ANCA-associated vasculitis (AAV) refers to a group of systemic small vessel vasculitides characterized primarily by the presence of antineutrophil cytoplasmic antibodies (ANCA) in the serum. AAV primarily affects small vessels, including small arteries, arterioles, capillaries, and venules, but medium-sized arteries may also be involved. Subtypes of AAV include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA).
Etiology and Pathogenesis
Genetic susceptibility and infections, particularly bacterial infections, are strongly associated with disease onset. Beyond the role of ANCA, direct vascular damage caused by infections plays a significant role. Although ANCA is involved in the pathogenesis, immune complex deposition in affected organs is minimal or absent.
Pathology
AAV is characterized by full-thickness inflammation and necrosis of small vessels, with or without granuloma formation. Histopathological examination demonstrates fibrinoid necrosis accompanied by infiltration of neutrophils, lymphocytes, and eosinophils. These findings serve as the "gold standard" for diagnosing AAV.
Clinical Manifestations
General Symptoms
Most patients experience systemic symptoms such as fever, joint pain or arthritis, muscle pain, fatigue, loss of appetite, and weight loss.
Skin and Mucous Membranes
The skin and mucous membranes are among the most commonly affected tissues in AAV. Manifestations include oral ulcers, rashes, purpura, livedo reticularis, skin infarction, ulcers, and gangrene. Recurrent fingertip ulcers are frequently observed.
Ocular Involvement
Common ocular manifestations include conjunctivitis, keratitis, scleritis, iritis, and blepharitis. Fundoscopic examination may reveal retinal exudates, hemorrhages, vascular inflammation, or thrombosis. A small number of patients may experience diplopia or diminished vision, and some develop pronounced proptosis.
Ear, Nose, and Throat (ENT)
Involvement of the larynx or tracheal cartilage may cause hoarseness, stridor, and inspiratory dyspnea. Auricular cartilage involvement can result in redness, swelling, warmth, and pain of the ear. Nasal cartilage damage may lead to saddle-nose deformity. Middle ear involvement commonly presents as otitis media and can result in conductive or sensorineural hearing loss. Symptoms of nasal sinus involvement include purulent or blood-streaked nasal discharge, crusting, and nasal obstruction. Some patients experience reduced or complete loss of the sense of smell.
Respiratory System
Cough and sputum production are common symptoms, while severe cases may develop dyspnea, wheezing, or hemoptysis. Imaging studies of the lungs often show infiltrates, multiple nodules, cavitary lesions, or interstitial changes.
Nervous System
The nervous system is one of the most frequently affected systems in AAV, with peripheral nerve involvement being the most common. Mononeuritis multiplex is the most frequently observed peripheral nerve lesion. Central nervous system involvement may present with symptoms such as headache, encephalopathy, seizures, stroke, or encephalomyelitis.
Renal Involvement
Hematuria, proteinuria, and hypertension are common manifestations. Elevated serum creatinine levels are observed in some patients, and a subset may progress to rapidly progressive renal failure.
Cardiac Involvement
Some patients develop conditions such as pericardial effusion, cardiac myopathy, or valvular insufficiency. Coronary artery involvement may result in angina or myocardial infarction.
Abdomen
Abdominal involvement in AAV often presents with symptoms such as abdominal pain, bloody diarrhea, bowel perforation, bowel obstruction, or signs of peritonitis.
Laboratory Tests
Common non-specific findings include anemia and elevated leukocyte and platelet counts. Proteinuria, hematuria, and red blood cell casts are frequently observed abnormalities. Elevated erythrocyte sedimentation rate (ESR) and increased C-reactive protein (CRP) levels are also typical. Serum creatinine levels may rise in cases of renal dysfunction. Positive ANCA testing is the most distinctive laboratory feature of this group of vasculitides.
Diagnosis and Differential Diagnosis
There are currently no universally accepted classification criteria for this group of systemic vasculitides. Diagnosis requires a comprehensive evaluation of clinical manifestations, serum ANCA testing, characteristic pathological changes, and imaging findings. Differential diagnosis should include infections, other systemic connective tissue diseases, and malignancies. Particular attention is necessary for distinguishing malignancies and certain infections that may mimic the clinical features of AAV.
In 2022, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) jointly updated the classification criteria. A weighted scoring system was introduced to evaluate the three types of AAV based on clinical manifestations and laboratory findings. When using these classification criteria, it must first be established that the patient's condition is AAV, while excluding other diseases that could produce similar clinical presentations, such as systemic rheumatic diseases, infections, and malignancies.
It is worth noting that the primary purpose of the classification criteria is to categorize patients with similar clinical features of AAV for the evaluation of therapeutic efficacy in clinical studies. These criteria were not specifically designed for clinical diagnosis, but they can serve as a supplementary reference for diagnosing AAV.
Treatment
Glucocorticoids are the first-line therapeutic agents. Induction of remission typically involves sufficient doses of glucocorticoids in combination with immunosuppressive agents, most commonly cyclophosphamide (CTX). Maintenance of remission generally involves low-dose glucocorticoids combined with immunosuppressive agents, such as azathioprine or methotrexate. In recent years, extensive clinical studies have demonstrated the efficacy of rituximab, a monoclonal antibody targeting CD20. Rituximab can be used for both induction and maintenance of remission and has become a first-line treatment for severe GPA and MPA during the remission induction phase.
Prognosis
Prognosis depends on the location and severity of organ involvement. Early diagnosis and appropriate treatment have significantly improved outcomes, with 80% of patients now surviving beyond five years. However, delayed diagnosis or the absence of adequate treatment continues to result in high mortality rates.