Granulomatosis with polyangiitis
Granulomatosis with polyangiitis is a rare autoimmune disorder characterized by blood vessel inflammation and abnormal tissue clumps that primarily damage the respiratory tract and kidneys.
Overview
Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is a condition that causes inflammation primarily affecting the respiratory tract (including the lungs and airways) and the kidneys. A characteristic feature of GPA is inflammation of blood vessels (vasculitis), particularly the small- and medium-sized blood vessels in the lungs, nose, sinuses, windpipe, and kidneys, although vessels in any organ can be involved.
Polyangiitis refers to the inflammation of multiple types of vessels, such as small arteries and veins. This vasculitis causes scarring and tissue death in the vessels, which impedes blood flow to tissues and organs.
Another characteristic feature of GPA is the formation of granulomas, which are small areas of inflammation composed of immune cells that aid in the inflammatory reaction. These granulomas usually occur in the lungs or airways, although they can occur in the eyes or other organs. As they grow, they can invade surrounding areas, causing tissue damage.
Symptoms
The signs and symptoms of GPA vary based on the tissues and organs affected by vasculitis. Many people experience general symptoms of the body's immune reaction, including:
- A vague feeling of discomfort (malaise)
- Fever
- Weight loss
In most people with GPA, inflammation begins in the vessels of the respiratory tract, leading to nasal congestion, frequent nosebleeds, shortness of breath, or coughing. Severe inflammation in the nose can lead to a hole in the tissue that separates the two nostrils (nasal septum perforation) or a collapse of the septum, causing a saddle nose deformity.
The kidneys are also commonly affected. Tissue damage caused by vasculitis in the kidneys can lead to decreased kidney function, which may cause increased blood pressure, blood in the urine, and life-threatening kidney failure. Depending on which other systems are involved, additional symptoms can include skin rashes, inner ear pain, swollen and painful joints, and numbness or tingling in the limbs.
GPA is most common in middle-aged adults, although it can occur at any age. If untreated, the condition is usually fatal within 2 years of diagnosis. Even after treatment, vasculitis can return.
Frequency
GPA is a rare disorder that affects an estimated 3 in 100,000 people in the United States.
Causes & Genetic Risk Factors
The genetic basis of GPA is not well understood, but it is likely that a combination of genetic and environmental factors leads to the condition. GPA is an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's own tissues and organs.
Approximately 90 percent of people with GPA have an abnormal immune protein called an anti-neutrophil cytoplasmic antibody (ANCA) in their blood. While antibodies normally bind to foreign particles and germs, ANCAs attack normal human proteins. Most people with GPA have an ANCA that attacks the human protein proteinase 3 (PR3). A few affected individuals have an ANCA that attacks a protein called myeloperoxidase (MPO). When these antibodies attach to their target proteins, they trigger inflammation.
The Role of the HLA-DPB1 Gene
Having a particular version of the HLA-DPB1 gene is the strongest genetic risk factor for developing GPA. This gene belongs to a family of genes called the human leukocyte antigen (HLA) complex, which helps the immune system distinguish the body's own proteins from foreign invaders. A particular variant called HLA-DPB1*0401 has been found more frequently in people with GPA, especially those with ANCAs, than in people without the condition.