Granulomatosis with polyangiitis

Granulomatosis with polyangiitis, sometimes abbreviated GPA, is a form of vasculitis that primarily affects the small to medium-sized blood vessels of the throat, nose, sinuses, kidneys, and lungs. The condition can affect the blood flow to various organs and can cause areas of inflammation called granulomas that can impact how the organs function. Prompt diagnosis and early treatment of GPA is typically successful in preventing serious and potentially fatal complications. It is also referred to as Wegener's granulomatosis.

Definition & Facts

GPA is a rare condition that affects approximately three people out of every 100,000. Incidences of the disease are relatively equal between men and women. Although GPA can occur at any age, it is most common among people in their 40s to 60s. Caucasians tend to develop GPA at a higher rate than other racial groups.

Although most patients with GPA can expect a full recovery provided they receive prompt treatment, about one-half of patients can expect a recurrence of the condition. If left untreated, GPA can cause serious damage to the lungs and kidneys, including kidney failure.

Symptoms & Complaints

• A cough, possibly with blood-tinged phlegm.
• Wheezing or shortness of breath.
• Nosebleeds.
• Fatigue and body aches.
• Fever.
• Numbness in the extremities, fingers, and toes.
• Bruising and skin sores.
• Unexplained weight loss.
• Eye pain, burning in the eyes, or redness in the eyes.
• Ear infections.
• Blood in urine.

In addition to organ damage, GPA can cause other complications, including hearing loss, heart disease, skin scarring, deep vein thrombosis, and a decrease in the height of the bridge of the nose as the cartilage weakens. Anyone with a persistent runny nose that does not respond to over-the-counter allergy medicine or cold medicines should consult a doctor, especially if they experience other symptoms associated with GPA.

Causes

The exact cause of GPA is not clear. Some experts believe that it may occur when an infection or another inflammatory event causes an abnormal response in the body’s immune system. This theory is supported by the fact that most patients with GPA have anti-neutrophil cytoplasmic antibodies in their bloodstreams. Under normal circumstances, these antibodies protect the body against harmful pathogens. In some cases, however, they can also trigger an autoimmune response that can cause blood vessels to become inflamed and constricted and the development of inflamed tissue masses called granulomas. The constricted blood vessels mean that tissues and organs receive less blood and oxygen. Granulomas can ultimately destroy healthy tissue.

Diagnosis & Tests

A patient’s history of clinical symptoms, physical examination, lab tests, and imaging studies are all used to diagnose GPA. Blood tests are used to detect signs of inflammation, such as elevated C-reactive protein and erythrocyte sedimentation rates. The tests may also be used to look for antibodies that are often present in the blood of individuals with active GPA. They can also be useful in detecting anemia and decreased kidney function, which are common with GPA.

Urine tests can identify the presence of red blood cells or proteins that may indicate that the disease is affecting the kidneys. Chest X-rays, CT scans, or MRIs can help determine which organs and blood vessels are affected by the disease. The only definitive way to diagnose GPA is through a biopsy of a portion of the affected tissue. This involves surgically removing a small portion of tissue for microscopic analysis. 

Treatment & Therapy

The treatment of GPA typically requires a team approach based on the specific organs and systems affected by the disease. It is common for a GPA patient to see numerous specialists including:

• Rheumatologists.
• Nephrologists.
• Otolaryngologists.
• Ophthalmologists.
• Pulmonologists.

The medications used to treat the condition depend on the severity of symptoms and the organs involved. Patients with an active, severe form of the disease typically receive a combination of the corticosteroid, prednisone and a chemotherapy drug called cyclophosphamide. The steroid is usually started at a high dose to reduce inflammation and gradually decreased. A lower dose of steroids may be required for up to a year.

Cyclophosphamide is normally only given for three to six months before the patient is switched to methotrexate or azathioprine. As long as symptoms are in remission, the methotrexate or azathioprine may be discontinued after approximately six months. Both prednisone and cyclophosphamide can reduce the body’s ability to fight infections and cause other potentially serious side effects. As a result, antibiotics may be prescribed to prevent lung infections and other types of infections.

Bisphosphonates may be used to prevent bone loss, and folic acid may help prevent skin sores and other symptoms caused by folate deficiency. Rituximab and mycophenolate mofetil are alternative immunosupressants that may be used in patients who cannot tolerate cyclophosphamide, who are considering having children, or who have kidney problems.

Patients whose kidneys are affected by GPA may benefit from plasmapheresis. This procedure involves removing blood plasma that contains disease-causing cells and replacing it with fresh plasma or a substance that allows the body to make its own new plasma. Patients with extensive kidney damage or renal failure may require a kidney transplant to regain normal kidney function. 

Prevention & Prophylaxis

Many patients are able to achieve long-term remissions lasting 20 years or more, allowing them to lead relatively normal lives. Patients undergoing treatment for GPA need to commit to regular follow-ups with their doctors to monitor for potential drug toxicity. Once in remission, patients should still be monitored periodically for possible recurrences.