What is the Wegener disease?: Understanding Granulomatosis with Polyangiitis (GPA)

Affecting only about 3 in 100,000 people, what is the Wegener disease, formally known as Granulomatosis with Polyangiitis (GPA), is a rare autoimmune disorder that causes inflammation of the blood vessels. It can impact nearly any organ system in the body, but primarily affects the respiratory tract and kidneys.

Quick Summary

Wegener's disease, or GPA, is an autoimmune condition causing inflammation in small-to-medium blood vessels, primarily affecting the respiratory system and kidneys. It causes the formation of inflammatory masses known as granulomas, which can damage healthy tissue.

Key Points

• Autoimmune Disorder: GPA, or what is the Wegener disease, is an autoimmune disorder causing the body's immune system to attack healthy blood vessels.

• Primary Targets: The condition primarily affects the small-to-medium blood vessels in the respiratory tract and kidneys, though it can impact other organs.

• Symptoms Vary: Symptoms are often non-specific initially, resembling a persistent cold or flu, and can vary depending on which organs are affected.

• Biopsy for Diagnosis: While blood tests for ANCA antibodies are helpful, a definitive diagnosis requires a tissue biopsy of an affected organ.

• Treatment is Crucial: Prompt treatment with immunosuppressive drugs is vital to achieve remission and prevent life-threatening organ damage.

• Lifelong Management: The disease is characterized by periods of remission and relapse, requiring long-term medical management and monitoring.

A Renamed Condition: From Wegener Disease to GPA

Granulomatosis with Polyangiitis (GPA) is the official medical name for what was once known as Wegener's granulomatosis. The name was changed in 2012 by major medical organizations, including the American College of Rheumatology, after revelations about the Nazi affiliations of Dr. Friedrich Wegener. This change aimed to remove the association with his name and adopt a more descriptive title for the condition.

GPA is a type of vasculitis, a group of rare autoimmune disorders that cause inflammation of the blood vessels. The inflammation can lead to the narrowing or complete obstruction of blood vessels, impeding blood flow and depriving tissues and organs of oxygen and nutrients. A key feature of GPA is the formation of granulomas, small masses of inflamed tissue that can further damage healthy organs. While the respiratory system and kidneys are the most commonly affected organs, the disease can manifest in various parts of the body.

Understanding the Causes of GPA

The exact cause of Granulomatosis with Polyangiitis remains unknown. However, it is an autoimmune disease, which means the body's immune system mistakenly attacks its own healthy tissues and organs. Instead of targeting harmful invaders like viruses or bacteria, the immune system launches an inflammatory response against the body's own small- and medium-sized blood vessels.

While the underlying trigger is not clear, researchers speculate that a combination of factors may contribute to its development. These include potential genetic predispositions and environmental triggers. Some research suggests that an initial inflammatory event, possibly an infection, might set off the abnormal immune reaction in certain individuals. However, no specific infectious agent has been consistently linked to the condition. GPA is not hereditary and does not spread from person to person.

Common Symptoms of Granulomatosis with Polyangiitis

The symptoms of GPA can be vague and appear gradually over weeks or months, making early diagnosis challenging. Symptoms can also vary widely depending on which organs are affected. Some of the most common signs include:

• General symptoms: Fatigue, fever, loss of appetite, and unintended weight loss.
• Respiratory system:
  • Persistent sinus infections and sinus pain.
  • Frequent or unexplained nosebleeds.
  • Nasal crusting, stuffiness, and pus-like drainage.
  • Chronic cough, sometimes with bloody phlegm.
  • Shortness of breath and wheezing.
  • Hoarseness or a narrowing of the windpipe (subglottic stenosis).
  • Collapse of the nasal bridge, leading to a "saddle nose" deformity.
• Kidney involvement: Bloody or foamy urine, swelling in the legs or face (edema) due to kidney issues, and high blood pressure.
• Skin: Red or purple skin patches (purpura), lesions, or ulcers.
• Eyes: Redness, burning, pain, and inflammation. Severe cases can lead to vision loss.
• Ears: Earaches, fluid drainage, and potential hearing loss.
• Nervous system: Tingling, numbness, weakness, or pain in the limbs due to nerve damage.
• Musculoskeletal: Joint pain and swelling.

The Diagnostic Process

Diagnosing GPA involves a comprehensive approach, as its symptoms can mimic many other conditions. Doctors typically use a combination of physical examination, patient history, laboratory tests, and imaging studies.

• Blood Tests: A blood test for antineutrophil cytoplasmic antibodies (ANCA) is a key diagnostic tool. Most people with GPA will test positive for ANCA, specifically targeting a protein called proteinase 3 (PR3-ANCA). However, a negative ANCA test does not rule out GPA, as up to 20% of patients may test negative.
• Urine Tests: A urinalysis can reveal signs of kidney involvement, such as the presence of protein or blood in the urine.
• Imaging: A chest X-ray or CT scan may be performed to check for lung damage or nodules. CT scans of the sinuses can also reveal inflammation.
• Biopsy: A tissue biopsy from an affected organ is the only way to obtain a definitive diagnosis. Pathologists examine the tissue for signs of vasculitis and granulomas, which are characteristic of GPA.

Treatment and Management of GPA

Treatment for GPA is a long-term process designed to induce and maintain remission. It involves powerful anti-inflammatory and immunosuppressive medications to stop the immune system from attacking the body. The treatment is typically divided into two phases:

1. Induction Therapy: Used to achieve remission in patients with active disease. It often involves high doses of corticosteroids (like prednisone) in combination with a strong immunosuppressant, such as cyclophosphamide or rituximab.
2. Maintenance Therapy: Once remission is achieved, the goal shifts to maintaining it and preventing relapse. This involves lower doses of milder immunosuppressants like methotrexate, azathioprine, or rituximab, often for at least 12 to 24 months or longer.

A Comparison of GPA and Other Vasculitides

GPA is part of a broader category of disorders called ANCA-associated vasculitides (AAVs). Here is a comparison of GPA with two other related conditions:

Feature	Granulomatosis with Polyangiitis (GPA)	Microscopic Polyangiitis (MPA)	Eosinophilic Granulomatosis with Polyangiitis (EGPA)
Key Characteristic	Vasculitis + Granulomas	Vasculitis only (no Granulomas)	Vasculitis + High Eosinophil Count
Primary Organs	Respiratory tract, kidneys	Kidneys, lungs	Lungs, skin, nerves, heart
ANCA Type	Primarily PR3-ANCA	Primarily MPO-ANCA	MPO-ANCA often, but not always
Respiratory Tract	Very common, often severe	Common, but typically less severe	Common, often associated with asthma
Eosinophil Count	Normal or low	Normal or low	High (key feature)
Granuloma Formation	Yes	No	Yes

Long-Term Outlook and Conclusion

With effective treatment, the long-term outlook for people with GPA has improved dramatically. Whereas the condition was almost universally fatal within months if left untreated, most patients today can achieve remission and lead relatively normal lives. However, GPA is a chronic condition that requires ongoing care, as relapses are common and can occur even while on medication. Regular monitoring is essential to detect any recurrence of the disease and to manage potential side effects from immunosuppressive therapies.

Early diagnosis is critical to preventing permanent organ damage. Anyone with persistent, unexplained symptoms like chronic sinus issues, fatigue, or shortness of breath should seek medical evaluation. Modern treatment strategies have transformed GPA from a fatal disease into a manageable, long-term condition. For more information, the Vasculitis Foundation offers extensive resources and patient support.

Frequently Asked Questions

Why is it now called Granulomatosis with Polyangiitis?

The name was officially changed from Wegener's Granulomatosis to Granulomatosis with Polyangiitis (GPA) in 2012 due to the discovery of its namesake, Friedrich Wegener, and his association with the Nazi Party. This change was made to remove the association with his name and provide a more accurate, descriptive title for the condition.

What is a vasculitis?

Vasculitis is the general term for a group of diseases that cause inflammation of the blood vessels. This inflammation can weaken, narrow, or stretch the vessels, disrupting blood flow and potentially damaging organs.

How rare is GPA?

Granulomatosis with Polyangiitis is a rare condition, affecting approximately 3 in every 100,000 people. It most commonly develops in middle-aged adults, though it can occur at any age.

Can GPA be cured?

While there is no known cure for GPA, modern treatment can effectively manage the disease, induce remission, and prevent severe organ damage. Lifelong management with medication is typically required to control inflammation and prevent relapses.

What are granulomas?

Granulomas are small, inflamed masses of tissue that form around the blood vessels in GPA. These inflammatory masses can damage healthy tissue and further impair organ function.

Is GPA contagious?

No, Granulomatosis with Polyangiitis is an autoimmune disease and is not contagious. It is not possible to spread it from person to person.

What happens if GPA is not treated?

If left untreated, GPA is a very serious and often fatal condition. It can lead to severe organ damage, especially to the kidneys and lungs, resulting in respiratory or kidney failure.