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Clinical Features

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a group of rare autoimmune hematological conditions characterized by inflammation and the destruction of blood vessels throughout the body. 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

The clinical manifestations vary, given that ANCA-associated vasculitis can affect almost any region of the body. However, it most frequently affects the upper airways, lungs, kidneys, nervous system, and eyes.²

The specific clinical presentation depends on the subtype of ANCA-associated vasculitis. Patients who have GPA often present with granulomatous lesions of the upper and/or lower respiratory tract.³ Those with EGPA present with hypereosinophilia on peripheral blood testing, as well as eosinophilic infiltration of various organs, especially the heart.³

Respiratory Features

Lower Airway

Lower respiratory signs and symptoms of lung disease include:

Hemoptysis, shortness of breath, and acute decline in hemoglobin, suggestive of alveolar hemorrhaging^1,2,4;
Progressive shortness of breath, cough, and wheezing (especially when accompanied by constitutional symptoms or fine crackles on auscultation, which may indicate pulmonary fibrosis,² often associated with MPA)⁴;
Refractory asthma requiring steroid treatment²; and
Lung nodules on imaging.^1,4

According to studies, lower respiratory tract involvement is one of the predominant clinical features, occurring in 45% to 67% of patients with ANCA-associated vasculitis.^2,5

Symptoms of ANCA vasculitis can be severe and fatal, including alveolar hemorrhage, lung nodules, and, rarely, tracheal stenosis.¹

It is important to note that if cavitating lung lesions are detected in patients with GPA, they can easily be misdiagnosed with lung cancer. Correct diagnosis can be delayed or missed due to symptoms in disparate organs as they are not recognized as manifestations of a single disease.²

Read more about AAV complications

Upper Airway/Ear/Nose/Throat

Signs and symptoms suggestive of upper airway involvement in patients with ANCA-associated vasculitis include:

Bloody nasal discharge or nasal crusting^1,2;
Chronic recurrent or persistent sinusitis^1,2;
Nasal ulceration¹;
Damage to the nasal cartilage or bridge of the nose causing a saddle nose deformity¹ (late sign of advanced disease)²;
Chronic otitis media^1,2;
Hearing loss or earache²; and
Subglottic tracheal stenosis(discovered rarely during workup for stridor or dyspnea, or discovered incidentally during intubation for general anesthesia).^1,2

Read more about AAV diagnosis

Renal Features

Renal involvement is another leading clinical feature of ANCA-associated vasculitis, occurring in approximately 50% to 65% of patients.^2,5

Signs and symptoms of renal involvement include:

Elevated serum creatine²;
Declining estimated glomerular filtration rate (eGFR)²;
New onset of proteinuria suggestive of glomerulonephritis (more than trace amounts on urinalysis)^1,2;
Active urinary sediments indicative of hematuria or leukocyturia (more than trace amounts on urinalysis)^1,2;
Hypertension¹; and
Rapid progression to renal failure.¹

It is important to note that in the early stages of ANCA-associated vasculitis, the eGFR may be nearly normal, and symptoms indicating renal disease may be absent.² In some cases, glomerulonephritis may be the only clinical manifestation of the disease, potentially indicating renal-limited ANCA-associated vasculitis or MPA.⁴

Read more about AAV types

Neurological Features

Up to approximately 30% of patients with ANCA-associated vasculitis may present clinically with muscle weakness, difficulty walking, paresthesias such as numbness, and peripheral neuropathy — particularly manifesting as foot drop or wrist drop — in the absence of another possible etiological factor such as diabetes or vitamin B12 deficiency.²

Read more about AAV comorbidities

Constitutional Symptoms

Some patients with ANCA-associated vasculitis present with constitutional or systemic symptoms indicative of chronic inflammatory disease, including fatigue/malaise, fever, night sweats, weight loss, myalgia, and polyarthralgia.² ANCA-associated vasculitis can be misdiagnosed as polymyalgia rheumatica in patients whose predominant clinical feature is myalgia. A further complication is that corticosteroid treatment is effective in both conditions, potentially delaying a correct diagnosis of ANCA-associated vasculitis until the steroid dose is tapered.²

Read more about AAV signs and symptoms

Dermatologic Features

Skin lesions, such as a purpuric or vasculitic rash, accompanied by constitutional symptoms and abnormal findings on urinalysis, may appear in fewer than 20% of patients with ANCA-associated vasculitis.²

An isolated rash without constitutional symptoms or abnormal findings on urinalysis may point to immune complex vasculitis, including immunoglobulin A vasculitis (previously known as Henoch-Schönlein purpura).²

Read more about AAV differential diagnosis

Ocular Features

Patients with ANCA-associated vasculitis may present with painful, red eyes (scleritis) and diplopia with proptosis, which is caused by retro-orbital granulomatous masses.^2,4

Read more about AAV pathophysiology

References

Qasim A, Patel JB. ANCA positive vasculitis. StatPearls [Internet]. Updated May 29, 2022. Accessed February 23, 2023.
Hunter RW, Welsh N, Farrah TE, Gallacher PJ, Dhaun N. ANCA associated vasculitis. BMJ. 2020;369:m1070. doi:10.1136/bmj.m1070
Gross WL, Holle JU. Clinical features of ANCA-associated vasculitis. In: Watts RA, Conaghan PG, Denton C, Foster H, Isaacs J, Müller-Ladner U, eds. Oxford Textbook of Rheumatology, 4th ed. Oxford University Press; 2013. doi:10.1093/med/9780199642489.003.0131_update_001
Weiner M, Segelmark M. The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA) Autoimmun Rev. 2016;15(10):978-982. doi:10.1016/j.autrev.2016.07.016
Alahmari H, Daajani HA, Alsayed F, Alrashid A. ANCA-associated vasculitis clinical presentation and clinical predictors of relapse in Saudi Arabia. Open Access Rheumatol. 2021;13:213-220. doi:10.2147/OARRR.S314421

Reviewed by Debjyoti Talukdar, MD, on 2/28/2023.

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.

ANCA-Associated Vasculitis (AAV)