Tests for Drug Allergy

Houwerzijl, J; Gast, G. C. De; Jp, Nater

doi:10.1016/s0140-6736(74)91980-1

Cited by 11 publications

(6 citation statements)

References 11 publications

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“…This phenomenon can be explained by the fact that keratinocytes express high levels of certain cytochrome P-450 (CYP) isozymes [26]; therefore, it is possible that keratinocytes metabolize anticonvulsants locally, generating sufficient quantities of a reactive species to haptenate protein and initiate an immune response. In support of this hypothesis, Wolkenstein et al [27] demonstrated The results of both LTTs and patch tests appear to be dependent on the time of testing [8]. In some studies [8,10], LTTs and/or patch tests produced negative results during and within one month after hypersensitivity reactions, and positive ones afterwards.…”

Section: Phenytoin Phenobarbitalmentioning

confidence: 93%

“…In support of this hypothesis, Wolkenstein et al [27] demonstrated The results of both LTTs and patch tests appear to be dependent on the time of testing [8]. In some studies [8,10], LTTs and/or patch tests produced negative results during and within one month after hypersensitivity reactions, and positive ones afterwards. This "refractory period", during which false-negative results may occur, has been ascribed both to an impaired lymphocyte responsiveness [8] and to the fact that the selective recruitment of antigen-specific lymphocytes into target organs transiently leads to low specific Tcell number in the peripheral blood [10].…”

Section: Phenytoin Phenobarbitalmentioning

confidence: 93%

“…The LTT measures a cellular response involving drug-related T-cell activity [6,7]. Demonstration in LTT studies of drug-specific proliferation of peripheral blood mononuclear cells (PBMCs) from anticonvulsant sensitive patients, but not from subjects who tolerate them, is indicative of the involvement of the immune system in the development of the clinical symptoms [6,[8][9][10][11][12][13]. Immunohistochemical studies have shown the presence of activated CD4+ and CD8+ T cells in such patients [14,15].…”

Section: Phenytoin Phenobarbitalmentioning

confidence: 99%

“…In some studies [8,10], LTTs and/or patch tests produced negative results during and within one month after hypersensitivity reactions, and positive ones afterwards. This "refractory period", during which false-negative results may occur, has been ascribed both to an impaired lymphocyte responsiveness [8] and to the fact that the selective recruitment of antigen-specific lymphocytes into target organs transiently leads to low specific Tcell number in the peripheral blood [10]. On the other hand, the LTT measures a memory T-cell response, and can be positive for many years, even though some patients seem to loose reactivity in a time frame of 3-4 years [7].…”

Section: Phenytoin Phenobarbitalmentioning

confidence: 99%

“…Several studies regarding patients with hypersensitivity reactions to aromatic anticonvulsants assessed immunologic cross-reactivity among the latter by patch tests and/or LTTs and found positive responses to more than one drug [13,[38][39][40][41][42][43][44][45][46][47][48][49]. However, most of such studies are reports of single patients [38-40, 42, 43, 45, 46, 48].…”

Section: Immunologic Cross-reactivitymentioning

confidence: 99%

See 4 more Smart Citations

Hypersensitivity to Aromatic Anticonvulsants: In Vivo and In Vitro Cross-Reactivity Studies

Romano¹,

Pettinato²,

Andriolo³

et al. 2006

CPD

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Aromatic antiepileptic drugs (phenytoin, carbamazepine, oxcarbazepine, and phenobarbital) are frequently associated with cutaneous eruptions. A cell-mediated pathogenic mechanism has been demonstrated in most of such reactions on the basis of positive responses to patch tests and/or lymphocyte transformation tests. Therefore, such tests are useful tools for evaluating anticonvulsant hypersensitivity reactions. Moreover, an in vitro lymphocyte toxicity assay, which exposes the patient's lymphocytes to arene oxides, has detected lymphocyte susceptibility to toxic metabolites in a large percentage of patients with hypersensitivity reactions to aromatic anticonvulsants. Although several hypersensitivity reactions to sequential exposure to more than one aromatic anticonvulsant (i.e., clinical cross-reactivity) have been reported, there are few studies performed with patch tests and/or lymphocyte transformation tests assessing immunologic cross-reactivity, and their data are contradictory. In any case, considering studies performed in samples of at least 10 patients, the immunologic cross-reactivity rate among aromatic anticonvulsants appears to be low. On the other hand, the reported rate of the toxic cross-reactivity (i.e., assessed by lymphocyte toxicity assays) is high. Further in vivo and in vitro studies in large samples of subjects are needed to evaluate cross-reactivity among aromatic anticonvulsants.

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