Phenytoin hypersensitivity syndrome with positive patch test. A possible cross-reactivity with amitriptyline

A 34-year-old woman, after 2 weeks of treatment with phenytoin and amitriptyline, developed fever and cutaneous lesions consisting of a generalized maculopapular rash and eosinophilia. Her biochemical data showed abnormal liver functions with increased levels of SGOT, SGPT, LDH, gamma-glutamyl transpeptidase and alkaline phosphatase. The skin biopsy pattern was compatible with phenytoin drug eruption of the erythemamultiforme-like type (lymphocytic exocytosis, isolated dyskeratotic cells, vacuolation of basal cells and incontinence of pigment). The patch tests were positive with phenytoin (patch test biopsy showed a typical eczematous pattern). The patch test with amitriptyline was negative. An oral challenge with amitriptyline showed an erythematous maculopapular rash. The challenge with phenytoin was not carried out because the previously abnormal liver function tests contraindicated the challenge. Although there are a few cases reported, the patch tests could be useful for diagnosing phenytoin allergy. Cross-reactivity between phenytoin and amitriptyline is possible.