Is pulmonary arterial hypertension associated with interferon-β therapy for multiple sclerosis reversible? A case study to explore the complexity (original) (raw)

Interferon (IFN)-β has been classified as a drug that is possibly associated with development of pulmonary arterial hypertension (PAH), a devastating disease that can lead to right heart failure and premature death [1]. Drug-and toxin-induced PAH is a well-known entity in the field of pulmonary hypertension (PH) since the epidemic of idiopathic PAH occurred in the central Europe, between 1967 and 1971, following the use of anorexigens. Τhe Sixth World Symposium on Pulmonary Hypertension, based on recent data, proposed a simplified characterisation of PAH associated with drugs and toxins into two subgroups (definite and possible) to help physicians to identify drugs requiring specific surveillance. According to this framework, and supported by case series and case reports, IFN-β is classified as a drug with possible association with PAH development [2]. In the literature, there are several cases of patients with multiple sclerosis (MS) on treatment with IFN-β who were diagnosed with PAH associated with the IFN-β exposure [3-9]. The need to identify and present related cases has been highlighted [4, 5]. We report a case of a patient with MS on treatment with IFN-β who subsequently developed PAH. The initial suspicion of PAH, the subsequent diagnosis and management, and the final outcome are presented in order to underline the reversibility of PAH following IFN-β discontinuation and specific PAH therapy administration, and the emerging need to early detect similar cases. A 32-year-old female was diagnosed with relapsing remitting MS on 2010 with an Expanded Disability Status Scale score of 1 and negative immunological indices. She had received therapy with IFN-β for 6 years when she presented to our PH clinic with a 4-month history of dyspnoea on exertion, fatigue, dizziness and episodes of presyncope. She thought her symptoms were MS-related. Her past medical history was otherwise unremarkable, with no known risk factors for PAH. Upon admission to the hospital, in New York Heart Association functional class (NYHA-FC) III, she was unable to complete the 6-min walking test (6MWT) due to a presyncopal episode during the fourth minute of the walk. A transthoracic echocardiography demonstrated right ventricular dilatation and systolic dysfunction, tricuspid regurgitant jet velocity of 4 m•s −1 , and left ventricular ejection fraction of 60%. Flattening of the intraventricular septum during both systole and diastole was also noted. High-resolution computed tomography and angiography of the lungs revealed dilatation of the right heart ventricle and an enlarged pulmonary arterial trunk (3.8 cm). There were no lung lesions nor signs of pulmonary embolism. A perfusion lung scan was unremarkable. Pulmonary function tests were normal with a mildly reduced diffusion capacity of 72% pred. Baseline blood work was normal, including thyroid function tests, @ERSpublications The possible causal relationship between interferon-β exposure and pulmonary arterial hypertension development requires close follow-up of patients on treatment with interferon-β http://bit.ly/2OPGSVP Cite this article as: Anthi A, Stagaki E, Rallidis L, et al. Is pulmonary arterial hypertension associated with interferon-β therapy for multiple sclerosis reversible? A case study to explore the complexity.