Hypersensitivity to aromatic anticonvulsants: In vivo and In vitro cross-reactivity studies

Indications:Unspecified number of patients with unspecified indications.Patients:44 subjects. Study group: 10 patients, 3 male and 7 female, aged 8 to 42 years (mean age, 21.50 years). Tegretol: 7 patients, 3 male and 4 female, aged 8 to 42 years. Tegretol + valproic acid (VPA): 1 female patient aged 38 years. Oxcarbazepine (OCBZ): 1 female patient aged 21 years. Phenobarbital (PHB): 1 female patient aged 14 years. Control group: 34 subjects, 11 male and 23 female, aged 7 to 55 years (mean age, 24.56 years).TypeofStudy:This study presented the results of lymphocyte transformation test (LTT) and patch test (in vivo and in vitro cross-reactivity) in evaluating hypersensitivity reactions associated with aromatic anticonvulsants (including Tegretol).DosageDuration:5% w/w in white petrolatum applied to the skin of the interscapular region of the patient's back using acrylate adhesive strips/patch (single dose).Results:Some of the results are given for the whole group of patients receiving anticonvulsants without separate for Tegretol, OCBZ, PHB, VPA, and phenytoin (DHP). The onset of anticonvulsant-associated hypersensitivity reactions in 10 patients commonly occurred 1 to 3 weeks after the onset of anticonvulsant therapy. Most of the patients experienced maculopapular reactions. 7/10 patients displayed positive results to the associated drug in patch testing (Tegretol 5, Tegretol + VPA 1, and PHB 1). 4/6 Tegretol-positive patients reacted to all the concentrations used, 1/6 patient reacted to the concentrations higher than 5% and the remaining 1/6 patient reacted only to concentrations of 15 and 20%. Positive responses to VPA and PGB were observed at all concentrations. None of the control subjects displayed positive responses to patch tests. LTT was positive in 4 patients (Tegretol 2, OCBZ 1, and PHB 1). 9/34 control subjects displayed positive responses to aromatic anticonvulsants (Tegretol 1, OCBZ 1, DHP 4, and PHB 7). 3/34 control subjects showed positive responses to more than one anticonvulsant. Anticonvulsant-associated and cell-mediated hypersensitivity was diagnosed in 8/10 patients. LTT specificity was high, which ranged from 97.1% with regard to Tegretol and 79.5% with regard to PHB. Immunologic cross-reactivity was detected in 2/10 patients: in 1 patient who experienced maculopapular rash during Tegretol therapy and showed patch-test positivity to both Tegretol and OCBZ, to which she had never been exposed, and in another patient who reacted to Tegretol and revealed LTT positivity to Tegretol and DHP, to which she had never been exposed.AdverseEffects:Cutaneous hypersensitivity reactions observed were maculopapular exanthema (6), bullous exanthema (1), and Stevens-Johnson syndrome (1). Other observed adverse reactions were fever (3), fever/adenopathy (1), leukocytopenia (2), eosinophilia and elevated alanine and aspartate aminotransferases (2), lymphocytopenia (1), and eosinophilia (1).FreeText:Patch test: occlusion time was 48 hours and patches were evaluated 15 minutes and 24 hours after removal of the strips. LTT: peripheral blood mononuclear cells from patients and controls were cultured and incubated with Tegretol, oxcarbazepine, phenytoin, and phenobarbital valproic acid at concentrations ranging from 10 to 200 mcg/m. Cell culture lasted for 5 days and T-cell proliferation was measured.AuthorsConclusions:Anticonvulsant-associated cutaneous hypersensitivity reactions are frequent, and many factors, including positive patch tests and LTTs, suggest an immune-mediated pathogenic mechanism. In any case, we must take into account literature data concerning clinical cross-reactivity as well as those obtained by assessing cross-reactivity by LTAs [lymphocyte toxicity assays]. Therefore, patients who have suffered hypersensitivity reactions should avoid all aromatic anticonvulsants.