Leflunomide-associated skin ulceration

Ann Pharmacother. 2002 Jun;36(6):1009-11. doi: 10.1345/aph.1A347.


Objective: To report a case of skin ulceration as a result of treatment with leflunomide for rheumatoid arthritis.

Case summary: A 78-year-old white woman developed bilateral leg ulcers after 6 months of treatment with leflunomide for rheumatoid arthritis. A history of leg ulcers after methotrexate therapy had been documented. Serologic and diagnostic tests did not support an alternate process. Other medications prescribed were oral ethinyl estradiol 0.05 mg/d, felodipine 5 mg/d, and paroxetine 20 mg/d, for which no documented correlation with the skin breakdown could be made.

Discussion: This is the first published case describing a possible relationship between the use of the immunosuppressant agent leflunomide and skin ulceration.

Conclusions: Skin breakdown and ulceration is a recognized adverse effect of drugs with immunosuppressant activity such as methotrexate. Leflunomide, a newer agent prescribed in the treatment of rheumatoid arthritis, may now be listed among the drugs in this category associated with this adverse drug effect.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Female
  • Humans
  • Isoxazoles / administration & dosage
  • Isoxazoles / adverse effects*
  • Isoxazoles / therapeutic use
  • Leflunomide
  • Skin Ulcer / chemically induced*
  • Skin Ulcer / etiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Isoxazoles
  • Leflunomide