Leflunomide에 의한 약물유발 간질성 폐렴 1예

A Case of Interstitial Pneumonitis Caused by Leflunomide

  • 이정화 (한림대학교 의과대학 내과학교실) ;
  • 천원석 (한림대학교 의과대학 내과학교실) ;
  • 서영일 (한림대학교 의과대학 내과학교실) ;
  • 엄광석 (한림대학교 의과대학 내과학교실) ;
  • 장승훈 (한림대학교 의과대학 내과학교실) ;
  • 반준우 (한림대학교 의과대학 내과학교실) ;
  • 김동규 (한림대학교 의과대학 내과학교실) ;
  • 정기석 (한림대학교 의과대학 내과학교실)
  • 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)
  • 투고 : 2004.11.05
  • 심사 : 2004.12.15
  • 발행 : 2005.01.30

초록

Leflunomide는 최근에 개발된 항류마티스 약물로서 기존의 약물과 작용기전이 다르면서 효과가 우수하여 활동성 류마티스관절염에 널리 사용되고 있다. 알려진 부작용에는 간독성과 피부독성, 조혈기능부전, 위장관계 증상등이 있는데, 시판후 조사에서는 호흡기계 부작용도 드물지만 경한 정도에서 치명적인 경우까지 모두 보고 되었다. 세계 각 처에서의 시판후 조사에 의하면 호흡기계 부작용으로 사망한 경우가 있어서 심각한 폐독성의 가능성을 시사한다. 우리나라에서는 leflunomide로 인한 호흡기계 부작용에 대한 보고가 없었다. 저자들은 leflunomide에 의한 간질성 폐렴 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다.

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.

키워드

참고문헌

  1. 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
  2. McCurry J. Japan deaths spark concerns over arthritis drug. Lancet 2004;363:461
  3. 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 https://doi.org/10.1101/gad.10.8.934
  4. Silva HT, Morris RE. Leflunomide and malononitrilamides. Am J Med Sci 1997;313:289-301 https://doi.org/10.1097/00000441-199705000-00008
  5. Charatan F. Arthritis drug should be removed from market, says consumer group. BMJ 2002;324:869 https://doi.org/10.1136/bmj.324.7342.869
  6. Rozman B. Clinical experience with leflunomide in rheumatoid arthritis. J Rheumatol Suppl 1998;53:27-32
  7. 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 https://doi.org/10.1001/archinte.159.21.2542
  8. 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 https://doi.org/10.1016/S0140-6736(98)09403-3
  9. Adverse Drug Reactions Advisory Committee (ADRAC). Leflunomide: serious hepatic, blood, skin and respiratory reactions. Aust Adv Drug React Bull 2001;20:7
  10. Lili LS, Mano M. Leflunomide(Arava): hematologic, hepatic and respiratory reactions. Can Adv React Newsletter 2002;12:2-3
  11. Shadick NA, Fanta CH, Weinblatt M, O'Donnell W, Coblyn JS. Bronchiectasis: a late feature of severe rheumatoid arthritis. Medicine 1994;73:161-70 https://doi.org/10.1097/00005792-199405000-00005
  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. 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 https://doi.org/10.1034/j.1399-3003.2000.15b25.x
  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 https://doi.org/10.4046/trd.2004.56.2.203