You have had asthma for years, but recently it has become dramatically worse. Your eosinophil count is through the roof. You are developing numbness in your feet, unexplained skin rashes, and chronic sinus problems that will not go away. Your asthma medications are barely keeping up. This may not just be severe asthma. It could be eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome — a rare autoimmune vasculitis that nearly always begins with asthma and can become life-threatening if it progresses unrecognized.
Critical awareness: EGPA affects approximately 11–13 per million people per year, but because it begins as asthma — often years before other symptoms appear — the diagnosis is frequently delayed. More than 95% of EGPA patients have asthma, making pulmonologists and asthma specialists the front line of detection. Early recognition can prevent serious heart, nerve, and kidney damage.
What Is EGPA?
Eosinophilic granulomatosis with polyangiitis is a systemic autoimmune disease that causes inflammation of small and medium-sized blood vessels (vasculitis) throughout the body. The hallmark of the disease is the combination of:
- Asthma — present in virtually all patients, often preceding the vasculitic phase by years or decades
- Eosinophilia — markedly elevated blood eosinophil counts, typically >1,500 cells/μL and often >5,000
- Vasculitis — inflammation damages blood vessel walls, compromising blood flow to organs including the heart, peripheral nerves, skin, kidneys, and gastrointestinal tract
The disease was first described by pathologists Jacob Churg and Lotte Strauss in 1951. It was renamed EGPA in 2012 at the Chapel Hill Consensus Conference to more accurately describe its pathology.
The Three Phases of EGPA
EGPA classically progresses through three overlapping phases, though the timeline varies greatly between patients:
| Phase | Name | Duration | Key Features |
|---|---|---|---|
| 1 | Prodromal (Allergic) | Years to decades | Adult-onset asthma (often severe), allergic rhinitis, sinusitis, nasal polyps. May be the only manifestation for many years. Patients are typically diagnosed with “difficult asthma.” |
| 2 | Eosinophilic | Months to years | Marked blood eosinophilia (>1,500 cells/μL). Eosinophilic infiltration of tissues, especially lungs (eosinophilic pneumonia) and GI tract (eosinophilic gastroenteritis). Migratory pulmonary infiltrates on imaging. |
| 3 | Vasculitic | Acute onset | Small-vessel vasculitis causing: peripheral neuropathy (mononeuritis multiplex), cardiac disease (myocarditis, pericarditis), skin lesions (palpable purpura, nodules), renal involvement, constitutional symptoms (fever, weight loss, fatigue). This is the most dangerous phase. |
Important: The phases may overlap, and not every patient follows this sequence. Some patients develop vasculitic features while still in the eosinophilic phase. The prodromal asthma phase can last 3–10 years on average before other manifestations appear, creating a critical window for early detection.
Warning Signs: When Asthma May Be EGPA
The challenge is distinguishing EGPA from severe eosinophilic asthma, which shares many features. The following red flags should prompt evaluation:
| Feature | Severe Eosinophilic Asthma | EGPA |
|---|---|---|
| Blood eosinophils | Elevated (300–1,500 cells/μL) | Markedly elevated (>1,500, often >5,000 cells/μL) |
| Organ involvement beyond lungs | Not typical | Heart, nerves, skin, kidneys, GI tract |
| Peripheral neuropathy | Absent | Present in 50–75% (numbness, tingling, foot/wrist drop) |
| Skin lesions | Absent (may have eczema) | Palpable purpura, subcutaneous nodules, livedo reticularis |
| Cardiac symptoms | Not related | Chest pain, heart failure, pericarditis (leading cause of mortality) |
| Sinusitis/nasal polyps | May coexist | Nearly universal; often recurrent, treatment-resistant polyps |
| Constitutional symptoms | Not typical | Fever, malaise, weight loss, myalgias, arthralgias |
| ANCA positivity | Negative | Positive in ~40% (usually p-ANCA/anti-MPO) |
| Steroid response | Good but may relapse | Dramatic initial response, but disease relapses on taper |
| Disease trajectory | Stable with appropriate therapy | Progressive; new organ involvement over time without treatment |
Key Red Flags That Suggest EGPA Over Severe Asthma
- Symptoms outside the lungs — any new neurological (numbness, weakness), cardiac (chest pain, palpitations), skin (purpura, nodules), or GI symptoms in an asthma patient with high eosinophils
- Eosinophils >1,500 cells/μL persistently — especially >5,000
- New adult-onset asthma rapidly becoming severe — especially with sinusitis and polyps
- Migratory pulmonary infiltrates — fleeting opacities on chest imaging that come and go
- Dramatic steroid response followed by relapse on taper — the disease flares every time prednisone is reduced
Organ Involvement in EGPA
EGPA can affect virtually any organ. Understanding the pattern of involvement is crucial for both diagnosis and prognosis:
| Organ System | Frequency | Manifestations |
|---|---|---|
| Lungs | >95% | Asthma, eosinophilic pneumonia, migratory infiltrates, pleural effusion |
| ENT/Sinuses | 70–80% | Chronic sinusitis, nasal polyps, allergic rhinitis |
| Peripheral nerves | 50–75% | Mononeuritis multiplex (asymmetric nerve damage), peripheral neuropathy, foot drop, wrist drop |
| Skin | 40–70% | Palpable purpura, subcutaneous nodules, urticaria, livedo reticularis |
| Heart | 15–40% | Eosinophilic myocarditis, pericarditis, heart failure, coronary vasculitis. Leading cause of EGPA-related death. |
| GI tract | 20–40% | Abdominal pain, diarrhea, GI bleeding, eosinophilic gastroenteritis, mesenteric vasculitis |
| Kidneys | 10–25% | Glomerulonephritis (usually milder than in GPA or microscopic polyangiitis) |
Diagnosis of EGPA
There is no single test that confirms EGPA. Diagnosis relies on the American College of Rheumatology (ACR) classification criteria combined with clinical judgment. At Advanced Asthma Clinic, Dr. Frank Hull coordinates a thorough workup when EGPA is suspected:
ACR Classification Criteria (4 of 6 = classification)
- Asthma
- Eosinophilia >10% on differential white blood cell count
- Mononeuropathy or polyneuropathy
- Migratory or transient pulmonary infiltrates on imaging
- Paranasal sinus abnormality
- Biopsy showing extravascular eosinophilic infiltration
Diagnostic Workup
- Complete blood count (CBC) — eosinophil count is the cornerstone; typically >1,500 cells/μL
- ANCA testing — p-ANCA (perinuclear pattern) with anti-MPO specificity is positive in approximately 40% of patients. ANCA-positive patients tend to have more vasculitic features (neuropathy, glomerulonephritis), while ANCA-negative patients tend to have more cardiac and pulmonary involvement
- Inflammatory markers — ESR and CRP are typically elevated during active disease
- Total IgE — often elevated, though not as dramatically as in ABPA
- Spirometry — obstructive pattern from asthma, with possible restriction from pulmonary infiltrates
- Chest CT — ground-glass opacities, consolidation, nodules, pleural effusion
- Echocardiography and cardiac MRI — to evaluate for myocarditis, pericardial effusion, or ventricular dysfunction
- Nerve conduction studies/EMG — if neuropathy is suspected
- Tissue biopsy — from affected organ (skin, nerve, lung) showing eosinophilic infiltration, necrotizing vasculitis, or granulomas
- Urinalysis and renal function — to screen for glomerulonephritis
With over 20 years of experience in pulmonary medicine and clinical research, Dr. Hull understands that EGPA can hide behind a diagnosis of “difficult asthma” for years. When clinical suspicion arises, he coordinates with rheumatology, cardiology, and neurology to ensure comprehensive evaluation.
ANCA-Positive vs. ANCA-Negative EGPA
EGPA is increasingly recognized as having two distinct phenotypes based on ANCA status, which influences both presentation and prognosis:
| Feature | ANCA-Positive (~40%) | ANCA-Negative (~60%) |
|---|---|---|
| Predominant pathology | Vasculitis-driven | Eosinophilic tissue infiltration |
| Nerve involvement | More common and severe | Less common |
| Kidney involvement | Glomerulonephritis more likely | Less renal disease |
| Cardiac involvement | Less common | More frequent and more dangerous (eosinophilic myocarditis) |
| Lung involvement | Alveolar hemorrhage possible | Eosinophilic infiltrates and asthma predominate |
| Skin purpura | More common | Less common |
Treatment of EGPA
Treatment depends on disease severity and organ involvement. The Five-Factor Score (FFS) helps guide therapy by identifying poor prognostic features: cardiac involvement, GI involvement, renal insufficiency, proteinuria >1 g/day, and central nervous system involvement.
1. Corticosteroids
High-dose systemic corticosteroids remain the first-line treatment for all EGPA patients:
- Prednisone 1 mg/kg/day (typically 40–60 mg) for induction
- Gradual taper over 9–12 months or longer
- Many patients require long-term low-dose prednisone to maintain remission
Most patients show dramatic improvement within days to weeks. However, relapse during steroid taper is common, driving the need for steroid-sparing agents.
2. Immunosuppressive Agents
For patients with severe organ involvement (FFS ≥1) or steroid-dependent disease:
- Cyclophosphamide — for life-threatening cardiac, renal, or neurological involvement (induction)
- Azathioprine — for maintenance therapy after cyclophosphamide induction
- Methotrexate — alternative maintenance agent
- Mycophenolate mofetil — used in some centers for maintenance
3. Biologic Therapies
Biologic medications represent a major advance in EGPA treatment:
- Mepolizumab (Nucala) — an anti-IL-5 monoclonal antibody that is FDA-approved specifically for EGPA (since 2017). In the MIRRA trial, mepolizumab significantly increased remission rates and reduced steroid requirements. Administered as a 300 mg subcutaneous injection every 4 weeks for EGPA (higher dose than the 100 mg used for severe asthma).
- Benralizumab (Fasenra) — another anti-IL-5 pathway biologic showing promise in clinical trials for EGPA
- Rituximab — anti-CD20 B-cell depletion; used for ANCA-positive refractory EGPA, based on evidence from other ANCA-associated vasculitides
Dr. Hull has extensive experience prescribing biologic therapies and evaluates each EGPA patient for the most appropriate treatment based on their ANCA status, organ involvement, and prior treatment history.
4. Ongoing Asthma Management
Asthma management continues alongside EGPA treatment:
- Inhaled corticosteroids and long-acting bronchodilators
- Personalized asthma action plans
- Regular lung function monitoring
- Sinus management (may include surgery for refractory polyps)
The Biologic “Unmasking” Phenomenon
A topic of significant clinical interest: there have been case reports of EGPA symptoms appearing after patients start biologic therapy for severe asthma (particularly omalizumab and anti-IL-5 agents). Current understanding is that these biologics do not cause EGPA. Rather:
- The patient already had early, unrecognized EGPA
- Their oral corticosteroids (often prescribed for severe asthma) were suppressing the vasculitic features
- When the effective biologic therapy allowed steroid tapering, the previously masked EGPA features emerged
This underscores why careful monitoring during corticosteroid tapering is essential for any patient with severe eosinophilic asthma, regardless of biologic use.
Prognosis and Long-Term Outlook
With modern treatment, the prognosis for EGPA has improved substantially:
- 5-year survival exceeds 90% with appropriate treatment
- Cardiac involvement remains the leading cause of EGPA-related mortality — early cardiac screening is critical
- Relapse rate is approximately 25–35% within 5 years, necessitating long-term follow-up
- Nerve damage from mononeuritis multiplex may be partially irreversible, reinforcing the importance of early treatment
- Asthma typically persists even when EGPA is in remission and requires ongoing management
When to Seek Specialist Evaluation
Contact your physician or seek specialist evaluation if you have asthma and experience any of the following:
- Blood eosinophil count persistently above 1,500 cells/μL
- New numbness, tingling, weakness, or foot/wrist drop
- Unexplained skin rash, purplish spots, or nodules under the skin
- Chest pain, palpitations, or new shortness of breath beyond your usual asthma
- Unexplained weight loss, persistent fevers, or severe fatigue
- Asthma that has rapidly escalated from mild to severe, especially with sinus disease
- Recurrent “pneumonias” with migratory infiltrates on imaging
Contact Advanced Asthma Clinic at (954) 522-7226 to schedule a comprehensive evaluation with Dr. Frank Hull. Early recognition of EGPA can prevent serious, irreversible organ damage.
Related Resources
Medical disclaimer: This article is for educational purposes and does not replace professional medical advice. EGPA is a serious condition requiring specialized multidisciplinary care. Always consult your physician before making changes to your treatment. If you are experiencing chest pain, sudden weakness, or severe breathing difficulty, call 911 immediately.