Vasculitides

A diverse group of disorders characterised by inflammation of blood vessel walls, producing tissue ischaemia and organ damage through luminal narrowing, occlusion, aneurysm formation or rupture, classified principally by the calibre of vessel predominantly affected, which provides the essential framework for approaching diagnosis and recognising the characteristic clinical patterns of each specific condition.

Classification by vessel size

Large vessel vasculitis affects the aorta and its major branches, comprising giant cell arteritis and Takayasu arteritis.

Medium vessel vasculitis affects the main visceral arteries and their branches, comprising polyarteritis nodosa and Kawasaki disease.

Small vessel vasculitis affects arterioles, venules and capillaries, divided into antineutrophil cytoplasmic antibody associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis) and immune complex mediated small vessel vasculitis (IgA vasculitis, cryoglobulinaemic vasculitis, cutaneous small vessel vasculitis).

Variable vessel vasculitis, including Behçet disease, can affect vessels of any size.

Primary versus secondary vasculitis

Primary vasculitis occurs as an idiopathic condition in its own right, while secondary vasculitis occurs in association with another underlying disease (connective tissue disease, infection, malignancy) or as a drug reaction, an important distinction since treatment of secondary vasculitis centres on addressing the underlying trigger alongside any necessary immunosuppression.

Constitutional symptoms (fever, malaise, weight loss, fatigue) are common across the vasculitides, reflecting the systemic inflammatory burden, and are frequently the earliest presenting features before organ specific manifestations emerge.

Cutaneous features vary by vessel size affected, with palpable purpura characteristic of small vessel involvement, livedo reticularis and nodules more typical of medium vessel disease, and, in large vessel disease, cutaneous involvement is generally absent, with the clinical picture instead dominated by ischaemic symptoms in the territory of the affected large vessels.

Renal involvement, ranging from asymptomatic haematuria and proteinuria to rapidly progressive glomerulonephritis, is a major determinant of morbidity in several of the small and medium vessel vasculitides and requires active screening.

Pulmonary involvement (haemoptysis from alveolar haemorrhage, nodules, infiltrates) is a hallmark of several forms of antineutrophil cytoplasmic antibody associated vasculitis and can be life threatening.

Peripheral neuropathy (mononeuritis multiplex, a characteristic pattern in several medium and small vessel vasculitides), gastrointestinal ischaemia, and ocular involvement (episcleritis, scleritis, uveitis) reflect the multisystem nature of vessel inflammation affecting virtually any organ.

The specific pattern and combination of organ involvement, together with the characteristic demographic and serological profile, guides identification of the specific vasculitis subtype, each detailed in the following sections.

Inflammatory markers (erythrocyte sedimentation rate, C reactive protein) are typically elevated and useful for monitoring disease activity, though non specific and occasionally normal even in active disease.

Antineutrophil cytoplasmic antibody testing, with specific antigen testing (proteinase 3 and myeloperoxidase) where the screening test is positive, is central to diagnosis and classification of the antineutrophil cytoplasmic antibody associated small vessel vasculitides.

Full blood count, renal function and urinalysis with microscopy for red cell casts and dysmorphic red cells screen for renal involvement, which should be checked in every patient with suspected vasculitis given its frequently silent onset and major prognostic significance.

Tissue biopsy from an affected organ (skin, kidney, nerve, lung) remains the diagnostic reference standard for most vasculitides, demonstrating the characteristic pattern of vessel wall inflammation and, where present, granulomatous change or necrotising features specific to the subtype.

Imaging appropriate to the suspected vessel calibre and affected territory (magnetic resonance angiography or computed tomography angiography for large vessel disease, conventional angiography for medium vessel disease demonstrating microaneurysms) supports diagnosis, particularly where biopsy is not feasible or has been non diagnostic.

Exclude vasculitis mimics, particularly infection (infective endocarditis, disseminated infection) and other causes of multisystem disease, since treatment with immunosuppression in a missed infection can be catastrophic, making this exclusion a critical early step in every suspected vasculitis workup.

Management principles are broadly shared across the vasculitides though intensity and specific agents vary by subtype and severity: induction of remission with high dose corticosteroids, often combined with a second immunosuppressive agent for organ or life threatening disease, followed by a maintenance phase using a steroid sparing agent to sustain remission while minimising cumulative treatment toxicity.

Cyclophosphamide or rituximab are the standard induction agents for severe antineutrophil cytoplasmic antibody associated vasculitis with organ threatening disease, with methotrexate, azathioprine or rituximab used for maintenance.

Plasma exchange is reserved for the most severe presentations, particularly with rapidly progressive glomerulonephritis or diffuse alveolar haemorrhage.

Milder or limited disease may be managed with corticosteroids alone or in combination with a conventional steroid sparing agent, without the need for cyclophosphamide or rituximab induction.

Long term surveillance for disease relapse, treatment related toxicity (particularly infection given cumulative immunosuppression, and infertility or malignancy risk with cyclophosphamide) and for organ damage accrual underpins the chronic management of most vasculitides, given their typically relapsing remitting course.

Multidisciplinary input (rheumatology, nephrology, respiratory medicine, dermatology, ophthalmology) according to the pattern of organ involvement is essential, with the specific management of each named vasculitis detailed in the sections that follow.