Persistent itching nodules after the fourth dose of diphtheria-tetanus toxoid vaccines without evidence of delayed hypersensitivity to aluminium

Vaccine. 2004 Sep 9;22(27-28):3698-706. doi: 10.1016/j.vaccine.2004.03.036.


Studies in Gothenburg, Sweden, reported an exceptionally high rate of persistent itching nodules at the site of injection of aluminium containing vaccines, usually with positive epicutaneous tests to aluminium. When a new booster diphtheria-tetanus vaccine was introduced we performed a prospective cluster randomised active surveillance in 25,232 10-year-olds. Parental reports 6 months after vaccination with Duplex or diTeBooster were collected for 22,365 (88%) pupils in 851 schools. We identified 3-6 children per 10,000 with a local itching nodule persisting for at least 2 months. There were no significant differences between the vaccine groups. Contact allergy to aluminium was not detected. The findings support the use of the vaccine presently available in the Swedish vaccination program. Continued surveillance of persistent itching nodules and aluminium contact allergy is, however, warranted for vaccines containing pertussis toxoid and aluminium.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / adverse effects*
  • Aluminum / adverse effects*
  • Child
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypersensitivity, Delayed / pathology*
  • Immunization, Secondary / adverse effects
  • Infant
  • Male
  • Product Surveillance, Postmarketing
  • Pruritus / epidemiology
  • Pruritus / etiology*
  • Pruritus / pathology
  • Skin / pathology
  • Skin Tests
  • Surveys and Questionnaires


  • Adjuvants, Immunologic
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Aluminum