Review of systemic sclerosis and antineutrophil cytoplasmic antibody vasculitis overlap: Using autoantibodies for a personalised medicine approach

Abstract

Both antineutrophil cytoplasmic antibody-associated vasculitis and systemic sclerosis are rare autoimmune diseases. Both have the potential for significant multi-organ involvement, and both carry high morbidity and mortality. Disease-specific autoantibodies in these conditions allow for risk stratification for organ-based complications, and for personalised therapeutic strategies. The concomitant presentation of antineutrophil cytoplasmic antibody-associated vasculitis and systemic sclerosis is rare, and only reported in up to 1.3% of systemic sclerosis cases. These patients present more frequently with anti-myeloperoxidase and anti-topoisomerase antibody profiles, with increased incidence of interstitial lung disease and renal involvement than would be expected in either disease independently. Appreciating the role of the autoantibodies in each disease state, and where they overlap, allows for the potential of a more personalised approach to managing these complex patients.

Incidence of Systemic Vasculitis and Clinical Outcomes in Systemic Sclerosis: 2-Years Follow-Up of Asymptomatic Positive for Anti-Neutrophilic Cytoplasmic Antibody

“…In SSc, the prevalence of ANCA-positive using either method was approximately around 12–22%. 10 , 31 However, SSc overlap AAV is quite rare. In a large cohort study of 2200 SSc, the SSc overlap with AAV was 1.6%.…”

Biomarkers in the Pathogenesis, Diagnosis, and Treatment of Systemic Sclerosis

“…Renal manifestations of SSc are dominated by scleroderma renal crisis (SRC), while true immune-mediated glomerulonephritis and interstitial nephritis that occur in SSc are usually associated with overlap disease of SSc with vasculitis and/or systemic lupus erythematosus or drug reactions rather than pure SSc. [251][252][253] SRC is characterized by malignant hypertension, microangiopathic hemolysis, microthrombosis, thrombocytopenia, vasospasm, and progressive renal failure that can be provoked by corticosteroids, cocaine, cyclosporine, and tacrolimus. 251,254,255 Pathologically, SRC is characterized by rather bland or subtle findings, but may demonstrate the typical "onion bulb" histopathology, hyperplasia of the juxtaglomerular apparatus, membranoproliferation, renovascular endothelial injury, intimal proliferation, thrombotic angiopathy, fibrin microthrombi, hemolysis, mesangiolysis, narrowing of renal arterioles, vasospasm, vascular occlusion, ischemia, necrosis, vascular remodeling, and eventual fibrosis with associated with hyperreninemia and accelerated hypertension.…”