ANCA-associated vasculitis (AAV) is a group of autoimmune diseases in which the immune system attacks small blood vessels throughout the body, causing inflammation and organ damage. The “ANCA” refers to anti-neutrophil cytoplasmic antibodies, abnormal proteins the immune system produces that mistakenly target white blood cells called neutrophils. These activated neutrophils then damage the walls of small blood vessels in the kidneys, lungs, sinuses, skin, nerves, and other organs. AAV is rare, affecting roughly 20 to 25 people per million each year, but without treatment it can be life-threatening.
How AAV Damages Blood Vessels
Neutrophils are a type of white blood cell that normally fights infection. In AAV, ANCA antibodies latch onto neutrophils and switch them on in the wrong place and at the wrong time. Once activated, these neutrophils release toxic molecules, trigger inflammation pathways, and activate a cascade called the complement system, all of which chew into the walls of small blood vessels. The neutrophils are both the target of the rogue antibodies and the cells carrying out the damage, which is what makes AAV unusual among autoimmune diseases.
This process can happen anywhere small blood vessels exist, but it tends to concentrate in certain organs depending on the specific type of AAV a person has.
The Three Types of AAV
AAV is divided into three conditions based on which organs are most affected and what patterns of inflammation appear on biopsy.
Granulomatosis With Polyangiitis (GPA)
Formerly called Wegener’s granulomatosis, GPA typically involves the upper airways (sinuses, nose, ears), lungs, and kidneys. People often first notice chronic sinus infections that won’t clear up, nosebleeds, or a cough that produces blood. Kidney involvement may cause no symptoms at first but can progress to serious damage if untreated. GPA is most commonly associated with PR3-ANCA antibodies on blood testing.
Microscopic Polyangiitis (MPA)
MPA most often strikes the kidneys and lungs. It can cause rapidly declining kidney function and, in some cases, bleeding in the lungs. Unlike GPA, it does not form the granular tissue clusters (granulomas) seen on biopsy. MPA is more commonly linked to MPO-ANCA antibodies.
Eosinophilic Granulomatosis With Polyangiitis (EGPA)
Previously known as Churg-Strauss syndrome, EGPA is distinct because it’s associated with asthma and high levels of a white blood cell type called eosinophils. People with EGPA often have a history of adult-onset asthma or allergic nasal polyps before other vasculitis symptoms develop. It can affect the lungs, skin, heart, and nerves.
Common Symptoms
AAV often starts with vague, general symptoms that can last weeks or months before a diagnosis is made. Fatigue, fever, joint pain, muscle aches, and unexplained weight loss are common early signs. Because these overlap with many other conditions, AAV is frequently misdiagnosed at first.
More specific symptoms depend on which organs are involved:
- Kidneys: blood or protein in the urine, swelling in the legs, rising blood pressure. Kidney damage can progress silently, so it’s sometimes found only through lab tests.
- Lungs: coughing up blood, shortness of breath, chest pain.
- Sinuses and ears: persistent sinusitis, crusting in the nose, nosebleeds, hearing loss.
- Skin: purplish spots (purpura), ulcers, or small red bumps, usually on the legs.
- Nerves: numbness, tingling, or weakness in the hands or feet, often in an asymmetric pattern.
How AAV Is Diagnosed
Diagnosis relies on a combination of blood tests, imaging, and often a tissue biopsy. The key blood test checks for ANCA antibodies and identifies whether they are the PR3-ANCA type (more common in GPA) or the MPO-ANCA type (more common in MPA). However, a positive ANCA test alone isn’t enough to confirm the diagnosis, and a small percentage of people with AAV test ANCA-negative.
Doctors also check kidney function with blood and urine tests, look for signs of lung involvement on CT scans, and may take a small tissue sample from an affected organ (often the kidney) to look for the characteristic pattern of blood vessel inflammation under a microscope. Putting all of these pieces together, along with the pattern of organ involvement, allows specialists to distinguish between GPA, MPA, and EGPA.
Treatment: Getting the Disease Under Control
Treatment happens in two phases: induction (bringing the disease into remission) and maintenance (keeping it there).
Induction Therapy
For GPA or MPA that threatens organs, current guidelines recommend a combination of steroids and an immune-suppressing therapy. The two main options are rituximab (an infusion that depletes a type of immune cell called B cells) and cyclophosphamide (a traditional immunosuppressant). Both can achieve remission, but rituximab has shown strong results. In one study of GPA patients, 73% of those treated with rituximab reached remission at six months compared to 40% on cyclophosphamide. Rituximab is now preferred for relapsing disease.
Steroids are started at a relatively high dose and then tapered down over four to five months, aiming to reach a low dose within that window. A newer medication called avacopan, which blocks part of the complement inflammation pathway, can be added alongside standard treatment. It was designed to help reduce steroid exposure, though the degree to which it actually spares patients from steroid side effects is still debated.
For EGPA, the approach differs. Severe cases are treated with high-dose steroids and cyclophosphamide or rituximab. Milder cases may respond to steroids alone. A biologic medication called mepolizumab, which targets eosinophils, is recommended for people with relapsing or difficult-to-treat EGPA that isn’t immediately threatening organs.
Maintenance Therapy
Once remission is achieved, the goal shifts to staying there. Rituximab is the preferred maintenance treatment for GPA and MPA. Alternative options include azathioprine or methotrexate. Current guidelines recommend continuing maintenance therapy for at least two to four years after the first episode. People who relapse or have risk factors for relapse may need to stay on treatment longer, weighed against the long-term risks of immune suppression like increased infection susceptibility.
Relapse and Long-Term Outlook
AAV is a chronic condition with a significant risk of relapse even after successful treatment. In a large European cohort, the median time to first relapse was about 33 months (roughly two and a half years), and the timing was similar whether someone had GPA or MPA. This is why maintenance therapy lasts years rather than months.
With modern treatment, the five-year survival rate for AAV has improved dramatically compared to decades ago, when untreated disease was often fatal within a year. Most people now achieve remission and maintain it for extended periods, though relapses remain common across the lifetime of the disease. Kidney damage at diagnosis is one of the strongest predictors of long-term outcomes, which is why early detection matters.
Monitoring After Diagnosis
People with AAV need regular follow-up, including blood and urine tests to track kidney function and watch for signs of relapse. One question patients often have is whether their ANCA levels can predict a flare. The answer is nuanced.
A meta-analysis found that a rise in ANCA levels is associated with about a 3.5-fold higher chance of relapse within the following six months. This signal is particularly strong for MPO-ANCA, where a rise carried roughly a ninefold increased risk of relapse within six months. For PR3-ANCA, the link is weaker and more variable. When a relapse does occur, ANCA is almost always detectable, with about an 11-fold higher chance of being positive at the time of a flare.
However, a rising ANCA level doesn’t guarantee a relapse, and many rises happen without one following. Doctors use ANCA trends as one piece of the puzzle alongside symptoms and other lab results, not as a standalone trigger to change treatment. Regular monitoring visits, typically every one to three months during the first couple of years, help catch relapses early when they’re easier to treat.