Pulmonary arterial hypertension associated with interferon beta treatment for multiple sclerosis: a case report

Ledinek, AH; Jazbec, Sš; Drinovec, Igor; Rot, Uroš

doi:10.1177/1352458509104593

Cited by 43 publications

(35 citation statements)

References 9 publications

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“…Right-sided heart catheterization produces a definitive diagnosis, with measurement of mean pulmonary artery pressure (25 mmHg and above) and pulmonary artery wedge pressure (up to 15 mmHg), which was also the case with our patient [2]. Before the performance of the right-sided heart catheterization, heart disease, lung disease, and chronic thromboembolic pulmonary hypertension (CTEPH) were all considered to be possible causes of the patient's pulmonary hypertension; however, they were excluded in the process of differential diagnosis.…”

Section: Discussionsupporting

confidence: 79%

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Pulmonary Arterial Hypertension in a Patient with Multiple Sclerosis Treated with Interferon Beta: A Case Report

Novotná¹

2016

J Neurol Neurosci

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Pulmonary arterial hypertension (PAH) is characterized by elevation of mean pulmonary artery pressure to values conceivably approaching those seen in the systemic vascular bed. This occurrence is associated with a poor prognosis. PAH may result from a variety of causes, some of which are related to pharmacotherapy.Herein, we present a case of a 39-year-old female patient with relapsing-remitting multiple sclerosis (MS), who was receiving immunomodulatory therapy and subsequently developed severe PAH. We presume a causal relationship between the condition and the patient's interferon beta therapy, which had spanned 10 years. The interferon beta therapy was stopped because its continued administration could have led to more rapid progression of severe pulmonary hypertension.Due to the severity of pulmonary arterial hypertension, PAH-specific pharmacotherapy was indicated, using sildenafil. Since 1998, only several cases of pulmonary arterial hypertension in patients treated with interferon beta have been documented in the scientific literature. In some of these instances, including in two case studies involving patients with multiple sclerosis, it was concluded that there was a possible association with this therapy.

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Section: Discussionsupporting

confidence: 79%

“…PAH is characterized by elevation of mean pulmonary artery pressure to values conceivably approaching those seen in the systemic vascular bed. The prognosis of the disease is poor, and most untreated individuals die within three years due to right-sided heart failure [2].…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Arterial Hypertension in a Patient with Multiple Sclerosis Treated with Interferon Beta: A Case Report

Novotná¹

2016

J Neurol Neurosci

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“…12 other cases of PAH potentially associated with IFN therapy have been reported in the literature [7][8][9][10][11][12][13]; only five of which were diagnosed using right heart catheterisation. The first case, published in 1993, described reversible acute right heart failure in a patient with renal cell carcinoma after IFN therapy, suggesting for the first time a possible causative mechanism [13].…”

Section: Discussionmentioning

confidence: 99%

“…This is supported by the publication of several isolated case reports [7][8][9][10][11][12][13][14] and by experimental studies [15][16][17][18]. IFNs have powerful actions within the immune system where they play key anti-viral, anti-bacterial and anti-tumoural roles.…”

Section: Introductionmentioning

confidence: 93%

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Pulmonary arterial hypertension in patients treated with interferon

et al. 2014

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Isolated cases of pulmonary arterial hypertension (PAH) in patients treated with interferon (IFN) a or b have been reported in the literature.The aim of this study was to describe all consecutive cases of PAH patients with a history of IFN exposure identified in the French reference centre for severe pulmonary hypertension between 1998 and 2012.A total of 53 patients with PAH and a history of IFN therapy were identified. 48 patients had been treated with IFNa for chronic hepatitis C. Most of them had portal hypertension (85%) and 56% had HIV coinfection. Five additional patients had been treated with IFNb for multiple sclerosis. The diagnosis of PAH was made within 3 years after IFN therapy in 66% of patients. Repeated haemodynamic assessment was available in 13 out of 16 patients exposed to IFN after the diagnosis of PAH. Increased pulmonary vascular resistance .20% was observed in 11 out of 13 cases (median 43% increase; IQR 32-67%). In five of these patients, IFN withdrawal resulted in spontaneous haemodynamic improvement.This retrospective analysis suggests that IFN therapy may trigger PAH. However, most of these patients had other risk factors for PAH. A prospective case-control study is necessary to definitively establish a link between IFN exposure and PAH. @ERSpublications Clinical data suggest that interferon therapy may be a trigger for pulmonary arterial hypertension

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Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension

Christmann¹,

Hayes²,

Pendergrass³

et al. 2011

Arthritis & Rheumatism

126

124

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Objective To explore the relationship between biomarkers of pulmonary arterial hypertension (PAH), interferon (IFN)–regulated gene expression, and the alternative activation pathway in systemic sclerosis (SSc). Methods Peripheral blood mononuclear cells (PBMCs) were purified from healthy controls, patients with idiopathic PAH, and SSc patients (classified as having diffuse cutaneous SSc, limited cutaneous SSc [lcSSc] without PAH, and lcSSc with PAH). IFN-regulated and “PAH biomarker” genes were compared after supervised hierarchical clustering. Messenger RNA levels of selected IFN-regulated genes (Siglec1 and MX1), biomarker genes (IL13RA1, CCR1, and JAK2), and the alternative activation marker gene (MRC1) were analyzed on PBMCs and on CD14− and CD14+ cell populations. Interleukin-13 (IL-13) and IL-4 concentrations were measured in plasma by immunoassay. CD14, MRC1, and IL13RA1 surface expression was analyzed by flow cytometry. Results Increased PBMC expression of both IFN-regulated and biomarker genes distinguished SSc patients from healthy controls. Expression of genes in the biomarker cluster, but not in the IFN-regulated cluster, distinguished lcSSc with PAH from lcSSc without PAH. The genes CCR1 (P < 0.001) and JAK2 (P < 0.001) were expressed more highly in lcSSc patients with PAH compared with controls and mainly by CD14+ cells. MRC1 expression was increased exclusively in lcSSc patients with PAH (P < 0.001) and correlated strongly with pulmonary artery pressure (r = 0.52, P = 0.03) and higher mortality (P = 0.02). MRC1 expression was higher in CD14+ cells and was greatly increased by stimulation with IL-13. IL-13 concentrations in plasma were most highly increased in lcSSc patients with PAH (P < 0.001). Conclusion IFN-regulated and biomarker genes represent distinct, although related, clusters in lcSSc patients with PAH. MRC1, a marker for the effect of IL-13 on alternative monocyte/macrophage activation, is associated with this severe complication and is related to mortality.

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Pulmonary arterial hypertension associated with interferon beta treatment for multiple sclerosis: a case report

Cited by 43 publications

References 9 publications

Pulmonary Arterial Hypertension in a Patient with Multiple Sclerosis Treated with Interferon Beta: A Case Report

Pulmonary Arterial Hypertension in a Patient with Multiple Sclerosis Treated with Interferon Beta: A Case Report

Pulmonary arterial hypertension in patients treated with interferon

Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension

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