Anticonvulsant-induced toxic epidermal necrolysis: monitoring the immunologic response.
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.
Leyva
L
L
Research Unit for Allergic Diseases, Carlos Haya Hospital, Malaga, Spain.
Torres
M J
MJ
Posadas
S
S
Blanca
M
M
Besso
G
G
O'Valle
F
F
del Moral
R G
RG
Santamaría
L F
LF
Juárez
C
C
D000328:Adult; D000917:Antibody Formation; D000927:Anticonvulsants / Q000009:adverse effects*; D001773:Blood Cells / Q000378:metabolism / Q000473:pathology; D017252:CD3 Complex / Q000032:analysis; D002220:Carbamazepine / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013262:Stevens-Johnson Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D000927:Anticonvulsants; D017252:CD3 Complex; D016207:Cytokines; D019040:E-Selectin; D016201:Receptors, Lymphocyte Homing; D002220:Carbamazepine; D010672:Phenytoin