hemophagocytic lymphohistiocytosis; hemophagocytic syndrome

Etiology

• several inherited immune deficiencies may predispose children
• most adults have no underlying immune disorder
• triggers include Herpesvirus & less frequently other infectious agents
• malignant lymphomas may predispose, especially in adults
• complication of dengue
• lamotrigine

Pathology

• severe inflammation
• hemophagocytosis by activated, morphologically benign macrophages
• impaired function of NK cells & cytotoxic T-cells

Clinical manifestations

• prolonged fever
• cytopenia
• hepatosplenomegaly
• lymphadenopathy
• bleeding
• neurologic manifestations: seizures, ataxia, visual disturbances

Laboratory

• serum ferritin is elevated & is used as a marker for macrophage activation during treatment
• serum triglycerides are low
• plasma fibrinogen is low
• elevated CD25 cells in blood

Diagnostic procedures

• hemophagocytosis identified through
  • bone marrow biopsy
  • spleen biopsy
  • lymph node biopsy

Complications

• may be fatal

Differential diagnosis

• infection

Management

• low risk patients:
  • cyclosporine, glucocorticoids, or intravenous immunoglobulin
    • intravenous immunoglobulin within hours of disease onset
• high risk:
  • etoposide plus dexamethasone for 8 weeks
    • cyclosporine may be added at the beginning
  • intrathecal methotrexate is used only with persistently abnormal CSF analysis or progressive neurologic symptoms
  • alemtuzumab may be effective for refractory disease
• treat associated malignancy
• cure with bone marrow transplantation

More general terms

• lymphohistiocytosis
• macrophage activation syndrome

More specific terms

• familial histiocytic reticulosis; familial hemophagocytic reticulosis; familial hemophagocytic lymphohistiocytosis; familial erythrophagocytic lymphohistiocytosis

Patient information

hemophagocytic lymphohistiocytosis patient information