Granulomatosis with Polyangiitis · What It Is, Causes, Signs and Symptoms, Diagnosis, and More

Signs and symptoms of GPA may vary between individuals, but most people experience respiratory symptoms. Respiratory tract symptoms include persistent runny nose (i.e., rhinorrhea); formation of sores on the nares or nasal septum, saddle deformity (i.e., collapse of nasal bridge); nasal pain; nasal discharge from persistent inflammation of the nose, throat, and lungs; cough with or without bloody phlegm; shortness of breath; and in severe cases, pulmonary hemorrhage. Inflammation of the kidney vasculature is also common, therefore additional signs include hematuria, decreased urine output, and flank pain. The classic triad of GPA is necrotizing granulomatous of the upper and lower respiratory system, systemic vasculitis, and kidney (e.g., glomerulonephritis) vasculature. 

Individuals may also experience middle ear inflammation which may manifest as otitis media and ear pain. If left untreated, this may lead to permanent hearing loss. If the blood vessels that supply the brain are involved (i.e., cerebral vasculitis), neurologic symptoms may be apparent including altered mental status, headache, and muscle weakness. Involvement of the cardiac vasculature may lead to hypertension, myocarditis (i.e., inflammation of the myocardium), or pericarditis (i.e., inflammation of the pericardium). Other symptoms may include eye inflammation or pressure behind the eye; proptosis or bulging of one or both of the eyes; joint pain; gastrointestinal bleeding; and skin sores. 

Diagnosis of granulomatosis with polyangiitis begins with a thorough review of symptoms and medical history. A focused physical examination of the ears, nose, and throat can help identify signs and symptoms of systemic disease involvement (e.g., sinusitis, nasal discharge, bloody sputum). Laboratory blood tests including a complete blood count (CBC), comprehensive metabolic panel (CMP), inflammatory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), liver function tests (e.g., AST/ALT, bilirubin), serum creatinine level, and urine tests (e.g., urinalysis) can be helpful in the initial work-up.  

Additional rheumatologic serology tests, which include anti-nuclear antibody (ANA), anti-glomerular basement membrane (anti-GBM) antibodies, serum complement levels, hepatitis B and C viral titers, and HIV, can be performed to exclude other alternative diagnoses that can manifest in similar ways. Testing for antineutrophil cytoplasmic antibodies (ANCA) should be pursued in any individual who presents with clinical symptoms suggestive of vasculitis. ANCA is usually detected using an indirect antigen-specific enzyme-linked immunosorbent assay (ELISA) and approximately 80-94% of individuals with GPA will test positive for this antibody assay. However, a negative ANCA serology does not exclude the diagnosis of GPA.  
 
In individuals who present with pulmonary symptoms and are suspected of having GPA, imaging tests, which include computed tomography (CT) of the chest, are indicated. A CT scan will demonstrate lesions, alveolar opacities, pleural-based lesions, or large areas of airway inflammation that are not seen in plain radiographs (e.g., X-ray). Additional imaging of other areas of the body (e.g., CT of the sinus, orbits, and mastoids) is tailored to the individual’s symptom presentation.  
 
Whenever possible, the diagnosis of GPA should be confirmed by obtaining a tissue biopsy of an area where there is suspected active disease. Common biopsy sites include the skin, lungs, and kidneys. Kidney biopsy pathology findings range from mild focal to segmental glomerulonephritis and diffuse, necrotizing, and crescentic glomerulonephritis. Skin histopathology typically reveals a “nonspecific” vasculitis of the dermal capillaries and venules (i.e., leukocytoclastic vasculitis) with little or no complement fixation seen on immunofluorescence. Finally, respiratory tract and lung histopathology may show acute or chronic inflammation associated with the capillaries and less commonly granulomatous features (e.g., areas of clustered immune cells that are walled off).

Treatment for GPA depends on the severity, extent, and etiology of the disease. In non-life-threatening GPA with no internal organ involvement (i.e., no evidence of active glomerulonephritis and normal serum creatinine; only symptoms include rhinosinusitis, arthritis, pulmonary nodules), treatment consists of induction therapy with glucocorticoids (e.g., prednisone) for 3 to 4 months, followed by a slow taper to prevent disease relapse and glucocorticoid-related complications (e.g., adrenal insufficiency). Treatment is continued with maintenance methotrexate weekly for a minimum of 6 months.  

In individuals who experience disease relapse or are intolerant of glucocorticoids, alternative immunosuppressive agents (e.g., azathioprine, methotrexate) can be added for maintenance therapy. In life-threatening GPA (i.e., internal organ involvement including active glomerulonephritis, pulmonary hemorrhage, cerebral vasculitis, gastrointestinal bleeding secondary to vasculitis, and pericarditis) a chemotherapy agent, such as cyclophosphamide or rituximab, is typically added to the glucocorticoid regimen for remission induction. For maintenance therapy, individuals are typically initiated on an immunosuppressive agent such as methotrexate, azathioprine, or mycophenolate mofetil.  

Management of GPA is medically complex and long-term use of immunosuppressants can lead to side effects (e.g., increased risk of severe infections). Therefore, individuals may benefit from a multidisciplinary team of professionals including a rheumatologist, pulmonary specialist, neurologist, cardiologist, nephrologist, dermatologist, mental health specialist, and occupational and physical therapist to help tailor therapy and co-manage disease-related complications.