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



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