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🌱 來自: autoinflammatory syndromes

Hemophagocytic lymphohistiocytosis

• ↑↑ immune activity;
• failure to ↓ activated macrophages by NK cells/CTLs → ↑ cytokines (IFNλ, IL18) → macrophages phagocytize other blood cells, cytokine storm, organ failure
• Triggered by disruption of immune homeostasis:
  • immune activation (infxn, autoimmune flare) or immunodeficiency;
  • ~25% familial (mutations in perforin-mediated cytotoxicity)
• HLH 2/2 rheumatologic disease termed macrophage activation syndrome (MAS)
• Fever, ↑ spleen, cytopenias, ↑ TG, ↓ fibrinogen, ↑ LFTs, hemophagocytosis, ↓ NK cell activity, ↑ ferritin, ↑ soluble IL2R;
• H-score for HLH likelihood (Arthritis Rheum 2014;66:2613)
• Rx trigger (eg, rheum flare w steroids/biologics);
  • if insufficient, HLH-04 protocol
    • etoposide + steroids ± CsA ± intrathecal MTX;
    • BMT if genetic or relapsed/refractory; Blood 2017;130:2728
  • anti-IL1/IVIg/steroids (Lancet Rheumatol 2020:2:e358),
  • emapalumab (anti-IFNγ) (NEJM 2020;382:1811);
• high mortality if no Rx (Blood 2019;133:2465)