Leflunomide-induced toxic epidermal necrolysis in a patient with rheumatoid arthritis

Joint Bone Spine. 2008 Oct;75(5):597-9. doi: 10.1016/j.jbspin.2007.08.013. Epub 2008 Sep 20.


Introduction: Leflunomide is an immunomodulating agent with proven efficacy in rheumatoid arthritis. Although its overall safety profile is good, a few cases of toxic epidermal necrolysis have been reported.

Case report: This 36-year-old woman had rheumatoid arthritis that proved refractory to sulfasalazine and methotrexate, which were used successively in combination with symptomatic drugs. Leflunomide was started. A maculopapular rash and a fever developed 2 weeks later. The skin lesions spread rapidly to most of the body, and ulcers of the ocular and oral mucosa appeared. Leflunomide was stopped. Cholestyramine washout and prednisolone (60 mg/day) were given. The skin lesions healed over the next month. Punctate keratitis with keratinization of the cornea led to complete loss of vision.

Discussion: The main adverse effects of leflunomide consist of diarrhea, nausea, liver enzyme elevation, hypertension, alopecia, and allergic skin reactions. A few cases of severe skin reactions such as toxic epidermal necrolysis have been reported. They require immediate discontinuation of the drug and a washout procedure to hasten drug elimination from the body.

Conclusion: Close monitoring for severe skin reactions is in order when using leflunomide.

Publication types

  • Case Reports

MeSH terms

  • Adjuvants, Immunologic / adverse effects*
  • Adult
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Cholestyramine Resin / therapeutic use
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Ion Exchange Resins / therapeutic use
  • Isoxazoles / adverse effects*
  • Leflunomide
  • Prednisolone / therapeutic use
  • Stevens-Johnson Syndrome / drug therapy
  • Stevens-Johnson Syndrome / etiology*
  • Stevens-Johnson Syndrome / pathology


  • Adjuvants, Immunologic
  • Glucocorticoids
  • Ion Exchange Resins
  • Isoxazoles
  • Cholestyramine Resin
  • Prednisolone
  • Leflunomide