Síndrome hemofagocítico: expresión de diversas entidades nosológicas / Haemophagocytic syndrome: A common pathogenic mechanism of various aetiologies

Introducción: El síndrome hemofagocítico (SH) se caracteriza por una activación y proliferación incontrolada de histiocitos y linfocitos T, que produce un estado de hipercitocinemia. Hay 2 formas: primaria y secundaria. Objetivo: Análisis de los pacientes diagnosticados de SH según los criterios diagnósticos de los protocolos HLH (hemophagocytic lymphohistiocytosis ‘linfohistiocitosis hemofagocítica’)-94 y HLH-2004. Pacientes y métodos: Se revisó de forma retrospectiva la historia clínica de los pacientes diagnosticados de SH, se analizaron los criterios diagnósticos, la forma de presentación, la etiología, el tratamiento administrado y el curso evolutivo. Resultados: Se diagnosticó a 22 pacientes: 6 con formas familiares, 11 con formas asociadas a infección, 3 con formas asociadas a neoplasia y 2 con síndromes de activación macrofágica (estos pacientes con artritis idiopática juvenil y enfermedad de Crohn [EC]). En el 83,3% de los casos de linfohistiocitosis hemofagocítica familiar (LHF) la edad al diagnóstico fue inferior al año de vida. En un paciente adolescente se diagnosticó una forma primaria de la enfermedad (mutación del gen MUNC13-4). Las manifestaciones clínicas fueron fiebre (100%), hepatoesplenomegalia (85%), adenopatías (31%), palidez (21%), exantema (14%) y alteraciones neurológicas (14%); los hallazgos de laboratorio fueron citopenia (100%), hipertrigliceridemia (93%), hiperferritinemia (86%), elevación de las enzimas hepáticas (78%) e hipofibrinogenemia (40%). Se encontró una reducción de actividad de los linfocitos citolíticos naturales en el 100% de los casos. Se observó hemofagocitosis en la médula ósea en 20 pacientes. En 2 pacientes se realizó una biopsia hepática y ganglionar que demostró hemofagocitosis. Evolución: de los 22 pacientes diagnosticados de SH, 10 pacientes recibieron tratamiento según los protocolos HLH-94 y HLH-2004: 6 con LHF, 3 con formas secundarias al virus de Epstein-Barr y uno a la EC. De éstos, 6 pacientes recibieron un trasplante de progenitores hematopoyéticos (TPH), con evolución favorable en 2 de los casos con LHF. Los otros 12 pacientes con formas secundarias recibieron tratamiento etiológico, con buena evolución en el 83,3%. Conclusiones: Las formas familiares de SH se diagnostican generalmente antes de los 2 años de edad, aunque se presentan formas primarias en edades más avanzadas. El tratamiento quimioterapéutico e inmunosupresor y el TPH constituyen la base del tratamiento de las formas familiares. Las formas secundarias deben recibir tratamiento etiológico y, si la evolución no es favorable, tratamiento quimioterapéutico e inmunosupresor (AU)

Introduction: Haemophagocytic syndrome (HPS) is a rare syndrome characterised by the uncontrolled activation and proliferation of histiocytes and T cells, leading to a cytokines overproduction. There are two forms of HPS: primary and secondary. Objective: To analyse patients diagnosed with HPS at the Oncohaematology Department, using HLH-94 and 2004 protocol diagnostic criteria. Materials and methods: Retrospective study of clinical files of patients diagnosed with HPS, analysing the following features: diagnostic criteria, variability in clinical presentation, aetiology, treatment and outcome. Results: Twenty-two patients were diagnosed with HPS: 6 familial haemophagocytic lymphohistiocytosis (FHL), 11 HPS with evidence of infection, 3 HPS associated with malignant disease and 2 macrophage activation syndrome (MAS) in patients with Crohn's disease and Juvenile Idiopathic Arthritis. The onset of FHL was within 1 year of age in 83.3%, except for 1 patient who was adolescent (MUNC13-4 mutations). Symptoms: All patients (100%) had fever at diagnosis, 18 (85%) hepatosplenomegaly, 7 (31%) lymphadenopathy, 5 (21%) pallor, 3 (14%) rash and 3 (14%) neurological symptoms. Laboratory analysis: all patients (100%) had cytopenias at diagnosis, 20 (90.9%) hypertriglyceridaemia, 19 (86%) hyperferritinaemia, 17 (77%) elevated serum liver enzymes, and 9 (40%) hypofibrinogenaemia. Decreased or absent NK-cell activity was detected in all patients (100%). Haemophagocytosis was found more frequently in bone marrow; however, liver or lymph node biopsies were required in two patients to demonstrate this. Outcome: Of the ten patients (6 FHL, 3 Epstein-Barr virus-associated HPS and 1 MAS) treated with HLH-94 and 2004 protocols, six received a stem-cell transplant; of these, 2 with FHL had a favourable outcome. The remaining 12 patients received aetiological/supportive therapy, with complete remission in 83.3%. Conclusions: The diagnosis of FHL should be made before the age of 2 years. Advances in genetic studies allow the detection of early and late forms of FHL. Immunochemotherapy and stem-cell transplantation constitute the treatment of FHL and aetiological/supportive therapy of acquired haemophagocytic lymphohistiocytosis, except in severe forms (AU)

[Haemophagocytic syndrome: A common pathogenic mechanism of various aetiologies]. / Síndrome hemofagocítico: expresión de diversas entidades nosológicas.

INTRODUCTION: Haemophagocytic syndrome (HPS) is a rare syndrome characterised by the uncontrolled activation and proliferation of histiocytes and T cells, leading to a cytokines overproduction. There are two forms of HPS: primary and secondary. OBJECTIVE: To analyse patients diagnosed with HPS at the Oncohaematology Department, using HLH-94 and 2004 protocol diagnostic criteria. MATERIALS AND METHODS: Retrospective study of clinical files of patients diagnosed with HPS, analysing the following features: diagnostic criteria, variability in clinical presentation, aetiology, treatment and outcome. RESULTS: Twenty-two patients were diagnosed with HPS: 6 familial haemophagocytic lymphohistiocytosis (FHL), 11 HPS with evidence of infection, 3 HPS associated with malignant disease and 2 macrophage activation syndrome (MAS) in patients with Crohn's disease and Juvenile Idiopathic Arthritis. The onset of FHL was within 1 year of age in 83.3%, except for 1 patient who was adolescent (MUNC13-4 mutations). SYMPTOMS: All patients (100%) had fever at diagnosis, 18 (85%) hepatosplenomegaly, 7 (31%) lymphadenopathy, 5 (21%) pallor, 3 (14%) rash and 3 (14%) neurological symptoms. LABORATORY ANALYSIS: all patients (100%) had cytopenias at diagnosis, 20 (90.9%) hypertriglyceridaemia, 19 (86%) hyperferritinaemia, 17 (77%) elevated serum liver enzymes, and 9 (40%) hypofibrinogenaemia. Decreased or absent NK-cell activity was detected in all patients (100%). Haemophagocytosis was found more frequently in bone marrow; however, liver or lymph node biopsies were required in two patients to demonstrate this. OUTCOME: Of the ten patients (6 FHL, 3 Epstein-Barr virus-associated HPS and 1 MAS) treated with HLH-94 and 2004 protocols, six received a stem-cell transplant; of these, 2 with FHL had a favourable outcome. The remaining 12 patients received aetiological/supportive therapy, with complete remission in 83.3%. CONCLUSIONS: The diagnosis of FHL should be made before the age of 2 years. Advances in genetic studies allow the detection of early and late forms of FHL. Immunochemotherapy and stem-cell transplantation constitute the treatment of FHL and aetiological/supportive therapy of acquired haemophagocytic lymphohistiocytosis, except in severe forms.

Conducta ante el paciente neutropénico febril / Management of the patient with neutropenic fever

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