[Development and/or increase of rheumatoid nodules in RA patients following leflunomide therapy]

Z Rheumatol. 2004 Feb;63(1):84-7. doi: 10.1007/s00393-004-0537-z.
[Article in German]


This is the first description of the development of rheumatoid nodules in 3 rheumatoid arthritis patients following leflunomide therapy. The nodules were localized at typical sites with preference of the extensor side of hands and elbow. One nodule examined histologically revealed the typical architecture of RA nodules. In all 3 patients the time of onset of nodulosis was about 6 months after initiating the leflunomide therapy. In all 3 patients leflunomide was clinically efficacious concerning RA: remission or near remission was achieved. Due to the extent of nodulosis, the leflunomide therapy had to be stopped in 2 patients. Progression and acceleration of nodulosis is well known following MTX therapy in RA patients. It is caused by adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes. Leflunomide has no known influence on adenosine metabolism, so different pathogenetic mechanisms must be assumed for the induction of nodulosis by leflunomide.

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Drug Therapy, Combination
  • Elbow / pathology
  • Female
  • Follow-Up Studies
  • Hand / pathology
  • Humans
  • Isoxazoles / adverse effects*
  • Isoxazoles / therapeutic use
  • Leflunomide
  • Male
  • Rheumatoid Factor / blood
  • Rheumatoid Nodule / chemically induced*
  • Rheumatoid Nodule / diagnosis
  • Rheumatoid Nodule / pathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Isoxazoles
  • Rheumatoid Factor
  • Leflunomide