ANCA-Associated Vasculitis (AAV)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare, autoimmune conditions characterized by inflammation and swelling that results in damage to small blood vessels throughout the body.¹ 

ANCAs are autoantibodies that mistakenly attack healthy, normal neutrophils in 2 distinct patterns: perinuclear ANCA (pANCA) patterns against neutrophil myeloperoxidase (MPO) and cytoplasmic ANCA (cANCA) patterns against neutrophil proteinase 3 (PR3).²

Three main clinical disease entities fall under the classification of ANCA-associated vasculitis: granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA).^2,3 

Left untreated, severe ANCA-associated vasculitis can be fatal within months, especially in cases that affect the respiratory system. Because of this, it is essential for patients to receive an accurate and rapid diagnosis that dictates a path for treatment.^3,4

Challenging Diagnosis

However, confirming a diagnosis of ANCA-associated vasculitis can be challenging. Multiple factors and conditions can lead to the development of vasculitis, including infective endocarditis, chronic hepatitis, and antiglomerular basement membrane diseases, such as Goodpasture syndrome. As vasculitis impacts multiple systems throughout the body, it requires a comprehensive differential diagnosis.²

A comprehensive examination, including a detailed medical history and physical evaluation, is required for initial assessment of ANCA-associated vasculitis. It is important to obtain a complete list of current medications because ANCA-associated vasculitis can be drug induced.²

Read more about AAV differential diagnosis 

Diagnostic Testing for ANCA-Associated Vasculitis

The 2 diagnostic mainstays for ANCA-associated vasculitis include serological testing and biopsy to confirm the diagnosis, rule out other conditions, determine disease severity, and assess which organ systems are affected.²

Serological Tests for ANCA-Associated Vasculitis

Serological tests initially detect signs of vascular inflammation, including high concentrations of C-reactive protein.⁴ Repeat serological testing for these inflammatory biomarkers, electrolyte and urea tests for kidney function, and microscopic urinalysis for protein quantification allow clinicians to assess disease activity and severity during treatment. The ANCA test detects the presence of ANCA antibodies in the peripheral blood using immunofluorescent antibody techniques with a substrate of ethanol-fixed human neutrophils.^5,6

True pANCA pattern antibodies can be further differentiated from antinuclear antibodies (ANAs) via repeat testing using a formalin-fixed substrate.⁶ ANAs are seen in other autoimmune conditions, such as systemic lupus erythematosus (SLE), which can present with similar clinical signs and symptoms to ANCA-associated vasculitis.²

It is important to note that positive ANCA serology can be found in other systemic conditions, such as rheumatoid arthritis and inflammatory bowel disease, or even in asymptomatic individuals, so a positive ANCA test is not necessarily exclusive to an ANCA-associated vasculitis diagnosis.^3,7,8 

Some studies have questioned the diagnostic and predictive values of serological ANCA testing in routine clinical settings, as not all patients with ANCA-associated vasculitis test positive. One study published in 2001 reported that the positive predictive value of indirect immunofluorescent (IIF) ANCA testing for ANCA-associated systemic vasculitis was around 59%, while the negative predictive value was 84%. The positive predictive value for ANCA-associated vasculitis increased to 79% and the negative predictive value decreased to 63% when enzyme-linked immunosorbent assays (ELISA) were performed in conjunction with IIF ANCA samples that tested positive.⁹ 

Read more about AAV testing

Biopsy for ANCA-Associated Vasculitis

Ideally, a combination of serological testing and tissue biopsy is needed to confirm the diagnosis of ANCA-associated vasculitis.³ Physicians often require confirmation with a tissue biopsy due to the high-risk nature of ANCA-associated vasculitis treatment.² 

A combination of serological testing and biopsy can also differentiate the ANCA-associated vasculitis disease subtype: GPA, EGPA, or MPA.²

In patients with GPA, tissue biopsy reveals vasculitis with necrotizing granulomas throughout the body except for kidney tissue. Kidney biopsy in patients with GPA shows vasculitis without granulomas.²

In patients with EGPA, serological testing is often positive for either MPO or PR3 autoantibodies; however, up to around 40% of patients with EGPA are ANCA negative. Peripheral blood tests and biopsy of involved tissues indicate eosinophilia, a characteristic feature of EGPA necessary for diagnosis.²

In MPA, serological tests are often positive for MPO autoantibodies following a pANCA pattern.²

Read more about AAV histology

Diagnostic Criteria

The American College of Rheumatology (ACR) published guideline recommendations in 1990 specifically for GPA diagnosis to assist with differentiation from other forms of ANCA-associated vasculitis. The ACR diagnostic criteria for GPA include:^10,11

• Urinary sediment showing red blood cell casts or more than five red blood cells per high power field;
• Abnormal findings on chest radiograph;
• Oral ulcer or nasal discharge; and 
• Granulomatous inflammation on biopsy. 

The presence of two or more of these four criteria is associated with a 92% specificity and 88% sensitivity.^10,11

Read more about AAV guidelines

References

1. What is ANCA vasculitis? ANCA Vasculitis News. Updated May 20, 2021. Accessed February 20, 2023.
2. Qasim A, Patel JB. ANCA positive vasculitis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated May 29, 2022. Accessed February 20, 2023. 
3. Houben E, Bax WA, van Dam B, et al. Diagnosing ANCA-associated vasculitis in ANCA positive patients: a retrospective analysis on the role of clinical symptoms and the ANCA titre. Medicine (Baltimore). 2016;95(40):e5096. doi:10.1097/MD.0000000000005096
4. Walton EW. Giant-cell granuloma of the respiratory tract (Wegener’s granulomatosis). Br Med J. 1958;2(5091):265-270. doi:10.1136/bmj.2.5091.265
5. Antineutrophil cytoplasmic antibodies (ANCA) test. MedlinePlus. Updated March 2, 2021. Accessed February 20, 2023.
6. Antineutrophil cytoplasmic antibodies (ANCA). Labcorp. Accessed February 20, 2023.
7. Jennette JC, Falk RJ, Wilkman AS. Anti-neutrophil cytoplasmic autoantibodies–a serologic marker for vasculitides. Ann Acad Med Singap. 1995;24(2):248-253. 
8. de Bandt M, Meyer O, Haim T, Kahn MF. Antineutrophil cytoplasmic antibodies in rheumatoid arthritis patients. Br J Rheumatol. 1996;35(1):38-43. doi:10.1093/rheumatology/35.1.38
9. McLaren JS, Stimson RH, McRorie ER, Coia JE, Luqmani RA. The diagnostic value of anti-neutrophil cytoplasmic antibody testing in a routine clinical setting. QJM. 2001;94(11):615-621. doi:10.1093/qjmed/94.11.615
10. Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis & Rheumatism. 1990;33(8):1101-1107. doi:10.1002/art.1780330807
11. Garlapati P, Qurie A. Granulomatosis with polyangiitis. In: StatPearls. StatPearls Publishing; 2022. Accessed February 22, 2023.

Reviewed by Kyle Habet, MD, on 2/22/2023.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.