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A Case of Interstitial Pneumonitis Caused by Leflunomide  

Lee, Jung Hwa (Hallym University College of Medicine, Department of Internal Medicine)
Cheon, Won Seok (Hallym University College of Medicine, Department of Internal Medicine)
Seo, Young Il (Hallym University College of Medicine, Department of Internal Medicine)
Eom, Kwang-Seok (Hallym University College of Medicine, Department of Internal Medicine)
Jang, Seung Hun (Hallym University College of Medicine, Department of Internal Medicine)
Bahn, Joon-Woo (Hallym University College of Medicine, Department of Internal Medicine)
Kim, Dong-Gyu (Hallym University College of Medicine, Department of Internal Medicine)
Jung, Ki-Suck (Hallym University College of Medicine, Department of Internal Medicine)
Publication Information
Tuberculosis and Respiratory Diseases / v.58, no.1, 2005 , pp. 83-88 More about this Journal
Abstract
Leflunomide is a new disease modifying anti rheumatic drug (DMARD) for the treatment of active rheumatoid arthritis. Its mechanism of action differs from other DMARDs in that it inhibits the de novo pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase and therefore prevents the proliferation of activated lymphocytes. As it has been prescribed worldwide, there is a great deal of much concerns regarding its potential adverse effects. Because leflunomide has an active metabolite with a long elimination half-life of approximately 2 weeks, serious adverse reactions may occur even after the leflunomide treatment has been stopped. The profile of serious reactions includes liver dysfunction, hematological disorders, severe skin reactions and respiratory dysfunction. Respiratory dysfunctions with leflunomide therapy are very rare and its incidence is lower than that of methotrexate therapy. However, there are reports in Japan showing that 5 patients died of interstitial pneumonitis and another 11 patients developed serious lung complications associated with leflunomide. This suggests the possibility of fatal respiratory toxicity of leflunomide. There are no reports of interstitial pneumonitis associated with leflunomide in Korea. We report a case of a 62-year old woman who developed interstitial pneumonitis, which might have been induced by leflunomide during the treatment of rheumatoid arthritis.
Keywords
Leflunomide; Interstitial pneumonitis; Rheumatoid arthritis; Methotrexate;
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1 Silva HT, Morris RE. Leflunomide and malononitrilamides. Am J Med Sci 1997;313:289-301   DOI   ScienceOn
2 Smolen JS, Kalden JR, Scott DL, Rozman B, Kvien TK, Larsen A, et al. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blinded, randomised, multicenter trial. Lancet 1999;353:259-66   DOI   PUBMED   ScienceOn
3 Shadick NA, Fanta CH, Weinblatt M, O'Donnell W, Coblyn JS. Bronchiectasis: a late feature of severe rheumatoid arthritis. Medicine 1994;73:161-70   DOI   ScienceOn
4 Linke SP, Clarkin KC, di Leonardo A, Tsou A, Wahl GM. A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev 1996;10:934-47   DOI   ScienceOn
5 Adverse Drug Reactions Advisory Committee (ADRAC). Leflunomide: serious hepatic, blood, skin and respiratory reactions. Aust Adv Drug React Bull 2001;20:7
6 Charatan F. Arthritis drug should be removed from market, says consumer group. BMJ 2002;324:869   DOI   PUBMED   ScienceOn
7 Lili LS, Mano M. Leflunomide(Arava): hematologic, hepatic and respiratory reactions. Can Adv React Newsletter 2002;12:2-3
8 McCurry J. Japan deaths spark concerns over arthritis drug. Lancet 2004;363:461
9 Imokawa S, Colby TV, Lesilie KO, Helmers RA. Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. Eur Respir J 2000;15:373-81   DOI   ScienceOn
10 Williamson RA, Yea CM, Robson PA, Curnock AP, Gadher S, Hambleton AB, et al. Dihydroorotate dehydrogenase is a target for the biological effects of leflunomide. Transplant Proc 1996;28:3088-91
11 Strand V, Cohen S, Schiff M, Weaver A, Fleischmann R, Cannon G, et al. Treatment of active rheumatoid arthritis with leflunomide compared to placebo and methotrexate. Arch Intern Med 1999;159:2542-50   DOI   ScienceOn
12 Kim JY, Kim WU, Kim SI, Yoo WH, Park SH, Hong YS, et al. A case of methotrexate-associated interstitial pneumonitis in rheumatoid arthritis. J Korean Rheum Assoc 1998;5:126-32
13 Rozman B. Clinical experience with leflunomide in rheumatoid arthritis. J Rheumatol Suppl 1998;53:27-32
14 Suh HJ, Park EH, Chung MP, Shin SC, Jeon KM, Yu CM, et al. A case of hypersensitivity pneumonitis caused by methotrexate. Tuberc Respir Dis 2004;56:203-9   DOI