title: Hypersensitivity to aromatic anticonvulsants: in vivo and in vitro cross-reactivity studies.
abstract: 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.
authors.affiliation: Department of Internal Medicine and Geriatrics, UCSC-Allergy Unit, Complesso Integrato Columbus, Rome, Italy. columbus.romano@linet.it.
authors.forename: Antonino
authors.initials: A
authors.lastname: Romano
authors.forename: Rosa
authors.initials: R
authors.lastname: Pettinato
authors.forename: Maria
authors.initials: M
authors.lastname: Andriolo
authors.forename: Marinella
authors.initials: M
authors.lastname: Viola
authors.forename: Rosa-Maria
authors.initials: RM
authors.lastname: Guéant-Rodriguez
authors.forename: Rocco Luigi
authors.initials: RL
authors.lastname: Valluzzi
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Elia
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ventura
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D003429:Cross Reactions / Q000276:immunology; D004342:Drug Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000927:Anticonvulsants; D011084:Polycyclic Aromatic Hydrocarbons