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 blood vessels throughout the body, especially in the small blood vessels. ANCA-associated vasculitis group consists of 3 central subtypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).¹ 

In these conditions, ANCA autoantibodies attack protein components within neutrophils, including myeloperoxidase (MPO) and proteinase 3 (PR3).¹ Depending on which protein is targeted by the ANCA autoantibodies, the neutrophils respond in either a perinuclear (pANCA) pattern with MPO or a cytoplasmic (cANCA) pattern with PR3.^1,2 These ANCA-bound proteins cause neutrophil activation and degranulation, resulting in inflammation and endothelial cell damage within blood vessels.³ 

The clinical features of AAV are linked to this pathophysiological inflammation, which is the primary feature of the condition. It can result in bleeding, disruption of vascular structures, and organ dysfunction. Effects may manifest beyond the immediate site of vascular inflammation and affect distant organs and tissues. Patients often experience respiratory, cardiac, and renal involvement along with constitutional symptoms, such as fever, muscle aches, and weight loss.⁴

Given the multisystemic nature of AAV, a comprehensive workup and differential diagnosis are required for an accurate diagnosis and effective treatment. It is important to rule out conditions that present with similar features, as several disorders may mimic signs and symptoms of AAV. A key feature of AAV is the presence of ANCA autoantibodies. However, a small percentage of patients test negative for both the pANCA and cANCA patterns.^1,4 

Immune Complex Vasculitis

Immune complex vasculitis also affects small blood vessels, and the signs and symptoms are similar to those of ANCA-associated vasculitis.¹ 

The difference between the 2 conditions is revealed in histopathology. In immune complex vasculitis, abundant immune complex deposition is seen in affected tissues, whereas in ANCA-associated vasculitis, this feature is absent.¹

Immune complex vasculitis may be triggered by infections including hepatitis B, hepatitis C, HIV infection, and endocarditis. Chronic hepatitis C may contribute to the development of cryoglobulinemia, a type of immune complex vasculitis. Autoimmune conditions such as Sjögren syndrome, rheumatoid arthritis, and systemic lupus erythematosus may also trigger immune complex vasculitis.¹ 

Read more about AAV histology

Antiglomerular Basement Membrane Disease

Antiglomerular basement membrane disease, also known as Goodpasture syndrome, affects the kidneys and lungs similarly to AAV. Features of Goodpasture syndrome may include diffuse pulmonary hemorrhage, hemosiderosis, alveolitis, and primary crescentic glomerulonephritis.⁵ 

Approximately 10% to 40% of patients with Goodpasture syndrome test positive for ANCA antibodies in addition to anti-basement membrane antibodies (dual positivity).^1,5 

In one case report, over 90% of the patients who tested positive for ANCA had pauci-immune crescentic glomerulonephritis, which is defined as an absence or paucity of immune complex deposition in the glomeruli.^5,6 The researchers stated they had observed a correlation among ANCA positivity, pulmonary hemorrhage and hemosiderosis with neutrophil margination, suggestive of subtle MPA, and pauci-immune crescentic glomerulonephritis on renal biopsy.⁵ 

Read more about AAV testing

Atrial Myxoma

Atrial myxoma is a noncancerous tumor located in the upper left or right chamber of the heart that is frequently found on the atrial septum.⁷ Patients with atrial myxoma may present with constitutional symptoms, such as fatigue, weight loss, and fever, as well as purpura, neurological deficits, and pulmonary injury due to embolism.¹ Echocardiography may effectively identify atrial myxoma as differentiated from ANCA-associated vasculitis.⁸

Read more about AAV clinical features

Hematologic Malignancies

Rarely, malignancies such as lymphomas and paraneoplastic diseases may mimic ANCA vasculitis.¹ Lymphoproliferative disorders increase the likelihood that an autoimmune comorbidity such as AAV will develop.⁹

One retrospective study identified 16 patients with both AAV and a hematopoietic malignancy (eg, non-Hodgkin lymphoma, myelodysplasia, Hodgkin lymphoma, multiple myeloma, and other hematologic neoplasms).⁹ 

Read more about AAV risk factors

References

1. Qasim A, Patel JB. ANCA positive vasculitis. StatPearls [Internet]. Updated May 29, 2022. Accessed March 8, 2023.
2. 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
3. Cartin-Ceba R, Peikert T, Specks U. Pathogenesis of ANCA-associated vasculitis. Rheum Dis Clin North Am. 2010;36(3):463-477. doi:10.1016/j.rdc.2010.05.006
4. ANCA vasculitis. UNC Kidney Center. Accessed March 8, 2023.
5. Ward ND, Cosner DE, Lamb CA, et al. Top differential diagnosis should be microscopic polyangiitis in ANCA-positive patient with diffuse pulmonary hemorrhage and hemosiderosis. Case Rep Pathol. 2014;2014:286030. doi:10.1155/2014/286030
6. Lin W, Shen C, Zhong Y, et al. Glomerular immune deposition in MPO-ANCA associated glomerulonephritis is associated with poor renal survival. Front Immunol. 2021;12:625672. doi:10.3389/fimmu.2021.625672
7. Atrial myxoma. MedlinePlus. Accessed March 8, 2023. 
8. Sargin G, Senturk T. Left atrial myxoma mimicking polyarteritis nodosa. Yonsei Med J. 2015;56(4):1165-1166. doi:10.3349/ymj.2015.56.4.1165
9. Folci M, Ramponi G, Shiffer D, Zumbo A, Agosti M, Brunetta E. ANCA-associated vasculitides and hematologic malignancies: Lessons from the past and future perspectives. J Immunol Res. 2019;2019:1732175. doi:10.1155/2019/1732175

 

Reviewed by Harshi Dhingra, MD, on 3/11/2023.

---

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.