Pulmonary hypertension (PH) is a clinical syndrome that is subdivided into five groups according to the World Health Organization (WHO) classification, based largely on hemodynamic and pathophysiologic criteria. WHO Group 1 PH, termed pulmonary arterial hypertension (PAH) can be idiopathic, heritable, or associated with a variety of conditions. Connective tissue diseases (CTD) make up the largest portion of these associated conditions, most commonly systemic sclerosis (SSc), followed by mixed connective tissue disease and systemic lupus erythematous. These etiologies (namely SSc and Lupus) have been grouped together as connective tissue disease-associated PAH, however emerging evidence suggests they differ in pathogenesis, clinical course, prognosis, and treatment response. There is an autoimmune element to PAH pathophysiology even in the non-CTD-PAH.
The etiology of PAH involves in part endothelial cell and vascular smooth muscle cell dysfunction. The dysregulated immune mechanisms underlying the disease pathogenesis of SSc and SLE may contribute to the known immunologic and inflammatory factors at play in the development of PAH. The difference in survival rates and the fact that clinical studies suggest more benefit of immunomodulatory therapies in SLE-PAH compared to SSc-PAH suggest that there may be differences in the etiology and course of the immunologic component of PAH in these two conditions. More research is needed into the mechanisms underlying the development of the different CTD-associated PAH, accurate screening methods, and targeted therapies. SLE- and SSc- associated PAH behave differently and it is best if they are studied separately as their prognosis and response to therapies including the risk/benefit ratios of such therapies may be different.