Revisiting ANCA-associated vasculitis in systemic sclerosis: clinical, serological and immunogenetic factors

Objectives. To define the clinical, serological, histological and immunogenetic features of patients with scleroderma and ANCA-associated vasculitis (AAV). Methods. We examined a clinical database of 2200 patients with either limited or diffuse cutaneous systemic sclerosis (SSc). Patients with a confirmed diagnosis of vasculitis who were ANCA positive with either MPO or PR3 reactivity had their clinical features, serology, histology and HLA haplotypes examined in detail. Results. From this SSc cohort, 35 patients (1.6%) had evidence of vasculitis, and the SSc autoantibody profiles in this group were comparable to those previously published from the whole cohort. Of these 35 patients, 8 (0.4% of whole SSc cohort) had either anti-MPO or anti-PR3 antibodies and two further patients were ANCA positive without defined specificities. Of the eight ANCA-positive patients, seven had limited cutaneous SSc and anti-MPO antibodies and only one had anti-PR3 antibodies, associated with diffuse cutaneous SSc. Two ANCA-positive patients had anti-U3RNP antibodies, usually associated with overlap disease. None of the patients had granulomatous disease. The majority had glomerulonephritis, renal arteritis and pulmonary fibrosis. There were several shared HLA haplotypes from the DP and DQ loci in these overlap patients. Conclusion. SSc in overlap with ANCA-associated vasculitis is rare, and clinical features are more mixed than when either of these two conditions occurs separately. From our database, U3RNP antibodies may be more associated with overlap AAV than the other scleroderma-specific antibodies.