Granulomatosis with polyangiitis
Granulomatosis with polyangiitis is a rare disease that causes inflammation of small blood vessels throughout the body, affecting mainly the respiratory system and kidneys, and requiring early treatment to prevent serious organ damage.
Wegener’s granulomatosis, Wegener granulomatosis, GPA
Table of contents
- What is granulomatosis with polyangiitis?
- Symptoms and how the disease affects the body
- Who develops this condition?
- What causes granulomatosis with polyangiitis?
- How is the disease diagnosed?
- Treatment options
- Outlook and living with the disease
What is granulomatosis with polyangiitis?
Granulomatosis with polyangiitis, or GPA, is a rare disease that causes swelling and inflammation of small blood vessels throughout the body[1]. The condition was previously known as Wegener’s granulomatosis, but was renamed to better describe what happens in the disease[2].
GPA is a type of vasculitis, which means inflammation of blood vessels. The word “polyangiitis” refers to inflammation affecting many different types of blood vessels, particularly the small arteries and veins[4]. When blood vessels become inflamed, they can swell, break, and bleed. The inflammation can also cause scarring that blocks blood flow, preventing oxygen and nutrients from reaching tissues and organs[2].
A key feature of GPA is the formation of granulomas—small areas of inflammation made up of immune cells. These granulomas usually occur in the lungs or airways, but can develop in other organs too. As granulomas grow, they can invade surrounding areas and cause tissue damage[6].
This condition mainly affects three parts of the body: the upper respiratory tract (including the nose, sinuses, and throat), the lungs, and the kidneys[1]. However, because the disease affects small blood vessels throughout the body, it can potentially impact any organ[2].
Symptoms and how the disease affects the body
The symptoms of granulomatosis with polyangiitis vary widely from person to person. They can start suddenly or develop slowly over many months[3]. Early symptoms are often general and can be easily mistaken for a cold or flu[1].
General symptoms
Many people with GPA first experience vague symptoms that affect the whole body. These may include fever, night sweats, extreme tiredness (also called malaise), weakness, joint pain and stiffness, loss of appetite, and weight loss without trying[1][3]. Muscle aches and pain are also common[1].
Respiratory system symptoms
Most people with GPA—about 90 percent—first notice symptoms in their respiratory system[7]. These symptoms often resemble a cold or infection but linger too long[2].
Ear, nose, and throat symptoms can include a constantly blocked or runny nose with crusting, frequent nosebleeds, sinus pain and pressure, repeated sinus infections, sores in the nose or mouth, and earaches or fluid draining from the ear[1][3][7].
Lung and windpipe symptoms may include a cough that doesn’t go away (sometimes with bloody or discolored mucus), shortness of breath or wheezing, chest pain, and a hoarse voice[1][3].
As the disease progresses, inflammation can affect the cartilage in the ears, nose, and throat. Severe nasal swelling can cause the bridge of the nose to collapse, creating what is called a “saddle nose” deformity[2][7]. Narrowing of the windpipe just below the vocal cords, called subglottic stenosis, can cause breathing difficulties, a high-pitched breathing sound, and may require emergency treatment[2][7]. Inner ear inflammation can cause dizziness (vertigo) and hearing loss[2].
Kidney symptoms
The kidneys are commonly affected in people with GPA[1]. Many people don’t feel kidney pain, but may notice blood in their urine or foamy urine. Swelling in the face or feet can also signal kidney problems[2]. While the kidneys aren’t always involved early in the disease, they are affected eventually in almost all cases[2]. Without treatment, kidney inflammation can lead to high blood pressure and kidney failure[7].
Other affected areas
GPA can also affect the eyes, causing redness, swelling, pain, pressure, and in severe cases, vision loss[2][3][7].
Skin symptoms may include rashes, sores, ulcers, or small spots[2][3].
The nervous system can be affected, causing numbness, tingling, or loss of movement in the fingers, toes, or limbs[2][7].
- Nose and sinuses
- Ears
- Throat and windpipe
- Lungs
- Kidneys
- Eyes
- Skin
- Joints
- Nerves
- Heart
- Brain
Who develops this condition?
Granulomatosis with polyangiitis is a rare disease. It affects approximately 3 out of every 100,000 people in the United States[4][6].
The disease most commonly occurs in middle-aged adults[1], typically between the ages of 40 and 65[4]. However, GPA can occur at any age, including in children and elderly people. While it’s unusual in childhood, it’s not uncommon for someone to be diagnosed in their 70s or even 80s[7].
The disease affects men and women nearly equally, with a slight male predominance[7].
What causes granulomatosis with polyangiitis?
The exact cause of GPA is not well understood[6]. Scientists believe the disease involves a combination of genetic and environmental factors[6].
GPA is an autoimmune disorder, meaning the body’s immune system mistakenly attacks its own healthy tissues[6]. The immune system normally protects us from germs and foreign invaders, but in GPA, it malfunctions and causes damage to blood vessels and organs.
Approximately 90 percent of people with GPA have an abnormal immune protein in their blood called anti-neutrophil cytoplasmic antibody, or ANCA[6][8]. Antibodies normally attach to foreign particles and germs to mark them for destruction, but ANCAs attack normal human proteins instead. Most people with GPA have an ANCA that attacks a protein called proteinase 3 (PR3), while a few have an ANCA that attacks a protein called myeloperoxidase (MPO)[6]. When these antibodies attach to their target proteins, they trigger inflammation that contributes to the signs and symptoms of the disease[6].
Having a particular version of the HLA-DPB1 gene is the strongest genetic risk factor for developing GPA, although several other genes may also be involved[6]. The HLA-DPB1 gene belongs to a family of genes that helps the immune system tell the difference between the body’s own proteins and those made by foreign invaders like viruses and bacteria[6].
How is the disease diagnosed?
There is no single test that can diagnose granulomatosis with polyangiitis, and it can be difficult to diagnose[3]. The diagnostic process involves several steps and different types of tests.
Medical history and physical examination
A doctor will ask about symptoms and medical history, then perform a physical examination[1][8]. If GPA is suspected, the doctor will refer the patient to a specialist, such as a rheumatologist (a doctor who specializes in autoimmune diseases)[3].
Blood tests
Several blood tests can help with diagnosis. Tests can check for signs of inflammation, such as high levels of C-reactive protein or a high erythrocyte sedimentation rate (also called sed rate), which measures how quickly red blood cells settle in a test tube[8].
The presence of antineutrophil cytoplasmic antibodies (ANCA) in the blood is a key marker for GPA[3][8]. These antibodies appear in the blood of most people who have GPA, although a positive ANCA test suggests but doesn’t confirm the diagnosis. About 10 to 20 percent of people with GPA test negative for ANCA[7][14].
Blood tests can also check for low levels of healthy red blood cells (a condition called anemia, which is common in people with GPA) and signs that the kidneys aren’t properly filtering waste products[8].
Urine tests
Urine tests can reveal whether the urine contains red blood cells or too much protein, which might indicate that the disease is affecting the kidneys[8].
Imaging tests
If there are lung symptoms, chest X-rays and CT scans (computed tomography scans) can help determine if GPA is the cause[8]. CT scans use X-rays and a computer to create detailed images of the organs inside the body. These scans can also help identify if GPA is causing head or neck symptoms[8]. Once treatment begins, CT scans can show whether the treatment is working[8].
Biopsy
A biopsy is often needed to confirm the diagnosis. During this procedure, a doctor removes a small sample of tissue from an affected area of the body and examines it under a microscope[8]. Because the changes caused by GPA are patchy, the chance of finding them depends on where the biopsy is taken and how much tissue is obtained. Surgical biopsies that provide more tissue generally have better results[14].
Treatment options
Treatment for granulomatosis with polyangiitis is essential because, without it, the disease can lead to organ damage and is often fatal[1]. Before effective treatments were available in the 1970s, up to 90 percent of patients with untreated severe GPA died within 2 years, usually from respiratory or kidney failure[10].
Today, with proper treatment, most people with GPA can achieve remission and live relatively normal lives[1]. Treatment is typically divided into two phases: bringing the disease under control (remission induction) and keeping it under control (remission maintenance)[3][10].
Bringing the disease under control
The main goal of initial treatment is to stop the inflammation and damage caused by GPA. Treatment usually involves a combination of medicines.
Corticosteroids (also called steroids) are almost always used in the initial treatment. These powerful medicines help reduce inflammation quickly[3][10].
For mild GPA, steroids may be combined with an immunosuppressant medicine such as methotrexate. Immunosuppressants work by calming down the overactive immune system[3].
For severe GPA, doctors may prescribe a biological medicine such as rituximab or avacopan, along with steroids[3]. Rituximab is a special type of medicine that targets certain immune cells called B-cells. It was approved in 2011 for treating GPA and has become a preferred treatment because it works as well as older medicines but is considered less toxic[10][12].
Some patients may receive a type of chemotherapy medicine, such as cyclophosphamide. While effective, cyclophosphamide can have serious side effects and has largely been replaced by rituximab for initial treatment[3][10].
Keeping the disease under control
Once the disease is in remission, the goal shifts to preventing symptoms from returning. Patients may take lower doses of their medicines or switch to different types of medicine[3]. Common medicines used for maintenance include azathioprine, methotrexate, or continued rituximab[10].
If symptoms return
If symptoms come back or new symptoms appear (called a relapse), treatment may need to be changed or restarted[3]. Between 30 and 50 percent of people who initially respond to treatment experience at least one relapse[10].
Treating severe cases
In very severe cases affecting the kidneys, patients may need dialysis or even a kidney transplant[3]. Surgery may be needed to repair damage caused by GPA, such as reconstructive surgery if the bridge of the nose has collapsed[3][7].
Outlook and living with the disease
With early diagnosis and proper treatment, the outlook for people with granulomatosis with polyangiitis has improved dramatically. Approximately 90 percent of patients respond to treatment, with about 75 percent achieving complete remission[10]. Early treatment helps people live full and active lives[1].
However, GPA is a chronic disease that requires ongoing management. People with GPA need regular check-ups because the disease can return even after successful treatment[3]. Regular laboratory tests, imaging scans, and clinic visits help spot any problems early so prompt treatment can begin[7].
Living with GPA means learning to manage symptoms and making necessary lifestyle adjustments. Many people find that the disease makes them less able to handle stress and physical demands, requiring more rest and the ability to say “no” more often[18]. Some patients need to change their work arrangements or reduce their activity levels[16].
Support from family, friends, or support groups can help people cope with the emotional impact of living with a chronic disease[1]. Understanding the disease, being an active partner with healthcare providers, and maintaining a positive attitude are important for successfully managing GPA[16][18].
Patients should report any new symptoms to their doctor right away, as relapses may involve different symptoms than earlier episodes[7]. With proper medical care, self-advocacy, and lifestyle adjustments, people with GPA can maintain good quality of life despite the challenges of this rare disease.
