Epidemiology Screening Diagnosis and Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

Systemic sclerosis (SSc) is a very rare rheumatologic disorder with systemic involvement including pulmonary, gastrointestinal, renal and musculoskeletal complications. Pulmonary hypertension is an important manifestation of SSc with multiple etiologies, including pulmonary arterial hypertension (PAH), left heart dysfunction, interstitial lung disease and chronic thromboembolic disease. PAH is present in 7-12% of SSc patients and is a leading cause of death in this population with a 2-year mortality of >60%. Routine screening for pulmonary hypertension is warranted in this group and results in earlier detection and initiation of therapy, which may result in improved outcomes. PAH treatment includes use of prostanoids, endothelin receptor antagonists, and/or phosphodiesterase-5 inhibitors/guanylate cyclase stimulators as monotherapy or in combination. This review will consider the multiple etiologies of pulmonary hypertension in SSc and address the epidemiology, clinical manifestations, screening guidelines, diagnostic considerations, current treatment and prognosis of SSc-associated PAH. Kavita B Khaira1*, Mark V Avdalovic2, Charles K Whitcomb3, Roblee Allen2 and Ezra A Amsterdam3 1Department of Internal Medicine, UC Davis Medical Center, USA 2Department of Pulmonary and Critical Care Medicine, UC Davis Medical Center, USA 3Department of Cardiovascular Medicine, UC Davis Medical Center, USA Kavita B Khaira, et al. Journal of Respiratory Medicine and Lung Disease Remedy Publications LLC. 2016 | Volume 1 | Issue 1 | Article 1003 2 Risk Factors For The Development of PAH in Ssc Patients Include: older age, post menopausal status, longer disease duration, diffusing capacity of carbon monoxide (DLCO) <50% predicted, limited cutaneous/CREST syndrome variant, telangiectasias, digital ulcers, positive anti-centromere, anti-U1-ribonucleoprotein and antiphospholipid antibodies and negative anti-Scl-70 antibody [1618]. However, it is important to recognize that PAH can also affect patients with diffuse cutaneous involvement and can occur early in the disease course [16]. Hemodynamic findings associated with progression to PAH include: exercise-induced PAH, an annual increase in right ventricular systolic pressures by >3 mmHg per year, a mean pulmonary artery pressure (mPAP) between 21-24 mmHg and a transpulmonary gradient >11mmHg [16]. Clinical Manifestations Many SSc patients with PAH remain asymptomatic for a prolonged period until they have reached the advanced stages of disease with right heart failure. Symptoms are nearly indistinguishable from patients with idiopathic PAH (IPAH) and initially include dyspnea on exertion, lethargy, fatigue and later progress to chest pain, presyncope/syncope, edema, and rest symptoms as right heart failure develops [19,20]. Clinical signs include elevated jugular venous pressure, hepatomegaly, peripheral edema, ascites, cool extremities, pronounced pulmonary component of the second heart sound, pansystolic murmur of tricuspid regurgitation, diastolic murmur from pulmonary insufficiency and/or right ventricular fourth heart sound [21]. These patients may also have signs and symptoms related to other organ involvement in SSc including characteristic dermatologic changes, gastrointestinal reflux, dysphagia, diarrhea, arthritis, muscle weakness, acute renal injury, severe hypertension and calcinosis [1,7].