Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis)

What EGPA is

EGPA is one of the ANCA-associated vasculitides, a family that also includes granulomatosis with polyangiitis and microscopic polyangiitis. In EGPA, the immune system drives two processes:

1. Eosinophilic inflammation: eosinophils, white blood cells normally involved in allergy and parasite defense, multiply and invade tissues, causing damage.
2. Vasculitis: inflammation of blood vessel walls, which can cut off blood supply to nerves and organs.

Small inflammatory nodules called granulomas also form in tissues. It is rare, with a few new cases per million people each year.

Phases and symptoms

EGPA often develops in three overlapping phases over years:

1. Allergic (prodromal) phase

• adult-onset asthma, often becoming more severe
• allergic rhinitis, chronic sinusitis and nasal polyps

2. Eosinophilic phase

• high blood eosinophils (often above 10% of white cells or 1,500 cells per microliter)
• shifting patches of pneumonia-like inflammation in the lungs
• eosinophilic gastroenteritis: belly pain, diarrhea
• fever, weight loss and fatigue

3. Vasculitic phase

• nerves: numbness, tingling, burning pain and weakness in a patchy pattern (mononeuritis multiplex), often causing foot drop or wrist drop. Affects up to 3 in 4 people.
• skin: purple spots (purpura), nodules, hives or ulcers
• heart: inflammation of the heart muscle (myocarditis), pericarditis and heart failure. Heart involvement is the leading cause of death in EGPA.
• kidneys: blood or protein in the urine, sometimes kidney impairment
• gut: pain, bleeding or perforation from vasculitis
• joints and muscles: aches and arthritis
• eyes and brain, less often

Causes

The cause is unknown. Genetic susceptibility and environmental triggers, such as allergens, infections and certain drugs, are thought to play a role. Some cases were unmasked when asthma patients reduced oral steroids after starting newer asthma medicines. These drugs uncover rather than cause the disease.

Diagnosis

There is no single test. Diagnosis combines:

• blood tests: eosinophil count, inflammatory markers (ESR, CRP), IgE, kidney function and urine tests
• ANCA antibodies: positive (usually MPO-ANCA) in about a third of people. ANCA-positive EGPA is more often linked to kidney disease and nerve problems. ANCA-negative EGPA more often affects the heart and lungs
• chest CT and sinus imaging
• heart tests: ECG, troponin, echocardiogram and cardiac MRI for everyone diagnosed, because heart involvement can be silent
• nerve conduction studies for nerve symptoms
• biopsy of skin, nerve, lung or other tissue showing eosinophil-rich vasculitis or granulomas
• exclusion of other causes of high eosinophils, such as parasites, drug reactions, allergic bronchopulmonary aspergillosis and hypereosinophilic syndrome

The 2022 ACR/EULAR classification criteria give points for obstructive airway disease, nasal polyps, mononeuritis multiplex, high eosinophils and biopsy findings.

Treatment

Treatment depends on whether organ- or life-threatening disease is present, guided by a rheumatologist or vasculitis specialist.

Inducing remission

• Corticosteroids (prednisone) for everyone, often high-dose initially, with IV pulses for severe disease.
• Severe disease (heart, kidney, nerve, gut or brain involvement): add cyclophosphamide or rituximab.
• Non-severe disease: add mepolizumab (an anti-IL-5 antibody) or benralizumab (an anti-IL-5 receptor antibody). Both are approved for EGPA and reduce relapses and steroid needs.

Maintaining remission

• gradual reduction of steroids to the lowest possible dose
• mepolizumab or benralizumab, or methotrexate, azathioprine or rituximab, to prevent relapses
• continued asthma and sinus care, including inhaled steroids

Supportive care

• protecting bones on long-term steroids with calcium, vitamin D and bone-strengthening drugs if needed
• preventing infection with vaccines, and sometimes antibiotics to prevent pneumocystis pneumonia during strong immune suppression
• physical therapy and orthotics for nerve damage
• heart failure treatment where needed

Outlook

With treatment, most people achieve remission, and five-year survival exceeds 90% in recent studies. Relapses are common, especially as steroids are reduced, and many people need long-term asthma treatment and some steroid. Nerve damage may improve slowly over months to years but can leave lasting numbness or weakness. Regular follow-up with heart checks is important.

Frequently asked questions

What is Churg-Strauss syndrome?

Churg-Strauss syndrome, now called eosinophilic granulomatosis with polyangiitis (EGPA), is a rare disease in which blood vessels become inflamed and eosinophils build up in tissues. It occurs almost always in people with asthma and can affect the nerves, skin, heart, gut and kidneys.

What are the first symptoms of EGPA?

EGPA usually begins with adult-onset asthma, sinus problems and nasal polyps, sometimes years before other symptoms. Later signs include fever, weight loss, fatigue, rashes, numbness or weakness in the hands or feet, and worsening asthma.

Is EGPA life-threatening?

It can be if vital organs such as the heart, kidneys, gut or brain are involved, especially without treatment. With modern treatment, most people achieve remission and survival rates are high. Early diagnosis and heart screening improve outcomes.

How is Churg-Strauss syndrome treated?

Treatment starts with corticosteroids. Severe organ involvement needs cyclophosphamide or rituximab. Non-severe disease is increasingly treated with mepolizumab or benralizumab, biologic drugs that target eosinophils and reduce relapses and steroid use.

Is EGPA the same as asthma?

No. Asthma is part of EGPA in nearly everyone with it, but EGPA is a systemic vasculitis that affects many organs. Most people with asthma, even severe asthma with high eosinophils, do not have EGPA.