RESUMEN
X-linked inhibitor of apoptosis protein deficiency is a rare illness and although stem cell transplant is curative, full intensity conditioning is associated with high mortality rates. We describe a child with unusual complications associated with residual host lymphocytes following reduced intensity stem cell transplant. Recipient derived, donor directed, antigranulocyte antibodies led to life-threatening and prolonged neutropenia and residual recipient lymphocytes reestablished hemophagocytic lymphohistiocytosis after withdrawal of immune suppression despite high levels of whole blood chimerism. Hemophagocytic lymphohistiocytosis was abolished following specific improvement in donor T-cell chimerism after donor lymphocyte infusions, and alloimmune cytopenias were no longer evident.
Asunto(s)
Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfocitos/citología , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/terapia , Acondicionamiento Pretrasplante/efectos adversos , Proteína Inhibidora de la Apoptosis Ligada a X/deficiencia , Adolescente , Terapia Combinada , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Humanos , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/patología , Linfohistiocitosis Hemofagocítica/prevención & control , Trastornos Linfoproliferativos/patología , Masculino , Agonistas Mieloablativos/uso terapéutico , Pancitopenia/etiología , Pancitopenia/patología , Pancitopenia/prevención & control , Pronóstico , Quimera por Trasplante , Trasplante Homólogo , Proteína Inhibidora de la Apoptosis Ligada a X/genéticaRESUMEN
Lymphoma-associated hemophagocytic syndrome (LAHS) is a serious disorder, and its early diagnosis and treatment with appropriate chemotherapy are very important. However, reliable markers for early diagnosis of LAHS have not been identified. We screened serum cytokines using a newly introduced assay system, cytometric bead array (CBA), and identified interferon-inducible protein 10 (IP-10)/CXCL10 and monokine induced by interferon gamma (MIG)/CXCL9 as useful markers. Serum concentrations of IP-10 and MIG at the time of LAHS diagnosis were greater than 500 and 5,000 pg/ml, respectively. The sensitivity and specificity for LAHS diagnosis were 100 and 95 %, respectively, when we set the above values as the cut-off levels. Serum levels of these two chemokines were already elevated at the time of admission and significantly decreased after successful treatment, indicating their usefulness for both the diagnosis and therapeutic outcomes for LAHS. IP-10 and MIG were also useful in distinguishing severe from moderate/mild LAHS, and B-cell-type LAHS from T-cell/natural killer cell-type LAHS. Furthermore, IP-10 and MIG were of use to distinguish LAHS from sepsis in patients with hematologic malignancies. Rapid measurement of IP-10 and MIG by CBA appeared to be important for early diagnosis and treatment of LAHS.
Asunto(s)
Biomarcadores de Tumor/sangre , Quimiocina CXCL10/sangre , Quimiocina CXCL9/sangre , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfoma no Hodgkin/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Diagnóstico Diferencial , Estudios de Seguimiento , Hospitales Urbanos , Humanos , Linfohistiocitosis Hemofagocítica/sangre , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/prevención & control , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Juego de Reactivos para Diagnóstico , Estudios Retrospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Adulto JovenAsunto(s)
Antirreumáticos/uso terapéutico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Linfohistiocitosis Hemofagocítica/prevención & control , Piebaldismo/complicaciones , Enfermedades de Inmunodeficiencia Primaria/complicaciones , Humanos , Lactante , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/patología , Masculino , PronósticoRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening extreme whole body inflammatory state. It results from the pathological hyperactivation of the immune system, because of congenital or acquired abnormalities of cytotoxicity and NK or T cells. Uncontrolled stimulation of lymphocytes and macrophages lead to hypercytokinemia, organ infiltration by these cells and multiple organ failure. There are genetic HLH and secondary HLH, associated with infections, autoimmune disorders, malignancies. The frequency of the secondary form is difficult to estimate because of the wrong and difficult diagosis. The clinical course is often insidious and nonspecific. Symptoms are varied. The most important are: unremitting fever, hepatosplenomegaly. Generalized edema, rash, lymphadenopathy may occur. Liver failure, respiratory, circulatory and multiple organ failure could develop in a very short time. Most common abnormalities in additional tests are: cytopenias, hypofibrinogenaemia, hypertriglyceridaemia, hyperferritinaemia, hypertransaminasaemia, elevated parameters of inflammation (excepting lowering erythrocyte sedimentaion rate). Criteria for diagnosis and therapeutic protocols referto the genetic forms of HLH. Currently, there are no guidelines for secondary HLH. Diagnostic and therapeutic difficulties also arise from clinical picture, similar as in the systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome. We present the clinical presentation, diagnostic pitfalls and treatment of secondary HLH, based on a review of the current literature and our own observations.
Asunto(s)
Anomalías Congénitas , Citotoxicidad Inmunológica , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/etiología , Diagnóstico Diferencial , Humanos , Linfohistiocitosis Hemofagocítica/prevención & control , Activación de Macrófagos , Insuficiencia Multiorgánica/etiología , PronósticoRESUMEN
Cytokine release and macrophage activation contribute to immunopathology after SARS-CoV-2 infection. We discuss approaches to decrease the morbidity and mortality in patients with COVID-19 by repurposing existing drugs previously developed for cancer therapy.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Inmunoterapia/métodos , Inflamación/terapia , Neumonía Viral/complicaciones , Animales , COVID-19 , Inhibidores de la Calcineurina/uso terapéutico , Tratamiento Basado en Trasplante de Células y Tejidos , Infecciones por Coronavirus/epidemiología , Citocinas/metabolismo , Reposicionamiento de Medicamentos , Humanos , Inflamación/epidemiología , Inflamación/etiología , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/prevención & control , Linfohistiocitosis Hemofagocítica/terapia , Activación de Macrófagos , Morbilidad , Neoplasias/terapia , Neoplasias/virología , Pandemias , Neumonía Viral/epidemiología , Receptores de Antígenos de Linfocitos T/inmunología , SARS-CoV-2Asunto(s)
Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/diagnóstico , Enfermedad de Still del Adulto/complicaciones , Adulto , Resultado Fatal , Femenino , Humanos , Linfohistiocitosis Hemofagocítica/prevención & control , Linfohistiocitosis Hemofagocítica/terapiaRESUMEN
BACKGROUND: Tuberculosis is common, can involve various organs of the body and may have diverse presentations. Haemophagocytic syndrome is one of the rare presentations of tuberculosis carrying a very high mortality. Early detection and institution of anti-tuberculosis medications can be life-saving. CASE PRESENTATION: A 23-year-old Bengali man presented with prolonged fever, weight loss, hepatosplenomegaly, pancytopenia and altered liver function. He had high erythrocyte sedimentation rate, positive tuberculin test, granuloma in liver biopsy, and haemophagocytosis was evidenced by histopathological examination of bone marrow. He recovered with anti-tuberculosis therapy. CONCLUSION: This case demonstrates that consideration of tuberculosis as an underlying cause of haemophagocytic syndrome could be rewarding and life-saving in this rapidly fatal condition.
Asunto(s)
Fiebre de Origen Desconocido/etiología , Linfohistiocitosis Hemofagocítica/etiología , Tuberculosis/complicaciones , Tuberculosis/diagnóstico , Antituberculosos/uso terapéutico , Diagnóstico Diferencial , Fiebre de Origen Desconocido/prevención & control , Humanos , Linfohistiocitosis Hemofagocítica/prevención & control , Masculino , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Adulto JovenRESUMEN
Trypanotolerance is the capacity of certain West-African, taurine breeds of cattle to remain productive and gain weight after trypanosome infection. Laboratory studies, comparing Trypanosoma congolense infections in trypanotolerant N'Dama cattle (Bos taurus) and in more susceptible Boran cattle (Bos indicus), confirmed the field observations. Experiments using haemopoietic chimeric twins, composed of a tolerant and a susceptible co-twin, and T cell depletion studies suggested that trypanotolerance is composed of two independent traits. The first is a better capacity to control parasitaemia and is not mediated by haemopoietic cells, T lymphocytes or antibodies. The second is a better capacity to limit anaemia development and is mediated by haemopoietic cells, but not by T lymphocytes or antibodies. Weight gain was linked to the latter mechanism, implying that anaemia control is more important for survival and productivity than parasite control. Anemia is a marker for a more complex pathology which resembles human haemophagocytic syndrome: hepatosplenomegaly, pancytopenia and a large number of hyperactivated phagocytosing macrophages in bone marrow, liver and other tissues. Thus, mortality and morbidity in trypanosome-infected cattle are primarily due to self-inflicted damage by disproportionate immune and/or innate responses. These features of bovine trypanotolerance differ greatly from those in murine models. In mice, resistance is a matter of trypanosome control dependent on acquired immunity. However, a model of anaemia development can be established using C57BL/6J mice. As in cattle, the induction of anaemia was independent of T cells but its development differed with different trypanosome strains. Identification of the molecular pathways that lead to anaemia and haemophagocytosis should allow us to design new strategies to control disease.
Asunto(s)
Anemia/veterinaria , Linfohistiocitosis Hemofagocítica/veterinaria , Trypanosoma congolense , Tripanosomiasis Africana/veterinaria , Tripanosomiasis Bovina/complicaciones , Anemia/parasitología , Anemia/prevención & control , Animales , Bovinos , Infecciones Protozoarias del Sistema Nervioso Central/parasitología , Infecciones Protozoarias del Sistema Nervioso Central/veterinaria , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades/veterinaria , Linfohistiocitosis Hemofagocítica/parasitología , Linfohistiocitosis Hemofagocítica/prevención & control , Ratones , Especificidad de la Especie , Subgrupos de Linfocitos T/inmunología , Tripanosomiasis Africana/complicacionesRESUMEN
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease resulting from excessive activation and non-malignant proliferation of macrophages and T lymphocytes. Whether it can be caused by cholecystitis has not yet been reported in the world. CASE REPORT: A 4-year-old girl was admitted to hospital with cholecystitis. The patient was diagnosed with hemophagocytic lymphohistiocytosis after 3days of admission based on the results of laboratory tests showing hypofibrinogenemia, hypertriglyceridemia, thrombocytopenia, anemia and leukopenia. CONCLUSIONS: From this case experience, if a timely symptomatic treatment is given, the condition of the patient with secondary HLH can be alleviated. This is the first report of cholecystitis-induced hemophagocytic syndrome in the world also.
Asunto(s)
Colecistitis/complicaciones , Linfohistiocitosis Hemofagocítica/etiología , Preescolar , Diagnóstico Precoz , Femenino , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/prevención & control , Factores de TiempoRESUMEN
Hemophagocytic syndrome (HPS) is a rare but serious complication after allogeneic transplantation which has been reported to be particularly high after unrelated cord blood transplantation. We report on the incidence, risk factors and outcome of HPS in 51 patients (age 2-64 years) after haploidentical peripheral blood stem cell (PBSC) transplantation with post-transplantation cyclophosphamide (PTCY). The incidence of HPS was 12.2 %, occurring at a median of 18 days. The non-relapse mortality in patients with HPS was 83.3 % compared to 11.6 % in patients without HPS. Complete donor chimerism was documented in all patients with HPS. Definite infective etiology was identified in two patients only. The others were refractory to multiple lines of treatment and 3 patients underwent a second transplant. Even though the symptoms and biochemical markers of HPS showed prompt response in 2/3 patients undergoing a second allograft, they succumbed to infections before haematological recovery. The others succumbed to multi-organ failure or infections. Age < 10 years, transplantation for non-malignant disease and high CD34 content of the graft were identified as risk factors for HPS. Considering the fact that post-transplant HPS is usually a refractory and fatal condition, we discuss further attempts at deciphering the pathogenesis, developing modalities to prevent this complication and improve the outcome.
Asunto(s)
Ciclofosfamida/administración & dosificación , Haploidia , Inmunosupresores/administración & dosificación , Linfohistiocitosis Hemofagocítica/etiología , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Cuidados Posoperatorios , Adolescente , Adulto , Aloinjertos , Antígenos CD34 , Niño , Preescolar , Femenino , Humanos , Incidencia , Linfohistiocitosis Hemofagocítica/epidemiología , Linfohistiocitosis Hemofagocítica/prevención & control , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , Donantes de Tejidos , Quimera por Trasplante , Adulto JovenRESUMEN
Primary hemophagocytic syndromes represent a group of rare immunodeficiencies, which are characterized by development of life-threatening systemic inflammatory manifestations, so-called accelerated phases. Immunosuppressive therapies are only temporarily effective to control this complication and the prognosis is dismal unless treated by hematopoietic SCT (HSCT). At present, optimal modalities of this potentially curative approach remain incompletely defined. In this study, we analyzed our experience in 18 patients with primary hemophagocytic syndromes treated since 1984 in our center by HSCT. Ten of these patients had previously developed accelerated phases and were in remission at the time of HSCT, whereas five patients had findings of active disease, with two cases in early phases of recurrences of less than 2 weeks duration and three cases with persistent central nervous system disease, whereas three patients had never experienced accelerated phases. In the group with active disease, four of five patients are long-term survivors and are well, whereas one patient died of CMV pneumonia. This outcome compares favorably with results in patients transplanted in remission, where 6 of 10 are long-term survivors. Our findings indicate that HSCT can have a favorable prognosis even in patients with active disease of primary hemophagocytic syndrome.
Asunto(s)
Enfermedades del Sistema Nervioso Central/terapia , Síndrome de Chediak-Higashi/terapia , Trasplante de Células Madre Hematopoyéticas , Hipopigmentación/terapia , Síndromes de Inmunodeficiencia/terapia , Linfohistiocitosis Hemofagocítica/terapia , Acondicionamiento Pretrasplante , Enfermedades del Sistema Nervioso Central/prevención & control , Niño , Preescolar , Quimerismo , Progresión de la Enfermedad , Femenino , Enfermedad Injerto contra Huésped/complicaciones , Reacción Injerto-Huésped , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Hipopigmentación/complicaciones , Hipopigmentación/prevención & control , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/prevención & control , Lactante , Recién Nacido , Depleción Linfocítica , Linfohistiocitosis Hemofagocítica/prevención & control , Masculino , Embarazo , Pronóstico , Recurrencia , Inducción de Remisión , Sobrevivientes , Factores de Tiempo , Resultado del TratamientoRESUMEN
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