ANCA-Associated Vasculitis (AAV)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a group of rare autoimmune conditions characterized by inflammation and the destruction of predominantly small blood vessels. These conditions include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA). Additional ANCA-associated disorders include renal-limited vasculitis and drug-induced vasculitis.1

Epidemiology of AAV

ANCA-associated vasculitides are rare conditions, affecting between 10 and 20 individuals per million people. GPA is the most common of the 3 main forms, affecting between 5 and 10 individuals per million people. MPA has the second-highest incidence rate and affects men more frequently than women (2:1 ratio). EGPA is the rarest form of ANCA-associated vasculitis.1

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Etiology of AAV

In ANCA-associated vasculitis, which is an autoimmune condition, 2 types of ANCA may attach to specific proteins within the cytoplasm of neutrophils, a type of white blood cell.2 

The pattern of the autoimmune response may be perinuclear (pANCA, surrounding the cell nucleus) or diffuse (cANCA, occurring throughout the cytoplasm).1 pANCA targets neutrophils containing myeloperoxidase (MPO), whereas cANCA attaches to neutrophils containing proteinase 3 (PR3).1 In patients with MPO-ANCA vasculitis, features of MPA predominate, whereas in those with PR3-ANCA vasculitis, clinical features of GPA are more common.3 

Neutrophils become partially activated by tumor necrosis factor alpha (TNFα), complement C5a, or a lipopolysaccharide. Once the ANCA binds to either MPO or PR3 protein in the neutrophil cytoplasm, the neutrophils become fully activated, degranulating and causing endothelial cell damage within blood vessels.1 

Other studies indicate that ANCA also activate intracellular signaling pathways that promote neutrophil migration and adhesion to vascular endothelium.1

There is some debate over whether the autoimmune response is triggered by such factors as infection and environmental exposures or if a genetic component is involved (polymorphisms in the HLA gene).1

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Symptoms of AAV

Common symptoms of ANCA-associated vasculitis include1:

  • Fatigue
  • Myalgia
  • Peripheral neuropathy causing weakness and numbness in the extremities
  • Fever
  • Cough
  • Hemoptysis
  • Abdominal pain
  • Hematuria/proteinuria

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Diagnosis of AAV

The diagnosis of ANCA-associated vasculitis requires a comprehensive physical examination and history, specific serological testing for anti-PR3 or anti-MPO antibodies, and tissue biopsy to confirm the ANCA-associated vasculitis subtype.1 

Biopsy of GPA-affected tissues reveals vasculitis with necrotizing granulomas, except in the kidneys, which exhibit vasculitis in the absence of granulomas. Patients with MPA frequently test positive for anti-MPO antibodies with a pANCA pattern. In EGPA, biopsy of the tissues and testing of the peripheral blood reveal excessive amounts of eosinophils; however, approximately 40% of patients with EGPA are ANCA-negative.1 

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Complications of AAV

Disease-related complications include end-organ damage (especially the lungs and kidneys), increased risk of cardiovascular disease and events, and increased risk of hemorrhage, which may be life-threatening if it occurs in the brain, lungs, or gastrointestinal tract.1 Peripheral neuropathy may affect a patient’s ability to feel, walk, or perform daily activities as related to weakness, pain, or lack of sensation.4 

Treatment-related complications include bone marrow failure, malignancy, chemical cystitis, diabetes, osteoporosis, and gonadal failure leading to infertility.1 

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Prognosis of AAV

With advancements in treatments and technology, the prognosis for patients with ANCA-associated vasculitis has improved from a 1-year mortality rate of 80% to prolonged remission, and the mortality rate has decreased to 10%. However, relapses are frequent, often occurring within 5 years in over 50% of patients with GPA.1

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Treatment of AAV

ANCA-associated vasculitis is treated in 3 phases: induction of disease remission, maintenance to prevent relapse, and treatment of relapse. Treatment objectives are to prevent or slow the progression of end-organ damage and reduce widespread inflammation.1

In cases of moderate-to-severe ANCA-associated vasculitis, induction involves a combination of high-dose glucocorticoids to reduce inflammation and either Rituxan® (rituximab) or Cytoxan® (cyclophosphamide) to achieve remission. Sometimes, plasma exchange may be added to the induction treatment, particularly in the context of severe kidney disease or life-threatening, disease-related sequelae.1 Patients with milder forms of ANCA-associated vasculitis may receive treatment with methotrexate or CellCept® (mycophenolate mofetil) to achieve remission.1 

Maintenance involves reduction or elimination of the steroid dose and withdrawal from the immunosuppressive regimen before initiation of treatment with either methotrexate or Imuran® (azathioprine). The duration of maintenance therapy may range from 18 to 24 months to prevent relapse.5

In cases of relapse, Rituxan is more often the treatment of choice because of its superior performance vs Cytoxan.1,6 

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  1. Qasim A, Patel JB. ANCA positive vasculitis. StatPearls [Internet]. Updated May 29, 2022. Accessed February 23, 2023. 
  2. ANCA vasculitis. UNC Kidney Center. Accessed February 23, 2023.
  3. Xiao H, Hu P, Falk RJ, Jennette JC. Overview of the pathogenesis of ANCA-associated vasculitis. Kidney Dis (Basel). 2016;1(4):205-215. doi:10.1159/000442323
  4. Koike H, Nishi R, Ohyama K, et al. ANCA-associated vasculitic neuropathies: a review. Neurol Ther. 2022;11(1):21-38. doi:10.1007/s40120-021-00315-7
  5. Yates M, Watts R. ANCA-associated vasculitis. Clin Med (Lond). 2017;17(1):60-64. doi:10.7861/clinmedicine.17-1-60
  6. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232. doi:10.1056/NEJMoa0909905

Reviewed by Harshi Dhingra, PhD, on 2/25/2023.