macrophage activation syndrome

Etiology

• complication of rheumatoid disease
  • systemic juvenile idiopathic arthritis
  • adult-onset Still disease
  • systemic lupus erythematosus
  • Kawasaki disease
• viral infections (influenza, Herpes simplex, & EBV)

Pathology

• hepatosplenomegaly
  • hepatic insufficiency
• coagulopathy
• neurologic disorder
• activation & uncontrolled proliferation of T-cells & well-differentiated macrophages, leading to widespread hemophagocytosis & cytokine overproduction
• decreased NK-cell cytolytic function resulting from decreased perforin gene (PRF1) expression
• expansion of cytotoxic T lymphocytes that produce macrophage- activating cytokines, including IFN-gamma
• alternative pathway of macrophage differentiation
• elevated IL-18 in serum

Laboratory

• complete blood count: pancytopenia
• liver function tests
  • serum transaminases may be moderate elevated
• serum ferritin: very elevated
• prothrombin time, INR often prolonged
• aPTT often prolonged
• D-dimer: fibrin degradation products often present
• plasma fibrinogen: hypofibrinogenemia
• serum triglycerides: hypertriglyceridemia
• IL-18 in serum elevated

Complications

• may be rapidly fatal (8-60%)

Management

• parenteral administration of high doses of corticosteroids
• high-dose intravenous immunoglobulins, cyclophosphamide, plasma exchange, & etoposide has been used with conflicting results
• cyclosporine A may be useful in corticosteroid-resistant disease
• stem cell transplantation provides only long-term disease-free survival
• consults:
  • rheumatology
  • hematology/oncology
  • infectious disease

More general terms

• leukocyte disorder
• syndrome

More specific terms

• hemophagocytic lymphohistiocytosis; hemophagocytic syndrome