Histopathological Features of Methotrexate Induced Pulmonary Lesions in Rheumatoid Arthritis Patients: A Systematic Review of Case Reports
DOI:
https://doi.org/10.3889/oamjms.2017.049Keywords:
Methotrexate, Pulmonary, Histopathology, Rheumatoid arthritis, Case reportsAbstract
BACKGROUND: Methotrexate (MTX) is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA); however, it causes many side effects, including pulmonary lesions. In this review, we characterised the histopathological features of MTX-induced pulmonary lesions in RA patients.
AIM: We carried out an electronic search of the relevant literature published during the period from 1990 to 2016. We included only the cases with definitive histo-pathological findings caused by MTX therapy.
MATERIAL AND METHODS: The total number of cases is 27. Male: female ratio was 1:3, and ages ranged from 48 to 87 years old, with a mean (SD) = 65.7 (1.0). The cases were originally from Asia (55%), Europe (41%), and America (4%). The major complications of methotrexate therapy were lymphoproliferative disorders (42%) followed by interstitial fibrosis (33), and infections (25%). The incidence of these complications significantly increases with the duration of MTX treatment (p = 0.044). Among the infections, the most common causative organism was pneumocystis jiroveci. The majority of patients who developed infections following methotrexate therapy were from Europe whereas the majority of those who developed lymphoproliferative disorders were from Asia (p = 0.003).
CONCLUSION: In conclusion, methotrexate therapy in rheumatoid arthritis patients causes different types pulmonary complications.Downloads
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Bilgici A, Ulusoy H, Kuru O, Celenk C, Unsa M, and Danaci M. Pulmonary involvement in rheumatoid arthritis. Rheumatol Int. 2005;25: 429-435. https://doi.org/10.1007/s00296-004-0472-y PMid:16133582
Corcoran JP, Ahmad M, Mukherjee R, et al. Pleuro-pulmonary complications of rheumatoid arthritis. Respir Care. 2014;59: e55–e59. https://doi.org/10.4187/respcare.02597 PMid:23962501
Ortendahl M, Holmes T, Schettler JD, and Fries JF. The methotrexate therapeutic response in rheumatoid arthritis. http://aramis.stanford.edu/downloads/MTX_Orten.pdf Accessed 2nd November 2015.
Cornstein, B. Low dose methotrexate: A mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev. 2005;57:163–172. https://doi.org/10.1124/pr.57.2.3 PMid:15914465
Provenzano G. Chronic pulmonary toxicity of methotrexate and rheumatoid arthritis. Rheumatology. 2003;42:802–803. https://doi.org/10.1093/rheumatology/keg188 PMid:12771440
Saravanan V, Kelly C. Drug-related pulmonary problems in patients with rheumatoid arthritis. Rheumatology (Oxford). 2006;45:787. https://doi.org/10.1093/rheumatology/kel075 PMid:16527879
Amital H, Arnson Y, Chodick G, Shalev V. Hepatotoxicity rates do not differ in patients with rheumatoid arthritis and psoriasis treated with methotrexate. Rheumatology. 2009;48:1107–1110. https://doi.org/10.1093/rheumatology/kep176 PMid:19578136
Kremer JM, Alarcon GS, Weinblatt ME et al. Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. Arthritis Rheum. 1997;40(10):1829–37. https://doi.org/10.1002/art.1780401016 PMid:9336418
Cho I, Mori S, Imamura F, Kiyofuji C, Sugimoto M. Methotrexate pneumonia lacking dyspnea and radiographic interstitial patterns during treatment for early rheumatoid arthritis: bronchoalveolar lavage and transbronchial lung biopsy in a differential diagnosis. Mod Rheumatol. 2007;17(3):256-261. https://doi.org/10.3109/s10165-007-0578-7 PMid:17564786
Romagnoli M, Bigliazzi C, Casoni G, et al. The role of transbronchial lung biopsy for the diagnosis of diffuse drug-induced lung disease: a case series of 44 patients. Sarcoidosis Vasc Diffuse Lung Dis. 2008;25:36–45. PMid:19070259
Padley SP, Adler B, Hansell DM, Muller NL. High-resolution computed tomography of drug- induced lung disease. Clin Radiol. 1992;46:232–6. https://doi.org/10.1016/S0009-9260(05)80161-8
Cornelissen JJ, Bakker LJ, Van der Veen MJ, Rozenberg-Arska M, Bijlsma JW. Nocardia asteroides pneumonia complicating low dose methotrexate treatment of refractory rheumatoid arthritis. Ann Rheum Dis. 1991;50(9):642-644. https://doi.org/10.1136/ard.50.9.642 PMid:1929588 PMCid:PMC1004510
Hilliquin P, Menkes CJ. Lung diseases and treatment with methotrexate in rheumatoid arthritis. Rev Pneumol Clin. 1991;47(4):179-182. PMid:1775874
Wollner A, Mohle-Boetani J, Lambert RE, Perruquet JL, Raffin TA, McGuire JL. Pneumocystis carinii pneumonia complicating low dose methotrexate treatment for rheumatoid arthritis. Thorax. 1991;46(3):205-207. https://doi.org/10.1136/thx.46.3.205 PMid:2028435 PMCid:PMC463037
Okuda Y, Oyama T, Oyama H, Miyamoto T, Takasugi K. Pneumocystis carinii pneumonia associated with low dose methotrexate treatment for malignant rheumatoid arthritis. Ryumachi. 1995;35(4):699-704. PMid:7482069
Roux N, Flipo RM, Cortet B, et al. Pneumocystis carinii pneumonia in rheumatoid arthritis patients treated with methotrexate. A report of two cases. Rev Rhum Engl Ed. 1996;63(6):453-456. PMid:8817757
Schnabel A, Richter C, Bauerfeind S, Gross WL. Bronchoalveolar lavage cell profile in methotrexate induced pneumonitis. Thorax. 1997;52(4):377-379. https://doi.org/10.1136/thx.52.4.377 PMid:9196524 PMCid:PMC1758545
Ebeo CT, Girish MR, Byrd RP, Roy TM, Mehta JB. Methotrexate-induced pulmonary lymphoma. Chest. 2003;123(6):2150-2153. https://doi.org/10.1378/chest.123.6.2150 PMid:12796204
Hsu P-C, Lan J-L, Hsieh T-Y, Jan Y-J, Huang W-N. Methotrexate pneumonitis in a patient with rheumatoid arthritis. J Microbiol Immunol Infect. 2003;36(2):137-140. PMid:12886966
Shimada T, Nishimura Y, Funada Y, et al. A case of pneumocystis carinii pneumonia associated with low dose methotrexate treatment for rheumatoid arthritis and trimethoprim- sulphamethoxazole induced pancytopenia. Arerugi. 2004;53(6):575-581. PMid:15247519
Kameda H, Okuyama A, Tamaru J-I, Itoyama S, Iizuka A, Takeuchi T. Lymphomatoid granulomatosis and diffuse alveolar damage associated with methotrexate therapy in a patient with rheumatoid arthritis. Clin Rheumatol. 2007;26(9):1585-1589. https://doi.org/10.1007/s10067-006-0480-2 PMid:17200802
Shimada K, Matsui T, Kawakami M, et al. Methotrexateâ€related lymphomatoid granulomatosis: a case report of spontaneous regression of large tumours in multiple organs after cessation of methotrexate therapy in rheumatoid arthritis. Scand J Rheumatol. 2007;36(1):64-67. https://doi.org/10.1080/03009740600902403 PMid:17454938
Minagawa S, Takayanagi N, Hara K, et al. A case of rheumatoid arthritis complicated with methotrexate-induced pneumonitis and pneumocystis pneumonia. zasshi = J Japanese Respir Soc. 2008;46(3):237-242.
Inaba M, Ushijim S, Hirata N, Saisyoji T, Kitaoka M, Yoshinaga T. Methotrexate-related lymphomatoid granulomatosis in a patient with rheumatoid arthritis. Nihon zasshi = J Japanese Respir Soc. 2011;49(8):597-601.
Kudoh M, Harada H, Matsumoto K, Sato Y, Omura K, Ishii Y. Methotrexate-associated lymphoproliferative disorder arising in the retromolar triangle and lung of a patient with rheumatoid arthritis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;118(4):e105-e110. https://doi.org/10.1016/j.oooo.2014.02.029 PMid:24811204
Sakai T, Tamura S, Miyoshi T, Nesumi N, Nagai K, Oshima K. Development of myeloid sarcoma after long-term methotrexate use for rheumatoid arthritis. Int J Hematol. 2014;99(4):493-498. https://doi.org/10.1007/s12185-014-1506-1 PMid:24504437
Tokuyama K, Okada F, Matsumoto S, et al. EBV-positive MTX-diffuse large B cell lymphoma in a rheumatoid arthritis patient. Jpn J Radiol. 2014;32(3):183-187. https://doi.org/10.1007/s11604-013-0280-y PMid:24408079
Yamakawa H, Yoshida M, Katagi H, et al. Pulmonary and retroperitoneal lesions induced by methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthritis. Mod Rheumatol. 2014;1(4). https://doi.org/10.3109/14397595.2014.898559
Tajima S, Takanashi Y, Koda K, Fukayama M. Methotrexate-associated lymphoproliferative disorder presenting as extranodal NK/T-cell lymphoma arising in the lungs. Pathol Int. 2015;65(12):661-665. https://doi.org/10.1111/pin.12346 PMid:26459854
Akiyama N, Toyoshima M, Kono M, Nakamnuva Y, Funai K, and Suda T. Methotrexate induced accelerated pulmonary nodulosis. Am J Respi Crit Care Med. 2015;192(20;252-253.
Koji H, Yazawa T, Nakabayashi K, Fujioka Y, Kamma H, Yamada A. CD8-positive T-cell lymphoproliferative disorder associated with Epstein-Barr virus-infected B-cells in a rheumatoid arthritis patient under methotrexate treatment. Mod Rheumatol. 2016;26(2):271-275. PMid:24386983
Furst DE. The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases. British Journal of Rheumatology. 1997;36: 1196-1204. https://doi.org/10.1093/rheumatology/36.11.1196 PMid:9402864
Balk RA. Methotrexate induced lung injury. Wolters Kluwer, 2016.
Imokawa S, Colby TV, Leslie KO, and Helmers RA. Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. Eur Respir. 2000;15: 373-381. https://doi.org/10.1034/j.1399-3003.2000.15b25.x
Gaulard P, Swerdlow SH, Harris L, Jaffe ES, Sundstrom C. Other iatrogenic immunodeficiency-associated lymphoproliferative disorders. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edn. Lyon: IARC Press, 2008; 350–51.
Bajraktari IH, Teuta BC, Vjollca SM, Bajraktari H, Krasniqi VSB, Muslimi F. Demographic Features of Patients with Rheumatoid Arthritis in Kosovo. Med Arch. 2014;68(6): 407–410. https://doi.org/10.5455/medarh.2014.68.407-410 PMid:25649180 PMCid:PMC4314179
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