Hemophagocytic syndrome associated with an infection

Hemophagocytic syndrome associated with an infection, also known as infection-associated hemophagocytic lymphohistiocytosis (HLH) or secondary hemophagocytic syndrome, is a severe and potentially life-threatening hyperinflammatory condition triggered by an infectious agent. Unlike primary (familial) HLH, which is caused by inherited genetic defects in immune regulation, this acquired form occurs when an infection — most commonly Epstein-Barr virus (EBV), cytomegalovirus (CMV), or other herpesviruses, but also bacterial, fungal, or parasitic infections — triggers an uncontrolled and excessive activation of the immune system. This leads to widespread inflammation and tissue damage across multiple organ systems. The hallmark of this condition is hemophagocytosis, in which activated macrophages and histiocytes engulf red blood cells, white blood cells, and platelets in the bone marrow, spleen, liver, and lymph nodes. Key clinical features include prolonged high fever, enlarged spleen (splenomegaly) and often liver (hepatomegaly), cytopenias (low blood cell counts affecting red cells, white cells, and platelets), markedly elevated serum ferritin, elevated triglycerides, low fibrinogen, liver dysfunction, and coagulopathy. Patients may also develop neurological symptoms including seizures, altered consciousness, and meningeal signs. Without prompt recognition and treatment, the condition can rapidly progress to multi-organ failure and death. Treatment typically involves addressing the underlying infection with appropriate antimicrobial therapy alongside immunosuppressive treatment to control the hyperinflammatory response. The HLH-2004 protocol, which includes etoposide, dexamethasone, and cyclosporine A, is frequently used, though treatment is tailored based on the triggering infection and disease severity. In milder cases triggered by certain infections, treating the underlying infection alone may be sufficient. Intravenous immunoglobulin (IVIG) and corticosteroids may also be employed. More recently, emapalumab (an anti-interferon-gamma antibody) and ruxolitinib (a JAK inhibitor) have been explored as therapeutic options. Early diagnosis and aggressive treatment are critical, as mortality rates remain significant even with appropriate therapy.

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