Chediak Higashi syndrome are typically associated with albinism due to an effect upon melanocyte pigment secretion. Griscelli syndrome type 2 is identified by mutations in RAB27A while Chediak Higashi syndrome is associated with LYST mutations. Mutations of both these gene impair proteins important for formation and/or trafficking of secretory lysosomes [24] . In these syndromes, a gene defect interferes with lytic granules reaching the cytotoxic lymphocyte membrane, thus leading to impaired NK cell cytotoxicity. Patients with X-linked lymphoproliferative disease have difficulty clearing Epstein-Barr virus (EBV) infected B-cells, with subsequent extensive lymphocytic expansion into multiple organs. The SH2D1A mutation, which encodes for the signaling lymphocyte activation molecule (SLAM)-associated protein SAP, is identified in XLP1. Impaired cytolytic function in XLP1 is thought to cause accumulation EBV-infected B cells and persistence of reactive inflammatory cells, which combine to produce an exaggerated immune response [25] . Treatment for HLH is described in the HLH 2004 revised guidelines [14] and is divided into acute and long-term management. Initial treatment with an immunomodulatory regimen is recommended. Patients with primary HLH who fail to reach disease resolution within 8 weeks of treatment should continue on this regimen for an additional treatment course. Hematopoetic stem cell transplantation should be pursued as soon as a suitable donor is available for all patients with primary HLH, relapsed HLH, or those failing to progress on therapy [4] . There is no standard for the treatment of secondary HLH or MAS in the context of rheumatologic disease. High dose corticosteroids, biologic agents, cyclosporine and high dose intravenous immunoglobulin have been used with varying success. Anakinra, a recombinant IL-1 receptor antagonist, has been increasingly used for sJIA patients with MAS [24] . If initial treatment fails, HLH salvage therapy may be pursued according to the HLH 2004 chemotherapeutic regimens [14, 12] . Confirmation of a genetic mutation is not needed for immediate management but is important in differentiating familial HLH and secondary HLH for long-term patient management and family genetic counseling.