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Joint Bone Spine
Volume 85, n° 6
pages 761-763 (décembre 2018)
Doi : 10.1016/j.jbspin.2017.12.014
Received : 6 September 2017 ;  accepted : 20 December 2017
Case report

Pulmonary arterial hypertension in four patients treated by leflunomide

Valentin Coirier a, , Alain Lescoat a, f, Céline Chabanne b, Maxime Fournet b, Guillaume Coiffier c, Stéphane Jouneau d, f, Elisabeth Polard e, Patrick Jégo a, f
a Department of Internal Medicine, Rennes University Hospital, 35203 Rennes, France 
b Department of Cardiology, Rennes University Hospital, 35203 Rennes, France 
c Department of Rheumatology, Rennes University Hospital, 35203 Rennes, France 
d Department of Pneumology, Rennes University Hospital, 35203 Rennes, France 
e Department of Pharmacovigilance, Rennes University Hospital, 35203 Rennes, France 
f UMR INSERM U1085, Research Institute in Health, Environment and Occupation/Institut de Recherche sur la Santé, l’Environnement et le Travail (IRSET), Universisty of Rennes 1, 35203 Rennes, France 

Corresponding author. Department of Internal Medicine, South Hospital, Rennes University Hospital, 16, boulevard de Bulgarie, BP 90347, 35203 Rennes cedex 2, France.Department of Internal Medicine, South Hospital, Rennes University Hospital, 16, boulevard de Bulgarie, BP 90347, 35203 Rennes cedex 2, France.

Pulmonary arterial hypertension (PAH) is a rare disorder that can be drug-induced, mostly following treatment by appetite-suppressant drugs. We report four cases of patients who developed PAH following a treatment by leflunomide for rheumatoid arthritis, psoriatic arthritis or undetermined connective tissue disease. All patients described a progressive dyspnea from grade II to IV of NYHA classification; clinical examination found signs of heart failure. PAH was finally diagnosed and confirmed by right heart catheterisation. Haemodynamic explorations found pre-capillary pulmonary hypertension with mean pulmonary arterial pressure above 25mmHg, and pulmonary capillary wedge pressure under 15mmHg. Explorations of this pre-capillary pulmonary hypertension were conducted according to international guidelines: pulmonary or chronic thromboembolic aetiologies were excluded after ventilation/perfusion lung scan and high-resolution computed tomography. All other etiologic explorations were negative. Imputability of leflunomide was finally retained. Leflunomide was stopped for all patients; three of them received specific PAH treatments. A favourable clinical and/or haemodynamic evolution was observed for all patients. The conclusions of the investigations conducted by our pharmacovigilance centre were communicated to the European Medicines Agency, leading to the addition of “pulmonary hypertension” in the paragraph “special warning and precautions of use” of the package leaflet of leflunomide.

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Keywords : Leflunomide, Pulmonary arterial hypertension

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