Association between treatment with central nervous system stimulants and Raynaud's syndrome in children: a retrospective case-control study of rheumatology patients

Arthritis Rheum. 2008 Feb;58(2):563-6. doi: 10.1002/art.23301.


Objective: To investigate whether central nervous system (CNS) stimulants used for the treatment of attention deficit hyperactivity disorder (ADHD) are associated with the development of Raynaud's syndrome (RS).

Methods: A case-control design was used for this study. All patients seen in a pediatric rheumatology practice during a 5-year period who had signs and symptoms of RS and met diagnostic criteria for RS as determined by pulse volume recording were studied as cases. Controls were randomly selected patients at the same clinic who did not have signs or symptoms of RS. They were matched to the cases for age, sex, and time of presentation. We tested for associations between various CNS medications and presence of RS. We also evaluated differences in laboratory test results between RS cases and matched controls.

Results: Sixty-four patients were enrolled in the study (32 cases with RS [23 female, 9 male] and 32 control patients). McNemar's test showed a significant association between the presence of RS and past or current use of ADHD stimulants (methylphenidate and dextroamphetamine) (chi(2) = 5.00, P = 0.01). The use of other CNS medications was not found to be significantly associated with RS (chi(2) = 1.33, P = 0.25 by McNemar's test). C-reactive protein levels and erythrocyte sedimentation rates were significantly higher in controls than in cases.

Conclusion: The results of this study indicate that there is a significant association between development of RS and therapy with CNS stimulants used for the treatment of ADHD. Although this was a small study, these findings provide preliminary evidence of an adverse effect of CNS stimulant medications in patients seen in rheumatology practice.

MeSH terms

  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Case-Control Studies
  • Central Nervous System Stimulants / adverse effects*
  • Child
  • Dextroamphetamine / adverse effects*
  • Female
  • Humans
  • Male
  • Methylphenidate / adverse effects*
  • Raynaud Disease / chemically induced*
  • Retrospective Studies
  • Rheumatic Diseases / chemically induced


  • Central Nervous System Stimulants
  • Methylphenidate
  • Dextroamphetamine