Table 1.
| Causes of HLH |
|---|
| Primary mutations |
| Defects in cytolytic function: |
| PRF1 (10q21-22), UNC13D (17q2), STX11 (6q24), STXBP2 (19p13), RAB27A (15q21), LYST (1q42-43), SH2D1A (Xq24-25) |
| Defects in inflammasome regulation: |
| BIRC4 (Xq25), NLRC4 (2p22.3) |
| Secondary aetiologies |
| Infections: |
| Viruses – EBV, CMV, HSV, HHV-6 and -8, VZV, hepatitis, HIV, parvovirus B19, influenza A and B, adenovirus, enterovirus, dengue, Ebola and others |
| Bacteria – Mycobacteria spp., Rickettsia spp., Staphylococcus spp., Escherichia coli, Legionella spp. and others |
| Parasites – Leishmania spp., Plasmodium spp., Toxoplasma spp. and others |
| Fungi – Aspergillus spp., Candida spp., Histoplasma spp., Pneumocystis jiroveci and others |
| Autoimmune conditions: |
| SLE, sJIA, AOSD, RA, systemic vasculitides, periodic fever syndromes, IBD and others |
| Malignancy: |
| Haematological – T-cell, NK-cell, B-cell or Hodgkin’s lymphoma, leukaemia and others |
| Solid organ tumours |
| Miscellaneous: |
| Transplantation – Solid organ or HSCT |
| Iatrogenic – Immunosuppression, vaccination, surgery, haemodialysis |
| Pregnancy |
AOSD: adult-onset Still’s disease; CMV: cytomegalovirus; EBV: Epstein-Barr virus; HHV: human herpesvirus; HIV: human immunodeficiency virus; HSCT: haematopoietic stem cell transplantation; HSV: herpes simplex virus; IBD: inflammatory bowel disease; NK: natural killer; RA: rheumatoid arthritis: sJIA: systemic juvenile inflammatory arthritis; SLE: systemic lupus erythematosus; spp.: species; VZV: varicella zoster virus.