10 Key Signs and Symptoms of Granulomatosis with Polyangiitis (Wegener’s Disease)

Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a rare autoimmune disorder that causes inflammation of blood vessels throughout the body. This condition primarily affects the respiratory tract and kidneys, but can impact multiple organ systems. Understanding the symptoms of GPA is crucial for early detection and prompt medical intervention, as timely diagnosis can significantly improve outcomes and prevent serious complications.

The disease occurs when the immune system mistakenly attacks healthy blood vessels, causing them to become inflamed and narrowed. This inflammation can restrict blood flow to various organs and tissues, leading to damage. While GPA can affect anyone, it most commonly occurs in middle-aged adults. The symptoms can vary widely depending on which organs are affected, ranging from mild to severe and potentially life-threatening.

1. Persistent Nasal and Sinus Problems

One of the most common early symptoms of granulomatosis with polyangiitis involves the upper respiratory tract, particularly the nose and sinuses. Patients often experience chronic sinusitis that doesn’t respond well to conventional treatments.

Common nasal manifestations include:

• Persistent runny nose with thick discharge that may be bloody or crusty
• Frequent nosebleeds that can range from minor to severe
• Nasal congestion and obstruction
• Formation of crusts inside the nasal passages
• Pain and tenderness in the sinus areas
• Loss of sense of smell

In advanced cases, the inflammation can be so severe that it causes destruction of nasal cartilage, leading to a saddle-nose deformity where the bridge of the nose collapses. This structural damage occurs because the chronic inflammation compromises the blood supply to the nasal cartilage, causing it to deteriorate over time.

2. Chronic Cough and Respiratory Difficulties

Lower respiratory tract involvement is another hallmark of GPA, with the lungs being one of the most frequently affected organs. Patients may develop various pulmonary symptoms that can significantly impact their quality of life.

Respiratory symptoms include:

• Persistent cough that may be dry or produce bloody sputum (hemoptysis)
• Shortness of breath, especially during physical activity
• Chest pain or discomfort
• Wheezing or abnormal breath sounds
• Feeling of tightness in the chest

The lung involvement in GPA can manifest as nodules, cavities, or infiltrates visible on chest imaging. These lung abnormalities occur due to inflammation of the small blood vessels in the lungs, which can lead to tissue damage and the formation of granulomas—small areas of inflamed tissue. Some patients may develop pleurisy, an inflammation of the lining around the lungs, causing sharp chest pain that worsens with breathing.

3. Kidney Dysfunction and Urinary Changes

Kidney involvement in granulomatosis with polyangiitis is particularly concerning as it often occurs silently without obvious symptoms in the early stages. The kidneys are affected in a significant percentage of GPA patients, and kidney damage can progress rapidly if left untreated.

Signs of kidney involvement include:

• Blood in the urine (hematuria), which may or may not be visible to the naked eye
• Protein in the urine (proteinuria), often detected through laboratory testing
• Foamy or frothy urine due to excess protein
• Decreased urine output
• Swelling (edema) in the legs, ankles, feet, or around the eyes
• High blood pressure
• Fatigue and weakness due to declining kidney function

The kidney damage in GPA is caused by inflammation of the glomeruli, the tiny filtering units in the kidneys. This condition, called glomerulonephritis, can impair the kidneys’ ability to filter waste products from the blood. Regular monitoring of kidney function through blood and urine tests is essential for all GPA patients, even those without obvious urinary symptoms.

4. Eye and Vision Problems

Ocular involvement occurs in approximately half of patients with granulomatosis with polyangiitis and can range from mild irritation to severe complications that threaten vision. The inflammation can affect various parts of the eye and surrounding structures.

Eye-related symptoms include:

• Redness and inflammation of the eyes
• Eye pain or discomfort
• Excessive tearing or discharge
• Blurred or decreased vision
• Double vision (diplopia)
• Bulging of one or both eyes (proptosis)
• Sensitivity to light (photophobia)
• Feeling of grittiness or foreign body sensation in the eyes

The eye complications can result from inflammation of various ocular structures, including conjunctivitis, scleritis (inflammation of the white part of the eye), uveitis (inflammation of the middle layer of the eye), or orbital inflammation affecting the tissues around the eye. In severe cases, the inflammation can damage the optic nerve or retina, potentially leading to permanent vision loss if not treated promptly.

5. Ear Symptoms and Hearing Loss

Ear involvement is common in GPA and can significantly impact a patient’s quality of life. The inflammation can affect the middle ear, inner ear, or the eustachian tube, leading to various auditory problems.

Ear-related manifestations include:

• Ear pain or discomfort (otalgia)
• Sensation of fullness or pressure in the ears
• Hearing loss, which can be conductive or sensorineural
• Chronic ear infections (otitis media)
• Discharge from the ear
• Tinnitus (ringing or buzzing in the ears)
• Dizziness or vertigo

The hearing loss associated with GPA can occur suddenly or gradually. It may result from inflammation and fluid accumulation in the middle ear, damage to the small bones that transmit sound, or inflammation affecting the inner ear structures or auditory nerve. Some patients develop chronic otitis media that is resistant to standard antibiotic treatments. Regular audiological assessments are important for monitoring and managing hearing problems in GPA patients.

6. Joint Pain and Muscle Aches

Musculoskeletal symptoms are frequently reported by patients with granulomatosis with polyangiitis, often appearing early in the disease course. These symptoms can sometimes precede other more specific manifestations of GPA.

Musculoskeletal symptoms include:

• Joint pain (arthralgia) affecting multiple joints
• Joint swelling and inflammation (arthritis)
• Muscle pain and aches (myalgia)
• Stiffness, particularly in the morning
• Limited range of motion in affected joints
• General weakness

The joint pain in GPA typically affects multiple joints symmetrically, similar to rheumatoid arthritis, but is usually non-erosive, meaning it doesn’t cause permanent joint damage. The most commonly affected joints include the knees, ankles, wrists, and small joints of the hands and feet. The muscle pain can be diffuse and may be accompanied by muscle weakness in some cases.

7. Skin Manifestations and Rashes

Skin involvement occurs in approximately 40-50% of GPA patients and can present with various dermatological findings. The skin manifestations result from inflammation of small blood vessels in the skin (cutaneous vasculitis).

Skin symptoms include:

• Palpable purpura—small, raised purple or red spots that don’t blanch when pressed
• Ulcers or open sores on the skin
• Nodules or lumps under the skin
• Papules (small raised bumps)
• Vesicles or blisters
• Areas of skin necrosis (tissue death)
• Livedo reticularis—a mottled, purplish discoloration of the skin

These skin lesions most commonly appear on the lower extremities but can occur anywhere on the body. The purpura results from bleeding into the skin due to inflamed blood vessels, while ulcers develop when the inflammation is severe enough to cause tissue breakdown. Some patients may also experience subcutaneous nodules, which are firm lumps beneath the skin surface caused by granulomatous inflammation.

8. Constitutional Symptoms and General Malaise

Many patients with granulomatosis with polyangiitis experience systemic symptoms that affect their overall well-being. These constitutional symptoms reflect the systemic nature of the disease and the body’s inflammatory response.

General symptoms include:

• Persistent fatigue and exhaustion
• Fever, which may be low-grade or high
• Unintentional weight loss
• Loss of appetite
• Night sweats
• General feeling of being unwell (malaise)
• Weakness and reduced energy levels

These symptoms are often non-specific and can be mistaken for other conditions such as infections or other systemic diseases. The fatigue associated with GPA can be debilitating and may persist even when other symptoms are controlled. Weight loss can be significant in some patients, particularly when the disease is active. The presence of these constitutional symptoms often indicates active disease and systemic inflammation.

9. Neurological Manifestations

Although less common than respiratory or kidney involvement, neurological complications can occur in granulomatosis with polyangiitis and may affect both the peripheral and central nervous systems.

Neurological symptoms include:

• Peripheral neuropathy—numbness, tingling, or burning sensations in the hands and feet
• Weakness in the extremities
• Foot drop or wrist drop due to nerve damage
• Headaches, which can be severe and persistent
• Seizures in rare cases of central nervous system involvement
• Stroke-like symptoms if brain blood vessels are affected
• Cognitive changes or confusion
• Cranial nerve palsies affecting eye movement, facial sensation, or facial muscles

Peripheral neuropathy in GPA typically results from vasculitis affecting the blood vessels that supply the nerves (vasculitic neuropathy). This can cause a condition called mononeuritis multiplex, where multiple individual nerves are affected in an asymmetric pattern. Central nervous system involvement is rare but serious and may occur due to vasculitis of brain blood vessels or the formation of granulomatous masses.

10. Oral and Throat Symptoms

The oral cavity and throat can be affected by granulomatosis with polyangiitis, causing symptoms that may interfere with eating, speaking, and swallowing.

Oral and throat symptoms include:

• Mouth ulcers or sores
• Gum inflammation and swelling (gingivitis)
• A distinctive gum appearance called “strawberry gingivitis” with a red, bumpy texture
• Tooth pain or loosening of teeth
• Sore throat that doesn’t improve with standard treatments
• Difficulty swallowing (dysphagia)
• Hoarseness or voice changes
• Subglottic stenosis—narrowing of the airway below the vocal cords

Strawberry gingivitis, though rare, is considered a highly specific finding for GPA. Subglottic stenosis is a particularly serious complication that can cause progressive breathing difficulties, stridor (high-pitched breathing sounds), and in severe cases, life-threatening airway obstruction. This condition may require specialized interventions to maintain an open airway and can sometimes occur independently of other disease activity.

Main Causes of Granulomatosis with Polyangiitis

The exact cause of granulomatosis with polyangiitis remains unknown, but researchers believe it results from a combination of genetic, environmental, and immunological factors. Understanding these potential causes can help identify risk factors, though they cannot fully explain why some people develop the disease while others do not.

Autoimmune Dysfunction: GPA is fundamentally an autoimmune disease where the immune system mistakenly attacks the body’s own blood vessels. In most GPA patients, the immune system produces abnormal antibodies called anti-neutrophil cytoplasmic antibodies (ANCA), specifically the PR3-ANCA or c-ANCA subtype. These antibodies target proteins in white blood cells called neutrophils, triggering an inflammatory cascade that damages blood vessel walls.

Genetic Predisposition: While GPA is not considered a hereditary disease, certain genetic factors may increase susceptibility. Research has identified associations between GPA and specific genetic markers, particularly those related to immune system function. However, having these genetic factors does not guarantee someone will develop the disease, and most people with GPA do not have a family history of the condition.

Environmental Triggers: Various environmental factors have been proposed as potential triggers for GPA in genetically susceptible individuals. Chronic exposure to silica dust has been associated with an increased risk of developing ANCA-associated vasculitis. Infections, particularly chronic nasal infections with bacteria such as Staphylococcus aureus, have been suggested as possible triggers or factors that worsen the disease. However, GPA is not contagious and cannot be transmitted from person to person.

Other Contributing Factors: Certain medications, though rarely, have been associated with ANCA-positive vasculitis. Smoking has also been identified as a potential risk factor. Some researchers believe that a combination of genetic susceptibility and environmental exposure may be necessary for the disease to develop, with an environmental trigger activating the immune system in a genetically predisposed individual.

Frequently Asked Questions

Is granulomatosis with polyangiitis contagious?

No, GPA is not contagious. It is an autoimmune disorder and cannot be transmitted from one person to another through contact, air, or any other means.

What is the difference between Wegener’s granulomatosis and granulomatosis with polyangiitis?

They are the same disease. The condition was previously called Wegener’s granulomatosis but was renamed granulomatosis with polyangiitis (GPA) in 2011 to use more descriptive medical terminology rather than an eponymous name.

Who is most at risk for developing GPA?

GPA can affect anyone but most commonly occurs in middle-aged adults between 40 and 65 years old. It affects men and women approximately equally and is more common in people of European descent, though it can occur in all racial and ethnic groups.

Can GPA symptoms come and go?

Yes, GPA can have periods of active disease (flares) and periods of remission when symptoms improve or disappear. The disease course varies significantly between individuals, and some people may experience multiple flares over time.

How quickly do GPA symptoms develop?

The onset of symptoms can vary. Some patients experience a rapid onset with severe symptoms developing over weeks, while others have a more gradual progression over months. Early symptoms are often non-specific, which can make initial diagnosis challenging.

What should I do if I suspect I have GPA symptoms?

If you experience persistent symptoms such as chronic sinusitis, unexplained nosebleeds, coughing up blood, blood in urine, or any combination of the symptoms described above, consult a healthcare provider promptly. Early diagnosis and treatment are important for preventing serious complications.

Can GPA be cured?

While there is no cure for GPA, the disease can often be effectively managed with appropriate medical treatment. Many patients achieve remission, though ongoing monitoring and maintenance therapy are typically necessary to prevent relapse.

Is GPA a rare disease?

Yes, GPA is considered a rare disease, affecting approximately 3 to 12 people per million population annually. Due to its rarity, many primary care physicians may see only a few cases during their careers, which can sometimes lead to delays in diagnosis.

Can lifestyle changes help with GPA symptoms?

While medical treatment is essential for managing GPA, certain lifestyle measures may help support overall health. These include avoiding smoking, maintaining good nasal hygiene, getting adequate rest, eating a nutritious diet, and staying physically active as tolerated. However, lifestyle changes alone cannot control the disease.

What tests are used to diagnose GPA?

Diagnosis typically involves a combination of blood tests (including ANCA testing), urine tests, imaging studies (chest X-ray or CT scan), and often a biopsy of affected tissue. The diagnosis is based on clinical symptoms, laboratory findings, and histological evidence of vasculitis and granulomatous inflammation.

References:

• Mayo Clinic – Granulomatosis with polyangiitis
• Johns Hopkins Medicine – Granulomatosis with Polyangiitis
• National Institute of Diabetes and Digestive and Kidney Diseases – Granulomatosis with Polyangiitis
• Vasculitis Foundation – Granulomatosis with Polyangiitis
• National Organization for Rare Disorders – Granulomatosis with Polyangiitis