T cell involvement in cutaneous drug eruptions.
BACKGROUND
The most frequent side-effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear.


OBJECTIVE
In this prospective study we investigated the T cell activation and drug specificity in different forms of drug-induced exanthemas from 22 patients.


METHODS
During acute drug allergy, liver parameters and T cell subset activation in the circulation (up-regulation of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causative drug was identified by lymphocyte transformation (LTT) and scratch-patch tests.


RESULTS
Seventeen of 22 (17/22) patients had maculo-papular exanthema, 4/22 bullous exanthema and 1/22 urticaria. The causative drugs were mainly antibiotics, anti-epileptics and anti-hypertensives. Up-regulation of HLA-DR on circulating CD4(+) and/or CD8(+) T cells was detected in 17 patients, being most marked in patients with bullous reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the patch test in 7/15. All patients showed lymphocytic infiltration in the skin biopsy of the acute lesion. Generally CD4(+) T cells dominated; a higher percentage of circulating CD8(+) T cells was found in patients with bullous skin reactions or hepatic involvement.


CONCLUSIONS
Our data demonstrate activation and drug specificity of T cells in drug-induced skin eruptions. A predominant CD8(+) T cell activation leads to more severe (bullous) skin symptoms or liver involvement, while predominant activation of CD4(+) cells elicits mainly maculo-papular reactions.
Hari
Y
Y
Allergy Division of the Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, Bern, Switzerland.
Frutig-Schnyder
K
K
Hurni
M
M
Yawalkar
N
N
Zanni
M P
MP
Schnyder
B
B
Kappeler
A
A
von Greyerz
S
S
Braathen
L R
LR
Pichler
W J
WJ
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004342:Drug Hypersensitivity / Q000209:etiology; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*