Vasculitides

Vasculitides and Anti-Neutrophil Cytoplasmic Antibody (ANCA) Testing

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. Whilst requesting ANCA testing may not be required routinely or often through Primary Care, there may be situations when this could help in earlier diagnosis of ANCA associated vasculitis in some patients.

Vasculitides

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

Large: no immunology tests¹

• Giant cell arteritis
• Takayasu vasculitis
  

Medium: no immunology tests

• Polyarteritis nodosa
• Kawasaki disease

Small: ANCA²

Small/ Medium Vessel Vasculitis

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

It is RARE with an incidence of 5-15 per million annually in the UK.

Differential diagnosis: primary or secondary causes

Primary small vessel vasculitis	Secondary small vessel vasculitis
Granulomatosis with polyangiitis (GPA, previously known as Wegener’s granulomatosis)*	Rheumatoid arthritis
Microscopic polyangiitis*	SLE
Eosinophilic granulomatosis with polyangiitis (EGPA, previously known as Churg Strauss Syndrome)*	Sjogren’s syndrome
Ig A vasculitis (previously known as Henoch Schonlein purpura)	Drugs
Cryoglobulinaemic vasculitis	Infections – e.g. HIV and Hepatitis C
Isolated cutaneous leukocytoclastic vasculitis

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
• Kidney disease: asymptomatic urinary abnormalities (haematuria, proteinuria), abnormal kidney function through to rapidly declining kidney function
• Eye disease: conjunctivitis, scleritis & episcleritis, uveitis, optic tract granulomata & proptosis
• Nerve disease: mononeuritis multiplex, CNS vasculitis (uncommon)
• Skin involvement: purpuric rashes, nail fold infarcts
• EGPA is associated with blood eosinophilia and asthma.

Essential investigations: 

Inflammatory markers (C-reactive protein, serum albumin), full blood count, renal function and urinalysis to look for microscopic haematuria and proteinuria, CXR if any respiratory symptoms.

ANCA testing

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

It is essential to note that negative ANCA / MPO / PR3 test results do not exclude a diagnosis of vasculitis, and where there is clinical concern, tissue biopsy for histological diagnosis is recommended, as this remains the gold standard test for vasculitis diagnosis.

1999 International consensus statement on testing and reporting of ANCA advises that ANCA testing should be considered for the following clinical indications:³

• 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
• Scleritis

The updated consensus on ANCA testing in 2017⁴ highlighted the importance of having a high pre-test probability (clinical parameters to indicate a diagnosis of ANCA associated vasculitis) when requesting ANCA testing in order to yield most effective utility of these tests, as false positive tests and false negative tests can often be seen. Early signs and symptoms of vasculitis may be non-specific and may mimic PMR type symptoms in some individuals, and therefore a careful clinical screen and monitoring for any other features of vasculitis in this group of patients may be helpful in the earlier diagnosis of vasculitis.

Urgent (same day) ANCA testing is offered through the Immunology laboratory and should be arranged only after discussion with clinical teams in secondary care.  This test can be arranged by telephoning the laboratory, with details found: Test Directory | Edinburgh and Lothians Laboratory Medicine

Recommendation: ANCA testing is unlikely to be required to be initiated by primary care. ANCA associated vasculitis is rare, and GPs who suspect vasculitis should discuss their patient promptly with secondary care. The NHS Lothian Vasculitis Service can be contacted through Prof Neeraj Dhaun (Bean.Dhaun@nhs.scot )

References:

1. Kitching, A.R., Anders, HJ., Basu, N. et al. ANCA-associated vasculitis. Nat Rev Dis Primers 6, 71 (2020). https://doi.org/10.1038/s41572-020-0204-y
2. Pugh, D., Karabayas, M., Basu, N. et al. Large-vessel vasculitis. Nat Rev Dis Primers 7, 93 (2021). https://doi.org/10.1038/s41572-021-00327-5
3. Judy Savige, David Gillis, Elizabeth Benson, David Davies, Vincent Esnault, Ronald J. Falk, E. Chris Hagen, David Jayne, J. Charles Jennette, Bill Paspaliaris, Wendy Pollock, Charles Pusey, Caroline O. S. Savage, Roger Silvestrini, Fokko van der Woude, Jorgen Wieslander, Allan Wiik, International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA), American Journal of Clinical Pathology, Volume 111, Issue 4, 1 April 1999, Pages 507–513
4. Bossuyt, X., Cohen Tervaert, JW., Arimura, Y. et al. Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol 13, 683–692 (2017). https://doi.org/10.1038/nrrheum.2017.140

C.M. & C.C/N.D. 23-01-25