Eosinophilic Granulomatosis with Polyangiitis

The exact etiology of EGPA is not fully understood, but it is widely considered an autoimmune disorder where the immune system overreacts to an unknown trigger. This overreaction leads to the excessive production and activation of eosinophils. Research published in Nature Reviews Rheumatology (2023) suggests that a combination of genetic predisposition and environmental exposure initiates the inflammatory cascade. Once activated, these eosinophils release toxic proteins that damage the lining of blood vessels and surrounding tissues.

Non-Modifiable Risk Factors

• Genetics: Certain genetic markers, particularly in the HLA (Human Leukocyte Antigen) region, have been linked to an increased risk of developing EGPA.
• History of Atopy: A personal history of asthma, nasal polyps, or chronic allergies is the most significant non-modifiable risk factor.
• Age: Most diagnoses occur in individuals aged 30 to 50.

Modifiable Risk Factors

• Environmental Triggers: While not fully proven, some studies suggest that exposure to certain allergens, chemicals, or infections may trigger the onset of the vasculitic phase in susceptible individuals.
• Medication Sensitivity: Historically, there were concerns regarding leukotriene modifiers, though current consensus suggests these medications may simply unmask underlying EGPA by allowing for the reduction of corticosteroids.

The population most at risk includes individuals with severe, adult-onset asthma that becomes progressively harder to manage. According to the Vasculitis Foundation (2024), approximately 90% of EGPA patients have a history of asthma. Those with chronic sinusitis and high levels of eosinophils in their blood should be monitored closely for signs of systemic vasculitis.

Currently, there are no known strategies to prevent the development of EGPA. Because the cause is idiopathic (unknown), prevention focuses on early detection and aggressive management of the prodromal (allergic) stage. Regular monitoring of blood eosinophil levels in patients with severe asthma may help healthcare providers identify the transition to the eosinophilic or vasculitic stages earlier, potentially preventing major organ damage.

Diagnosing EGPA is often a complex process because its symptoms overlap with more common conditions like severe asthma or other forms of vasculitis. The diagnostic journey typically involves a combination of clinical evaluation, laboratory testing, and imaging. Healthcare providers look for a pattern of symptoms that match the established classification criteria.

A physician will perform a comprehensive exam, focusing on the respiratory system, skin, and neurological function. They will look for signs of nasal polyps, skin lesions (purpura), and assess nerve sensitivity and muscle strength in the extremities to check for mononeuritis multiplex.

• Complete Blood Count (CBC): This is used to identify eosinophilia, defined as an eosinophil count greater than 10% of the total white blood cell count or an absolute count exceeding 1,500 cells/µL.
• ANCA Testing: A blood test to check for Anti-Neutrophil Cytoplasmic Antibodies. While positive in only about 40% of cases, it helps confirm the diagnosis and classify the subtype.
• Imaging: Chest X-rays or CT scans are used to identify "fleeting opacities" (migratory shadows in the lungs) or sinus inflammation.
• Biopsy: Taking a small tissue sample from the skin, lung, or nerve is the gold standard. A pathologist looks for extravascular eosinophilic infiltration and granulomatous inflammation.

The American College of Rheumatology (ACR) established six criteria for EGPA diagnosis. A patient must typically meet at least four of the following:

1. 1Asthma.
2. 2Eosinophilia (>10% of differential WBC count).
3. 3Mononeuropathy or polyneuropathy.
4. 4Migratory or transitory pulmonary opacities on imaging.
5. 5Paranasal sinus abnormality.
6. 6Extravascular eosinophils on biopsy.

Healthcare providers must rule out other conditions, including:

• Hypereosinophilic Syndrome (HES): High eosinophils without the vasculitis component.
• Granulomatosis with Polyangiitis (GPA): A different form of vasculitis that rarely involves asthma.
• Severe Allergic Bronchopulmonary Aspergillosis (ABPA): A fungal reaction that mimics EGPA symptoms.

The primary goals of treatment for EGPA are to induce and maintain remission, prevent organ damage, and manage the underlying asthma and sinus symptoms. Successful treatment is measured by the normalization of eosinophil counts, the disappearance of vasculitic symptoms, and the ability to taper high-dose medications without a relapse.

According to the American College of Rheumatology/Vasculitis Foundation guidelines (2021), the standard first-line therapy for nearly all patients is systemic corticosteroids. These are used to rapidly reduce inflammation. In cases of severe or life-threatening organ involvement (e.g., heart or kidney disease), corticosteroids are often combined with potent immunosuppressive agents to achieve control.

• Corticosteroids: These act as powerful anti-inflammatory agents. While highly effective for inducing remission, long-term use can lead to side effects like osteoporosis, weight gain, and increased infection risk.
• Interleukin-5 (IL-5) Inhibitors: This newer class of monoclonal antibodies specifically targets the protein responsible for eosinophil survival and activation. They are often used in non-severe cases to reduce the need for corticosteroids and prevent relapses.
• Antimetabolite Immunosuppressants: These drugs interfere with the growth of immune cells. They are frequently used as "steroid-sparing" agents to help maintain remission once the initial inflammation is controlled.
• Cytotoxic Agents: Reserved for severe, life-threatening cases, these medications work by suppressing the entire immune system to stop the vasculitic process quickly.

If first-line treatments are ineffective or if a patient experiences a relapse, healthcare providers may use B-cell depleting monoclonal antibodies. These therapies target specific white blood cells that contribute to the autoimmune response. Combination therapy is common in the maintenance phase to ensure the disease remains dormant.

• Plasma Exchange (Plasmapheresis): In very severe cases of kidney involvement, this procedure filters the blood to remove harmful antibodies.
• Physical Therapy: Essential for patients who have suffered nerve damage or muscle weakness due to vasculitis.
• Surgery: May be required to remove nasal polyps or address complications like intestinal perforations.

Treatment is typically long-term, often lasting several years or even a lifetime. Patients require frequent blood tests to monitor eosinophil levels and inflammatory markers (CRP/ESR), as well as regular lung and heart function tests.

• Pregnancy: EGPA must be tightly controlled before and during pregnancy; certain immunosuppressants are contraindicated.
• Elderly: Older patients require careful monitoring for corticosteroid-induced side effects like hypertension and cataracts.

> Important: Talk to your healthcare provider about which approach is right for you.

While no specific diet cures EGPA, an anti-inflammatory eating pattern may support overall health. Research suggests that a Mediterranean-style diet—rich in omega-3 fatty acids from fish, antioxidants from fruits and vegetables, and whole grains—can help manage systemic inflammation. Because long-term corticosteroid use increases the risk of bone loss, patients should ensure adequate intake of Calcium and Vitamin D, as recommended by the Bone Health & Osteoporosis Foundation.

Physical activity is encouraged but must be tailored to the individual's current disease state. During a flare, rest is paramount. During remission, low-impact aerobic exercises like swimming or walking can improve lung capacity and combat the weight-gain side effects of steroids. Patients with peripheral neuropathy should consult a physical therapist to develop a safe balance and strength routine.

Chronic inflammation and medication side effects can disrupt sleep. Maintaining a consistent sleep schedule and practicing good sleep hygiene (e.g., a dark, cool room and no screens before bed) is vital. Managing asthma symptoms at night is also key to ensuring restorative rest.

Living with a chronic, rare disease is inherently stressful. Stress can potentially trigger asthma flares. Evidence-based techniques such as Mindfulness-Based Stress Reduction (MBSR), deep breathing exercises, and cognitive-behavioral therapy (CBT) have been shown to improve the quality of life in patients with chronic vasculitis.

Some patients find relief through acupuncture for nerve pain or yoga for flexibility and stress. However, these should never replace conventional medical treatment. Always discuss supplements with a doctor, as some (like echinacea) may stimulate the immune system and interfere with immunosuppressive therapy.

Caregivers should educate themselves about the signs of a flare, such as increased coughing or new numbness. Providing emotional support and assisting with medication adherence is crucial. Encourage the patient to join support groups, such as those offered by the Vasculitis Foundation, to connect with others facing similar challenges.

The prognosis for EGPA has improved dramatically over the last few decades. Before the use of modern immunosuppressants, the condition was often fatal. Today, with appropriate treatment, the five-year survival rate is estimated to be over 90%, according to data published in Annals of the Rheumatic Diseases (2023). Most patients are able to achieve remission, although many will require long-term, low-dose medication to prevent the disease from returning.

If left untreated or if the disease is particularly aggressive, complications can include:

• Cardiac Damage: Myocarditis or heart failure (the leading cause of mortality in EGPA).
• Permanent Nerve Damage: Chronic pain or loss of function in the hands or feet.
• Kidney Failure: Though less common than in other forms of vasculitis, it can occur.
• Lung Scarring: Permanent damage to the airways from chronic inflammation.

Management is a lifelong process. Relapses occur in approximately 25% to 50% of patients, often appearing as a return of asthma symptoms or a rise in eosinophil counts. Regular follow-ups with a rheumatologist, pulmonologist, and sometimes a cardiologist are necessary to monitor for these signs.

Many people with EGPA lead full, active lives. Success depends on early diagnosis, strict adherence to treatment plans, and proactive management of side effects. Utilizing a multidisciplinary medical team ensures that all aspects of the disease—from the lungs to the nerves—are addressed.

Contact your healthcare provider if you notice a return of asthma symptoms, new skin rashes, unexplained weight loss, or any new numbness or tingling in your limbs. Early intervention during a relapse is key to preventing permanent organ damage.