Vasculitis
Reproduced from Issue 107 of Arthritis Today
Professor David Scott, of the Norfolk and Norwich Hospital, explains the various diseases classed as vasculitis, and highlights ever-improving treatments.
What it is
Vasculitis means inflammation of blood vessels. That means blood vessels – arteries, veins and capillaries – are the site of inflammation and can be potentially damaged by the inflammatory process. Vasculitis can occur out of the blue (primary vasculitis) or as a result of infection or in association with some chronic diseases including rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome.
Blood vessels carry blood and, therefore, oxygen to all organs and tissues in the body, so any part of the body can be involved in vasculitis. The consequences, therefore, depend on the site of the blood vessels involved, the size of the blood vessels involved and also the number of blood vessels involved. When small arteries are involved the inflammation often causes the artery to become blocked so the tissues supplied by that artery will die (i.e. become gangrenous). Surprisingly, when larger vessels are involved only part of the wall may become inflamed which can become weak and, because of the high pressure inside arteries, this weakness can cause the wall to expand forming an aneurysm (swelling) which can occasionally rupture with severe bleeding into the surrounding tissues.
Some types of vasculitis have very restricted areas of involvement – for example, giant cell arteritis almost always involves the arteries of the head and neck (though not the brain). Symptoms include headaches, and investigations show evidence of inflammation. Other types of vasculitis are more widespread and can involve vessels supplying the heart, lung, kidneys and skin with very different consequences.
When only very small blood vessels (capillaries) are involved affecting the skin, the result is usually a rash called purpura. This type of vasculitis is usually not serious and can easily be treated. One particular organ most at risk from vasculitis is the kidney. When small blood vessels supplying the main functioning part of the kidney – the glomerulus – are inflamed this can lead to kidney failure.
Who gets it and how it's diagnosed
Vasculitis is rare. Around 5,00 people in the UK develop one of its various forms every year, including the more severe types such as polyarteritis nodosa, Wegener's granulomatosis, Churg–Strauss syndrome and microscopic polyangiitis. These names are partly historical (relating to the doctors who first described the condition) and partly descriptive.
The cause of vasculitis is usually unknown. Some viruses are known to be associated with vasculitis, particularly hepatitis B and hepatitis C. Some types of cancer are very occasionally complicated by vasculitis, as are the connective tissue diseases (see above). The commonest cause of secondary vasculitis is rheumatoid arthritis. In these cases patients often notice small black marks around the nail edge, but the vasculitis can spread to involve internal organs with potentially very serious consequences. Some patients develop damage to peripheral nerves causing numbness and weakness, and occasionally blood vessels in the gut can be involved leading to potentially fatal gut perforation and blockage. Patients with severe rheumatoid vasculitis may have a significantly reduced life expectancy as a consequence of their vasculitis.
Disease such as microscopic polyangiitis, Wegener's granulomatosis and Churg–Strauss syndrome are also serious, with up to 20% of patients dying within five years. Many more patients used to die until effective treatment was established in the 1970s. These diseases are also now recognised as 'autoimmune diseases' (like SLE and rheumatoid arthritis). The auto-antibody found in the blood of these patients is called anti-neutrophil cytoplasmic antibody (ANCA) which was first linked with vasculitis in 1985. This antibody has different forms, one of which is particularly linked with Wegener's granulomatosis.
When patients first develop vasculitis they undergo tests for a number of reasons.
- To assess the activity of the vasculitis. These include the ESR and CRP tests which are non-specific but tell us how much inflammation/activity there is.
- To test which organs are involved. These include chest X-ray for lung involvement, kidney function tests (blood and urine tests); these are particularly important because kidney inflammation, if undetected, can lead to kidney failure; liver function tests; angiograms (this is a way of looking at blood vessels on X-ray and is used for the diagnosis particularly of polyarteritis nodosa), X-rays of the ears, nose and throat (particularly for Wegener's granulomatosis) and ENT assessments. Some tissues may be biopsied to confirm the diagnosis e.g. kidney, skin and upper airways.
- Blood tests are also undertaken to help diagnosis and classify vasculitis. The most important of these is the ANCA test (see above).
Treatment
The introduction of corticosteroids in the 1950s had a significant impact on the outcome of most forms of primary vasculitis. In polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis and Churg–Strauss syndrome survival rates rose from 10% survival to nearly 50% survival after five years. The next change in treatment was the introduction of the cytotoxic drug cyclophosphamide which has improved the outlook for most of these patients, with 80% surviving for ten years. Some patients still die from systemic vasculitis especially if the diagnosis is delayed. Patients with giant cell arteritis have a life expectancy not significantly different to the normal population. But it can have a catastrophic effect on vision due to involvement of an artery in the eye, which, if untreated, can lead to blindness, occasionally in both eyes. Early treatment with high doses of corticosteroids will prevent this. Patients with pure small vessel disease (eg Henoch–Schönlein purpura) have diseases with less severe consequences and are often treated with much lower doses of steroids and other drugs. Occasionally simply removing the triggering food or drug that caused the vasculitis is sufficient.
With the improved survival rate in patients thanks to modern treatments, attention is now being concentrated on ways of avoiding the side effects of these strong drugs, particularly steroids and cyclophosphamide. Doses of cyclophosphamide have been altered from daily to every two weeks (or longer) to try to avoid the dangerous effects of cyclophosphamide on the bladder. Patients are encouraged to drink lots of fluid and are sometimes treated with a drug called Mesna to try and prevent bladder damage. Treatment is now usually continued for only 3–6 months – previously was often continued for two years. When the vasculitis is adequately controlled the cyclophosphamide is stopped and patients are given other drugs such as azathioprine or methotrexate. Research is still being carried out to try and assess the most effective regimes for inducing remission in patients and for maintaining remission.
Many multi-centre studies are being undertaken in Europe. Other studies have looked at different induction regimes with modern biological agents including monoclonal antibodies. Future studies hopefully will help us understand the different causes of vasculitis, and lead to more effective and less toxic treatments.
