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.

We report about a patient with polyarticular rheumatoid arthritis taking methotrexat and 5 mg prednisolone who developed in the course of a RA flare a septic arthritis in the right shoulder. Listeria monocytogenes could be identified as the causative bacteria. Clinically, the Listeria-induced septic arthritis could not be differentiated from rheumatoid arthritis; fever was not present. The synovial analysis showed a granulocytic effusion with 19,000 cells/ml; there was no microbiological growth within the first 24 hours. Only the low glucose level indicated a possible septic arthritis. After 48 hours, gram-positive bacterial growth was evident and Listeria monocytogenes could be isolated after 72 hours. Therapy was initiated by antibiotic treatment and arthrotomy with synovectomy followed by extensive irrigation which proved effective in bacterial elimination but joint destruction resulted. During the whole course, Listeria antibodies were negative and proved to be too insensitive. The incidence of Listeria-induced arthritis is very low; a review of the literature revealed only 24 reported cases. It occurs primarily in patients with rheumatic diseases under immunosuppression and in prosthetic joints. The diagnosis is based on cultural detection. It is important to cultivate synovial effusions for longer than 24 hours in order to identify Listeria. This is of relevance since Listeria serology is not sensitive.

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Zusammenfassung Hintergrund: Untersucht wurden RA Pat., die nach TNF-? Versagen mit wiederholten Rituximab Zyklen therapiert wurden. Material und Methoden: 22 RA Pat. wurden von 5 Rheumatologen in der Praxis oder Erm?chtigungsambulanz mit bis zu 4 Rituximab Zyklen behandelt. Untersucht wurden DAS28, BSG und CRP zum Zeitpunkt 0, 4, 6 Monate. Ergebnisse: Bei allen 22 Pat. bestand eine aktive Arthritis, DAS28 im Median 5,8, CRP 2,7?mg/dl, BSG 51?mm. Eine zunehmende signifikante Verbesserung des DAS28 und der Entz?ndungsparameter wurde im Behandlungsverlauf beobachtet, der DAS28 reduzierte sich von 5,8 auf 2,8 vor dem 4. Rituximab Zyklus. 13/22 (59%) erzielten einen low DAS28 (<3,2), 8/22 (36%) eine Remission (DAS28<2,6). Die Durchf?hrung der Behandlungszyklen gestaltete sich problemlos in den Praxen, signifikante Nebenwirkungen traten nicht auf. Schlussfolgerungen: Das Ansprechen auf Rituximab nach TNF-? Versagen nimmt bei RA Pat. im Verlauf weiterer Behandlungszyklen zu. Trotz des h?heren logistischen Aufwands ist die Therapie problemlos in der Praxis durchf?hrbar.