Syndromes d'activation lymphohistiocytaire constitutionnels

Familial haemophagocytic lymphohistiocytosis is a rare disease of the immune system that is fatal in the absence of treatment. Prior to allogeneic haematopoietic stem cell transplantation, the only curative therapy, a specific treatment is required to obtain remission from the haemophagocytic lymphohistiocytosis. Familial forms are essentially observed in young infants, but are increasingly also found in older children and even in adults. Different genetic forms of autosomal recessive inheritance have been identified. The common pathophysiology is characterised by a defect in the cytotoxicity of natural killer cells and cytotoxic T cells. A defect in the exocytosis of lytic granules results in an abnormal overwhelming and uncontrolled immune response with activation and expansion of CD8+ T cells, histiocytes and macrophages. Despite important progress, diagnosis and treatment of patients with familial haemophagocytic lymphohistiocytosis remain a challenge. A better understanding of the pathophysiology of familial haemophagocytic lymphohistiocytosis opens the way for novel therapeutic approaches by immunotherapy. The present document summarises the current knowledge on the clinical presentation, diagnostic criteria, genetic background and different treatment options.