Background/Purpose: Pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) has a substantially worse prognosis as compared to other connective tissue diseases (CTD)-PAH. Although SSc-PAH are generally treated with pulmonary vasodilators, they could be additionally considered with intensive immunosuppressive therapies (IIT), if overlapping inflammatory autoimmune diseases such as SS and SLE. However, it has not been known their outcome. We assessed the detailed autoantibodies and discriminative clinical symptoms and followed up their outcomes.

Methods: This retrospective study included 50 PAH patients associated with SSc (n=17), SLE (n=18), primary SS (n=8), and MCTD (n=7) referred to our hospital between 2000 and 2018. We performed right-heart catheterization and PAH defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg and the pulmonary arterial wedge pressure (PCWP) ≤15 mmHg at rest. We obtained their serum and determined autoantibodies against cytoplasmic and cell-nuclear antigens, including centromere, Scl-70, RNA-polymerase III, centriole, NuMA1, RNP, Sm, SSA/Ro, SSA/Ro52, SSB, PM-Scl, fibrillarin, Th/To, Ku, dsDNA, nucleosomes, histones, ribosomal P-proteins. We treated all patients with pulmonary vasodilators, and additionally treated with IIT, including cyclophosphamide (IVCY500mg/month x 10 times) and steroid (prednisolone 1mg/kg for 4 weeks and tapered to 5-10mg) for most of SLE, pSS, and MCTD, and some of SSc overlapping inflammatory autoimmune symptoms. Survival analysis was performed using the Kaplan-Meier method, and cumulative survival rates were compared by log-rank tests.

Results: In terms of SSc, we divided into three groups because those were different outcomes, which were (1) overlapping SS diagnosed by ACR criteria(n=7), (2) with centriole antibodies(n=3), or (3) without SS/ centriole antibody(n=7). We treated some severe PAH with SSc overlapping SS by IVCY with half dose steroid(0.5mg/kg) and PAH improved. All of centriole-SSc had discriminative digital ulcer. The one of them had quite severe ulcer and IVCY was remarkably effective for both ulcer and PAH, then treated in the same way for others. There was significantly worse cumulative survival rate in SSc than in SLE, pSS. In terms of SSc subgroup, there was a trend towards a better survival rate in centriole and overlapping SS than in other SSc (Figure). Th/To, which was one of the marker of lcSSc, existed in two patients although the one did not have scleroderma. Ribosomal P antibody existed in 4 patients, however, 3 of them did not have any neuro-psychiatric-SLE symptoms.

Conclusion: Although SSc-PAH has a substantially poor prognosis, we found that SSc overlapping SS and centriole type SSc-PAH might have better outcome than other SSc associated PAH and we could consider IIT for them. However, we should consider the risk of renal crisis, digestive symptoms and other life-threatening symptoms before utilizing IIT for SSc.