What is Vasculitis?

Vasculitis is defined as inflammation in blood vessels leading to damage to the tissue or organs supplied by that blood vessel. It can affect one or usually many blood vessels and because most parts of the body have a blood supply it can occur in many different guises. At the most extreme end of the spectrum, it can be a fatal disease because it causes many essential organs of the body(especially the kidneys and lungs) to fail very quickly (multi organ failure). Vasculitis is not a common set of conditions.  The word represents a family of  unusual and uncommon diseases. Vasculitis may be “primary”, in other words there are no recognised associated disease, or “secondary”, usually in response to a drug or in patients with an existing disease such as rheumatoid arthritis or systemic lupus erythematosus.

The primary forms of vasculitis are a family of conditions with overlapping clinical features to a greater or larger extent. Conventionally, the vasculitides are classified according to the size of the blood vessels involved into large vessel vasculitis, medium vessel vasculitis and small vessel vasculitis.. Even though we know that these disease probably have very separate mechanisms, they are currently grouped together because they share a number of clinical and laboratory features.

Large vessel vasculitis includes: giant cell arteritis which commonly affects older people above the age of 50 and presents with unaccustomed headache accompanied by feeling generally unwell, with an elevated blood inflammatory response (high erythrocyte sedimentation rate and high C-reactive protein) and can be complicated by loss of sight in around 20% of patients and rarely by stroke; Takayasu arteritis is another form of large vessel vasculitis, usually affecting younger persons but not exclusively so and typically involving the main blood vessel in the body (aorta) and its branches; a third form of large vessel vasculitis that we term “aortitis” is being increasingly recognised and does have some overlap between giant cell arteritis and Takayasu arteritis

Medium vessel vasculitis. Polyarteritis nodosa (PAN) mainly affects medium sized vessels and may present with general ill health, abdominal pain, nerve damage, and skin rashes. The most common form was linked to infection with hepatitis B virus, but as a result of  immunisation programmes and avoidance of risk of hepatitis B, this is now a very rare condition.  There is still a form of PAN that is not related to hepatitis B, but this is also very rare. Kawasaki disease is a childhood vasculitis presenting in a way which mimics an acute infectious disease in a child with fever, swollen lymph glands, skin rashes and sore mouth but its most important characteristic is its involvement of the arteries supplying the heart (coronary arteries).  These may become swollen and then suddenly rupture, which is fatal.

Small vessel vasculitis. The small vessel vasculitides are dominated by a group characterised by an association with an auto antibody termed anti-neutrophil cytoplasm antibody (ANCA).  These conditions can be life threatening because of the typical pattern of involvement of the kidney and the lung. The two main forms are granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis. These forms of vasculitis require strong immunosuppressive treatment, such as cyclophosphamide and steroid.  Milder forms of the disease may respond to methotrexate and steroid instead. Eosinophillic granulomatosis with polyangiitis (Churg-Strauss syndrome) is the third form of ANCA associated vasculitis although it is less associated with ANCA than the first two types. It is typically characterised by late onset asthma, a history of allergy and may present with significantly high blood level of eosinophils (one type of white cell normally found in the blood) and vasculitis complications such damage to nerves, the kidney, heart and gut.

There are a variety of other forms of vasculitis including one that is closely linked to the presence of hepatitis C (termed mixed essential cryoglobulinemic vasculitis). A common childhood vasculitis is IgA disease which typically presents with a purple/red rash affecting the legs and sometimes the arms and is associated with stomach pain sometimes bloody diarrhoea, and blood may be found on microscopic examination of the urine. This condition (previously called Henoch Schonlein purpura) is often in response to an infection or a medicine in children;  however the same condition can occur in adults and has much more serious consequences especially when it involves the kidney and can lead to kidney failure eventually. Anti-glomerular basement membrane disease (Good pastures syndrome) is another form of very aggressive vasculitis which can present with rapidly renal failure as well as severe lung bleeding. It is due to an antibody (anti-GBM antibody) which binds directly to the kidney and lung and causes extensive damage very quickly.

Other forms of vasculitis occur especially in some parts of the world such as Bechets syndrome which typically presents with oral and genital ulceration, eye inflammation and may also involve the skin, nervous system, the lungs and the gut.

In summary the vasculitides represent a fascinating set of conditions with a wide range of manifestations all centred on interference with blood supply to various organs or tissues, the DCVAS project aims to characterise these conditions more precisely so that studies and trials of new treatments can be more effective in improving outcome for patients.