presence of EBV infection, the children were divided into EBV@*RESULTS@#Among the 21 children, 14 were divided into the EBV@*CONCLUSION@#PE+CRRT combined with chemotherapy can reduce serum ferritin quickly, then improve organ function, and increase the overall survival rate of severe HLH, and it is a good effect on children with severe EBV-HLH and non-EBV-HLH.

Child , Continuous Renal Replacement Therapy , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , Humans , Lymphohistiocytosis, Hemophagocytic , Plasma Exchange , Retrospective Studies
Article in Chinese | WPRIM | ID: wpr-880063


OBJECTIVE@#To present one patient initially diagnosed with dermatomyositis(DM) who was eventually revealed to be diffuse large B-cell lymphoma(DLBCL) complicated with hemophagocytic syndrome(HPS), and to improve the understanding of the disease.@*METHODS@#The clinical characteristics, diagnostic approach, treatment of the patient were retrospectively analyzed, and some related literatures were reviewed.@*RESULTS@#A 52-year-old female patient suffered from muscle weakness, elevated serum creatine kinase activity, electromyography changes and characteristic skin rashes and diagnosed as DM. The patient was treated with glucocorticoid therapy and the muscle strength, skin rashes, and creatine kinas index turns into remission. Subsequently, subcutaneous nodules appeared during treatment, and the patient was confirmed as DLBCL based on pathological biopsy; And the patient was considered HPS because of presenting with repeated fever, splenomegaly, cytopenias, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, high levels of sCD25, low NK-cell activity and hemophagocytosis in bone marrow. But the patient refused chemotherapy, and only treated with "DXM+VP-16" to control hemophagocytic syndrome, and unfortunately died due to the disease progression.@*CONCLUSION@#Cutaneous involvement in diffuse large B-cell lymphoma and hemophagocytic syndrome patients with first presentation of dermatomyositis is relatively rare. Malignacy screening should be performed as soon as possible after newly diagnosed DM, so that the patient can get early diagnosis and effective treatment to improve survival rate.

Dermatomyositis/complications , Etoposide , Female , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphoma, Large B-Cell, Diffuse/complications , Middle Aged , Retrospective Studies
Autops. Case Rep ; 11: e2021285, 2021. graf
Article in English | LILACS | ID: biblio-1249016


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.

Humans , Male , Aged , Lymphohistiocytosis, Hemophagocytic/complications , Hyperferritinemia/diagnosis , Dexamethasone/therapeutic use , Acute Coronary Syndrome/complications , Glucosephosphate Dehydrogenase Deficiency
Rev. cuba. med. trop ; 72(3): e524, sept.-dic. 2020. tab, graf
Article in English | LILACS, CUMED | ID: biblio-1156542


Introduction: Leishmaniasis is a tropical and subtropical disease highly reported in Southeast Asia, East Africa, Latin America, and the Mediterranean basin, with an incidence of two million new cases by year and 500,000 cases of visceral leishmaniasis. One of the more severe and rare complications of visceral leishmaniasis is hemophagocytic lymphohistiocytosis. Objective: To describe the clinical characteristics of hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis Methods: We performed a literature review based on the case reports indexed in MEDLINE/PubMed. Results: Twenty-five cases were included; 52 percent under two years of age. All cases presented splenomegaly and 84 percent hepatomegaly. Cytopenias were described in all patients: 100 prcent thrombocytopenia, 96 percent anemia, and 84 percent leukopenia or neutropenia. Hypertriglyceridemia and hypofibrinogenemia were found in 68 percent and 32 percent, respectively, and hyperferritinemia in 80 percent. Additionally, hemophagocytosis was documented in 84 percent, with Leishmania detection in 92 percent. All patients were treated against Leishmania: 80% with liposomal amphotericin B. regarding the treatment for hemophagocytic lymphohistiocytosis; corticosteroid were used in 36 percent, endovenous immunoglobulin in 28 percent, cyclosporine in 28 prcent and etoposide in 16 percent The complications reported included gastrointestinal hemorrhage (8 percent), disseminated intravascular coagulation (8 percent), autoimmune hemolytic anemia (12 percent), multiple-organ dysfunction/septic shock (12 prcent), petechial rash (16 percent), and four patients deceased. Variables such as fever (p=0.031), hemoglobin level (p=0.031), platelet count (p=0.0048), and ferritin (p=0.0072) were associated with mortality Conclusions: During visceral leishmaniasis, the hemophagocytic syndrome is a rare condition that mainly affects pediatric patients, but with excellent outcomes using liposomal amphotericin B. However, there is a lack of strong evidence to make a recommendation(AU)

Introducción: La leishmaniasis es una enfermedad tropical y subtropical con una elevada incidencia, dos millones de casos nuevos por año y 500 000 de leishmaniasis visceral. La linfohistiocitosis hemofagocítica es una complicación grave y rara de la leishmaniasis visceral. Objetivo: Describir las características clínicas de la linfohistiocitosis hemofagocítica asociada con leishmaniasis visceral. Métodos: Se realizó una revisión bibliográfica basada en los informes de casos indexados en MEDLINE/PubMed. Se identificaron 34 publicaciones; después de analizarlas en función de los criterios de inclusión se trabajó con 22 trabajos. Resultados: En los trabajos incluidos se informaron 25 casos; el 52 por ciento fueron pacientes menores de 2 años. Todos presentaron esplenomegalia y 84 por ciento hepatomegalia. Se describieron citopenias en todos los pacientes: 100 por ciento trombocitopenia, 96 por ciento anemia y 84 por ciento leucopenia o neutropenia. Se encontró hipertrigliceridemia e hipofibrinogenemia en 68 por ciento y 32 por ciento, respectivamente, e hiperferritinemia en 80 por ciento. Todos los pacientes fueron tratados contra leishmania, 80 por ciento con anfotericina B liposomal. Las complicaciones incluyeron: hemorragia gastrointestinal, coagulación intravascular diseminada, anemia hemolítica autoinmune, falla multiorgánica/shock séptico, erupción petequial y cuatro pacientes fallecieron. Conclusiones: En la leishmaniasis visceral, el síndrome hemofagocítico es una afección poco frecuente que afecta principalmente a pacientes pediátricos. Para el tratamiento, usando la anfotericina B liposomal se obtienen excelentes resultados; sin embargo, la evidencia es insuficiente para hacer una recomendación(AU)

Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Amphotericin B/therapeutic use , Lymphohistiocytosis, Hemophagocytic/epidemiology , Neglected Diseases/epidemiology , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/epidemiology
Rev. ecuat. pediatr ; 21(2): 1-8, 31 de agosto del 2020.
Article in Spanish | LILACS | ID: biblio-1141283


Introducción:El síndrome hemofagocítico (SHF) es reconocido como un conjunto de signos clínicos y hallazgos laboratoriales que tienen un grave compromiso en la salud y vitalidad de los niños con una incidencia de 1.2 casos/millón/año. Puede pasar subdiagnosticado y confundido con sepsis de foco inespecífico Caso clínico:Niño de 4 años de edad, sin antecedentes de importancia. Ingresado desde el servicio de emergencia por presentar 20 días de fiebre y dolor abdominal. Requirió intubación por franca falla respiratoria y el ingreso a la Unidad de Cuidados Intensivos Pediátricos. Con hipotensión e insuficiencia hepática, pancitopeniay esplenomegalia. Evolución: Se descartaron infecciones bacterianas con policultivos, SARS-Cov 2negativo,se descartaron inmunodeficiencias congénitas y adquiridas.TORCHnegativo, VDRL no reactivo.La prueba de Epstein Barr fue positivo para IgM.Se determinó endocarditis con derrame pericárdico global. Estudio de biopsia medular normocromía, normocitosis, pancitopenia y blastos <5%, sin infiltración tumoral. Se estableció el Diagnóstico de SHFse inicióciclosporina y corticoterapia.Requirió ventilación mecánica por 20 días con período de pronación de 36 horas. Fue dado de alta a pediatríay posteriormente a domicilio, para control por consulta externa. Conclusión: El diagnóstico del SHF es inusual y subestimado al momento de la evaluación clínica. En el presente reporte se asocia a la presencia del Virus Epstein Barr

Introduction: Hemophagocytic syndrome (HPS) is recognized as a set of clinical signs and laboratory findings that have a serious compromise on the health and vitality of children with an incidence of 1.2 cases / million / year. It can be underdiagnosed and confused with sepsis with a non-specific focus. Clinical case: 4-year-old boy, with no significant history. Admitted from the emergency service due to 20 days of fever and abdominal pain. She required intubation due to frank respiratory failureand admission to the Pediatric Intensive Care Unit. With hypotension and liver failure, pancytopenia and splenomegaly. Evolution: Bacterial infections were ruled out with polycultures, SARS-Cov 2 negative, congenital and acquired immunodeficiencies were ruled out. Negative TORCH, non-reactive VDRL. The Epstein Barr test was positive for IgM. Endocarditis with global pericardial effusion was determined. Medullary biopsy study normochromia, normocytosis, pancytopenia, and blasts <5%, without tumor infiltration. The diagnosis of SHF was established, cyclosporine and corticosteroid therapy were started. He required mechanical ventilation for 20 days with a 36-hour pronation period. He was discharged to pediatrics and later at home, for outpatient control. Conclusion: The diagnosis of HHS is unusual and underestimated at the time of clinical evaluation. In this report it is associated with the presence of the Epstein Barr Virus

Humans , Herpesvirus 4, Human , Epstein-Barr Virus Infections , Lymphohistiocytosis, Hemophagocytic , Case Reports , Perforin
Infectio ; 24(2): 126-128, abr.-jun. 2020. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1114852


Resumen La linfohistiocitosis hemofagocítica (LHH) por Histoplasma capsulatum, presentación rara de la histoplasmosis diseminada, es causada por la fagocitosis de las células hematopoyéticas por macrófagos tisulares. Presentamos el caso de un paciente masculino de 44 años con trasplante renal que asiste por fiebre sin otra sintomatología. Inicialmente se obtiene una gota gruesa positiva para P. vivax, iniciando manejo antimalárico. A los 2 días de tratamiento, el paciente presenta disfunción multiórganica, se rectifica diagnóstico en centro de referencia reportando en extendido de sangre periférica la presencia de levaduras de H. capsulatum en polimorfonucleares, resultado confirmado con prueba de inmunodifusión. Se ajusta manejo, pero el paciente fallece. El diagnóstico de infecciones por gérmenes inusuales con presentaciones inespecíficas es un reto en pacientes con inmunosupresión.

Abstract Hemophagocytic Lymphohistiocytosis (HLH) induced by Histoplasma capsulatum is a rare entity who is characterized by phagocytosis of hematopoietic cells by tissue macrophages. A 44-year-old male patient with kidney transplantation was admitted to our ambulatory service with fever. Initially, we performed a thick drop test who was positive for P. vivax, so antimalarial therapy was initiated. Patient then progressed to multiple organ dysfunction after 2 days of treatment. Thus, a reference center went back over the blood smear which revealed the presence of yeast cells H. capsulatum within polymorphonuclear cells. This result was confirmed by an immunodifussion assay. Despite of antifungal treatment, patient passed away. The diagnosis for unusual microorganism with unspecific clinical presentation could be a challenge in immunosupressive patients.

Humans , Male , Adult , Lymphohistiocytosis, Hemophagocytic , Phagocytosis , Hematopoietic Stem Cells , Kidney Transplantation , Histoplasma
Arch. argent. pediatr ; 118(2): e174-e177, abr. 2020.
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1100429


La linfohistiocitosis hemofagocítica (LHH) puede ser primaria (hereditaria) o secundaria a infecciones, tumores malignos, trastornos reumatológicos, síndromes de inmunodeficiencia y metabolopatías. Se informaron casos de intolerancia a la proteína lisinúrica, deficiencia de múltiples sulfatasas, galactosemia, enfermedad de Gaucher, síndrome de Pearson y galactosialidosis. No se sabe cómo se desencadena la LHH en las metabolopatías. Se diagnosticó LHH en un lactante de 2 meses con letargo, palidez, alimentación deficiente, hepatoesplenomegalia, fiebre y pancitopenia, y se instauró el protocolo HLH-2004. Se realizaron, en conjunto, análisis para detectar mutaciones genéticas y pruebas metabólicas; los resultados fueron negativos para las mutaciones genéticas de LHH primaria, pero se detectaron hiperamoniemia y concentración elevada de metilcitrato. Se diagnosticó acidemia propiónica. Aquí informamos sobre un caso de LHH secundaria a acidemia propiónica. Es posible la realización simultánea de pruebas de detección de trastornos metabólicos y de mutaciones genéticas para el diagnóstico temprano en los lactantes con LHH

Hemophagocytic lymphohystiocytosis (HLH) may be primary (inherited/familial) or secondary to infections, malignancies, rheumatologic disorders, immune deficiency syndromes and metabolic diseases. Cases including lysinuric protein intolerance, multiple sulfatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis have previously been reported. It is unclear how the metabolites trigger HLH in metabolic diseases. A 2-month-old infant with lethargy, pallor, poor feeding, hepatosplenomegaly, fever and pancytopenia, was diagnosed with HLH and the HLH-2004 treatment protocol was initiated. Analysis for primary HLH gene mutations and metabolic screening tests were performed together; primary HLH gene mutations were negative, but hyperammonemia and elevated methyl citrate were detected. Propionic acidemia was diagnosed with tandem mass spectrometry in neonatal dried blood spot. We report this case of HLH secondary to propionic acidemia. Both metabolic disorder screening tests and gene mutation analysis may be performed simultaneously especially for early diagnosis in infants presenting with HLH.

Humans , Male , Infant , Lymphohistiocytosis, Hemophagocytic/diagnosis , Propionic Acidemia/diagnosis , Pancytopenia , Splenomegaly , Lymphohistiocytosis, Hemophagocytic/drug therapy , Propionic Acidemia/drug therapy , Torpor , Continuous Renal Replacement Therapy , Hepatomegaly
Rev. cuba. hematol. inmunol. hemoter ; 36(1): e1048, ene.-mar. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1126547


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)

Humans , Male , Female , Middle Aged , Early Diagnosis , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis
Rev. méd. Chile ; 148(3): 371-380, mar. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1115801


Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HLH) is a highly lethal hyper-inflammatory disorder that leads to a storm of cytokines, hemophagocytosis and multiple organ failure. It can be primary, which is inherited, or secondary. In the latter, virus infections are a frequent trigger, predominantly the family of herpes viruses, such as Epstein-Barr virus. An early treatment is recommended. Until recently there was no consensus about the management of secondary cases. The protocols for the treatment of primary HLH were used, which include cytotoxic agents and corticosteroids. We herein review the current diagnostic and therapeutic approach of HLH, based on a case associated with a reactivation of the Epstein-Barr virus in an immunocompetent adolescent. We highlight the importance of suspecting this disease in patients with a persistent inflammatory response state or with a fever of unknown origin, in order to carry out a timely treatment, with the least toxicity, and appropriate to the characteristics of each individual, which is the current therapeutic trend.

Humans , Lymphohistiocytosis, Hemophagocytic , Cytokines , Adrenal Cortex Hormones , Epstein-Barr Virus Infections
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 25-28, mar. 2020. ilus
Article in Spanish | LILACS | ID: biblio-1102210


Introducción: la zigomicosis es una infección fúngica poco frecuente, con alta tasa de mortalidad y de mal pronóstico. Afecta principalmente a pacientes inmunocomprometidos. La asociación con el síndrome hemofagocítico es extremadamente inusual, más aún en pacientes inmunocompetentes, con pocos ejemplos registrados en la literatura. Caso clínico: se presenta el caso de un paciente masculino inmunocompetente de 40 años con diagnóstico de mucormicosis y síndrome hemofagocítico que evoluciona desfavorablemente, con fallo multiorgánico, a pesar de los esfuerzos médicos. Conclusión: la asociación de mucormicosis con síndrome hemofagocítico en un paciente inmunocompetente es extremadamente rara; existen pocos casos informados en Latinoamérica. Debemos tener presente esta asociación, ya que requiere un tratamiento agresivo y soporte vital avanzado. (AU)

Introduction: zygomycosis is a rare fungal infection that carries with high mortality rates. This poor prognosis, rapidly progressive infection mainly affects immunocompromised patients. The association with hemophagocytic lymphohistiocytosis is extremely unusual, even more in immunocompetent patients, with few cases reported. Case: we present the case of an immunocompetent male patient who was diagnosed with zygomycosis and hemophagocytic lymphohistiocytosis. Despite medical efforts he developed multiorganic failure. Conclusion: the association of mucormycosis with hemophagocytic lymphohistiocytosis in an immunocompetent patient is exceptional with few cases reported in Latin America. We must always suspect this association considering they require aggressive treatment and advanced life support. (AU)

Humans , Male , Adult , Zygomycosis/diagnosis , Lymphohistiocytosis, Hemophagocytic/diagnosis , Pancytopenia/blood , Psychomotor Agitation , Vancomycin/therapeutic use , Norepinephrine/administration & dosage , Norepinephrine/therapeutic use , Amphotericin B/therapeutic use , Exophthalmos/diagnostic imaging , Immunocompromised Host/immunology , Colistin/therapeutic use , Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Zygomycosis/etiology , Zygomycosis/mortality , Zygomycosis/epidemiology , Delirium , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/mortality , Fever , Meropenem/therapeutic use , Immunocompetence/immunology , Jaundice , Mucormycosis/complications , Multiple Organ Failure/diagnosis
Rev. Soc. Bras. Med. Trop ; 53: e20190491, 2020. tab, graf
Article in English | LILACS, ColecionaSUS, SES-SP | ID: biblio-1136840


Abstract INTRODUCTION Visceral leishmaniasis (VL) is an ill-studied disease that is endemic to several regions of Brazil. It is often complicated by hemophagocytic lymphohistiocytosis (HLH), a potentially fatal disorder resulting from excessive non-malignant activation/proliferation of T lymphocytes and macrophages. Considering the overlapping clinical and laboratory characteristics of these diseases, diagnosing HLH is a challenge. Therefore, tracking the association between VL and HLH is necessary in endemic areas. Although HLH can be inapparent and resolve with antileishmanicides, this may not always occur. HLH causes high lethality; therefore, immunosuppressive therapy should be instituted immediately in order to avoid a fatal outcome. METHODS: We described the epidemiological, clinical, laboratory, and therapeutic profile of this association in a region of Brazil endemic for VL. RESULTS We presented 39 patients with this association in a retrospective cohort of 258 children who were admitted from January 2012 to June 2017. Of the 39 patients, 31 were from urban areas (79.5%), and 21 (53%) were males. The mean age and weight were 2.86 (2.08) years and 14.03 (5.96) kg, respectively. The main symptoms were fever (100%), hepatosplenomegaly (100%), pallor of the skin and mucosa (82.5%), edema (38.5%), bleeding (25%), and jaundice (7.5%). Hemophagocytosis was identified in 16/37 (43.24%) patients, and direct examination revealed that 26/37 (70.27%) patients were positive for VL. The patients were treated as recommended by the Ministry of Health. CONCLUSIONS It was observed that HLH is a common complication in endemic areas, and its diagnosis must consider the overlapping of clinical characteristics and pancytopenia.

Humans , Male , Female , Infant , Child, Preschool , Child , Lymphohistiocytosis, Hemophagocytic/etiology , Leishmaniasis, Visceral/complications , Brazil , Retrospective Studies , Lymphohistiocytosis, Hemophagocytic/therapy
Article in English | WPRIM | ID: wpr-785340


PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.

Agammaglobulinemia , Diagnosis , Exome , Flow Cytometry , Genetic Testing , Granulomatous Disease, Chronic , Humans , Immunophenotyping , Korea , Leukocytes , Lymphocyte Subsets , Lymphohistiocytosis, Hemophagocytic , Phenotype , Retrospective Studies , Seoul , Severe Combined Immunodeficiency , Tertiary Healthcare
Article in Chinese | WPRIM | ID: wpr-828696


OBJECTIVE@#To study the effect of genetic variation on the prognosis of children with Epstein-Barr virus (EBV)-positive hemophagocytic lymphohistiocytosis (HLH) and its association with cytokines.@*METHODS@#A total of 81 EBV-positive HLH children who received the sequencing of related genes were enrolled. According to the results of gene detection, they were divided into a non-mutation group and a mutation group. According to the pattern of gene mutation, the mutation group was further divided into three subgroups: single heterozygous mutation (SHM), double heterozygous mutation (DHM), and homozygous or compound heterozygous mutation (H-CHM). The serum levels of cytokines were measured and their association with HLH gene mutations was analyzed.@*RESULTS@#UNC13D gene mutation had the highest frequency (13/46, 28%). The STXBP2 c.575G>A(p.R192H) and UNC13D c.604C>A(p.L202M) mutations (likely pathogenic) were reported for the first time. The mutation group had a significantly higher level of tumor necrosis factor alpha (TNF-α) than the non-mutation group, while it had a significantly lower level of interferon gamma (IFN-γ) than the non-mutation group (P<0.05). The IL-4 level of the DHM subgroup was higher than that of the non-mutation group, while the IL-4 level of the H-CHM subgroup was lower than that of the DHM group (P<0.0083). The H-CHM subgroup had a significantly lower 1-year overall survival rate than the non-mutation group, the SHM subgroup, and the DHM subgroup (39%±15% vs 85%±6%/86%±7%/91%±9%, P=0.001).@*CONCLUSIONS@#There is a significant reduction in IFN-γ level in the mutation group. Children with homozygous or compound heterozygous mutation tend to have poorer prognosis, while other mutations do not have a significant impact on prognosis.

Child , Cytokines , Epstein-Barr Virus Infections , Genetic Testing , Herpesvirus 4, Human , Humans , Lymphohistiocytosis, Hemophagocytic , Genetics , Membrane Proteins , Th1 Cells , Th2 Cells
Article in Chinese | WPRIM | ID: wpr-828673


OBJECTIVE@#To study the clinical features of children with severe adenovirus pneumonia (SAP) and hemophagocytic syndrome (HPS).@*METHODS@#A retrospective analysis was performed from the chart review data of 30 children with SAP and HPS who were admitted from January 2014 to June 2019. According to the prognosis, the children were divided into a good prognosis group (n=18) and a poor prognosis group (n=12).@*RESULTS@#Among the 30 children with SAP and HPS, the ratio of male to female was 2:1. The median age of onset was 1 year and 3 months (range 3 months to 5 years), and the mean course of fever was 19±7 d. Of the 30 children, 28 (93%) experienced disease onset in January to June. High-throughput gene detection of serum pathogens showed that 16 (53%) children were positive for human adenovirus type 7 (HAdV-7), and the other 14 (47%) children were positive for HAdV antigen based on immunofluorescence assay for throat swab, with unknown type. Of all 30 children, 29 (97%) had respiratory complications, 24 (80%) had cardiovascular complications, 16 (53%) had gastrointestinal complications, and 9 (30%) had toxic encephalopathy. Eighteen children (60%) improved or recovered and 12 (40%) did not recover (3 died). Compared with the good prognosis group, the poor prognosis group had a significantly longer course from onset to diagnosis of HPS (P<0.05), significantly higher levels of fibrinogen and tumor necrosis factor-α (P<0.05), and a significantly lower level of interferon-γ (P<0.05). The mean follow-up time was 6±2 months; 11 (41%) children recovered, 1 (4%) experienced recurrence of HPS, and 15 (56%) had the sequela of post-infectious bronchiolitis obliterans (PIBO).@*CONCLUSIONS@#HPS may be observed in children with SAP, and PIBO is the most common sequela of SAP.

Adenoviridae , Adenoviridae Infections , Child, Preschool , Female , Humans , Infant , Lymphohistiocytosis, Hemophagocytic , Male , Pneumonia, Viral , Retrospective Studies
Article in Chinese | WPRIM | ID: wpr-828672


OBJECTIVE@#To study the clinical features of children with adenovirus pneumonia and hemophagocytic lymphohistiocytosis (HLH).@*METHODS@#A retrospective analysis was performed on the mediacal data of 7 children with adenovirus pneumonia and HLH from March to September, 2019.@*RESULTS@#The age of these children ranged from 11 months to 5 years, and among these children, 5 were aged <2 years and 5 were boys. None of these children had underlying diseases. All children were hospitalized due to persistent high fever and cough, and the peak temperature of fever was 39°C to 41°C. With disease progression, 7 children developed hepatomegaly and 6 developed splenomegaly. Routine blood test results showed reductions in two or three lineages of blood cells, with increases in serum ferritin (SF), C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH). Phagocytosis of blood cells was observed in 6 children. Radiological examination of lungs showed pneumonia changes. All 7 children were diagnosed with human adenovirus type 7 infection based on pathogenic metagenome detection. No abnormality was found by HLH gene detection and the children were diagnosed with secondary HLH. All children received intravenous immunoglobulin. Among these children, 4 received dexamethasone and etoposide chemotherapy, 3 received dexamethasone alone, and 4 received plasma exchange. Of the 7 children, 2 died and 5 were recovered. Compared with those who survived, the children who died had significantly greater reductions in the three lineages of blood cells and significantly greater increases in serum levels of CRP, PCT, SF, and LDH.@*CONCLUSIONS@#The children with adenovirus pneumonia and HLH have main clinical features of persistent high fever, progressive reductions in two or three lineages of peripheral blood cells, and involvement of other organ systems, including hepatosplenomegaly. Significant increases in serum levels of CRP, PCT, SF, and LDH may suggest a poor prognosis.

Adenoviridae , Child, Preschool , Etoposide , Female , Humans , Immunoglobulins, Intravenous , Infant , Lymphohistiocytosis, Hemophagocytic , Male , Retrospective Studies
Journal of Experimental Hematology ; (6): 1006-1011, 2020.
Article in Chinese | WPRIM | ID: wpr-827170


OBJECTIVE@#To investigate the expression and clinical significance of soluble B7-H3 (sB7-H3) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).@*METHODS@#The plasma samples of 85 newly diagnosed sHLH patients from December 2012 to April 2018 were collected. The patients were divided into lymphoma-related HLH(LHLH)group and infection-related HLH(IHLH)group. The expression of sB7-H3 in plasma was detected by ELISA, and the clinical data were collected for analysis. Fifteen healthy people were chosen as control group.@*RESULTS@#The expression level of sB7-H3 in lymphoma-related HLH and infection-related HLH group significant increased as compared with the control group, (P<0.05), and the expression level of sB7-H3 in lymphoma-related HLH group was significant higher than that in infection-related HLH group [(35.75± 9.90) vs (28.70±8.95) ng/ml)] (P<0.001). There were no significant statistical difference in the expression of some clinical factors (including age, fever, splenomegaly, ANC, Plt, FIB, calcium ion, serum albumin, LDH, serum ferritin, sCD25) in lymphoma-related HLH and infection-related HLH group (P>0.05). The evaluation of expression and significance of sB7-H3 in sHLH by using ROC curve, showed that the area under ROC curve comparison of patients in lymphoma-related HLH group and infection-related HLH group was 0.718 (95% CI 0.610-0.810) (P=0.0002), and predicting the sensitivity and specificity of the lymphoma-related HLH patients were 77.36% and 59.38%, respectively. The best cut-off value of patients in sB7-H3 was 29.81 ng/ml, the overall survival time of sB7-H3 high-expression group (≥29.81 ng/ml) was significant shorter than that in low-expression group (<29.81 ng/ml) (24 vs 440 d) (P<0.001). The clinical factors affecting the survival status of sHLH patients were neutrophils, albumin, serum ferritin, serum calcium ions and sB7-H3 levels.@*CONCLUSION@#sB7-H3 associates with poor prognosis of sHLH patients, and may be involved in disease progression.

Enzyme-Linked Immunosorbent Assay , Humans , Lymphohistiocytosis, Hemophagocytic , Lymphoma , ROC Curve
Journal of Experimental Hematology ; (6): 1376-1380, 2020.
Article in Chinese | WPRIM | ID: wpr-827109


OBJECTIVE@#To establish a secondary hemophagocytic lymphohistiocytosis(HLH) mouse model, and to investigate the effect of ruxolitinib on the disease manifestation of model mice.@*METHODS@#Wild type C57BL/6 mice were randomly divided into 4 groups: two groups of mice were intraperitoneally injected with CpG oligodeoxynucleotide 1826 (CpG-ODN1826) every other day to induce HLH, and other two groups were control groups. One group of the CpG-ODN1826 groups and one of the control groups were given ruxolitinib, and other two groups were given the same amount of PBS. Blood samples, serum ferritin and hepatic/spleen weights of experimental mice were detected and serum cytokine levels were measured by ELISA.@*RESULTS@#Compared with the control groups, the levels of white blood cells, hemoglobin and platelets in the CpG-ODN1826 groups were significantly lower (P<0.05); and liver/body weight, spleen/body weight, serum ferritin, sCD25, IL-10, IL-1β, IFN-Ƴ, IL-12p70, GM-CSF, TNF-α and IL-18 levels significantly increased (P<0.05). There was no significant difference in the levels of IL-2, IL-4, IL-5, IL-6, IL-22, IL-13, IL-27 and IL-23 between the two groups (P>0.05). The spleen in CpG group had disordered internal structure, expanding red pulp and hyperplastic nucleated cells. The liver had severe perivascular inflammations. The spleen/weight of the ruxolitinib-treated mice in the CpG-ODN1826 group was significantly smaller than that of the unapplied ruxolitinib (P<0.05).@*CONCLUSION@#The CpG-ODN1826 can induce secondary HLH symptoms in wild type C57BL/6 mice. Ruxolitinib can alleviate the symptoms of splenomegaly in HLH model mice.

Animals , Disease Models, Animal , Lymphohistiocytosis, Hemophagocytic , Mice , Mice, Inbred C57BL , Pyrazoles