Pulmonary Hypertension Associated with Connective Tissue Disease

Abstract

Pulmonary hypertension (PH) is common in most forms of connective tissue disease (CTD); the prevalent type of PH depends on the particular CTD. Thus, pulmonary arterial hypertension (PAH) is dominantly associated with scleroderma, while postcapillary PH is most common in rheumatoid arthritis and lung disease-associated PH is typically found in myositis and sarcoidosis.Considerable expertise is required to identify, diagnose, and manage CTD-PH, as the primary physicians providing the majority of care for this population, rheumatologists, need a good working knowledge of CTD-PH, its rather subtle presentation, and how to access the necessary investigations to screen for and identify patients with PH. The role of the rheumatologist does not stop at diagnosis; in some conditions such as lupus, optimizing immunosuppression is key to the management of PH, and unlike simple idiopathic PAH, the natural history of CTD-PH is often punctuated by complications of the CTD rather than just events due to progression of PH or therapy-related adverse events.The aim of this article is to provide an overview of all forms of CTD-PH, and to provide an easy reference source on current best practice.

Connective Tissue Disease, Interstitial Lung Disease, and Pulmonary Hypertension (CTD PH-ILD): A Distinct Entity and Potential Opportunity

“…The most common CTDs that present with group 3 PH-ILD are SSc, mixed CTD, sarcoidosis, and idiopathic inflammatory myositis. 4,9 The widespread variation in prevalence is because of the diagnostic techniques used to define PH and/or ILD. Furthermore, there are concomitant and multifactorial mechanisms leading to PH, and many of the studies diagnosed PH patients without RHC and through doppler echocar-…”

“…In SSc patients, emphysema can occur regardless of smoking status. 3 Based on the results of the Framingham study, a PA ≥ 29 mm in males and ≥ 27 mm in females is considered to represent abnormal dilation. 36 This is not as sensitive in patients with ILD or CTD that have other reasons for dilated pulmonary arteries.…”

“…It is ideal to obtain a wedge saturation >90% to ensure accuracy. 9 Finally, in patients with significant pulmonary disease and PH, pressure measurements during a RHC can be affected by changes in intrathoracic pressures during a breathing cycle. The 6 th World Symposium for PH recommends that clinicians use the average mPAP and pulmonary capillary wedge pressure after several breaths (without a breath hold).…”

“…2 More commonly, ILD causing hypoxic vasoconstriction and pulmonary arterial hypertension (PAH) due to a small vessel vasculopathy are the predominant causes of PH in CTD. 3 CTD-PH may therefore develop either as a consequence of progressive ILD or as an unfortunate complication of the autoimmune disease process itself. On a molecular level, this setting is a fraught with inflammatory cells including granulomas, myofibroblast, and extracellular matrix populations.…”

SOX17 Loss-of-Function Mutation Underlying Familial Pulmonary Arterial Hypertension

“…7,8) The pathogenesis of PAH is highly complex, and both environmental and genetic pathogenic factors can impair pulmonary vascular structure and function, thus leading to PAH. 9) The well-established environmental risk factors encompass congenital heart disease (CHD), [10][11][12][13] valvular heart disease, 14,15) virus infection, 16,17) connective tissue disease, [18][19][20] chronic thromboembolism, [21][22][23][24] chronic obstructive pulmonary disease, 25) pulmonary tumor thrombotic microangiopathy, 26,27) intake of chemical drugs or toxins, [28][29][30][31] and long-term exposure to hypoxia. [32][33][34][35] However, emerging evidence has demonstrated that genetic defects play a pivotal role in the pathogenesis of idiopathic PAH, especially for familial PAH, and deleterious mutations in multiple genes, including BMPR2 encoding a receptor of the transforming growth factor-β superfamily, TBX4 encoding a transcription factor, and KCNK3 as well as ABCC8 encoding potassium channels, have been found to cause PAH.…”