Eosinophilic Granulomatosis with Polyangiitis
(aka Churg-Strauss Syndrome)
What is Eosinophilic Granulomatosis with Polyangiitis?
Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome, is a rare autoimmune disorder characterized by inflammation of blood vessels and presence of high numbers of white blood cells known as eosinophils. The inflammation can restrict the flow of blood to organs and tissues, in turn causing damage. Without treatment, the disease may be fatal.
The cause of EGPA is not known, although it is believed to result from an interaction of genetics and the environment, complicated by an overactive immune system.
Because all patients with EGPA have high levels of eosinophils at some point during their disease, it is thought that there may be some dysregulation of eosinophil production, maturation, or development.
Anti- neutrophil cytoplasmic antibodies (ANCA) are also present in many patients with EGPA and may also play a role in EGPA disease development. While the exact role of ANCA in EGPA and other vasculitides remains unclear, it is felt that the binding of ANCA to vascular walls contributes to vascular inflammation and injury as well as chemotaxis of inflammatory cells.
While EGPA has been associated with various asthma therapies, including leukotriene modifiers(5;6), Anti IgE therapy (omalizumab) and inhaled corticosteroids(7), no causal link has been established. It appears that the syndrome either occurs coincidental to these medications or that these medications facilitate systemic steroid withdrawal that unmasks the syndrome.
Who is Affected?
It has been estimated that EGPA occurs in about 5 cases per million people per year, with a rate in asthmatics of as high as 80 cases per million per year(8). However, it is probable that EGPA occurs with greater frequency and is underreported due to underdiagnosis or due to masking of findings by treatment with corticosteroids of what is perceived to be just severe asthma.
Both men and women are affected by EGPA. While it is generally diagnosed in adulthood, it has also rarely been described in children. Usually, individuals have asthma and allergic rhinitis that persists for years. It often arises later in life and occurs in individuals with no family history of asthma or allergies.
The symptoms of EGPA may vary greatly and may affect different organ systems such as the sinuses, lungs, and nerves. It can also affect the heart, gastrointestinal tract, reproductive organs, skin, and urinary system.
Some people may have mild symptoms, while others may experience more severe complications. Fever, weight loss, fatigue and malaise often accompany the syndrome and are frequently debilitating.
The lungs are the most frequently involved organ system involved by EGPA. In addition to asthma, most patients develop pneumonia and have symptoms of shortness of breath and cough. Neurologic symptoms occur in three quarters of patients, with damage to nerves outside of the brain and spinal cord (mononeuritis multiplex) being the most frequent manifestation.
Weakness and tingling or pricking “pins and needles” sensation (paresthesias) can be disabling and often fail to respond to treatment. Half of patients present with rashes of all types that are often biopsied to help establish a diagnosis.
Involvement of the heart, usually with cardiomyopathy or myocarditis, often portends a worse prognosis. Gastrointestinal symptoms can occur and usually include abdominal pain and diarrhea; ischemic bowel disease and inflammation of the pancreas or gallbladder are often the culprits.
While high levels of blood eosinophils in the presence of asthma and pneumonia are the tip-off for diagnosis, elevated sedimentation rates (ESR) or C-reactive protein, and the presence of anti-neutrophil cytoplasmic antibodies are supportive evidence.
A biopsy of an affected organ is not required to establish the diagnosis of EGPA, however it is often done to distinguish EGP from Wegener’s Granulomatosis, eosinophilic pneumonia, fungal and parasitic infections and malignancy.
EGPA has three stages, although not everyone will experience all three or in the same order:
- Hay fever
- Sinus problems
- Loss of appetite/weight loss
- Abdominal pain
- Gastrointestinal bleeding
Vasculitic stage (severe blood vessel inflammation, reducing blood flow to organs and tissues)
- Rash or skin sores
- Joint aches and swelling
- Severe pain, numbness and tingling in hands/feet
- Severe abdominal pain
- Diarrhea, nausea and vomiting
- Shortness of breath
- Coughing up blood
- Chest pain
- Irregular heartbeat
- Blood in urine
Complications of EGPA depend on the organs affected, and may include peripheral nerve damage, scarring of the skin, heart disease, and kidney damage.
EGPA can be difficult to diagnose because its symptoms are similar to other diseases. There are no specific tests to confirm EGPA, although the disease is considered present when a person has at least four of the following six features:
- Elevated number of eosinophils (higher than 10%)
- Nerve damage (numbness and pain in hands/feet)
- Pulmonary infiltrates
- Sinus problems
- Presence of eosinophilic vasculitis
High levels of blood eosinophils along with asthma and pneumonia are often the first clues that lead to a diagnosis.
Your doctor may refer you to a specialist in disorders that cause inflamed blood vessels, such as a rheumatologist or immunologist, or to a pulmonologist, or allergist who often treat severe asthma, or even to a hematologist who has experience with eosinophilia. To help determine whether you meet any of the criteria above, your doctor may order blood tests, imaging tests, and may biopsy affected tissue.
The most common medications used to treat EGPA are listed below. You may be prescribed other treatments that are not listed here. Discuss your treatment options with your doctor and the benefit-to-risk ratios. Be sure to discuss how you will be monitored for side effects during and after treatment.
Systemic Corticosteroids. Systemic corticosteroids, such as prednisone, are commonly used to treat patients with EGPA. This medication changes the way the immune system functions, and reduces inflammation. A higher dose may be prescribed initially to get symptoms under control quickly, and then gradually decreased to the lowest dose needed to keep symptoms at bay.
Some of the more common side effects of corticosteroids include headache, dizziness, changes to the deposit of fat around the body, facial bloating (moon face), heartburn, insomnia, moodiness, increased hair growth, weakness and fatigue, slow wound healing, acne, and osteoporosis. Long-term oral corticosteroid use may cause other side effects, including cataracts, high blood sugar (diabetes), increased risk of infections, osteoporosis, and suppressed hormone production of the adrenal gland.
Not all patients respond to corticosteroids initially, or some patients may require other therapies that facilitate corticosteroid tapering. These medications are listed below.
Immunosuppressant Drugs. Immunosuppressant drugs are used in conjunction with prednisone, when prednisone alone is not able to get symptoms of EGPA under control. Some immunosuppressant drugs are used to treat cancers and a variety of autoimmune diseases. Examples of these drugs that may be prescribed to treat EGPA include azathioprine (Imuran), mycophenolate (cellcept), cyclophosphamide (Cytoxan), and methotrexate.
These drugs are often well-tolerated, with few side effects. Common side effects reported include acne, blurred vision, diarrhea, dizziness, fatigue, insomnia, hair thinning, headaches, nausea, vomiting, and skin rashes. Those taking these medications may suppress the bone marrow and thus may be more susceptible to developing infections and anemia and, although rare, are at higher risk of developing certain cancers.
Intravenous immune globulin. For those who have not responded favorably to other treatments, a monthly infusion of immune globulin may be prescribed. Side effects of this treatment are mild, and include flu-like symptoms that last for about a day after treatment. The infusions are expensive, however, and not everybody has success with it.
Interferon-alpha (or interferon-alfa). Interferon-alpha is man-made reproduction of a protein that your body produces naturally. It is used to treat a variety of diseases, and has shown some success with inducing EGPA remission. Common side effects include flu-like symptoms, however other side effects may occur with long-term use.
Rituximab. Rituximab is a biological drug that alters the immune system’s response. It is given as an infusion and has been shown to improve symptoms and decrease eosinophil counts. It may be a course of treatment prescribed for those who haven’t had success with other treatments. Rituximab has not been studied in large trials, and the long-term safety and efficacy is not known. Mild side effects up to 24 hours after receiving treatment have been reported. Common symptoms included mild throat tightening, flu-like symptoms, rash, itchiness, dizziness, and back pain.
Omalizumab. Omalizumab (anti IgE) is approved for use in asthma and since a significant component of patients with EGPA have underlying severe asthma, this therapy is often given to patients with EGPA to help control the asthma component of their syndrome.
Other drugs under investigation include mepolizumab (anti IL-5). This experimental study is given by injection and suppresses eosinophil production. It is being studied currently in EGPA.
Benralizumab is a monoclonal antibody that binds directly to IL-5 receptor α on eosinophils and attracts other cells to induce rapid and near-complete depletion of eosinophils.
Fasenra®, a biologic that was approved in the U.S., EU, Japan, and several other jurisdictions as an add-on maintenance treatment in severe, eosinophilic asthma. In November 2018, the U.S. Food and Drug Administration granted Orphan Drug Designation (ODD) for Fasenra® for the treatment of EGPA. Phase III trials for Fasenra® in EGPA have not yet started.
There is no cure for EGPA, however, over the past three decades or so, the prognosis for patients with EGPA has improved greatly. It is estimated that more than 90% of the patients will achieve remission, and achieve resolution of symptoms. Vasculitis relapse may occur, and asthma may persist.
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- Warren P. Osler’s unusual case — Was it ChurgStrauss syndrome? Can Med Assn J 1999; 161(7):846-847.
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- Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis. Arthritis Rheum 1990; 33(8):1094-1100.
- Wechsler ME, Garpestad E, Flier SR, Kocher O, Weiland D.A., Polito AJ et al. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast. JAMA 1998; 279:455-457.
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The Churg-Strauss Syndrome Association: www.cssassociation.org
The Vasculitis Foundation www.vasculitisfoundation.org
Churg-Strauss Syndrome Support & Awareness: https://www.facebook.com/groups/ChurgStraussSupportAwareness/
Churg-Strauss Syndrome Association:
Churg-Strauss Syndrome Online Community: http://www.inspire.com/groups/eos-connections/topics/churg-strauss-syndrome-css/
Authored by Michael Wechsler, M.D. and Mary Jo Strobel. © American Partnership for Eosinophilic Disorders (APFED) 2008-2014. All rights reserved. Updated 9-19-14.