What is granulomatosis with polyangiitis?
Granulomatosis with polyangiitis, or GPA, is a rare autoimmune disease in which small blood vessels become inflamed (vasculitis) and clusters of inflammatory cells called granulomas form in the tissues. It was previously known as Wegener's granulomatosis. GPA belongs to a group of conditions called ANCA-associated vasculitis, because most patients have antineutrophil cytoplasmic antibodies in the blood.
The disease most often involves the upper airway (nose, sinuses and ears), the lungs and the kidneys, although the skin, eyes, nerves and joints can also be affected. Without treatment it can progress quickly and threaten the kidneys and life. With modern treatment, most patients achieve remission, and the condition is now managed as a long-term illness rather than a fatal one.
Because GPA affects several organs, care is shared between pulmonology, rheumatology and nephrology, with input from ENT and ophthalmology as needed.
Symptoms of GPA
Symptoms often develop over weeks to months and can be vague at first. Common features include:
- Nose and sinuses: persistent blocked or crusted nose, nosebleeds, sinus pain, and in some patients collapse of the bridge of the nose (saddle nose).
- Ears: ear pain, discharge or hearing loss that does not settle with usual treatment.
- Lungs: cough, breathlessness, chest pain and coughing up blood. Narrowing of the airway just below the vocal cords (subglottic stenosis) can cause noisy breathing and hoarseness.
- Kidneys: often silent at first, detected as blood or protein in the urine or a rising creatinine.
- General symptoms: fever, night sweats, weight loss, fatigue, joint pains, skin rash and red, painful eyes.
Coughing up blood with breathlessness may indicate bleeding into the lungs (diffuse alveolar haemorrhage), which is an emergency.
What causes GPA?
The exact cause is not known. GPA appears to arise when a genetically susceptible immune system reacts abnormally, possibly after an infection or other environmental trigger. ANCA antibodies, usually directed against an enzyme called proteinase 3 (PR3), activate white blood cells called neutrophils, which then damage the walls of small vessels.
GPA can occur at any age but is most often diagnosed in middle age. It is not infectious and is not caused by anything the patient has done. Nasal carriage of Staphylococcus aureus has been linked to a higher risk of relapse.
How GPA is diagnosed
Diagnosis combines clinical features, blood and urine tests, imaging and, wherever possible, a tissue biopsy. In India, cavitating lung nodules with cough and weight loss are often first treated as tuberculosis, so GPA should be considered when sputum tests are negative or symptoms involve the nose, ears or kidneys.
| Test | What it shows |
|---|---|
| ANCA (PR3 and MPO) | Antibodies that strongly support the diagnosis, although a negative result does not fully exclude it |
| Urine analysis and kidney function | Blood and protein in the urine and a rising creatinine, which indicate kidney involvement |
| CT scan of the chest | Nodules, cavities, patchy opacities or signs of bleeding into the lungs |
| CT of the sinuses | Thickening and destruction within the sinuses |
| Bronchoscopy | Airway narrowing, alveolar haemorrhage on lavage, and samples to exclude infection |
| Biopsy (nose, kidney or lung) | Vasculitis and granulomas, confirming the diagnosis |
Infection, including tuberculosis and fungal disease, and lung cancer must always be excluded before immunosuppressive treatment is started.
Treatment of GPA
Inducing remission
Treatment begins with glucocorticoids combined with either rituximab, a drug that removes antibody-producing B cells, or cyclophosphamide. Current guidance supports using lower and faster-reducing steroid courses than in the past to limit side effects. Avacopan, an oral drug that blocks a complement receptor, may be used to reduce steroid exposure in selected patients. Plasma exchange is considered in some patients with severe kidney failure or lung haemorrhage.
Maintaining remission
Once the disease is controlled, maintenance treatment, most often regular rituximab, or alternatively azathioprine or methotrexate, continues for a prolonged period to prevent relapse.
Supportive care
Prevention of Pneumocystis pneumonia with co-trimoxazole, vaccinations, bone protection during steroid therapy and blood pressure control are part of routine care. Subglottic or bronchial narrowing may need bronchoscopic dilation or other interventional pulmonology procedures alongside medical treatment.
Outlook and long-term follow-up
Most patients achieve remission with treatment, but relapse is common, especially in PR3-positive disease. Regular follow-up with urine tests, kidney function, blood counts and periodic lung imaging allows early detection of relapse and drug side effects. Long-term effects can include kidney impairment, hearing loss, nasal deformity and infections related to immunosuppression. Patients should report new symptoms promptly rather than wait for the next scheduled visit.
When to seek urgent care
Seek emergency attention for coughing up blood, sudden or worsening breathlessness, noisy breathing or difficulty breathing through a narrowed airway, a marked fall in urine output or swelling of the legs, high fever while on immunosuppressive treatment, or sudden loss of vision. These may indicate active vasculitis, lung haemorrhage or serious infection, all of which need same-day assessment.
Frequently asked questions
Is GPA the same as Wegener's granulomatosis?
Yes. Granulomatosis with polyangiitis is the current name for the condition previously called Wegener's granulomatosis. The disease itself is the same.
Is GPA a type of cancer or infection?
No. GPA is an autoimmune vasculitis, meaning the immune system inflames the blood vessels. It is not cancer and it is not contagious, although infections and cancer must be excluded during diagnosis.
Can GPA be cured?
GPA cannot be permanently cured, but most patients achieve remission with treatment. Some remain in remission for long periods, while others need ongoing maintenance treatment because relapse is common.
Why was I treated for tuberculosis first?
Lung nodules and cavities with cough and weight loss look very similar to tuberculosis on X-ray and CT, and tuberculosis is far more common in India. When tests for tuberculosis are negative or the nose, ears or kidneys are involved, GPA should be considered.
What are the side effects of rituximab?
Rituximab can cause infusion reactions, lower antibody levels and an increased risk of infections. Hepatitis B status is checked before treatment, and vaccinations and infection prevention are planned with the treating team.
Which specialists will be involved in my care?
GPA is usually managed jointly by a pulmonologist, a rheumatologist and a nephrologist, with ENT and eye specialists involved when the nose, ears or eyes are affected.
Related conditions and procedures
Consult Dr. Gogineni Ratnakara Rao
Apollo Hospitals, Financial District: Monday to Saturday, 8:30 AM to 5:00 PM. Anything in Lung Clinic, Chanda Nagar: Monday to Saturday (Thursday closed), 6:00 PM to 9:00 PM.