Hemophagocytic Lymphohistiocytosis (HLH) Pathophysiology: Triggering factor (infection,...)→Activation of CD8 T cells (IFN-y) → Excessive activation of macrophages that disrupts immune homeostasis → Phagocytosis of blood cells + production of pro-inflammatory cytokines (TNFa,lL1, IL6, IL12, IL18) → Auto-amplification loop Diagnosis: accumulation of clinical and biological evidences, Biological + Bone Marrow + Etiological Assessment • Clinical: fever +++, hepatosplenomegaly, adenopathies, confusion • Biological: Cytopenia +++ (Plt, Hb), Hepatic dysfunction, ↑ Ferritin >1000 ng/ml, ↑ Triglycerides, ↓ Fibrinogen level, ↑ sIL-2R >2400 Ul/ml, ↑ LDH • Bone marrow: Medullary hemophagocytosis = additional diagnostic argument, Interest for etiological assessment+++ Primary HLH: • Familial HLH, Chediak-Higashi, Griscelli, Purtilo (XLP) Acquired HLH: • Infections+++: Virus (EBV, CMV, HHV8,...), Bacteria (Mycobacteria, salmonella, ...), Parasites (Leishmaniosis, malaria, toxoplasmosis,...), Mycosis (Histoplasmosis, candidiasis,...) • Hemopathies+++: Hodgkin, T-cell lymphoma, B-cell lymphoma (DLBCL, intravascular B-LNH), solid cancers • Autoimmune diseases: SLE+++, Adult-onset Still disease, Infection under immunosuppressants or biologics (CMV +++, EBV) • Others: Cellular immune deficiency, Drugs, Unknown cause Treatment: • Etiological+++: Anti-infectious, chemotherapy, anti-CD20 (PTLD), allogeneic HSCT • Symptomatic: Glucocorticoids +++, Etoposide/VP16 (100 mg/m2) : in case of emergency, ICU in case of life-threatening manifestations, Anti-IFN-y and JAK inhibitors under evaluation By Dr. Nicolas Taar #HLH #Hemophagocytic #Lymphohistiocytosis #diagnosis #management #treatment #summary #rheumatology
