Vasculitis

British Medical Journal, May 13, 2000 by C O S Savage, L Harper, P Cockwell, D Adu, A J Howie

Wegener's granulomatosis

Upper respiratory tract disease occurs in more than 90% of cases and includes sinusitis; nasal crusting, bleeding, obstruction, and collapse of the nasal bridge; serous otitis media with conductive deafness; and tracheal stenosis. Limited Wegener's refers to disease that affects only the respiratory tract at the time of diagnosis; many cases evolve to systemic disease. Lung disease is common with cough, haemoptysis, and dyspnoea and may progress to life threatening pulmonary haemorrhage. The kidneys are affected in up to 80% of cases; blood, protein, and casts are present in the urine and should be examined by dipstick testing and microscopy. If untreated, there is loss of renal function, often within days. Other features include purpuric rashes, nail fold infarcts, and ocular manifestations including conjunctival haemorrhages, scleritis, uveitis, keratitis, proptosis, or ocular muscle paralysis due to retro-orbital inflammation. The disease can affect the gut causing haemorrhage, the heart causing coronary artery ischaemia, and the neurological system causing sensory neuropathy or mononeuritis multiplex.

The two pathological hallmarks of Wegener's disease are chronic granulomatous inflammation and vasculitis. Granulomas (localised microscopic collections of macrophages) are not always present. Granulomas in the lung may coalesce into large masses which cavitate. The vasculitis affects capillaries particularly in the lung, causing lung haemorrhage, and glomeruli, causing glomerulonephritis that may be segmental, global, focal, or diffuse with thrombosis, necrosis of capillary loops, and accumulation of cells in Bowman's space. Affected arteries or arterioles show an inflammatory infiltrate and fibrinoid necrosis. There is no deposition of immunoglobulins within the kidney or vessel walls.

Microscopic polyangiitis (microscopic polyarteritis)

Microscopic polyangiitis has many similarities to Wegener's granulomatosis, but disease of the upper respiratory tract is uncommon in microscopic polyangiitis, although pulmonary haemorrhage may occur. Patients with microscopic polyangiitis usually have glomerulonephritis, and, rarely, disease may be limited to the kidney. No granuloma formation is seen.

Diagnosis

Diagnosis is based on typical clinical features, biopsy (usually of kidney, occasionally of nasal mucosa or lung) and presence of antineutrophil cytoplasmic antibodies. These antibodies usually have specificity for the enzymes proteinase-3 or myeloperoxidase and can be detected by enzyme linked immunosorbent assay (ELISA). In indirect immunofluorescence tests, antineutrophil cytoplasmic antibodies against proteinase-3 produce a cytoplasmic staining pattern (cANCA) and antibodies against myeloperoxidase produce perinuclear staining pattern (pANCA). Combined testing by ELISA and indirect immunofluorescence is recommended as this increases specificity at the cost of a 10% reduction of sensitivity. Sometimes antineutrophil cytoplasmic antibody tests are negative, particularly if disease is limited to the upper respiratory tract. Antibody titres usually fall and may disappear completely when the disease is in remission.