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.

Evidence of infectious cause

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)

Possible mechanism for hemophagocytosis

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)

Relation to chronic infection

Notes and comments

So far, so good, Inge. Note the syntax for references. — Paul Albert 07.15.2010


1) , 7)
Hemophagocytic syndromes and infection.
Fisman DN
Emerg Infect Dis6p601-8(2000 Nov-Dec)
2) , 4) , 8)
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults characterized by high viral genome load within circulating natural killer cells.
Fox CP, Shannon-Lowe C, Gothard P, Kishore B, Neilson J, O'Connor N, Rowe M
Clin Infect Dis51p66-9(2010 Jul 1)
Typhoid fever presenting as infection-associated hemophagocytic syndrome: report of one case.
Chien YH, Lee PI, Huang LM, Lee CY, Lin DT, Lin KH
Acta Paediatr Taiwan40p339-40(1999 Sep-Oct)
Hemophagocytic Syndrome Revealing Primary HHV-6 Infection.
Marabelle A, Bergeron C, Billaud G, Mekki Y, Girard S
J Pediatrp(2010 Apr 16)
Severe hemophagocytic syndrome developing after treatment initiation for disseminated Mycobacterium tuberculosis: case report and literature review.
Balkis MM, Bazzi L, Taher A, Salem Z, Uthman I, Kanj N, Boulos FI, Kanj SS
Scand J Infect Dis41p535-7(2009)
Hemophagocytic macrophages harbor Salmonella enterica during persistent infection.
Nix RN, Altschuler SE, Henson PM, Detweiler CS
PLoS Pathog3pe193(2007 Dec)
home/diseases/hlh.txt · Last modified: 10.17.2018 by sallieq
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