Pulmonary Nodulosis Associated with Leflunomide Therapy in Rheumatoid Arthritis: Report of Four Cases and Review of the Literature

Abstract

Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterized by destructive synovitis and systemic extra-articular involvement. Leflunomide is a disease-modifying anti-rheumatic drug with anti-inflammatory and antiproliferative features. Leflunomide is an isoxazole immunomodulatory agent, which inhibits dihydroorotate dehydrogenase enzyme involved in de novo pyrimidine synthesis. It was shown that leflunomide can reduce signs and symptoms of rheumatoid arthritis (RA) with regression in structural damage. Pulmonary involvement is one of the extra-articular manifestations of rheumatoid arthritis and it can occur due to either disease itself or medications used in the treatment. We presented 4 cases with rheumatoid arthritis which developed pulmonary nodules with leflunomide therapy and reviewed literature. J Clin Exp Invest 2016; 7 (1): 98-102

Keywords

• Rheumatoid arthritis,leflunomide,pulmonary nodule

Kaynakça

1. 1. Atzeni F, Boiardi L, Salli S, et al. Lung involvement and drug-induced lung disease in patients with rheumatoid arthritis. Expert Rev Clin Immunol 2013;9:649-657.
2. 2. Kim SH, Yoo WH. Recurrent pneumothorax associated with pulmonary nodules after leflunomide theraphy in rheumatoid arthritis: a case report and review of the literature. Rheumatol Int 2011;31:919-922.
3. 3. Olsen NJ, Stein CM. New drugs for rheumatoid arthritis. N Engl J Med. 2004;350:2167-2179.
4. 4. Cannon GW, Kremer JM. Leflunomide. Rheum Dis Clin North Am 2004;30:295-309.
5. 5. McCurry J. Japan deaths spark concerns over arthritis drug. Lancet. 2004;363:461.
6. 6. Cannon GW, Strand V, Simon LS, et al. Interstitial lung disease in rheumatoid arthritis patients receiving leflunomide. Arthritis Rheum 2004;50:S561.
7. 7. Kalden JR, Schattenkirchner M, Sorensen H et al. The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a five-year follow-up study. Arthritis Rheum 2003;48:1513-1520.
8. 8. Braun MG, Van Rhee R, Becker-Cpeller D. Development and/or increase of rheumatoid nodules in RA patients following leflunomide therapy. Z Rheumatol 2003;63:84-87.

9. 9. Rozin A, Yigla M, Guralnik L, et al. Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy. Clin Rheumatol 2006;25:384-388.
10. 10. Horvath IF, Szanto A, Csiki Z, et al. Intrapulmonary rheumatoid nodules in a patient with long-standing rheumatoid arthritis treated with leflunomide. Pathol Oncol Res 2008;14:101-104.
11. 11. Watson P, Simler N, Screaton N, et al. Management of accelerated pulmonary nodulosis following etanercept therapy in a patient with rheumatoid arthritis. Rheumatology (Oxford) 2008;47:928-929
12. 12. van Ede A, den Broeder A, Wagenaar M, et al. Etanerceptrelated extensive pulmonary nodulosis in a patient with rheumatoid arthritis. J Rheumatol 2007;34:1590-1592
13. 13. Mackley CL, Ostrov BE, Ioffreda MD. Accelerated cutaneous nodulosis during infliximab therapy in a patient with rheumatoid arthritis. J Clin Rheumatol 2004;10:336-338
14. 14. Nannini C, Ryu JH, Matteson EL. Lung disease in rheumatoid arthritis. Curr Opin Rheumatol 2008;20:340-346.
15. 15. Adelman HM, Dupont EL, Flannery MT, et al. Case report: recurrent pneumothorax in a patient with rheumatoid arthritis. Am J Med Sci 1994;308:171-172.
16. 16. Yousem SA, Colby TV, Carrington CB. Lung biopsy in rheumatoid arthritis. Am Rev Respir Dis 1985;131:770- 777.
17. 17. Hindle W, Yates DA. Pyopneumothorax complicating rheumatoid lung disease. Ann Rheum Dis 1965;24:57-60.
18. 18. Ju JH, Kim SI, Lee JH, et al. Risk of interstitial lung disease associated with leflunomide treatment in Korean patients with rheumatoid arthritis. Arthritis Rheum 2007;56:2094- 2096.
19. 19. Sawada T, Inokuma S, Sato T, et al. Study committee for leflunomide-induced lung injury, Japan College of Rheumatology. Leflunomide-induced interstitial lung disease: prevelance and risk factors in Japanese patients with rheumatoid arthritis. Rheumatology (Oxford) 2009;48:1069- 1072.
20. 20. Yoshikawa GT, Dias GA, Fujihara S, et al. Formation of multiple pulmonary nodules during treatment with leflunomide. J Bras Pneumol 2015;41:281-284.
21. 21. Merril JT, Cronstein BN, Shen C. Reversal of new but not old rheumatoid nodules by colchicine: Evidence from an invitro model and case reports of patients (abstract-7) Arthritis Rheum (suppl) 1996:84.