Impact of phenytoin therapy on the skin and skin disease

Expert Opin Drug Saf. 2004 Nov;3(6):655-65. doi: 10.1517/14740338.3.6.655.


Phenytoin (diphenylhydantoin; Dilantin), ALZA Corp.) is a highly effective and widely prescribed anticonvulsant agent used in the treatment of focal and tonic clonic generalised seizures. The side effects of phenytoin can occassionally engender significant morbidity. Phenytoin can induce generalised eruptions that include: a maculopapular exanthem, Stevens-Johnson syndrome, generalised exfoliative dermatitis, toxic epidermal necrolysis, vasculitis and fixed drug eruptions. Phenytoin is linked to a hypersensitivity syndrome that manifests with fever, rash and lymphadenopathy. Patients receiving phenytoin may develop pseudolymphoma or, rarely, malignant lymphoma and mycosis fungoides-like lesions. Rarer cutaneous side effects include drug-induced lupus, purple hand syndrome, pigmentary alterations and IgA bullous dermatosis. Phenytoin can effect clotting function and alter vitamin and mineral levels. Prenatal exposure to phenytoin may result in a spectrum of structural, developmental and behavioural changes, known as the fetal hydantoin syndrome. Patients who use phenytoin in the long-term commonly manifest with gingival hyperplasia, coarsening of the facies, and hirsutism.

Publication types

  • Review

MeSH terms

  • Abnormalities, Drug-Induced / etiology
  • Adult
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use
  • Child
  • Connective Tissue Diseases / chemically induced
  • Drug Eruptions / etiology*
  • Drug Hypersensitivity / etiology
  • Epilepsy / drug therapy
  • Facies
  • Female
  • Gingival Hyperplasia / chemically induced
  • Hirsutism / chemically induced
  • Humans
  • Infant, Newborn
  • Lymphoma / chemically induced*
  • Male
  • Minerals / pharmacokinetics
  • Phenytoin / adverse effects*
  • Phenytoin / analogs & derivatives
  • Phenytoin / pharmacokinetics
  • Phenytoin / therapeutic use
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pseudolymphoma / chemically induced*
  • Vascular Diseases / chemically induced
  • Vitamins / pharmacokinetics


  • Anticonvulsants
  • Minerals
  • Vitamins
  • Phenytoin
  • fosphenytoin