Eosinophilic Granulomatosis with Polyangiitis

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 the presence of high numbers of white blood cells known as eosinophils. Almost all patients with EGPA have asthma, which is often severe. The inflammation can restrict the flow of blood to organs and tissues, in turn causing damage. It primarily affects small blood vessels. Without treatment, the disease may be fatal.

Causes

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.

Who is Affected?

The exact prevalence of EGPA is unknown, however, it is believed that there are roughly 14-15 cases per million people worldwide, equating to roughly 5,000 people in the U.S., though the number may be higher. 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.

EGPA can happen in a broad age range, though on average is diagnosed in adults 35-50 years old. It has rarely been seen in children. EGPA equally affects males and females.

Symptoms

While almost all patients with EGPA have asthma, the symptoms people experience with EGPA may vary greatly and may affect different organ systems such as the lungs, sinuses, and nerves. It can also affect the heart, gastrointestinal tract, reproductive organs, skin, urinary system, and other organs.

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.

The 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 EGPA from Wegener’s Granulomatosis, eosinophilic pneumonia, fungal and parasitic infections, and malignancy.

People with EGPA may experience the following symptoms:

Asthma
Allergic rhinitis (and sinusitis)
Fever
Loss of appetite/weight loss (may be rapid and sudden)
Fatigue/malaise
Shortness of breath and/or coughing
Abdominal pain
Diarrhea, nausea, and vomiting
Gastrointestinal bleeding
Rashes or skin sores
Joint aches and/or muscle pain
Severe pain, numbness, and tingling in the hands and feet
Chest pain
Irregular heartbeat
Blood in urine and/or stools
Kidney disease

Complications

Complications of EGPA depend on the organs affected and may include peripheral nerve damage, scarring of the skin, heart disease, and kidney damage.

Diagnosis

EGPA can be difficult to diagnose because its symptoms are similar to other diseases. There are no specific tests to confirm EGPA. High levels of blood eosinophils along with asthma and pneumonia are often the first clues that lead to a diagnosis. The disease is considered present when a person has at least four of the following six features:

Asthma
Elevated number of eosinophils
Nerve damage (numbness and pain in hands/feet)
Pulmonary infiltrates
Sinus problems
Presence of eosinophilic vasculitis

EGPA often presents in three phases, although not everyone will develop all of the symptoms, nor in order. Phase 1 usually presents with allergic conditions such as asthma, hay fever, and sinus or nasal pain and inflammation. Phase 2 often presents with high levels of eosinophils in the blood and tissue. In phase 3, patients may experience inflammation of blood vessels (vasculitis). A skin rash may develop, and patients may experience numbness and/or weakness.

To help guide the diagnosis, your doctor may order blood tests, imaging tests, nerve studies, and may biopsy tissue and/or organs.

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 treats severe asthma, or even to a hematologist who has experience with eosinophilia.

Treatment

When treating EGPA, the goal is to reduce inflammation and the number of eosinophils in the blood. Many patients who have EGPA respond well to systemic corticosteroids and some also need immunosuppressant drugs. Other patients may have symptoms that are resistant to these therapies.

The most common medications used to treat EGPA are listed below. You may be prescribed other treatments that are not listed here. Work with your healthcare provider(s) to determine the type of treatment, dosage, and duration of treatment based on your individual needs, as well as potential side-effects.

Systemic corticosteroids (e.g., prednisone) are often prescribed to treat 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 effective dose.
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.
Mepolizumab (e.g., Nucala®) is a humanized monoclonal antibody. It works to recognize and block IL-5 and helps to reduce eosinophils. Mepolizumab is given as monthly injections. It is available in auto-injectors and in pre-filled syringes for self-administration. It can help reduce the amount of corticosteroids that are needed to keep EGPA under control. This is important since corticosteroids can have many unwanted side effects. This therapy is also indicated for the treatment of eosinophilic asthma in some patients ages 6 and older.
Benralizumab (e.g., Fasenra) is a monoclonal antibody, which binds to the IL-5 receptor to block the IL-5 inflammatory response. It is available in auto-injectors and in pre-filled syringes for self-administration. This therapy has been approved for adults with EGPA.
Immunosuppressant drugs (e.g., azathioprine, mycophenolate, cyclophosphamide, methotrexate, mycophenolate mofetil) can be used in conjunction with systemic corticosteroids to get symptoms 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.

Other Treatments

For those who have not responded favorably to the treatments listed above, the following may be considered:

Intravenous immune globulin is an antibody therapy to help fight infections. It is given as an infusion. 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) is a targeted therapy given as an injection to suppress EGPA symptoms. It is a man-made reproduction of a protein that your body produces naturally. It may slow down or stop eosinophil cells from dividing. It is used to treat a variety of diseases and has shown some success in inducing EGPA remission. Common side effects include flu-like symptoms, however, other side effects may occur with long-term use.
Rituximab. Rituximab is a targeted therapy that alters the immune system’s response. It is given as an infusion and has been shown to improve symptoms of EGPA and decrease eosinophil counts. It has not been studied in large trials, and long-term safety and efficacy are not known. 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 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 is a targeted therapy that blocks the allergy antibody, IgE, lessening allergic reactivity. It is approved for use in the U.S. to treat moderate to severe persistent asthma that does not respond to inhalers and other usual asthma medications. 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.

Investigational Treatments

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. It is currently being studied as a potential therapy for EGPA. It was recently approved in the U.S. and several other countries as an add-on maintenance treatment in severe, eosinophilic asthma.

Prognosis

There is no cure for EGPA. It is estimated that more than 90% of patients will achieve remission and resolution of symptoms. Complications depend on the organs affected and may include peripheral nerve damage, scarring of the skin, heart disease, and kidney damage.

Relapses are common and asthma may persist. The involvement of the heart and airways will warrant ongoing follow-up with a healthcare provider who can closely monitor symptoms. Patients who have EGPA should receive ongoing medical care to maintain optimum health and for early detection of relapses.

Other Resources

References

Churg J, Strauss L. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol 1951; 27:277-301.
Warren P. Osler’s unusual case — Was it ChurgStrauss syndrome? Can Med Assn J 1999; 161(7):846-847.
Lanham JG, Elkon KB, Pusey CD, et al. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine 1983; 63:65-81.
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.
Wechsler ME, Finn D, Gunawardena D, Westlake R, Barker A, Haranath SP et al. Churg-strauss syndrome in patients receiving montelukast as treatment for asthma. Chest 2000; 117:708-713.
Le Gall C, Pham S, Vignes S, Garcia G, Nunes H, Fichet D, et al. Inhaled corticosteroids and Churg-Strauss syndrome: a report of five cases. Eur Resp J 2000; 15(5):978-981.
Wechsler ME, Pauwels R, Drazen JD. Leukotriene modifiers and Churg-Strauss Syndrome: Adverse effect or response to corticosteroid withdrawal? Drug Safety 1999; 21:241-251.

Contributors and reviewers: Praveen Akuthota, MD

Updated March 2020.