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Erschienen in: Cardiovascular Toxicology 2/2012

01.06.2012 | Case Report

Leflunomide-Induced Pulmonary Hypertension in a Young Woman with Rheumatoid Arthritis: A Case Report

verfasst von: Paulino A. Alvarez, Ariel K. Saad, Santiago Flagel, Octavio Mazzocchi, Manuel Vazquez Blanco

Erschienen in: Cardiovascular Toxicology | Ausgabe 2/2012

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Abstract

Leflunomide, a disease-modifying antirheumatic drug, has been shown to be effective in the management of rheumatoid arthritis (RA). Among other side effects, systemic hypertension has been described, and also a case of possible pulmonary hypertension (PH) has been reported. Symptomatic PH in RA is rare. We present a 28-year-old woman with a history of RA who consulted our hospital because of severe symptomatic pulmonary hypertension. Two years before admission, she was started on leflunomide. Due to previous evidence of the association of leflunomide with pulmonary hypertension, the drug was stopped. The patient became asymptomatic with normal pulmonary arterial pressure within a year. Given the poor prognosis of idiopathic pulmonary arterial hypertension, the recognition of potentially reversible causes is crucial. Until further evidence is available in a patient who develops pulmonary arterial hypertension, stopping leflunomide should be considered.
Literatur
1.
Zurück zum Zitat Rozman, B., Praprotnik, S., Logar, D., Tomsic, M., Hojnik, M., Kos-Golja, M., et al. (2002). Leflunomide and hypertension. Annals of the Rheumatic Diseases, 61, 567–569.PubMedCrossRef Rozman, B., Praprotnik, S., Logar, D., Tomsic, M., Hojnik, M., Kos-Golja, M., et al. (2002). Leflunomide and hypertension. Annals of the Rheumatic Diseases, 61, 567–569.PubMedCrossRef
2.
Zurück zum Zitat Martinez-Taboada, V. M., Rodriguez-Valverde, V., Gonzalez-Vilchez, F., & Armijo, J. A. (2004). Pulmonary hypertension in a patient with rheumatoid arthritis treated with leflunomide. Rheumatology (Oxford), 43, 1451–1453.CrossRef Martinez-Taboada, V. M., Rodriguez-Valverde, V., Gonzalez-Vilchez, F., & Armijo, J. A. (2004). Pulmonary hypertension in a patient with rheumatoid arthritis treated with leflunomide. Rheumatology (Oxford), 43, 1451–1453.CrossRef
3.
Zurück zum Zitat Condliffe, R., Kiely, D. G., Peacock, A. J., Corris, P. A., Gibbs, J. S., Vrapi, F., et al. (2009). Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. American Journal of Respiratory and Critical Care Medicine, 179, 151–157.PubMedCrossRef Condliffe, R., Kiely, D. G., Peacock, A. J., Corris, P. A., Gibbs, J. S., Vrapi, F., et al. (2009). Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. American Journal of Respiratory and Critical Care Medicine, 179, 151–157.PubMedCrossRef
4.
Zurück zum Zitat Hoeper, M. M. (2002). Pulmonary hypertension in collagen vascular disease. European Respiratory Journal, 19, 571–576.PubMedCrossRef Hoeper, M. M. (2002). Pulmonary hypertension in collagen vascular disease. European Respiratory Journal, 19, 571–576.PubMedCrossRef
5.
Zurück zum Zitat McLaughlin, V. V., Archer, S. L., Badesch, D. B., Barst, R. J., Farber, H. W., Lindner, J. R., et al. (2009). Accf/aha 2009 expert consensus document on pulmonary hypertension a report of the American college of cardiology foundation task force on expert consensus documents and the american heart association developed in collaboration with the american college of chest physicians; american thoracic society, inc.; and the pulmonary hypertension association. Journal of the American College of Cardiology, 53, 1573–1619.PubMedCrossRef McLaughlin, V. V., Archer, S. L., Badesch, D. B., Barst, R. J., Farber, H. W., Lindner, J. R., et al. (2009). Accf/aha 2009 expert consensus document on pulmonary hypertension a report of the American college of cardiology foundation task force on expert consensus documents and the american heart association developed in collaboration with the american college of chest physicians; american thoracic society, inc.; and the pulmonary hypertension association. Journal of the American College of Cardiology, 53, 1573–1619.PubMedCrossRef
6.
Zurück zum Zitat Farheen, K., & Agarwal, S. K. (2011). Assessment of disease activity and treatment outcomes in rheumatoid arthritis. Journal of Managed Care Pharmacy, 17, S09–S13.PubMed Farheen, K., & Agarwal, S. K. (2011). Assessment of disease activity and treatment outcomes in rheumatoid arthritis. Journal of Managed Care Pharmacy, 17, S09–S13.PubMed
7.
Zurück zum Zitat Macintyre, N., Crapo, R. O., Viegi, G., Johnson, D. C., van der Grinten, C. P., Brusasco, V., et al. (2005). Standardisation of the single-breath determination of carbon monoxide uptake in the lung. European Respiratory Journal, 26, 720–735.PubMedCrossRef Macintyre, N., Crapo, R. O., Viegi, G., Johnson, D. C., van der Grinten, C. P., Brusasco, V., et al. (2005). Standardisation of the single-breath determination of carbon monoxide uptake in the lung. European Respiratory Journal, 26, 720–735.PubMedCrossRef
8.
Zurück zum Zitat Castro, G. W., Appenzeller, S., Bertolo, M. B., & Costallat, L. T. (2006). Isolated pulmonary hypertension secondary to rheumatoid arthritis. Clinical Rheumatology, 25, 901–903.PubMedCrossRef Castro, G. W., Appenzeller, S., Bertolo, M. B., & Costallat, L. T. (2006). Isolated pulmonary hypertension secondary to rheumatoid arthritis. Clinical Rheumatology, 25, 901–903.PubMedCrossRef
9.
Zurück zum Zitat Macchia, A., Marchioli, R., Marfisi, R., Scarano, M., Levantesi, G., Tavazzi, L., et al. (2007). A meta-analysis of trials of pulmonary hypertension: A clinical condition looking for drugs and research methodology. American Heart Journal, 153, 1037–1047.PubMedCrossRef Macchia, A., Marchioli, R., Marfisi, R., Scarano, M., Levantesi, G., Tavazzi, L., et al. (2007). A meta-analysis of trials of pulmonary hypertension: A clinical condition looking for drugs and research methodology. American Heart Journal, 153, 1037–1047.PubMedCrossRef
10.
Zurück zum Zitat Rubin, L. J., Badesch, D. B., Barst, R. J., Galie, N., Black, C. M., Keogh, A., et al. (2002). Bosentan therapy for pulmonary arterial hypertension. New England Journal of Medicine, 346, 896–903.PubMedCrossRef Rubin, L. J., Badesch, D. B., Barst, R. J., Galie, N., Black, C. M., Keogh, A., et al. (2002). Bosentan therapy for pulmonary arterial hypertension. New England Journal of Medicine, 346, 896–903.PubMedCrossRef
11.
Zurück zum Zitat Galie, N., Ghofrani, H. A., Torbicki, A., Barst, R. J., Rubin, L. J., Badesch, D., et al. (2005). Sildenafil citrate therapy for pulmonary arterial hypertension. New England Journal of Medicine, 353, 2148–2157.PubMedCrossRef Galie, N., Ghofrani, H. A., Torbicki, A., Barst, R. J., Rubin, L. J., Badesch, D., et al. (2005). Sildenafil citrate therapy for pulmonary arterial hypertension. New England Journal of Medicine, 353, 2148–2157.PubMedCrossRef
12.
Zurück zum Zitat Hunter, S., & Robson, S. C. (1992). Adaptation of the maternal heart in pregnancy. British Heart Journal, 68, 540–543.PubMedCrossRef Hunter, S., & Robson, S. C. (1992). Adaptation of the maternal heart in pregnancy. British Heart Journal, 68, 540–543.PubMedCrossRef
13.
Zurück zum Zitat Olsen, N. J., & Stein, C. M. (2004). New drugs for rheumatoid arthritis. New England Journal of Medicine, 350, 2167–2179.PubMedCrossRef Olsen, N. J., & Stein, C. M. (2004). New drugs for rheumatoid arthritis. New England Journal of Medicine, 350, 2167–2179.PubMedCrossRef
14.
Zurück zum Zitat Burger, D., Begue-Pastor, N., Benavent, S., Gruaz, L., Kaufmann, M. T., Chicheportiche, R., et al. (2003). The active metabolite of leflunomide, a77 1726, inhibits the production of prostaglandin e(2), matrix metalloproteinase 1 and interleukin 6 in human fibroblast-like synoviocytes. Rheumatology (Oxford), 42, 89–96.CrossRef Burger, D., Begue-Pastor, N., Benavent, S., Gruaz, L., Kaufmann, M. T., Chicheportiche, R., et al. (2003). The active metabolite of leflunomide, a77 1726, inhibits the production of prostaglandin e(2), matrix metalloproteinase 1 and interleukin 6 in human fibroblast-like synoviocytes. Rheumatology (Oxford), 42, 89–96.CrossRef
15.
Zurück zum Zitat Curnock, A. P., Robson, P. A., Yea, C. M., Moss, D., Gadher, S., Thomson, T. A., et al. (1997). Potencies of leflunomide and hr325 as inhibitors of prostaglandin endoperoxide h synthase-1 and -2: Comparison with nonsteroidal anti-inflammatory drugs. Journal of Pharmacology and Experimental Therapeutics, 282, 339–347.PubMed Curnock, A. P., Robson, P. A., Yea, C. M., Moss, D., Gadher, S., Thomson, T. A., et al. (1997). Potencies of leflunomide and hr325 as inhibitors of prostaglandin endoperoxide h synthase-1 and -2: Comparison with nonsteroidal anti-inflammatory drugs. Journal of Pharmacology and Experimental Therapeutics, 282, 339–347.PubMed
16.
Zurück zum Zitat Das, U. N. (1980). Possible role of prostaglandins in the pathogenesis of pulmonary hypertension. Prostaglandins Med, 4, 163–170.PubMedCrossRef Das, U. N. (1980). Possible role of prostaglandins in the pathogenesis of pulmonary hypertension. Prostaglandins Med, 4, 163–170.PubMedCrossRef
17.
Zurück zum Zitat Stebel, S., & Wideman, R. F. (2008). Pulmonary hemodynamic responses to intravenous prostaglandin e2 in broiler chickens. Poultry Science, 87, 138–145.PubMedCrossRef Stebel, S., & Wideman, R. F. (2008). Pulmonary hemodynamic responses to intravenous prostaglandin e2 in broiler chickens. Poultry Science, 87, 138–145.PubMedCrossRef
18.
Zurück zum Zitat Lundequist, A., Nallamshetty, S. N., Xing, W., Feng, C., Laidlaw T. M., Uematsu, S., Akira, S., Boyce, J. A. (2010). Prostaglandin e(2) exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation. Journal of Immunology, 184, 433–441.CrossRef Lundequist, A., Nallamshetty, S. N., Xing, W., Feng, C., Laidlaw T. M., Uematsu, S., Akira, S., Boyce, J. A. (2010). Prostaglandin e(2) exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation. Journal of Immunology, 184, 433–441.CrossRef
19.
Zurück zum Zitat Fredenburgh, L. E., Liang, O. D., Macias, A. A., Polte, T. R., Liu, X., Riascos, D. F., et al. (2008). Absence of cyclooxygenase-2 exacerbates hypoxia-induced pulmonary hypertension and enhances contractility of vascular smooth muscle cells. Circulation, 117, 2114–2122.PubMedCrossRef Fredenburgh, L. E., Liang, O. D., Macias, A. A., Polte, T. R., Liu, X., Riascos, D. F., et al. (2008). Absence of cyclooxygenase-2 exacerbates hypoxia-induced pulmonary hypertension and enhances contractility of vascular smooth muscle cells. Circulation, 117, 2114–2122.PubMedCrossRef
20.
Zurück zum Zitat Chung, L., Liu, J., Parsons, L., Hassoun, P. M., McGoon, M., Badesch, D. B., et al. (2010). Characterization of connective tissue disease-associated pulmonary arterial hypertension from reveal: Identifying systemic sclerosis as a unique phenotype. Chest, 138, 1383–1394.PubMedCrossRef Chung, L., Liu, J., Parsons, L., Hassoun, P. M., McGoon, M., Badesch, D. B., et al. (2010). Characterization of connective tissue disease-associated pulmonary arterial hypertension from reveal: Identifying systemic sclerosis as a unique phenotype. Chest, 138, 1383–1394.PubMedCrossRef
21.
Zurück zum Zitat Mukerjee, D., St George, D., Knight, C., Davar, J., Wells, A. U., Du Bois, R. M., et al. (2004). Echocardiography and pulmonary function as screening tests for pulmonary arterial hypertension in systemic sclerosis. Rheumatology (Oxford), 43, 461–466.CrossRef Mukerjee, D., St George, D., Knight, C., Davar, J., Wells, A. U., Du Bois, R. M., et al. (2004). Echocardiography and pulmonary function as screening tests for pulmonary arterial hypertension in systemic sclerosis. Rheumatology (Oxford), 43, 461–466.CrossRef
22.
Zurück zum Zitat Nebeker, J. R., Barach, P., & Samore, M. H. (2004). Clarifying adverse drug events: A clinician’s guide to terminology, documentation, and reporting. Annals of Internal Medicine, 140, 795–801.PubMed Nebeker, J. R., Barach, P., & Samore, M. H. (2004). Clarifying adverse drug events: A clinician’s guide to terminology, documentation, and reporting. Annals of Internal Medicine, 140, 795–801.PubMed
23.
Zurück zum Zitat Kay, J. M., Smith, P., & Heath, D. (1971). Aminorex and the pulmonary circulation. Thorax, 26, 262–270.PubMedCrossRef Kay, J. M., Smith, P., & Heath, D. (1971). Aminorex and the pulmonary circulation. Thorax, 26, 262–270.PubMedCrossRef
24.
Zurück zum Zitat Rich, S., Rubin, L., Walker, A. M., Schneeweiss, S., & Abenhaim, L. (2000). Anorexigens and pulmonary hypertension in the United States: Results from the surveillance of North American pulmonary hypertension. Chest, 117, 870–874.PubMedCrossRef Rich, S., Rubin, L., Walker, A. M., Schneeweiss, S., & Abenhaim, L. (2000). Anorexigens and pulmonary hypertension in the United States: Results from the surveillance of North American pulmonary hypertension. Chest, 117, 870–874.PubMedCrossRef
25.
Zurück zum Zitat D’Alonzo, G. E., Barst, R. J., Ayres, S. M., Bergofsky, E. H., Brundage, B. H., Detre, K. M., et al. (1991). Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Annals of Internal Medicine, 115, 343–349.PubMed D’Alonzo, G. E., Barst, R. J., Ayres, S. M., Bergofsky, E. H., Brundage, B. H., Detre, K. M., et al. (1991). Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Annals of Internal Medicine, 115, 343–349.PubMed
Metadaten
Titel
Leflunomide-Induced Pulmonary Hypertension in a Young Woman with Rheumatoid Arthritis: A Case Report
verfasst von
Paulino A. Alvarez
Ariel K. Saad
Santiago Flagel
Octavio Mazzocchi
Manuel Vazquez Blanco
Publikationsdatum
01.06.2012
Verlag
Humana Press Inc
Erschienen in
Cardiovascular Toxicology / Ausgabe 2/2012
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-012-9153-3

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