Haemophagocytic syndrome: A common pathogenic mechanism of various aetiologies

Introduction: Haemophagocytic syndrome (HIPS) 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 Oncohaematotogy Department, using HLH-94 and 2004 protocol diagnostic criteria. Materials and methods: Retrospective study of clinical files of patients diagnosed with HIPS, 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: at[ 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 HIPS 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. (C) 2009 Asociacion Espanola de Pediatria. Published by Elsevier Espana, S.L. All rights reserved.