Hemophagocytic lymphohistiocytosis (HLH)

Hemophagocytic lymphohistiocytosis (HLH) or hemophagocytic syndrome has increased destruction of red and white blood cells as its major hallmark. Fever, splenomegaly, jaundice, lymphocytosis and histiocytosis are the most usual symptoms and findings in this syndrome.

HLH can be either primary or secondary. Secondary refers to the acquired form and is the form that will be described here.

Several findings link the syndrome to infections:

• The immune system is activated. High levels of serum TNF-α, interleukins, IFN-γ have been found in HLH patients.¹⁾ The actual hemophagocytosis is undertaken by macrophages.
• HLH has been associated with the following microbes: Epstein-Barr virus,²⁾ Salmonella thyphi,³⁾ Herpes simplex virus 1,⁴⁾ HHV-6,⁵⁾ Mycobacterium tuberculosis⁶⁾ and other infectious agents.⁷⁾
• Treatment of infections can reduce hemophagocytosis.⁸⁾

The actual hemophagocytosis may be viewed as a result of overstimulated macrophages. While blood cells may harbour infectious agents and therefore the infected individual could benefit from the macrophages attacking the blood cells, there is also the possibility that hemophagocytosis benefits the infectious agent. Bacteria in hemophagocytic macrophages could access nutrients from the ingested cells, or hemophagocytic macrophages could reduce bacteria-killing activity by killing the very cells that could attack them. Yet, other macrophages could still be sufficiently activated to generate additional hemophagocytic macrophages.⁹⁾

The significance of hemophagocytosis in chronic L-form disease is not well characterized.