Granulomatosis with Polyangiitis (GPA)

What granulomatosis with polyangiitis is

GPA is one of the ANCA-associated vasculitides, a group that also includes microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). In most people with GPA, the immune system makes antibodies called ANCA (anti-neutrophil cytoplasmic antibodies), usually against an enzyme called proteinase 3 (PR3). These antibodies activate white blood cells (neutrophils), which attack the walls of small blood vessels.

Two processes cause the damage:

• Vasculitis: inflamed, leaky small vessels, especially in the kidney filters (glomeruli) and lung capillaries
• Granulomas: destructive nodules of inflammatory cells, mainly in the nose, sinuses, airways and lungs

The cause is unknown. Genetic factors, infections (especially nasal Staphylococcus aureus carriage, linked to relapses) and environmental exposures such as silica dust may play a role. It is not contagious and not inherited in a simple way. The name changed from Wegener's granulomatosis in 2011.

Symptoms

GPA can be "limited" to the ears, nose, throat and lungs, or "generalized" with organ-threatening disease. Symptoms often build over weeks to months.

Ears, nose and throat (in about 9 in 10 people)

• persistent blocked nose, crusting and bloody discharge
• frequent nosebleeds
• chronic sinusitis that does not respond to antibiotics
• ear pain, fluid behind the eardrum and hearing loss
• a collapsed nasal bridge ("saddle nose") from cartilage damage
• narrowing below the vocal cords (subglottic stenosis), causing hoarseness and noisy breathing

Lungs

• cough, chest pain and breathlessness
• coughing up blood (hemoptysis)
• nodules or cavities seen on a chest X-ray or CT, sometimes mistaken for cancer or tuberculosis

Kidneys

Glomerulonephritis (inflamed kidney filters) is often silent at first, showing only as blood in the urine or protein on a dipstick. It can progress over days to weeks to acute kidney injury.

Other areas

• Whole body: fever, night sweats, fatigue, weight loss
• Joints: aching or swelling of several joints
• Eyes: red, painful eyes (scleritis), or a mass behind the eye pushing it forward
• Skin: purple spots (purpura), ulcers or nodules
• Nerves: numbness, tingling or sudden weakness in one nerve (mononeuritis multiplex)

How GPA is diagnosed

There is no single test, and diagnosis is often delayed because early symptoms look like ordinary sinus or ear problems. A rheumatologist or kidney specialist will combine:

1. ANCA blood test: about 80 to 90% of people with active generalized GPA are ANCA-positive, usually PR3-ANCA (shown as c-ANCA on older tests). A negative test does not rule out GPA, especially limited disease.
2. Urine tests: dipstick and microscopy for blood, protein and red cell casts.
3. Blood tests: creatinine for kidney function, inflammatory markers (CRP, ESR) and blood count.
4. Imaging: CT of the chest and sinuses.
5. Biopsy: of the nose, lung or kidney, showing vasculitis, granulomas or a characteristic kidney pattern. Kidney biopsy also guides treatment.

Treatment

Treatment has two phases and is managed by specialists.

Inducing remission

• Glucocorticoids (steroids such as prednisone), often starting with high-dose intravenous steroids for severe disease. Current regimens taper doses more quickly than in the past to reduce side effects.
• Rituximab (an antibody that removes B cells) or cyclophosphamide to switch off the immune attack. Rituximab is preferred for many people and for relapses.
• Avacopan, a newer oral drug, can help reduce steroid exposure.
• Plasma exchange may be considered for severe kidney failure or lung bleeding.
• Methotrexate may be used for milder, non-organ-threatening disease.

Remission typically takes 3 to 6 months.

Maintaining remission

Rituximab every 6 months, or azathioprine or methotrexate, continued for at least 2 to 4 years and sometimes longer. Steroids are reduced to the lowest effective dose or stopped.

Supportive care

• trimethoprim-sulfamethoxazole to prevent Pneumocystis pneumonia while on strong immune suppression
• vaccines (flu, COVID-19, pneumococcal; no live vaccines during treatment)
• bone protection while on steroids
• blood pressure control and kidney protection
• nasal saline rinses for crusting
• dialysis or kidney transplant for kidney failure

Complications

• chronic kidney disease or kidney failure
• hearing loss, saddle nose deformity and airway narrowing
• infections from immune-suppressing treatment
• higher risk of blood clots and cardiovascular disease
• side effects from long-term steroids and cyclophosphamide, including bladder problems and infertility

Outlook

Untreated, generalized GPA was usually fatal within a year. With modern treatment, about 9 in 10 people achieve remission, and most live for many years. Relapses occur in around half of people within 5 years, particularly those who are PR3-ANCA positive, so lifelong follow-up with regular urine and blood tests is needed. Early diagnosis, before kidneys are badly damaged, makes the biggest difference to long-term health.

Frequently asked questions

What are the first symptoms of granulomatosis with polyangiitis?

Early symptoms usually involve the ears, nose and sinuses: persistent congestion, crusting, bloody nasal discharge, sinus infections that do not respond to antibiotics and ear infections. Fatigue, fever, joint pain and weight loss are also common before the lungs and kidneys become involved.

Is granulomatosis with polyangiitis the same as Wegener's granulomatosis?

Yes. It was renamed granulomatosis with polyangiitis in 2011 to describe the disease rather than honor a person. The disease, tests and treatment are the same.

What is the life expectancy with GPA?

With modern treatment, most people with GPA live for many years and many have a near-normal life expectancy, especially if kidney damage is limited. Risks come mainly from severe kidney or lung involvement, infections and relapses, which is why ongoing monitoring matters.

What does a positive c-ANCA or PR3-ANCA test mean?

It means antibodies typical of GPA are present. In someone with matching symptoms, it strongly supports the diagnosis. A positive test alone is not enough: ANCA can occasionally appear with infections, other autoimmune diseases or certain drugs, so doctors often confirm with a biopsy.

Can granulomatosis with polyangiitis be cured?

There is no permanent cure, but long-term remission is common. Some people stay in remission for years after stopping treatment. Others need ongoing maintenance therapy because the disease tends to relapse.