SYSTEMIC VASCULITIDES

Systemic vasculitides:
an overview

Definitions
The primary systemic vasculitides are the most difficult to
define because of the lack of known aetiological factors in most
cases and the overlap of clinical features between syndromes.
Nevertheless, several syndromes have been recognized. In
1994, an international consensus conference attempted to
define the main syndromes to facilitate international understanding and awareness. No other system has yet superseded
the 1994 proposals.2

Caroline O S Savage

Relationship to age

Abstract

Vasculitis may occur at any age, but the clinical syndromes with
which it is associated show age-specific differences.
• Kawasaki disease is seen only in children.
• Henoch–Schönlein purpura occurs mainly in children, but can
present in adults.
• Microscopic polyangiitis and Wegener’s granulomatosis are
generally present in adults.
• Giant cell arteritis is predominantly a disease of the
­elderly.

Systemic vasculitides comprise a collection of disorders characterized by
the presence of fibrinoid necrosis and inflammation of blood vessels.
This article provides an overview of the following contributions on small,
medium and large vessel vasculitides.

Keywords systemic vasculitis; antineutrophil cytoplasm antibodies;
ANCA

Spectrum of vasculitis
Importance of diagnostic precision

There is no classification of vasculitis that is accepted without
dispute.1
• Vasculitic disorders may be divided into primary and secondary, distinguishing vasculitides in which the vasculitic process is the main focus of tissue injury (e.g. giant cell arteritis,
­microscopic polyangiitis) from those deemed to be associated
with another underlying disease (e.g. systemic lupus erythematosus, rheumatoid arthritis, malignancy).
• Another division is between vasculitides associated with the
presence of antineutrophil cytoplasm antibodies (ANCA) and
those in which ANCA are seldom detected. The three ANCA­associated forms of vasculitis are Wegener’s granulomatosis,
­microscopic polyangiitis and Churg–Strauss syndrome.
• Closer to a system of classification is subdivision of the primary
systemic vasculitides according to the predominant size and type
of the vessel affected and/or whether there are associated granulomata (Table 1).
Despite the term ‘systemic’, vasculitis may be localized to
a single organ and may or may not become systemic. This is
illustrated by so-called ‘idiopathic rapidly progressive glomerulonephritis’, which is now recognized as a form of microscopic
polyangiitis limited to the kidney. A limited form of Wegener’s
granulomatosis also occurs, affecting the head and neck; this is
usually granulomatous rather than vasculitic initially, but may
develop into a systemic vasculitic disease.

Distinguishing subsets of vasculitis is justified because the
aetiological factors or pathogenic mechanisms are likely to
differ, the requirements for therapy differ, and prognosis varies between different syndromes. Precision is also necessary
for therapeutic, epidemiological and national or international
studies.
Vasculitides are medical emergencies. Organ survival can be
threatened if a diagnosis is not made quickly and accurately,
enabling implementation of appropriate therapy. Blindness may
occur in an elderly patient in whom giant cell arteritis is missed,
cardiac infarction may occur in a child with Kawasaki disease,
and renal failure and life-threatening lung haemorrhage may
develop in an adult with microscopic polyangiitis or Wegener’s
granulomatosis. If in doubt about a diagnosis, consult an appropriate specialist.

New approaches to therapy
In recent years, understanding of how best to apply established
therapies has increased, and some new therapeutics have been
introduced.
In the ANCA-associated vasculitides,3 the CYCAZAREM trial
has been published indicating that shorter courses of cyclophosphamide followed by azathioprine are as effective as 12 months of
cyclophosphamide, so cyclophosphamide can be safely switched
to azathioprine after 3–6 months.
In Hepatitis B associated polyarteritis nodosa, use of the antiviral agent lamivudine, aids viral clearance which greatly reduces
the risk of relapse.4
Newer biologicals are being tested, especially in ANCA­associated vasculitides. Anti-cytokine agents, for example to
TNF, have been tested in pilot studies, while Etanercept was
used in a randomized controlled trial in Wegener’s granulomatosus where earlier promise was not substantiated.5 B cell

Caroline O S Savage PhD FRCP FMedSci is Professor of Nephrology at the
University of Birmingham and Consultant Nephrologist in the University
Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Competing interests: none declared.

MEDICINE 34:11

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© 2006 Elsevier Ltd. All rights reserved.

Savage C O S. ‘Medium-sized arteries’ are the main visceral arteries (e. Table 1 depleting agents are on the horizon and are showing promise in pilot studies. mesenteric). associated with asthma and blood eosinophilia Necrotizing vasculitis with few or no immune deposits affecting small vessels (capillaries. Note that some small and large vessel vasculitides may involve medium-sized arteries. arteries) Eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels. associated with mucocutaneous lymph node syndrome Granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels (capillaries.6 ◆ 2 Jennette J C. medium-sized and small arteries. venules. arterioles) Vasculitis with IgA-dominant immune deposits affecting small vessels (capillaries. venules. renal. Harper L. J Am Soc Nephrol 2006.SYSTEMIC VASCULITIDES Classification of vasculitis as adopted by the Consensus Conference on the Nomenclature of Systemic Vasculitis Large vessel vasculitis • Giant cell (temporal) arteritis • Takayasu’s arteritis Medium-sized vessel vasculitis • Polyarteritis nodosa* (classic polyarteritis nodosa) • Kawasaki disease Small vessel vasculitis • Wegener’s granulomatosis** • Churg–Strauss syndrome** • Microscopic polyangiitis** (microscopic polyarteritis) • Henoch–Schönlein purpura • Essential cryoglobulinaemic vasculitis • Cutaneous leucocytoclastic angiitis Granulomatous arteritis of the aorta and its major branches. the extremities. Anti-neutrophil cytoplasm associated glomerulonephritis. Weyand C M.g. 17: 1224–34. New York: Dekker. arterioles) Vasculitis with cryoglobulin immune deposits affecting small vessels (capillaries. . hepatic. arterioles.g. Andrassy K et al. capillaries or venules Arteritis involving large. venules. All rights reserved. coronary. **Strongly associated with antineutrophil cytoplasm antibodies. Falk R J. gut and glomeruli Associated with arthralgia or arthritis Skin and glomeruli often involved ‘Large arteries’ are the aorta and the largest branches directed towards major body regions (e. *Preferred term. 3 Morgan M D. Nomenclature of systemic vasculitides: The proposal of an international consensus conference. Inflammatory diseases of blood vessels. Williams J. arterioles) and associated with cryoglobulins in serum Isolated cutaneous leucocytoclastic angiitis without systemic vasculitis or glomerulonephritis Often involves the temporal artery Usually occurs > 50 years of age Often associated with polymyalgia rheumatica Usually occurs < 50 years of age Coronary arteries often involved Aorta and veins may be involved Usually occurs in children Necrotizing glomerulonephritis common Necrotizing arteritis involving small and medium-sized arteries may be present Necrotizing glomerulonephritis very common Pulmonary capillaritis often occurs Typically involves skin. venules. References 1 Hoffman G S. ‘Small arteries’ are distal arterial radicals that connect with arterioles. 2001. head and neck). but large and medium-sized vessel vasculitides do not involve vessels smaller than arteries. with a predilection for the extracranial branches of the carotid artery Granulomatous inflammation of the aorta and its major branches Necrotizing inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles. 37: 187–92. MEDICINE 34:11 454 © 2006 Elsevier Ltd. Arthritis Rheum 1994.

g. N Engl J Med 2005. 6 Keogh K A. and impact of treatment in 115 patients. outcome. 5 The Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group: Etanercept plus standard therapy for Wegener’s granulomatosis. All rights reserved. and may save lives 455 © 2006 Elsevier Ltd. Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics. Arthritis Rheum 2005. 52: 262–8. MEDICINE 34:11 Practice points • Vasculitis may present to various specialists. French Vasculitis Study Group. Wylam M E. Specks U. pyrexia of unknown origin) • Vasculitis of any type should always be regarded as a medical emergency – early treatment reduces organ damage and failure. 352: 351–61. febrile children. diagnosis is easy if the possibility is included in appropriate differential diagnoses (e.SYSTEMIC VASCULITIDES 4 Guillevin L. Mahr A. Medicine (Baltimore) 2005. . Callard P et al. 84: 313–22. Stone J H. Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis.