ANCA-Associated Vasculitis (AAV)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of 3 diseases: granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA).¹

The clinical features of AAV are closely related to its underlying pathophysiologic mechanisms. Inflammation of blood vessels is a hallmark feature, which can result in the disruption of vascular structures, bleeding, and consequential organ dysfunction. The effects of vasculitis can extend beyond the immediate site of vascular inflammation to affect distant organs and tissues, causing systemic manifestations.¹ 

There are many overlapping features in vasculitis that can be divided into local and systemic findings. Common systemic findings in vasculitis include fever of unknown origin (may present as high, spiking fevers), weight loss, weakness, general malaise, arthralgia and muscle pain. Local manifestations in vasculitis depend upon the different affected organs in a patient with vasculitis syndrome.¹ 

Granulomatosis With Polyangiitis

GPA can cause a wide range of signs and symptoms affecting multiple organ systems, which can lead to significant morbidity and mortality. It frequently presents with a triad of upper respiratory, lower respiratory, and renal involvement. 

Upper respiratory tract problems may include: sinusitis, rhinitis with crusting, mastoiditis, saddle nose deformity, otitis media, and hearing loss. Lower respiratory tract involvement includes signs such as pulmonary nodules, alveolar hemorrhage, cough, dyspnea, and pleuritic chest pain. Renal manifestations often present as glomerulonephritis, which develops in most patients within 2 years of disease onset. In addition, the disease may show overlap with MPA, which presents with similar clinical features such as alveolar hemorrhage and crescentic necrotizing glomerulonephritis.²

Respiratory Symptoms in GPA

Signs and symptoms in the upper respiratory tract are common; sinus and nasal pain, purulent nasal discharge, and otitis media are often the earliest complaints. Increased nasal inflammation can induce nasal ulcerations, septal perforation, and saddle nose deformity. The lower respiratory tract may also be affected, presenting with cough, dyspnea, hemoptysis, and pulmonary infiltrates. Tracheal obstruction and pleural effusion can also occur.² 

Symptoms of Renal Involvement in GPA

Only 10% to 20% of cases involve renal complications upon presentation, but it develops in 80% of patients within 2 years of disease onset. Rapidly progressive crescentic glomerulonephritis is the most common manifestation, and it may be identified through symptoms such as hematuria, proteinuria, decrease urination, and edema in face, hands, feet, or stomach.² 

Sensory Symptoms in GPA

Eye involvement is frequent, and scleritis and conjunctivitis are the most common manifestations. Scleritis can lead to necrotizing anterior scleritis, which can cause blindness. Peripheral ulcerative keratitis can lead to corneal melting syndrome. Ear involvement may also occur and can include sensorineural and conductive hearing loss, mastoiditis, and serous otitis media.² 

Other Signs and Symptoms in GPA

Dermatologic involvement is prevalent, with purpura frequently occurring in the lower extremities. Neurological symptoms can include peripheral neuropathies, mononeuritis multiplex, cranial neuropathies, seizures, pachymeningitis, and cerebritis. Arthralgia and myalgia are seen in 70% of patients, with joint symptoms commonly seen. Cardiac involvement is less common but can include pericarditis, valvular lesions or insufficiency, and coronary arteritis.² 

Read more about AAV clinical features

Eosinophilic Granulomatosis With Polyangiitis

EGPA is characterized by 3 phases, which may overlap and do not always present in every patient. The first phase (prodromal phase) presents with nonspecific symptoms such as malaise, fever, polyarthralgia, weight loss, and severe adult-onset asthma that is refractory to conventional treatment. The second phase is characterized by eosinophilic infiltrates in end organs along with peripheral eosinophilia. The third phase is marked by the onset of vasculitis, which may take several years following the onset of asthma, and is characterized by neurological symptoms.³ 

Respiratory Symptoms in EGPA

The most commonly affected body system is the respiratory system, as almost all patients experience asthma before the onset of EGPA. Upper respiratory symptoms are common but do not include nasal granulomas, erosion, crusting, or epistaxis, as seen in GPA. Other common respiratory manifestations include sinusitis, nasal polyposis, and chronic rhinitis. Patients may experience pulmonary involvement in the form of eosinophilic infiltration and vasculitic processes.³ 

Cardiovascular Symptoms in EGPA

Cardiac disease is seen in more than half of cases, although it may not always be symptomatic. The use of echocardiography and cardiac magnetic resonance imaging helps detect cardiac abnormalities even after the active phase of the disease. 

Neurological Symptoms in EGPA

Peripheral neuropathy is common, with wrist and foot drop being the most reported. Neurological involvement can also present as central nervous system vasculitis causing cerebral infarctions or hemorrhages.

Other Signs and Symptoms in EGPA

Gastrointestinal involvement may present as eosinophilic gastroenteritis, mesenteric vasculitis, and eosinophilic liver disease. Renal involvement is seen in about 25% of patients and may manifest as necrotizing crescentic glomerulonephritis. Dermatological manifestations like extravascular granulomas, leukocytoclastic vasculitis, and palpable purpura are seen in almost half of patients with EGPA.³

Read more about AAV comorbidities

Microscopic Polyangiitis

MPA can also cause a wide variety of multisystemic signs and symptoms, and at diagnosis, patients may present a large range in severity and affected systems. These can include constitutional symptoms, respiratory involvement, renal features, and neurological signs. Some patients may even present with acute onset of hematuria, hemoptysis, and renal failure. Prompt recognition and treatment of MPA are crucial to prevent end-organ damage and improve patient outcomes.⁴

Symptoms of Renal Involvement in MPA

Renal manifestations are the most common findings in MPA, and rapidly progressive glomerulonephritis is a major feature. Hematuria, proteinuria, and red blood cell casts in urine are typical clinical features.⁴ 

Respiratory Symptoms in MPA

Pulmonary involvement is present in 25% to 55% of cases, and diffuse alveolar hemorrhage is the most common pulmonary feature. Pulmonary examination may show rales or bronchial breath sounds.⁴

Neurological Symptoms in MPA

Neurological involvement is also frequent, with peripheral neuropathy being more common than central nervous system involvement. The most frequent type of peripheral neuropathy is mononeuritis multiplex, which presents as asymmetric sensorimotor deficits affecting multiple peripheral nerves. Neurological examination may reveal motor or sensory deficits localized to a particular dermatome.⁴

Other Signs and Symptoms in MPA

Gastrointestinal symptoms, such as abdominal pain, are common, and examination often finds gastrointestinal bleeding, bowel ischemia, and perforation. Skin lesions are present in 30% to 60% of cases, including palpable purpura, livedo reticularis, and skin ulcers with necrosis. Ocular examination can reveal retinal hemorrhage, scleritis, and uveitis. 

Read more about AAV diagnosis

References

1. Okazaki T, Shinagawa S, Mikage H. Vasculitis syndrome—diagnosis and therapy. J Gen Fam Med. 2017;18(2):72-78. doi:10.1002/jgf2.4

2. Garlapati P, Qurie A. Granulomatosis with polyangiitis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated December 5, 2022. Accessed February 24, 2023.

3. Chakraborty RK, Aeddula NR. Churg Strauss syndrome. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated August 10, 2022. Accessed February 24, 2023.

4. Hashmi MF, Jain V, Tiwari V. Microscopic polyangiitis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated November 27, 2022. Accessed February 24, 2023.

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

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Kyle Habet, MD

Kyle Habet, MD, is a physician at Belize International Institute of Neuroscience where he is a member of a multidisciplinary group of healthcare professionals involved in the care of patients with an array of neurological and psychiatric diseases. He is a published author, researcher and instructor of neuroscience and clinical medicine at Washington University of Health and Science.