Background/Purpose: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a spectrum of autoimmune disorders characterized by necrotizing small-to-medium vessel inflammation and circulating ANCAs. Represented by granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, AAV primarily affects the kidneys and respiratory tract. Concomitant AAV with systemic sclerosis (SSc) is exceedingly rare yet carries high morbidity risk. Few cases describe pulmonary arterial hypertension (PAH) in this overlap. We examine whether patients with AAV are associated with developing SSc. Then, we investigate if PAH in AAV patients is associated with development of SSc and SSc antibodies, anticentromere (ACA) and anti-topoisomerase I (Scl-70).

Methods: This retrospective analysis utilized real-world dynamic data from TriNetX clinical research platform, representing over 124 million patients in the Research network. We identified 27,648 patients with AAV and 124,294,351 patients without as controls. SSc prevalence and relative risk (RR) with 95% confidence interval (CI) were assessed between groups. Among patients with AAV, we identified 592 patients with PAH and 26,219 without as controls and assessed SSc, ACA, and Scl-70 prevalence and RR with 95% CI. Chi-square test was used to compare SSc prevalence between groups. Significance was defined as p-value < 0.05. Participants were identified based on ICD-10-CM diagnosis codes.

Results: Demographics of AAV cohort included: mean age 62, SD 18, female 55.99%, male 40.62%, unknown gender 3.39%. Demographics of controls without AAV cohort included: mean age 46, SD 25, female 52.31%, male 45.37%, unknown gender 2.32%.

Patients with AAV showed SSc prevalence of 102.7/10,000 patients compared to in controls 0.0.041/10,000 patients (p-value < 0.0001). Of 592 patients with AAV and PAH, 46(0.078) had SSc compared to 163(0.006) in the control group without PAH (p-value < 0.0001). Among patients with AAV and PAH, 10(0.017) had positive ACA compared to 243(0.009) of 26,219 in the control group (p-value < 0.0001), while 12(0.020) had Scl-70 compared to 264(0.010) in the control group without PAH (p-value < 0.0001). Association between AAV and SSc in patients with PAH was twelve times higher compared to patients without (RR: 12.7; 95% CI: 9.3 – 17.4). The association between AAV and ACA antibodies was not significant (RR: 1.8; 95% CI: 0.97 – 3.4). The association between AAV with PAH and Scl-70 was two times higher compared to controls (RR: 2; 95% CI: 1.4 – 3.6).

Conclusion: Patients with AAV have a statistically significant association with the development of SSc. The presence of PAH in patients with AAV has statistically significant associations with the development of SSc and Scl-70 yet not ACA with p-value slightly greater than 0.05. SSc in AAV portend worse prognosis with higher mortality risk compared to those without overlap. Prompt recognition and management of this unusual clinical overlap is crucial given the potential for life-threatening complications. Monitoring with transthoracic echocardiogram for PAH in AAV patients may be an effective screening tool for SSc and SSc antibodies, Scl-70 more than ACA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-anca-associated-vasculitis-and-development-of-ssc-and-ssc-associated-antibodies-impact-of-pulmonary-arterial-hypertension/