Evolving Concepts in Vasculitis

Abstract

The vasculitic disorders are easily dismissed as a rare and confusing set of diseases. Yet those patients with destructive lesions affecting arteries (the necrotising arteritides) demand attention both because they are serious disorders with a high mortality and because they do respond to treatment if it is early and aggressive (1). Indeed 'cure' has been claimed with cyclophosphamide for conditions such as Wegener's granulomatosis, polyarteritis nodosum, and systemic rheumatoid vasculitis although the precise dose, route, and duration of treatment with cytotoxic drugs still require definition (2). The diverse presentation of these disorders demands a high index of suspicion and a willingness to investigate if a diagnosis is to be made before there is irreversible tissue damage. Biopsy of the affected organ, especially renal biopsy where there is any evidence of kidney disease (3) may be usefully combined with arteriography. The latter may show positive results in 70 per cent of cases (4). Even if this does not aid in the precise diagnosis, it does define those patients with severe arteritis requiring aggressive treatment. The similarity in therapeutic response of the necrotising arteritides is matched by the similarity in the histological appearance of the inflamed arterial wall. This includes a mixed infiltrate of inflammatory cells, though either polymorphs or lymphocytes may predominate. This histological similarity raises the possibility of a common aetiopathogenic mechanism for the conditions within the group of necrotising arteritides. This concept has even been extended to other types of vasculitis, ranging from the small vessel leucocytoclastic vasculitis (polymorphs) to the large vessel granulomatous arteritis (lymphocytic), since these also show inflammatory cell infiltrates in the vessel walls. Great stress has been laid on a possible immune complex pathology, especially where polymorphs predominate, since the classical studies of Dixon (5) showed that the lesions could be reproduced experimentally by this mechanism. The proliferation of putative immune complex tests has led to descriptions of positive results in many types of vasculitis, but these may be misleading. In systemic rheumatoid vasculitis there is extensive evidence for rheumatoid factor containing, complement-fixing, immune complexes which correlate both with complement consumption and clinical manifestations (6). Elman and Ball suggested more than 30 years ago that systemic rheumatoid vasculitis was identical to polyarteritis nodosum, yet in the latter convincing evidence of pathogenic immune complexes is lacking except in those cases with hepatitis B infection, which represent less than 10 per cent of cases in the UK.