Autoimmune lymphoproliferative syndrome: etiology, diagnosis, and management

Autoimmune lymphoproliferative syndrome (ALPS) is a childhood disorder characterized by chronic, nonmalignant lymphoproliferation and autoimmunity, most commonly involving cells of hematopoietic origin. Mutations of the tumor necrosis factor receptor super family member 6 (TNFRSF6) gene, coding for the apoptosis-inducing protein Fas (Apo-1, CD95) are involved in the physiopathology of the syndrome, although the complete mechanism by which the syndrome is caused has not yet been unraveled. Although the syndrome has a benign nature, life-threatening complications can demand treatment. Treatment schedules, including corticosteroids, low doses of chemotherapy, granulocyte colony stimulating factor, or splenectomy, have varying results. Treatment with the antimalarial drug pyrimethamine/sulfadoxine (25/500mg per tablet) seems to be a new, well tolerated, and efficient approach, although larger studies will have to demonstrate the true value of this drug in patients with ALPS.