Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis is a rare disorder that causes inflammation in blood vessels throughout the body, primarily affecting people who have asthma or severe allergies.

EGPA, Churg-Strauss Syndrome, Allergic Granulomatosis, Churg-Strauss Syndrome (CSS)

Table of contents

• What is Eosinophilic Granulomatosis with Polyangiitis?
• Who is Affected?
• Symptoms and Disease Progression
• What Causes EGPA?
• How is EGPA Diagnosed?
• Treatment Options
• Outlook and Long-term Management

What is Eosinophilic Granulomatosis with Polyangiitis?

Eosinophilic granulomatosis with polyangiitis, known by the abbreviation EGPA, is a rare disorder that affects your blood vessels. It was previously called Churg-Strauss syndrome, named after the doctors Jacob Churg and Lotte Strauss who first described it in 1951^[3][15]. The name was changed to be more descriptive of what actually happens in the disease.

To understand EGPA, it helps to break down its name. Eosinophilic refers to an unusually high number of eosinophils in your blood. Eosinophils are a type of white blood cell that normally helps your immune system fight infections and plays a role in allergic reactions. In EGPA, eosinophil levels can be double the normal amount or even higher^[1]. Granulomatosis means that small masses of immune cells called granulomas form in your tissues when those tissues become inflamed. These are your immune system’s way of trying to wall off what it sees as a threat. Polyangiitis refers to inflammation in many small- to medium-sized blood vessels throughout your body^[1].

EGPA belongs to a group of diseases called vasculitis, which means inflammation of blood vessels. More specifically, it is classified as one of the ANCA-associated vasculitides, although only about 30% to 40% of people with EGPA test positive for a marker called ANCA (anti-neutrophil cytoplasmic autoantibodies)^[3][7].

When blood vessels become inflamed over time, their walls can weaken and stretch, potentially leading to an aneurysm (a bulge in the blood vessel wall), or they can break and cause internal bleeding. Inflammation also causes swelling and scarring that narrows blood vessels, which can restrict or stop blood flow to tissues and organs^[1]. This condition most commonly affects the respiratory system, especially the lungs, but it can also damage the kidneys, intestines, heart, skin, and nerves^[1][5].

• Lungs
• Sinuses
• Nasal passages
• Blood vessels
• Heart
• Kidneys
• Gastrointestinal tract
• Peripheral nerves
• Skin

Who is Affected?

EGPA is extremely rare. It is estimated that there are roughly 14 to 15 cases per million people worldwide, which means approximately 5,000 people in the United States may have the condition, though the actual number could be higher because the disease is sometimes underdiagnosed^[5]. The disease affects men and women equally^[5][15].

Most people are diagnosed with EGPA in middle age, with the average age of diagnosis around 35 to 50 years old^[5][9]. The typical person with EGPA is someone who has developed new asthma in adulthood or has experienced worsening asthma symptoms^[15]. Cases in children are extremely rare^[5][9].

Almost all people with EGPA have asthma, which is often severe. The presence of asthma combined with certain allergies is what distinguishes EGPA from other similar blood vessel diseases^[3][15].

Symptoms and Disease Progression

EGPA typically develops gradually over several years, and symptoms tend to appear in three distinct phases. However, not everyone experiences all three phases, and not everyone progresses through them in the same order^[8][9].

Phase 1: The Allergic Stage

The first phase is called the allergic or prodromal stage and can last for many years. During this time, people experience respiratory symptoms that are often misdiagnosed as ordinary allergies or asthma^[4][15].

Common early symptoms include:

• Adult-onset asthma with coughing, wheezing, and shortness of breath
• Chronic hay fever with sneezing, nasal itching, and congestion
• Chronic inflammation in the sinuses (sinusitis) and sinus pressure
• Nasal polyps (noncancerous growths in the nose)
• Generalized joint pain or muscle pain
• Fever, fatigue, and a general feeling of being unwell^[1][15]

Phase 2: The Eosinophilic Stage

In the second phase, the body produces too many eosinophils. These cells can build up in tissues and organs, causing damage. This stage commonly affects the lungs and digestive system^[4][15].

Additional symptoms during this phase may include:

• Chest pain and difficulty breathing
• Heart palpitations
• Skin rashes or lesions
• Stomach pain and diarrhea
• Nausea and vomiting
• Coughing or wheezing^[1][4]

Phase 3: The Vasculitic Stage

The third and final phase involves inflammation of blood vessels throughout the body. This is when the most serious complications can occur because reduced blood flow can damage vital organs^[4].

The lungs are the most frequently affected organ system. Beyond asthma, people may develop pneumonia-like symptoms with shortness of breath. The heart can be seriously affected, and cardiac complications are a major cause of serious illness and death in EGPA^[5][15].

Nerve involvement is particularly common and can be devastating. This condition, called mononeuritis multiplex, causes severe tingling, numbness, shooting pains, and severe loss of muscle strength in the hands or feet^[15].

Other organs and symptoms that may be affected include:

• Skin: rashes, red punctuated lesions (purpura), nodules, or recurrent hives
• Kidneys: inflammation of the filtering units (glomerulonephritis) and high blood pressure
• Digestive system: stomach pain and bleeding in the gastrointestinal tract
• Heart: inflammation that can lead to heart failure, heart attack, or irregular heartbeat
• Nerves: pain, numbness, tingling, or sudden loss of strength in the hands and feet^[7][15]

People often experience general symptoms such as fever, rapid and unintentional weight loss, and profound fatigue throughout the progression of the disease^[5][7].

What Causes EGPA?

The exact cause of EGPA is unknown. Researchers believe it results from a combination of genetic factors and environmental exposures, complicated by an overactive immune system^[5][15].

Because all people with EGPA have high levels of eosinophils at some point during their disease, scientists think there may be some problem with how eosinophils are produced, mature, or function. In many patients, antibodies called ANCA are present and may play a role in causing blood vessel inflammation and injury^[5].

Genetics may play a small role, but EGPA is almost never seen in two members of the same family. Environmental factors such as exposure to industrial solvents or inhaled allergens like silica dust may contribute to susceptibility, though this is largely speculative. Infections might trigger the disease, but there is no definitive evidence of this^[7][15].

Some potential risk factors include a history of asthma, allergic rhinitis, nasal polyps, and certain drug sensitivities such as to leukotriene modifiers or other medications^[7].

How is EGPA Diagnosed?

There is no single test that can diagnose EGPA. Instead, doctors use a combination of your medical history, physical examination, and several different tests to reach a diagnosis^[14].

Among all types of vasculitis, asthma is a distinctive feature of EGPA alone. However, only a tiny minority of people with asthma have vasculitis. The specific combination of symptoms and signs, the pattern of organ involvement, and the presence of certain abnormal blood test results help doctors make the diagnosis^[15].

Blood Tests

Blood tests are essential for diagnosing EGPA. They can detect high levels of eosinophils, which is a key finding. In EGPA, eosinophils may reach as high as 60% of the total white blood cell count, compared to the normal 5% or less^[15]. Blood tests can also check for ANCA antibodies, though these are present in only 30% to 40% of EGPA cases^[3][14].

Imaging Tests

X-rays, CT scans, or MRI scans can reveal problems in the lungs or sinuses. If heart issues are suspected, your doctor may order an echocardiogram to examine how your heart is working^[14][15].

Tissue Biopsy

If other tests suggest EGPA, a small sample of tissue may be taken from your lungs, skin, nerves, or another affected area. The sample is examined under a microscope to look for inflamed blood vessels (vasculitis), granulomas, and excessive numbers of eosinophils. Finding these specific features helps confirm the diagnosis^[3][14][15].

Your healthcare team will consider your complete medical history, all symptoms, and how you respond to treatment when making a final diagnosis^[14].

Treatment Options

Although there is no cure for EGPA, medicines can help reduce inflammation, manage symptoms, and prevent complications. Without treatment, the disease can be life-threatening^[5][14].

Corticosteroids

Corticosteroid therapy is the cornerstone of treatment for EGPA. The most commonly used medication is prednisone, which helps reduce inflammation quickly^[10][14]. You may start on a high dose of about 1 milligram per kilogram of body weight (with a maximum of 60 milligrams) for two to three weeks to get the condition under control^[10].

Your doctor will then gradually lower the dose to the smallest amount needed to keep symptoms controlled. The goal is typically to reduce to 20 milligrams per day by three months, 10 milligrams per day by six months, and 5 milligrams per day by one year. The standard length of treatment is usually 12 to 18 months^[10].

If you have severe, life-threatening organ involvement, your doctor may give pulse doses of intravenous methylprednisolone (1 gram per day for three days) along with other immunosuppressive drugs^[10].

Taking corticosteroids at high doses or for a long time can cause serious side effects, including weight gain, high blood sugar or diabetes, cataracts, infections, weakened bones, high blood pressure, and mood changes^[14].

Immunosuppressant Drugs

For patients with more severe disease, immunosuppressant medications are often added to corticosteroids. These drugs help calm the immune system and allow doctors to use lower doses of steroids^[14].

Common immunosuppressant drugs include:

• Cyclophosphamide, typically given in intravenous pulses for three months
• Azathioprine, often used for maintenance therapy after the initial three months
• Mycophenolate or methotrexate, which are alternatives for maintenance therapy^[10][14]

Rituximab, a drug approved for other similar blood vessel diseases, has proved useful in treating steroid-resistant EGPA and in preventing and treating relapses. However, it works much better in patients who test positive for ANCA antibodies^[10].

Biologics

Two newer medications called biologics that target a substance called interleukin-5 (IL-5) are now approved for use in adult patients with EGPA: mepolizumab and benralizumab. These monoclonal antibodies are typically used for patients who have disease that keeps coming back or doesn’t respond well to other treatments, and they are particularly helpful for controlling asthma and reducing the need for corticosteroids^[10][14].

Another biologic, omalizumab, which blocks IgE antibodies, has shown a corticosteroid-sparing effect in some patients with difficult-to-treat or relapsing EGPA^[10].

Asthma Management

Patients with EGPA also require ongoing management of their asthma. Treatment follows the same stepwise approach used for asthma in the general population, tailored to the severity of symptoms^[10].

Outlook and Long-term Management

With proper treatment, many people with EGPA can manage their symptoms and prevent serious complications. However, the disease requires long-term monitoring and treatment^[14].

Relapse rates in EGPA are substantial, ranging from 25% to 49% of patients. If symptoms return, your doctor will re-evaluate your condition and may restart or adjust your medications based on the severity of your symptoms^[10].

Cardiac complications remain a significant concern and are a major cause of serious illness in people with EGPA. Regular monitoring of heart function is important^[5][7].

Patients require continuous follow-up to ensure that disease flares or asthma-related complications are detected early and treated promptly. This typically involves regular visits with a team of specialists, including rheumatologists, pulmonologists, and sometimes cardiologists or neurologists, depending on which organs are affected^[7][14].

Living with EGPA can be challenging. Fatigue is a common ongoing problem, and the disease can limit some activities. However, many people find that with proper medication, regular medical care, exercise, proper nutrition, and a positive outlook, they can maintain a good quality of life^[21].