Anticonvulsant-induced toxic epidermal necrolysis: monitoring the immunologic response

J Allergy Clin Immunol. 2000 Jan;105(1 Pt 1):157-65. doi: 10.1016/s0091-6749(00)90191-x.

Abstract

Background: Toxic epidermal necrolysis is a severe reaction with skin involvement induced by different drugs and other agents. The mechanisms implicated in the induction of the reaction are poorly understood.

Objective: Our purpose was to study the involvement of T lymphocytes and other immunocompetent cells in the peripheral blood, blister fluid, and affected skin of 3 patients who had a severe reaction after receiving anticonvulsant medication.

Methods: Quantification of T lymphocytes expressing the skin-homing receptor (cutaneous lymphocyte-associated antigen ¿CLA) in peripheral blood, skin, and skin blister fluid and assessment of other adhesion molecules, activation markers, and inflammatory interleukins by flow cytometry, immunohistochemistry, and reverse transcription-PCR.

Results: An increase in CD3(+)CLA(+) cells paralleling the severity of the disease was observed in both peripheral blood and skin, tending to normalize as soon as patient's conditions improved. E-selectin was detected in endothelial vessels in parallel with CLA expression on lymphocytes. An overexpression of TNFalpha, IFN-gamma, and IL-2 was also observed in PBMCs. The expression of the different markers changed over the course of the disease.

Conclusions: These data show an increase in activated T cells expressing the skin-homing receptor in both tissue and peripheral blood accompanying clinical symptoms, with a recruitment of macrophages and an overexpression of cytokines. All these results suggest an important role for T cells in the production of toxic epidermal necrolysis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibody Formation
  • Anticonvulsants / adverse effects*
  • Blood Cells / metabolism
  • Blood Cells / pathology
  • CD3 Complex / analysis
  • Carbamazepine / adverse effects
  • Cytokines / metabolism
  • E-Selectin / metabolism
  • Endothelium / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenytoin / adverse effects
  • Receptors, Lymphocyte Homing / metabolism
  • Skin / metabolism
  • Skin / pathology
  • Stevens-Johnson Syndrome / immunology*
  • Stevens-Johnson Syndrome / metabolism
  • Stevens-Johnson Syndrome / pathology
  • Stevens-Johnson Syndrome / physiopathology

Substances

  • Anticonvulsants
  • CD3 Complex
  • Cytokines
  • E-Selectin
  • Receptors, Lymphocyte Homing
  • Carbamazepine
  • Phenytoin