Canterbury DHB


Haemophagocytic Lymphohistiocytosis

This section was inserted by Dr Blake Hsu in October 2018. The next review date is August 2021.

Haemophagocytic lymphohistiocytosis (HLH) is a rare condition caused by an inappropriate and severe activation of macrophages and T lymphocytes resulting in excessive cytokine production.

HLH can be primary or secondary.

In This Section

Primary HLH

Secondary HLH


Macrophage activation syndrome (MAS)



Primary HLH

Primary HLH is familial and autosomal recessive. It is usually diagnosed in the first two years of life, but can present later.

Familial HLH is subdivided into types 1 to 5. Common mutations associated with these types are listed below. These mutations are almost all null mutations that abolish critical proteins required for normal cytotoxic T cell and NK cell function. Samples can be sent overseas for testing of these mutations.

The following rare hereditary disorders diagnosed in childhood have a close association with HLH:

Secondary HLH

Secondary HLH can develop anytime during life. Causes include:


In the absence of a family history or detection of known molecular defects, HLH is diagnosed by the fulfillment of at least five of the following eight criteria:

  1. Fever.
  2. Splenomegaly.
  3. Cytopenias (affecting at least two of three lineages in the peripheral blood):
  4. Hypertriglyceridemia > 3 mmol/L and/or hypofibrinogenemia < 1.5 g/L.
  5. Haemophagocytosis in bone marrow (BM), spleen, or lymph nodes.

    Not all patients have haemophagocytosis at presentation – diagnosis should not be delayed for this single feature.

  6. Low or absent natural killer (NK) cell activity.
  7. Ferritin > 500 micrograms/L (in adults, some authors believe this should be 3000 micrograms/L).
  8. Soluble CD25 (that is, soluble IL-2 receptor) > 2400 units/mL (or per local reference laboratory).

NK activity and soluble CD25 cannot be measured in our lab.

Other features commonly seen with HLH that is not part of the diagnostic criteria include:

Macrophage activation syndrome (MAS)


Suggested HLH treatment algorithm

HLH Treatment Algorithm


About this Canterbury DHB document (155226):

Document Owner:

Blake Hsu (see Who's Who)

Last Reviewed:

October 2018

Next Review:

August 2021


Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 155226