Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.
Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,
In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.
Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.
The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.
Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).
The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.
Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.
“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.
Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.
SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.