26th February 2025

Small-vessel vasculitis

ANCA-associated vasculitides

These conditions are classically severe small-vessel vasculitides associated with anti-neutrophil proteins. However, confusingly, not all patients are ANCA-positive. They most commonly affect older adults.

These often start off with systemic features, including malaise, fevers, night sweats, weight loss, anorexia and arthralgia, which are commonly misdiagnosed before presenting with more classical symptoms.

Glucocorticoids are generally used to induce remission, followed by ongoing treatment to maintain remission, such as cyclophosphamide and rituximab.

The three key subtypes are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA).

Granulomatosis with polyangiitis

GPA was formerly known as Wegener’s granulomatosis.

Clinical features are as follows:

• Up to 90% of patients have ENT involvement, such as nasal crusting, sinusitis, rhinorrhoea, otorrhoea or otitis media. Hearing loss is common and can be conductive or sensorineural. Nasal bone and cartilage destruction can lead to saddle-nose deformity or nasal septal perforation.
• Renal involvement affects up to 90% of patients, usually as a rapidly progressive glomerulonephritis.
• Lung involvement can occur, affecting the airways or parenchyma, and presents with haemoptysis, dyspnoea, stridor or wheeze. Imaging can show nodules, pulmonary infiltrates or hilar lymphadenopathy.
• Cutaneous vasculitis is seen in around half of patients, commonly presenting as purpuric lesions on the lower limbs.
• Mononeuritis multiplex can be seen, but less commonly than in microscopic polyangiitis. It is usually associated with a worse prognosis.

Investigation findings include:

• If the disease is flaring, blood tests will often show elevated WCC, platelets and inflammatory markers.
• ANCA is positive in around 80-90% of patients, and GPA is most commonly associated with PR3-ANCA (C-ANCA). However, up to 20% are MPO-ANCA positive, and some are ANCA negative, particularly if the disease is quiescent.
• Urinalysis and microscopy may show microscopic haematuria or red cell casts.
• Diagnosis is confirmed by biopsy of involved tissue, usually renal or skin, which shows granulomatous inflammation. Renal biopsy will show ‘pauci-immune’ glomerulonephritis, meaning there are few immune deposits in the glomeruli.

Microscopic polyangiitis (MPA)

This shares many features with GPA; however, lacks the granulomatous inflammation. It is one of the pulmonary-renal syndromes, along with anti-GBM disease, and haemoptysis and renal involvement are the most common features.

Eighty percent of patients are ANCA-positive. This is usually an MPO-ANCA antibody with a P-ANCA (perinuclear) pattern on immunofluorescence.

Eosinophilic granulomatosis with polyangiitis (EGPA)

This was formerly known as Churg-Strauss syndrome.

Although classified as an ANCA-associated vasculitis, only around 50% of patients have a detectable ANCA antibody. It is a triad of features including late-onset asthma, eosinophilia and systemic vasculitis.

Specific clinical features are as follows:

• Respiratory involvement is the most common presentation of EGPA, with asthma generally presenting 8-10 years prior to systemic vasculitis. The asthma is often difficult to control, and patients will have required multiple courses of oral steroids. Leukotriene inhibitors such as montelukast have been associated with unmasking EGPA. Imaging can reveal ‘fleeting’ pulmonary infiltrates, nodules or pleural effusion.
• Cutaneous ulcers and nodules are common.
• Cardiac involvement can occur in severe disease and is an important cause of mortality, causing around half of all deaths. This can manifest with pericarditis, arrhythmias or heart failure. 
• Mononeuritis multiplex may be seen.

Investigation findings include:

• Eosinophilia, usually >1.5 x 109/L.
• In uncontrolled disease, there is often a leucocytosis with elevated inflammatory markers.
• ANCA is positive in around half of patients, and this will usually be MPO-ANCA.