Abstract
A 60-year-old rheumatoid arthritis (RA) female with lung fibrosis was treated with leflunomide (LEF) for only 12 days, and responded well. Twenty-five days after the withdrawal of the drug, she had fever, dyspnea, and an elevated serum C-reactive protein level. Chest CT revealed ground-glass opacities (GGOs) and consolidations forming a mosaic pattern, in lung fields including the upper, anterior and central areas, and honeycomb patterns in the lung bases and backs. The level of plasma A771726, an active metabolite of LEF, was still as high as that usually noted under LEF therapy. After pulsed steroid and cholestyramine administration, A771726 was depleted and she recovered. The peripheral blood lymphocyte count that had been approximately 1,000/μL, decreased to 220/μL just at the onset of lung injury, and rapidly and steadily returned to the preinjury level preceding recovery from the injury. Serum albumin level decreased in association with lung injury, and gradually returned to the preinjury level. Special caution is necessary when prescribing leflunomide to elderly patients with preexisting interstitial lung disease, and remains necessary until at least 1 month after its withdrawal.
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Nanke Y, Kotake S, Akama H, Tomii M, Kamatani N. Pancytopenia and colitis with Clostridium difficile in a rheumatoid arthritis patient taking methotrexate, antibiotics and non-steroidal anti-inflammatory drugs. Clin Rheumatol 2001;20(1):73–5.
Nanke Y, Yamada T, Kamatani N. Asymptomatic interstitial pneumonitis induced by bucillamine in a patient with rheumatoid arthritis. Mod Rheumatol 2005;15(5):381–2.
Kamata Y, Nara H, Kamimura T, Haneda K, Iwamoto M, Masuyama J, et al. Rheumatoid arthritis complicated with acute interstitial pneumonia induced by leflunomide as an adverse reaction. Intern Med 2004;43:1201–4.
Takeishi M, Akiyama Y, Akiba H, Adachi D, Hirano M, Mimura T. Leflunomide induced acute interstitial pneumonia. J Rheumatol 2005;32:1160–3.
Hirabayashi Y, Shimizu H, Kobayashi N, Kudo K. Leflunomide-induced pneumonitis in a patient with rheumatoid arthritis. Intern Med 2006;45:689–91.
Vallbracht II, Popper HH, Rieber J, Nowak F, Gallenberger S, Piper B, et al. Lethal pneumonitis under leflunomide therapy. Rheumatology (Oxford) 2005;44:1580–1.
Sato T, Sawada T, Inokuma S, Sagawa A, Matsuda T, Otsuka T, et al. Analysis of predictive factors for prognosis in Japanese patients with rheumatoid arthritis complicated with leflunomide-induced lung injury. Proceedings of 50th Annual Meeting of Japanese Society of Rheumatology 2006;16:88.
Strand V, Cohen S, Schiff M, Weaver A, Fleischmann R, Cannon G, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med 1999;159:2542–50.
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-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet 1999;353:259–66.
Prakash A, Jarvis B. Leflunomide—a review of its use in active rheumatoid arthritis. Drugs 1999;58:1137–64.
Manna SK, Aggarwal BB. Immunosuppressive leflunomide metabolite (A771726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. J Immunol 1999;162:2095–102.
Elkayam O, Yaron I, Shirazi I, Judovitch R, Caspi D, Yaron M. Active leflunomide metabolite inhibits interleukin 1beta, tumour necrosis factor alpha, nitric oxide, and metalloproteinase-3 production in activated human synovial tissue cultures. Ann Rheum Dis 2003;62:440–3.
Sawada T, Inokuma S, Sagawa A, Matsuda T, Otsuka T, Saeki Y, et al. Leflunomide-associated interstitial pneumonitis: overview of up-to-date occurrence, and analysis on clinical manifestations. Proceedings of 50th Annual Meeting of Japanese Society of Rheumatology 2006;16:88.
Ochi S, Harigai M, Mizoguchi F, Iwai H, Hagiyama H, Oka T, Miyasaka N. Leflunomide-related acute interstitial pneumonia in two patients with rheumatoid arthritis: autopsy findings with a mosaic pattern of acute and organizing diffuse alveolar damage. Mod Rheumatol 2006;16(5):316–20.
Inokuma S, Kono H, Kohno Y, Hiramatsu K, Ito K, Shiratori K, et al. Methotrexate-induced lung injury in patients with rheumatoid arthritis occurs with peripheral blood lymphocyte count decrease. Ann Rheum Dis 2006;65:1113–4.
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Otsuka, T., Koyama, T., Ohtani, R. et al. Leflunomide-induced lung injury that developed after its withdrawal, coinciding with peripheral blood lymphocyte count decrease. Mod Rheumatol 18, 96–99 (2008). https://doi.org/10.1007/s10165-007-0014-z
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DOI: https://doi.org/10.1007/s10165-007-0014-z