Vasculitides

Vasculitides and ANCA Testing

ANCA testing should not routinely be initiated by primary care. GPs who suspect ANCA associated vasculitis should discuss their patient promptly with secondary care: these diseases are exceptionally rare, require complex multi-system investigation but can also be associated with rapid (and at times life-threatening) clinical deterioration.

Vasculitides

The vasculitides are divided into large, medium and small vessel vasculitis.

Large: no immunology tests

• Giant cell arteritis
• Takayasu vasculitis
  

Medium: no immunology tests

• Polyarteritis nodosa
• Kawasaki disease

Small: ANCA

Small/Medium Vessel Vasculitis

Early non-specific symptoms: fever, malaise, arthralgia, myalgia, weight loss.

Differential diagnosis: primary or secondary causes

Primary small vessel vasculitis	Secondary small vessel vasculitis
Wegener’s granulomatosis*	Rheumatoid arthritis
Microscopic polyangiitis*	SLE
Churg Strauss*	Sjogren’s syndrome
Henoch Schonlein purpura	Drugs
Cryoglobulinaemic vasculitis	Infections – e.g. HIV and Hepatitis C
Isolated cutaneous leukocytoclastic vasculitis

*ANCA associated

Essential investigations: inflammatory markers, full blood count, renal function and urinalysis to look for microscopic haematuria and proteinuria.

Wegener’s Granulomatosis (WG) now known as Granulomatosis with Polyangiitis (GPA)

Incidence

• Rare 8.4 per million annually 

Features

• Triad of upper and lower airways plus renal disease (limited forms are recognised but may progress to generalised disease)
• Granulomatous inflammation involving respiratory tract
• Necrotising vasculitis affecting small to medium sized vessels of glomerulus

Clinical symptoms & signs

• Upper respiratory tract: sinusitis – nasal crusting, bleeding, obstruction and collapse of nasal bridge, serous otitis media, tracheal stenosis
• Lung disease: cough, haemoptysis, dyspnoea, pulmonary haemorrhage, lung nodules
• Renal disease: blood, protein, casts in urine, renal failure
• Other features: purpuric rashes, nail fold infarcts, conjunctival haemorrhages, scleritis, uveitis, keratitis, proptosis or ocular muscle paralysis due to retro-orbital inflammation

Microscopic polyangiitis (MPA)

• Necrotizing vasculitis of small and medium sized vessels of glomerulus and pulmonary capillaries
• No granuloma are seen and disease of the upper respiratory tract is uncommon

Churg Strauss Syndrome (CSS)

• Often necrotizing vasculitis affecting small to medium-sized vessels
• Eosinophil rise and granulomatous inflammation involving the respiratory tract
• associated with asthma

ANCA testing

ANCA is measured by indirect immunofluorescence (IIF) and/or ELISA screen.  IIF is reported as negative/borderline/positive/strongly positive and the following ANCA staining patterns are reported: pANCA, c-ANCA, atypical p-ANCA, atypical c-ANCA or atypical ANCA.  ELISA will identify PR3–ANCA which are auto-antibodies to proteinase 3 or MPO-ANCA auto-antibodies to myeloperoxidase.

C-ANCA is not equivalent to PR3-ANCA and p-ANCA is not equivalent to MPO-ANCA. P and c-ANCA are staining patterns which are positive to a variety of antigens, e.g. only 50% of positive c-ANCA is due to PR3-ANCA and only approx 25% of p-ANCA are due to autoantibodies to MPO.

Wegener’s Granulomatosis (WG) is associated with PR3-ANCA. Microscopic Polyangiitis (MPA) and Churg Strauss Syndrome (CSS) are associated with MPO-ANCA. However there is no absolute specificity and cross over may occur. In addition 10-20% of patients with WG or MPA and 45-50% of CSS have negative ANCA results. Levels of ANCA can also fluctuate and may be negative before and during a disease exacerbation.

If IIF and ELISA results are combined, the presence of p-ANCA and anti-MPO has 99% specificity for the diagnosis of primary systemic vasculitis, as does the combination of c-ANCA and anti-PR3. But this ‘dual testing’ has cost implications. At present our RIE laboratory recommends ELISA testing in the first instance as presence of PR3/MPO-ANCA has more clinical significance. But if needed IIF can be specifically requested as occasionally individuals can be negative in ELISA testing and positive with IIF.

In 1999 there was an international consensus statement on testing and reporting of ANCA. They advised it should be used for the following clinical indications:

• Glomerulonephritis, especially RPGN
• Pulmonary Haemorrhage, especially pulmonary renal syndrome
• Cutaneous vasculitis with systemic features
• Multiple lung nodules
• Chronic destructive disease of upper airways
• Long standing sinusitis or otitis
• Subglottic tracheal stenosis
• Mononeuritis multiplex or other peripheral neuropathy
• Retro-orbital mass

Recommendation: ANCA testing should not routinely be initiated by primary care. ANCA associated vasculitis is very rare. GPs who suspect vasculitis should discuss their patient promptly with secondary care.