[Anticonvulsant hypersensitivity syndrome and lamotrigine-associated anticonvulsant hypersensitivity syndrome]

Rev Neurol (Paris). 2009 Oct;165(10):821-7. doi: 10.1016/j.neurol.2009.02.009. Epub 2009 Apr 11.
[Article in French]

Abstract

Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Bipolar Disorder / complications
  • Drug Eruptions / physiopathology
  • Drug Hypersensitivity / physiopathology*
  • Eosinophilia / chemically induced
  • Eosinophilia / physiopathology
  • Epilepsy / complications
  • Epilepsy / drug therapy
  • Epilepsy, Generalized / complications
  • Epilepsy, Generalized / drug therapy
  • Epilepsy, Tonic-Clonic / complications
  • Epilepsy, Tonic-Clonic / drug therapy
  • Female
  • Fever / chemically induced
  • Fever / physiopathology
  • Humans
  • Lamotrigine
  • Male
  • Phenobarbital / adverse effects
  • Phenobarbital / therapeutic use
  • Syndrome
  • Triazines / adverse effects*
  • Triazines / therapeutic use

Substances

  • Anticonvulsants
  • Triazines
  • Lamotrigine
  • Phenobarbital