Skip to main content

Advertisement

Log in

Debilitating diarrhoea and weight loss due to colitis in two RA patients treated with leflunomide

  • Case Report
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Diarrhoea and weight loss are frequently reported adverse events in rheumatoid arthritis (RA) patients receiving the disease-modifying antirheumatic drug (DMARD) leflunomide. According to the available literature these side effects occur mostly during the first 6 months of treatment, are rather mild and rarely lead to treatment withdrawal. In this report, we describe the clinical, endoscopic and histologic findings in two RA patients with severe diarrhoea and important weight loss more than 12 months after starting treatment with leflunomide. In both cases the symptoms were caused by colitis, but one had ulcerative and the other microscopic colitis. Despite treatment with budesonide the complaints only improved after withdrawal of leflunomide, making a causal relationship between this drug and the pathogenesis of colitis probable. The heterogeneous histopathological findings in these two patients, however, do not allow us to draw any definitive conclusions about the mechanism by which leflunomide causes diarrhoea and weight loss in RA patients. We conclude that persistent diarrhoea or weight loss in patients taking leflunomide can be more serious than what is previously reported in the literature. In such cases leflunomide treatment should be stopped and an endoscopic examination of the colon is recommended. Given the long half-life of this drug a washout procedure with cholestyramine should be considered whenever the problem is severe or persistent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Strand V, Cohen S, Schiff M et al, Leflunomide Rheumatoid Arthritis Investigators Group (1999) Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch Intern Med 159:2542–2550

    Article  CAS  PubMed  Google Scholar 

  2. Smolen JS, Kalden JR, Scott DL et al (1999) Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multi-centre trial. Lancet 353:259–266

    Article  CAS  PubMed  Google Scholar 

  3. Emery P, Breedveld FC, Lemmel EM et al, Multinational Leflunomide Study Group (2000) A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology 39:655–665

    Article  CAS  PubMed  Google Scholar 

  4. Kremer JM, Genovese MC, Cannon GW, Caldwell RJ, Cush JJ, Furst DE et al (2002) Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. Ann Intern Med 137:716–733

    Article  Google Scholar 

  5. Larsen A, Kvien TK, Schattenkirchner, Rau R, Scott DL et al, European Leflunomide Study Group (2001) Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine. Scand J Rheumatol 30:135–142

    Article  CAS  PubMed  Google Scholar 

  6. Mladenovic V, Domljan Z, Rozman B et al (1995) Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomised, placebo-controlled, phase II study. Arthritis Rheum 38:1595–1603

    Article  CAS  PubMed  Google Scholar 

  7. Coblyn JS, Shadick N, Helfgott S (2001) Leflunomide-associated weight loss in rheumatoid arthritis. Arthritis Rheum 44:1048–1051

    Article  CAS  PubMed  Google Scholar 

  8. Kalden JR, Schattenkirchner M, Sörensen H et al (2003) The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a five-year follow-up study. Arthritis Rheum 48:1513–1520

    Article  CAS  PubMed  Google Scholar 

  9. Maes B, Dalle I, Geboes K et al (2003) Erosive enterocolitis in mycophenolate mofetil-treated renal-transplant recipients with persistent afebrile diarrhea. Transplantation 75:665–672

    Article  CAS  PubMed  Google Scholar 

  10. Hammer B (1994) Current developments in the diagnosis and therapy of Crohn disease and ulcerative colitis. Schweiz Med Wochenschr 124:452–460

    CAS  PubMed  Google Scholar 

  11. Davies NM, Can PD (1995) Toxicity of NSAIDs in the large intestine. Dis Colon Rectum 38:1311–1321

    Article  CAS  PubMed  Google Scholar 

  12. Wilcox GM, Mattia A (2002) Collagenous colitis associated with lansoprazole. J Clin Gastroenterol 34:164–166

    Article  PubMed  Google Scholar 

  13. Fernandez-Banares F, Salas A, Esteve M et al (2003) Collagenous and lymphocytic colitis. Evaluation of clinical and histological features, response to treatment, and long-term follow-up. Am J Gastroenterol 98:340–347

    Article  PubMed  Google Scholar 

  14. Püspök A, Kiener HP et al (2000) Clinical, endoscopic and histologic spectrum of nonsteroidal anti-inflammatory drug-induced lesions in the colon. Dis Colon Rectum 43:685–691

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Dr. G. Jacomen, A.Z. St-Maarten, campus Duffel Rooienberg 25 2570 Duffel and Dr. L. Cappelle, CAZ MIDDEN Limburg vzw campus Salvator Salvatorstraat 20 3500 Hasselt for their cooperation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. Verschueren.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Verschueren, P., Vandooren, A. & Westhovens, R. Debilitating diarrhoea and weight loss due to colitis in two RA patients treated with leflunomide. Clin Rheumatol 24, 87–90 (2005). https://doi.org/10.1007/s10067-004-1033-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-004-1033-1

Keywords

Navigation