Definition
Granulomatosis with polyangiitis (GPA) or Wegener’s Granulomatosis (WG) is an uncommon type of inflammation of small arteries and veins (vasculitis). It classically involves inflammation of the arteries that supply blood to the tissues of the lungs, the nasal passages (sinuses), and the kidneys. “Incomplete” forms exist that only involve one of these areas. When both lungs and kidneys are affected, the condition is sometimes referred to as generalized granulomatosis with polyangiitis. When only the lungs are involved, the condition is sometimes referred to as limited granulomatosis with polyangiitis.
Granulomatosis with Polyangiitis (GPA)
The terminology “granulomatosis with polyangiitis” highlights the two central pathologic features of the disease, granuloma formation and inflammation of blood vessels (angiitis or vasculitis). Granulomatosis with polyangiitis usually affects young or middle-aged adults. Although it is uncommon in children, it can affect people at any age. The cause of the condition is not known.
Vasculitis
Epidemiology of Granulomatosis with polyangiitis
The prevalence is estimated between 1/6,400 – 42,000 worldwide with annual incidence between 1/84,000-475,000. There is geographic and/or ethnic variation, with a higher incidence in colder regions and among Caucasians. Childhood-onset disease is characterized by female predominance, and adult-onset by a slight male predominance.
Risk factors
- GPA most often affects middle-aged adults between the ages of 40 and 65 years.
- It is rare in children. It affects men and women equally, but Caucasians tend to get the disease more often than other races. There is no known link to inheritance through a family history.
- One of the strongest risk factors for GPA is a specific variation of the HLA-DPB1 gene, which plays an important role in the immune system.
- The HLA-DPB1 gene variation occurs by chance in people with no known family history of GPA.
Causes of Granulomatosis with polyangiitis
The exact cause of granulomatosis with polyangiitis (GPA) is not well-understood. It is thought that GPA is an autoimmune disease. Autoimmune diseases occur when the immune system, which is responsible for protecting the body from infection, mistakenly attacks tissues of the body.
The immune system is supposed to release disease-fighting proteins called antibodies that attack potential sources of infection. People who have GPA frequently have specific antibodies called antineutrophil cytoplasmic antibodies (ANCA). These antibodies cause the immune system to attack the blood vessels. This causes swelling (inflammation) of blood vessels, which causes the signs and symptoms of GPA.
Exactly what causes the immune system to mistakenly attack the blood vessels is not clear. In general, it is thought that autoimmune diseases are caused by a combination of being born with an increased likelihood to develop the disease (genetic predisposition) as well as exposure to environmental factors.
It is not known exactly what environmental factors may be associated with GPA, but it may be that having a previous infection can increase the risk to develop the disease.
Granulomatosis with polyangiitis Symptoms
Sinus and lung symptoms are most common in GPA. Other early symptoms include fever, night sweats, fatigue and a general ill feeling (malaise). For some people, the disease is limited to the respiratory system and doesn’t involve the kidneys. Kidney involvement usually doesn’t cause symptoms early in the course of the disease. It may be detected only by blood and urine tests. Over time, kidney failure and anemia often occur.
Signs and symptoms may include:
- Sinus pain and inflammation
- Runny nose, with pus-filled discharge
- Nosebleeds
- Fever
- General ill feeling (malaise)
- Unintended weight loss
- Ear infections
- Cough
- Chest pain
- Coughing up blood
- Shortness of breath
- Joint aches and swelling
- Blood in urine
- Skin sores
- Eye redness, burning or pain
Skin inflammation with GPA
Granulomatosis with polyangiitis Complications
Complications most often occur when the disease is not treated. People with GPA develop tissue damage in the lungs, airways, and the kidneys. Kidney involvement may result in blood in the urine and kidney failure. Kidney disease can quickly get worse. The function may not improve even when the condition is controlled by medicines.
If untreated, kidney failure and possibly death occur in most cases.
Other complications may include:
- Eye swelling
- Lung failure
- Coughing up blood
- Nasal septum perforation (hole inside the nose)
- Side effects from medicines used to treat the disease
A characteristic saddle deformity of the nose can occur in people with GPA up to 28 per cent
Diagnosis and test
There is no single test for diagnosing GPA, so your doctor will consider a number of factors, including symptoms, medical history, physical exam findings, laboratory tests, and imaging studies. A biopsy of the affected tissue is sometimes required to confirm the diagnosis.
Urine tests: A urinalysis can detect red blood cells or excess protein in the urine, which can indicate whether the kidneys are being affected.
Blood tests: The most common blood test for GPA checks for an antibody called ANCA, or anti-neutrophil cytoplasmic antibody. The ANCA test is positive in most individuals with GPA, so it may help support a suspected diagnosis of GPA. However, a positive test alone does not confirm diagnosis.
Imaging studies: Chest X-rays can show changes in the lungs. Computed tomography (CT) scans and magnetic resonance imaging (MRI) provide more detailed images of the internal organs and can reveal abnormalities in the sinuses, chest, brain, blood vessels or abdominal organs.
Tissue biopsy: This surgical procedure removes a small tissue sample from an affected organ, such as the lung, kidney, skin or sinuses, which is examined under a microscope for signs of inflammation or tissue damage.
Treatment and medications
Most people with GPA can be treated. But the medicines used to treat this condition could have side effects of their own. Be sure to talk about these side effects with your healthcare provider.
These are common medicines used in treatment:
Corticosteroids: This steroid helps reduce inflammation. Long-term steroid use can affect your bone health, so your healthcare provider may also watch and treat changes in your bone density.
Rituximab: This is an antibody against certain immune cells (B-cells). These cells help cause the autoimmune state in GPA.
Cyclophosphamide: This is used to treat active GPA.
- This medicine may be given to keep symptoms in remission for 1 to 2 years.
- This is an alternative to methotrexate.
- This medicine may be given along with prednisone to treat GPA and bring about remission.
Antibiotics: Certain infections are more common among people with this condition. Antibiotics may be given to treat or prevent infection.
GPA may come back even after successful treatment. Continue to follow up with your healthcare provider, even when you are in remission.
Prevention of Granulomatosis with polyangiitis
- It is a very uncommon and deadly disease. No known prevention of the disease has been found out. There are hardly 2-3 patients who suffer from this disease and it does not involve treatment with only one specialist since it affects many organs.
- Whichever organ is the most affected one, the patient is advised to that particular specialist. It is suggested that people who suffer from continuous above-mentioned symptoms, should undergo ANCA test and biopsy to rule out the disease.
- The symptoms depend on which organ is damaged. In severe cases, the patient may develop kidney failure or even bleed from the lungs.