Wegener’s granulomatosis, now officially called granulomatosis with polyangiitis (GPA), is a rare disease that inflames and damages small and medium blood vessels throughout the body. It primarily targets the nose, sinuses, throat, lungs, and kidneys. About 97 out of every million people in Europe and North America live with this condition, and roughly 9 to 11 new cases per million are diagnosed each year.
The name changed in 2012 after a consensus conference updated the classification system for blood vessel diseases. The American College of Rheumatology, the European League Against Rheumatism, and the American Society of Nephrology all endorsed the switch. The goal was to replace eponyms (names based on the person who described the disease) with names that describe what the disease actually does. “Granulomatosis” refers to clusters of inflammatory cells that form in tissues, and “polyangiitis” means inflammation of multiple blood vessels.
What Happens Inside the Body
GPA is an autoimmune disease driven by misdirected antibodies called ANCA (antineutrophil cytoplasmic antibodies). Normally, white blood cells called neutrophils help fight infection. In GPA, ANCA antibodies mistakenly latch onto proteins on the surface of these neutrophils and switch them on when they shouldn’t be active.
Once activated, these neutrophils stick to blood vessel walls and burrow into them. They release toxic oxygen molecules and destructive enzymes that damage the vessel lining, killing both the neutrophils themselves and the surrounding tissue. This damage triggers a cascade: the immune system’s complement pathway generates chemical signals that attract even more neutrophils to the site, creating a self-reinforcing loop of inflammation. Over days, other immune cells replace the neutrophils and form granulomas, the inflammatory tissue clusters that give the disease its name.
Symptoms by Organ System
GPA can affect several parts of the body at once, or it can start in one area and spread over weeks to months. The classic pattern involves three regions: the upper airways, the lungs, and the kidneys.
Nose, Sinuses, and Ears
Upper airway symptoms are often the first to appear and can look deceptively like a stubborn sinus infection. Persistent stuffiness, crusty or pus-like nasal drainage, nosebleeds, and recurring sinus infections are common. Some people develop sores inside the nose or mouth. Inflammation can damage the cartilage supporting the bridge of the nose, causing it to collapse inward (sometimes called a saddle nose deformity). Ear pain, fluid draining from the ear, and hearing changes can also occur when inflammation reaches the ear cartilage or middle ear.
Lungs and Airways
Lung involvement can range from mild to severe. Symptoms include coughing (sometimes with bloody phlegm), shortness of breath, wheezing, and hoarseness. If inflammation narrows the windpipe, breathing may produce a high-pitched sound called stridor. Imaging often reveals nodules or cavities in the lungs that can be mistaken for infections or cancer on an initial scan.
Kidneys
Kidney inflammation is one of the most serious features of GPA, and it’s also one of the most silent. You may have no symptoms at all until significant damage has occurred. When symptoms do appear, they include blood in the urine, high blood pressure, and leg swelling. Without treatment, kidney failure develops in most cases.
How GPA Is Diagnosed
A blood test for ANCA antibodies is a key part of the diagnostic workup. There are two types of ANCA that matter: PR3-ANCA and MPO-ANCA. PR3-ANCA is far more closely linked to GPA, picking up about 74% of cases, while MPO-ANCA detects only about 11%. Both tests are highly specific, meaning a positive result is unlikely to be a false alarm (specificity averages around 97%).
Blood tests alone don’t confirm the diagnosis, though. Doctors typically combine ANCA results with imaging of the lungs and sinuses, urine tests checking for kidney involvement, and often a tissue biopsy showing the characteristic granulomas and blood vessel inflammation. The combination of symptoms, lab results, and biopsy findings together makes the diagnosis.
Treatment: Two Phases
Treatment for GPA follows a two-phase strategy. The first phase, called induction, aims to stop the active inflammation and push the disease into remission. The second phase, called maintenance, uses gentler medications to keep it there.
During induction, you’ll receive a powerful immune-suppressing medication alongside high-dose steroids to quickly reduce inflammation. There are two main options for the immune-suppressing component, and both are given by infusion. One is a targeted therapy that depletes a specific type of immune cell responsible for producing the harmful antibodies. The other is a broader chemotherapy-type drug that suppresses the immune system more widely. Both approaches are effective at achieving remission, and the choice depends on factors like disease severity, your age, and kidney function.
Once remission is achieved, you’ll switch to a milder maintenance regimen. This typically involves a daily oral medication or periodic infusions spaced about six months apart, continuing for at least two years. The goal is to use the least amount of immune suppression necessary to prevent flares while minimizing side effects.
Relapse and Long-Term Outlook
GPA is a chronic condition, and relapse is common. Up to 50% of patients experience a flare within five years of achieving remission. Relapses can involve the same organs as the original episode or new ones. Regular blood work and urine tests help catch early signs of returning disease before symptoms become obvious.
The prognosis has improved dramatically with modern treatment. Without any treatment, severe GPA can be fatal within months, primarily from kidney failure or lung damage. With treatment, most people achieve remission and can maintain a good quality of life for years. The main long-term risks include cumulative kidney damage from repeated flares, a perforated nasal septum (a hole between the nasal passages), lung scarring, eye inflammation that can threaten vision, and side effects from the immune-suppressing medications themselves, particularly increased vulnerability to infections.
Because the disease can quietly damage the kidneys and other organs between flares, ongoing monitoring matters even when you feel well. Most people with GPA stay on some form of maintenance therapy and follow a regular schedule of lab tests to track kidney function and ANCA levels over time.