Published: 5 September 2019


Lamotrigine and a rare immune system reaction: Haemophagocytic lymphohistiocytosis (HLH)

Prescriber Update 40(3): 59
September 2019

Key Messages

  • Haemophagocytic lymphohistiocytosis (HLH) has been reported in patients taking lamotrigine.
  • HLH is a very serious, possibly life-threatening, reaction arising from excessive activation of the body’s immune system.

What is haemophagocytic lymphohistiocytosis (HLH)?

HLH is a rare but life-threatening syndrome caused by excessive immune system activation1,2. Persistent fever is usually present, and several organs can be affected2.

HLH is more common in young children aged under 18 months, but also occurs in older children and adults3. Patients with HLH may have a predisposing genetic defect, and/or an immunologic trigger such as infection3.

Typical clinical features include fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, high serum ferritin, and liver function abnormalities3. Early diagnosis and prompt treatment are essential to improve patient outcomes and reduce mortality2,3.

HLH and lamotrigine

Internationally, HLH has been reported in patients taking lamotrigine2.

In New Zealand, lamotrigine is indicated for the treatment of epilepsy in children (from age 2 years) and adults, and bipolar disorder in adults1. HLH is included in the warnings and precautions section of the Logem data sheet1. Symptoms usually occur within four weeks of starting treatment1. Lamotrigine should be discontinued promptly if HLH is suspected.

Up to June 2019, the Centre for Adverse Reactions Monitoring (CARM) had not received any reports of HLH associated with lamotrigine.


  1. Mylan New Zealand Ltd. 2018. Logem New Zealand Data Sheet October 2018. URL: (accessed 24 June 2019).
  2. US Food and Drug Administration. 2018. FDA Drug Safety Communication: FDA warns of serious immune system reaction with seizure and mental health medicine lamotrigine (Lamictal). URL: (accessed 24 June 2019).
  3. McClain KL, Eckstein O. 2019. Clinical features and diagnosis of hemophagcytic lymphohistiocytosis. In: UpToDate. 11 July 2019. URL: (accessed 23 July 2019).
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