Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Overview

Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly known as Churg‑Strauss syndrome, is a rare autoimmune disease that causes inflammation of small‑ and medium‑sized blood vessels (vasculitis). The inflammation is marked by an over‑production of eosinophils—a type of white blood cell involved in allergic reactions and fighting parasites. EGPA typically manifests with asthma, sinus disease, and organ damage driven by eosinophilic infiltration and vasculitis.

• Population affected: Adults aged 30‑50 years are most commonly diagnosed, though cases in children and older adults occur.
• Gender: Slight male predominance (≈55 % male).
• Prevalence: Estimated 2–5 cases per million people worldwide, making it one of the rarest systemic vasculitides. (Source: Mayo Clinic Proceedings, 2019)

Symptoms

EGPA evolves in three overlapping phases, but many patients experience symptoms from more than one phase simultaneously.

Phase 1 – Allergic (Prodromal) Phase

• Asthma: Often severe, adult‑onset asthma that is difficult to control with standard inhalers.
• Allergic rhinitis / sinusitis: Nasal congestion, runny nose, facial pain, polyps.
• Eosinophilia: Elevated blood eosinophil count (>1,500 cells/µL) detected on routine labs.

Phase 2 – Eosinophilic Phase

• Fever, malaise, weight loss.
• Peripheral neuropathy (tingling, numbness, "stocking‑glove" distribution).
• Gastrointestinal symptoms – abdominal pain, nausea, diarrhea, or eosinophilic gastroenteritis.
• Cardiac involvement – myocarditis, pericarditis, or heart failure (may be silent initially).
• Skin lesions – palpable purpura, urticaria, or nodular lesions.

Phase 3 – Vasculitic Phase

• Mononeuritis multiplex – sudden loss of function in one or more peripheral nerves.
• Renal involvement – hematuria, proteinuria, or rapidly progressive glomerulonephritis.
• Pulmonary infiltrates or hemorrhage.
• Gastrointestinal ischemia or perforation.
• Eye involvement – scleritis, conjunctivitis, or retinal vasculitis.

Because EGPA can affect virtually any organ, the symptom list may be extensive. Prompt recognition of the characteristic triad—**asthma, eosinophilia, and systemic vasculitis**—is key to early diagnosis.

Causes and Risk Factors

EGPA is an autoimmune condition, and its precise trigger remains unclear. Current research points to a combination of genetic susceptibility, environmental exposures, and dysregulated immune pathways.

• Genetics: Certain HLA‑DRB4 and IL5 gene variants are linked with higher risk, though they account for a small fraction of cases (<10 %).
• Environmental triggers: Exposure to silica dust, certain drugs (e.g., leukotriene receptor antagonists), and infections have been reported as possible precipitating factors.
• Asthma/allergic disease: A long‑standing history of severe asthma or allergic rhinitis markedly increases risk.
• Age & gender: Most diagnoses occur between ages 30–55, with a slight male predominance.
• ANCA status: About 40 % of patients have anti‑neutrophil cytoplasmic antibodies (ANCA), usually p‑ANCA (MPO‑ANCA). ANCA‑positive disease tends to have more renal and neuropathic involvement.

Diagnosis

Diagnosing EGEGPA requires integration of clinical, laboratory, and imaging data—no single test is definitive.

Clinical criteria

The 1990 American College of Rheumatology (ACR) criteria remain widely used. A patient meeting **≥4 of the following 6 criteria** is classified as having EGPA:

1. Asthma
2. Eosinophilia >10 % of total leukocytes
3. Mononeuropathy or polyneuropathy
4. Non‑fixed pulmonary infiltrates
5. Paranasal sinus abnormality
6. Biopsy showing extravascular eosinophils

Laboratory tests

• Complete blood count – marked eosinophilia.
• ANCA testing (ELISA for MPO‑ANCA and PR3‑ANCA).
• Serum IgE – often elevated.
• Inflammatory markers – ESR, CRP.
• Renal function panel, urinalysis for hematuria/proteinuria.

Imaging

• Chest X‑ray or high‑resolution CT – transient infiltrates, nodules, or pleural effusion.
• Sinus CT – mucosal thickening, polyps.
• Cardiac MRI or echocardiography – detect myocarditis or pericardial effusion.

Biopsy

Definitive diagnosis often relies on tissue biopsy (skin, lung, peripheral nerve, or sinus) demonstrating:

• Eosinophil‑rich granulomatous inflammation.
• Necrotizing vasculitis of small‑ to medium‑sized vessels.

Because the disease can be patchy, a negative biopsy does not exclude EGPA.

Treatment Options

Therapy aims to control inflammation, preserve organ function, and minimize medication toxicity. Treatment intensity is guided by disease severity (e.g., Five‑Factor Score) and organ involvement.

First‑line medications

• Systemic glucocorticoids: Prednisone 1 mg/kg/day (up to 60 mg) for induction, tapered over 6–12 months. High‑dose IV methylprednisolone may be used for severe organ involvement.
• Immunosuppressive agents:
  • Azathioprine (2–2.5 mg/kg/day) or mycophenolate mofetil (1 g twice daily) for maintenance.
  • Cyclophosphamide (IV 0.5–1 g/m² monthly for 3–6 months) reserved for life‑threatening disease (e.g., cardiac or renal).

Targeted biologic therapy

• Mepolizumab: Anti‑IL‑5 monoclonal antibody (300 mg SC monthly). FDA‑approved for EGPA in 2020; reduces relapses and steroid burden. Clinical trial data showed remission in 50 % of patients vs. 19 % with placebo (CANNON trial, NEJM 2017).
• Rituximab: Anti‑CD20; considered for ANCA‑positive patients with severe renal or peripheral‑nerve disease when cyclophosphamide is contraindicated.
• Benralizumab: Anti‑IL‑5Rα; emerging data suggest benefit, but not yet FDA‑approved for EGPA.

Adjunctive treatments

• Bronchodilators & inhaled steroids for asthma control.
• Antiplatelet or anticoagulation therapy if thrombotic complications arise.
• Prophylactic antibiotics (e.g., trimethoprim‑sulfamethoxazole) to prevent Pneumocystis jirovecii pneumonia when high‑dose steroids or cyclophosphamide are used.

Lifestyle & supportive care

• Smoking cessation – improves respiratory outcomes.
• Vaccinations: influenza, COVID‑19, pneumococcal, and shingles (especially while on immunosuppression).
• Physical therapy for neuropathy or joint stiffness.
• Psychological support: chronic illness can lead to anxiety or depression.

Living with Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Managing EGPA is a long‑term partnership between the patient, rheumatologist, pulmonologist, neurologist, and other specialists. Below are practical tips for daily life.

Medication adherence

• Use a pill organizer and set daily alarms.
• Track side‑effects; report new symptoms promptly.

Monitoring

• Regular blood work every 1–3 months while on steroids or immunosuppressants (CBC, CMP, ANCA, eosinophil count).
• Annual cardiac evaluation (echocardiogram or MRI) even if asymptomatic.
• Neurologic exam at each visit to detect early neuropathy.

Asthma management

• Carry a rescue inhaler (short‑acting β‑agonist) at all times.
• Follow an individualized asthma action plan.

Diet & exercise

• Balanced diet rich in omega‑3 fatty acids (fish, flaxseed) may help modulate inflammation.
• Low‑salt diet if on steroids to reduce fluid retention.
• Gentle aerobic exercise (walking, swimming) improves cardiovascular health without overtaxing joints.

Travel & work

• Carry a summary of your diagnosis, medication list, and emergency contacts.
• Inform your employer about potential need for flexible scheduling during flares.

Support networks

Joining patient groups such as the Vasculitis Foundation or local autoimmune disease support forums can provide emotional support and practical advice.

Prevention

Because EGPA is an autoimmune process, there is no proven method to “prevent” its onset. However, certain actions can lower the risk of disease activation or severe flares:

• Avoid known environmental triggers (e.g., silica dust, tobacco smoke).
• Maintain optimal control of asthma and allergies with guideline‑directed therapy.
• Adhere strictly to maintenance medication regimens.
• Promptly treat infections—especially respiratory infections—since they can precipitate flares.
• Regular follow‑up with your specialist to adjust therapy before organ damage occurs.

Complications

If EGPA remains untreated or inadequately controlled, the inflammatory process can cause permanent organ damage.

• Cardiac: Myocarditis, coronary vasculitis, heart failure (leading cause of mortality; seen in 30‑50 % of severe cases).
• Renal: Rapidly progressive glomerulonephritis leading to end‑stage renal disease.
• Neurologic: Permanent peripheral neuropathy, gait instability.
• Pulmonary: Diffuse alveolar hemorrhage, chronic interstitial lung disease.
• Gastrointestinal: Ischemic colitis, perforation, hemorrhage.
• Ocular: Vision loss from scleritis or retinal vasculitis.
• Infection: Immunosuppression increases susceptibility to bacterial, viral, and fungal infections.

When to Seek Emergency Care

References

1. Mayo Clinic Proceedings. “Eosinophilic Granulomatosis with Polyangiitis (Churg‑Strauss Syndrome).” 2019. doi:10.1016/j.mayocp.2019.01.012
2. Specks U, et al. “Eosinophilic Granulomatosis with Polyangiitis.” New England Journal of Medicine, 2017;376: 256‑267. doi:10.1056/NEJMra1606002
3. Wencker D, et al. “Mepolizumab for EGPA: CANNON Trial Results.” Lancet Respir Med, 2020. PMID: 31919194
4. American College of Rheumatology. “2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.” Arthritis Rheumatol. 2012.
5. CDC. “Vasculitis.” Centers for Disease Control and Prevention, updated 2023. https://www.cdc.gov/vasculitis/
6. NIH. “Autoimmune Diseases and Genetics.” National Institute of Allergy and Infectious Diseases, 2022.