Pulmonary Arterial Hypertension Related to Scleroderma and Collagen Vascular Diseases

Abstract

Pulmonary arterial hypertension (PAH), defined as a mean pulmonary arterial pressure of greater than 25 mmHg in the absence of elevation of the pulmonary capillary wedge pressure, is a cause of significant morbidity and mortality. PAH is characterized by remodeling and occlusion of the small pulmonary arterioles leading to a progressive increase in pulmonary vascular resistance. Left untreated, this syndrome leads irremediably to right ventricular (RV) hypertrophy, pressure overload, and dilation resulting in death within 2–3 years. PAH encompasses a heterogeneous group of clinical entities, discussed in separate sections of this book, which share similar pathological changes. PAH can also be associated with various collagen vascular diseases (CVD) such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and mixed connective tissue disease (MCTD), which are the focus of this chapter. The mechanisms involved in the pathogenesis of PAH are unknown; however, several lines of evidence implicate a role for autoimmunity in the development of the pulmonary vascular changes, including the presence of circulating autoantibodies, proinflammatory cytokines (e.g. IL-1 and IL-6), and in particular the association of PAH with CVD. However, despite the presence of serologic and pathologic features suggestive of inflammation in both idiopathic PAH (IPAH) and SSc-related PAH (SSc-PAH), it is likely that inflammatory pathways and autoimmunity are more pronounced in SSc-PAH and may explain the survival discrepancies between the two syndromes and a differential response to current modern therapy. As such, SSc-PAH may be considered an ideal prototypic example to study inflammatory processes potentially operative in the pathogenesis of PAH. Other connective tissue diseases such as SLE, MCTD, and to a lesser extent RA, dermatomyositis, and Sjogren’s syndrome will be discussed separately in this chapter.