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Treatment of small vessel vasculitis

Induction therapy (to 3 months after remission, usually 6 months from diagnosis)

• Cyclophosphamide, 2.0 mg/kg/day (maximum 200 mg/day). Age > 60 years, reduce dose by 25%, > 75 years by 50%

• Prednisolone, 1 mg/kg/day (maximum 80 mg/day) reduced weekly to 25mg/day by 8 weeks and then more slowly to 10 mg/day by 6 months

In severe, life threatening disease (eg, pulmonary haemorrhage, severe crescentic glomerulonephritis with creatinine > 500 ^mol/l), consider plasma exchange, 7-10 treatments over 14 days, or three pulses of methylprednisolone, 15 mg/kg/day for 3 days

Maintenance therapy (to 18-24 months, longer if clinically indicated)

• Azathioprine, 2.0 mg/kg/day (maximum 200 mg/day). Age > 60 years, reduce dose by 25%, > 75 years by 50%

• Prednisolone, 5-10 mg/day Relapse therapy

• Major relapse: return to induction therapy

• Minor relapse: increase dose of corticosteroids

Stop cyclophosphamide or azathioprine if white blood count 4x109/l; restart with a dose reduced by at least 25 mg when white blood count >4x109/l on two consecutive tests

Consider gastric and bone protection, and fungal and Pneumocystis carinii prophylaxis more severe disease. Asthma requires conventional treatment but the recently introduced leukotriene receptor antagonist drugs have been causally linked with the Churg-Strauss syndrome and should be avoided in these patients.

Small vessel vasculitis without antineutrophil cytoplasmic antibodies

Henoch-Schonlein purpura

Henoch-Schonlein purpura is most common in children but can occur at any age. Typical clinical features are purpura over the lower limbs and buttocks, haematuria, abdominal pain, bloody diarrhoea, and arthralgia.The pathological hallmarks are deposition of immunoglobulin A at the dermoepidermal junction and within the glomerular mesangium, with a mesangial hypercellular glomerulonephritis. Some patients develop a glomerular lesion resembling that seen in small vessel vasculitis. Renal disease may occur without the rash or other typical features.

The disease is usually self limiting and only supportive treatment is required. Corticosteroids and immunosuppression may be needed for vasculitic glomerulonephritis or serious gut haemorrhage and ischaemia.

Cryoglobulinaemic vasculitis ("mixed, essential")

Cryoglobuins are immunoglobulins that precipitate in the cold. The mixed cryoglobulin consists of a monoclonal immunoglobulin M rheumatoid factor complexed to polyclonal immunoglobulin G. Vasculitis develops when cryoglobulins deposit in blood vessels. Mixed essential cryoglobulinaemia is due to hepatitis C virus infection in over 80% of cases. Other causes of cryoglobulinaemia include dysproteinaemias, autoimmune diseases, and chronic infections. Serum complement C4 and C3 concentrations are reduced. Clinical features include palpable purpura, arthralgia, distal necroses, peripheral neuropathy, abdominal pain, and glomerulonephritis. Renal biopsy specimens typically have the appearance of subendothelial membranoproliferative glomerulonephritis with intraglomerular deposits.

In cryoglobulinaemia associated with hepatitis C, treatment is directed at the viral infection. Interferon alfa over six months is beneficial, but many patients relapse when treatment is stopped. Prednisolone with or without immunosuppressants has been used successfully in acute severe disease. The role of plasma exchange remains unsubstantiated.

Isolated cutaneous leukocytoclastic vasculitis

This is often associated with a drug hypersensitivity response and improves when the drug is stopped. Occasional patients may require corticosteroids for severe disease.

Antiglomerular basement membrane antibody mediated disease (Goodpasture's disease)

No Chapel Hill definition exists for this rare disease, which has considerable overlaps with antineutrophil cytoplasmic antibody associated vasculitis. The hallmarks are a rapidly progressive global and diffuse glomerulonephritis, as seen in small vessel vasculitides, or presence of pulmonary haemorrhage, or both. Diagnosis depends on finding antibodies to glomerular basement membrane in the serum and linear staining for immunoglobulin G along the glomerular basement membrane. The antibodies have been implicated in disease pathogenesis. About 15-30% of patients have detectable antineutrophil cytoplasmic antibodies. Treatment is as for small vessel vasculitis with addition of daily plasma exchange until antiglomerular basement membrane antibodies are no longer detectable.

Definitions of non-ANCA associated small vessel vasculitis Henoch-Schonlein purpura

• Vasculitis with IgA dominant immune deposits affecting small vessels (capillaries, venules, or arterioles)

• Affects skin, gut, and glomeruli

• Associated with arthralgia or arthritis Cryoglobulinaemic vasculitis

• Vasculitis with cryoglobulin immune deposits affecting small vessels

• Associated with cryoglobulins in serum

• Skin and glomeruli often affected

Isolated cutaneous leukocytoclastic vasculitis

• Isolated cutaneous leukocytoclastic angiitis without systemic vasculitis or glomerulonephritis

• May evolve into systemic vasculitis

Leukocytoclastic Vasculitis
Purpuric rash on lower limb of patient with Henoch-Schonlein purpura
Rim Afetado Pela Purpura Henoch
Renal biopsy specimen showing intraglomerular deposit of cryoglobulins

COS Savage is professor of nephrology, University of Birmingham; L Harper is specialist registrar, P Cockwell is consultant physician, and D Adu is consultant physician, Queen Elizabeth Hospital, Birmingham; and A Howie is reader in renal pathology, University of Birmingham.

The ABC of arterial and venous disease is edited by Richard Donnelly, professor of vascular medicine, University of Nottingham and Southern Derbyshire Acute Hospitals NHS Trust ([email protected] nottingham.ac.uk) and Nick J M London, professor of surgery, University of Leicester, Leicester ([email protected]). It will be published as a book later this year.

BMJ 2000;320:1325-8

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