Lamotrigine-induced toxic epidermal necrolysis confirmed by in vitro granulysin and cytokine assays

Lamotrigine is a recent medication which is prescribed for various neuropsychiatric conditions. It is generally well-tolerated, but recent pharmacoepidemiological evidence suggests that lamotrigine is associated with risks of developing severe cutaneous drug reactions like toxic epidermal necrolysis (TEN). However, there still remains the diagnostic challenge regarding how to confirm the drug causality in suspected cases. In most cases so far, lamotrigine causality has not been objectively demonstrated, which was possibly due to high risk of oral challenge tests or the lack of useful in vitro drug assays. Here we report a case of lamotrigine-induced TEN, of which the drug causality was confirmed by in vitro granulysin and cytokine assays.

[1]  B. Thong.  Stevens-Johnson syndrome / toxic epidermal necrolysis: an Asia-Pacific perspective , 2013, Asia Pacific allergy.

[2]  W. Pichler,et al.  In vitro drug causality assessment in Stevens–Johnson syndrome – alternatives for lymphocyte transformation test , 2013, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[3]  R. Schwartz,et al.  Toxic epidermal necrolysis: Part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. , 2013, Journal of the American Academy of Dermatology.

[4]  R. Schwartz,et al.  Toxic epidermal necrolysis , 2020, Definitions.

[5]  H. Hashizume.  Recent progress of elucidating the mechanisms of drug hypersensitivity , 2012, Asia Pacific allergy.

[6]  Miguel Blanca,et al.  Immunologic Evaluation of Drug Allergy , 2012, Allergy, asthma & immunology research.

[7]  L. Naldi,et al.  Poor relevance of a lymphocyte proliferation assay in lamotrigine‐induced Stevens–Johnson syndrome or toxic epidermal necrolysis , 2012, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[8]  W. Song,et al.  Drug Hypersensitivity Syndrome: A Literature Review of Associated Viral Reactivation , 2011 .

[9]  A. Krensky,et al.  Granulysin activates antigen-presenting cells through TLR4 and acts as an immune alarmin. , 2010, Blood.

[10]  J. Roujeau,et al.  Open trial of ciclosporin treatment for Stevens–Johnson syndrome and toxic epidermal necrolysis , 2010, The British journal of dermatology.

[11]  A. Dunant,et al.  ALDEN, an Algorithm for Assessment of Drug Causality in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: Comparison With Case–Control Analysis , 2010, Clinical pharmacology and therapeutics.

[12]  Yuan-Tsong Chen,et al.  Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis , 2008, Nature Medicine.

[13]  C. González‐Herrada,et al.  Treatment of toxic epidermal necrolysis with cyclosporin A. , 2000, The Journal of trauma.

[14]  J. Tschopp,et al.  Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. , 1998, Science.

[15]  J. Messenheimer,et al.  Safety Review of Adult Clinical Trial Experience with Lamotrigine , 1998, Drug safety.

[16]  D. Loannides,et al.  Plasmapheresis in toxic epidermal necrolysis , 1997, International journal of dermatology.

[17]  H. Schuppe,et al.  Lamotrigine and toxic epidermal necrolysis , 1996, The Lancet.

[18]  P. Elias,et al.  Toxic epidermal necrolysis in a patient with graft-vs-host reaction. , 1972, Archives of dermatology.

[19]  L. Naldi,et al.  Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. , 2008, The Journal of investigative dermatology.

[20]  M. Jonkman,et al.  Dexamethasone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis. , 2007, Acta dermato-venereologica.