Vasculitis: determinants of disease patterns

Abstract

The vasculitides are a large group of heterogeneous diseases for which it has been assumed that pathogenesis is largely autoimmune. As clinicians, we distinguish one form of vasculitis from another on the basis of observed patterns of organ injury, the size of the vessels affected and histopathological findings. The terms 'small-vessel', 'medium-vessel' and 'large-vessel' vasculitis are useful clinical descriptors, but fail to inform us about why vessels of a certain calibre are favoured by one disease and not another. Classification based on vessel size also fails to consider that vessels of a specific calibre are not equally prone to injury. Distinct vulnerabilities undoubtedly relate to the fact that same-size vessels in different tissues may not be identical conduits. In fact, vessels become specialized, from the earliest stages of embryonic development, to suit the needs of different anatomical locations. Vessels of the same calibre in different locations and organs are as different as the organ parenchymal cells through which they travel. The dialogue between developing vessels and the tissues they perfuse is designed to meet special local needs. Added to the story of vascular diversity and vulnerability are changes that occur during growth, development and ageing. An improved understanding of the unique territorial vulnerabilities of vessels could form the basis of new hypotheses for the aetiopathogenesis of the vasculitides. This Review considers how certain antigens, including infectious agents, might become disease-relevant and how vascular diversity could influence disease phenotypes and the spectrum of vascular inflammatory diseases.