Last updated: 10/10/2024
Years published: 1989, 1990, 1997, 1999, 2002, 2003, 2007, 2010, 2024
NORD gratefully acknowledges Paneez Khoury, MD, MHSc, Allergy and Immunology Specialist, Bethesda, MD, for assistance in the preparation of this report.
Summary
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare immune disorder of the blood vessels that can affect multiple organ systems, especially the lungs. The disorder is characterized by the presence of white blood cells called eosinophils (hypereosinophilia) in the blood and tissues resulting in inflammation of blood vessels (vasculitis) and the development of inflammatory nodular lesions called granulomas (granulomatosis).
EGPA can develop over time with many affected individuals presenting initially with a history of nasal symptoms suggestive of allergies or sinusitis. In addition, worsening asthma and other associated lung abnormalities (i.e., pulmonary infiltrates) often precede the development of more severe symptoms and findings seen in EGPA. Asthma, a chronic respiratory disorder, is characterized by inflammation and sensitivity of the airways due to narrowing of the airways or obstruction due to mucus. When severely affected by eosinophils in the airways, as in the case of EGPA, it can cause breathing difficulties (dyspnea), cough, a high-pitched whistling sound while breathing (wheezing) and/or other symptoms and findings.
Nonspecific findings associated with EGPA typically include flu-like symptoms, such as fever, a general feeling of weakness and fatigue (malaise), loss of appetite (anorexia), weight loss, joint pain (arthralgia) and muscle pain (myalgia). Additional symptoms and findings vary depending on the specific organ systems affected. Other organ involvement can occur. For example, the gastrointestinal tract can be affected by eosinophils and cause symptoms of abdominal pain, nausea/vomiting and rarely more severe symptoms. The skin may be involved and include red bumps or rashes or hives. The nerves outside the central nervous system (peripheral nerves) can cause feelings of numbness or tingling in the arms or legs. The heart and kidneys may also be affected. EGPA can occur in children and in older adults; however, the average age of patients diagnosed with EGPA is 40 years old.
Often, people with EGPA have a long โprodromeโ of disease occurring over months to years, though some may present acutely with serious organ damage and potentially life-threatening complications. EGPA is a chronic disease without a known cause. Research has shown that abnormal functioning of the immune system plays an important role. Available treatments are used to put patients in remission by suppressing the immune system and reducing the inflammation associated with EGPA.
Introduction
EGPA was first described by two pathologists, Jacob Churg and Lotte Strauss, for whom the disease was previously named when it was referred to as Churg-Strauss syndrome. In 1951, these physicians noticed that some of their patients had symptoms of severe asthma, fever, high levels of eosinophils in their blood and vasculitis that involved small- and medium-sized blood vessels and the formation of granulomas, which occur from a persistent inflammatory response.
EGPA, formerly known as Churg-Strauss syndrome, is a rare inflammatory condition that primarily affects small to medium-sized blood vessels, leading to widespread organ damage. The hallmark of EGPA is an abnormally high number of eosinophilsโa type of white blood cell involved in allergic reactions, vasculitis, and multi-organ involvement.
EGPA impacts multiple organ systems, most commonly the lungs, skin, gastrointestinal (GI) tract, heart and nervous system. Since different organ systems are affected in each person, the symptoms, severity and progression of EGPA can vary widely.
Historically, EGPA was described in three phasesโthe prodromal phase, the eosinophilic phase, and the vasculitic phase, but these stages may not occur in all patients or follow a strict sequence.
Affected people may experience nonspecific symptoms common to many illnesses before more specific signs of EGPA appear:
These symptoms can mimic a variety of other conditions, making early diagnosis challenging.
Allergic and respiratory symptoms
Respiratory or allergic issues are often the earliest signs of EGPA, especially late-onset asthma and other allergic reactions.
Eosinophilic phase
During the eosinophilic phase, high levels of eosinophils accumulate in tissues, triggering inflammation, especially in the lungs, GI tract, nervous system and skin.
Vasculitic phase
In the vasculitic phase, inflammation affects blood vessels, leading to organ damage. The immune system attacks small to medium-sized blood vessels, which can lead to:
EGPA can lead to serious complications if left untreated including:
The exact cause of EGPA is unknown. Most researchers think that several different factors (e.g., environmental, immunological and genetic) all play a role in the development of the disorder. Researchers also think there may be two different types of EGPA. In one, EGPA is classified as an autoimmune disorder. Autoimmune disorders are caused when the bodyโs natural defenses against โforeignโ or invading organisms begin to attack healthy tissue for unknown reasons. Researchers do not know what sets off or โtriggersโ the abnormal immune system response in individuals with EGPA. An autoantibody called antineutrophil cytoplasmic antibodies (ANCAs) is sometimes present in EGPA. The immune system creates antibodies against granules in neutrophils and these may be found on neutrophils, a type of white blood cell, in the lining of blood vessels suggesting they may be part of the damage that occurs in vasculitis. ANCAs have been identified in other related blood vessel disorders (vasculitides) including granulomatosis with polyangiitis (GPA), or in medication induced vasculitis. The development of ANCAs after exposure to medications or infections suggests that exposures may play a role in the immune response though whether a separate immune process that causes vasculitis and development of ANCAs is not clear. In the autoimmune type of EGPA where ANCAs are present (in 30-50% of individuals with EGPA depending on the study), certain symptoms are more common. For example, the development of kidney involvement or bleeding in the lungs is more common in ANCA-associated EGPA.
For most patients with EGPA, an autoantibody such as ANCA is not found. In those individuals, an inflammatory or allergic response due to eosinophils or a dysregulated immune response is felt to play a role. Eosinophilic inflammation in tissues either in, or around, veins, capillaries and small- and medium-sized arteries and in some people inflammatory nodular lesions (granulomatosis) within tissues and the walls of blood vessels can be seen. Although the lungs are often predominantly affected, multiple organ systems may become involved, including the skin, heart and peripheral nerves (nerves outside the brain and spinal cord). ANCA-negative EGPA patients are less likely to develop kidney disease or bleeding in the lungs, but it can occur.
In the past, the development of EGPA was thought to be related to the initiation of certain asthma medications. It has become clearer due to the number and different types of medications involved that the development of EGPA may be related to the withdrawal of medications that would control allergic or eosinophilic inflammation (for example inhaled or systemic corticosteroids). Individuals receiving asthma medications should taper background medications with monitoring after starting corticosteroid-sparing therapies.
EGPA occurs equally in males and females. The disorder can affect individuals of almost any age, with children and elderly patients being reported. However, it is rarer in children, adolescents and older adults. Most patients are diagnosed between 38 and 54 years of age. The estimated mean prevalence varies globally but ranges from 3-30.7 individuals per million in the USA, among an insured population. Some researchers think that EGPA is underdiagnosed, making it difficult to determine its true frequency in the general population.
There are no validated diagnostic criteria for EGPA. Rather, the diagnosis of EGPA may be suspected based on a thorough clinical evaluation, characteristic physical findings and specialized tests particularly in those that present with asthma, sinusitis and blood eosinophilia. In 2022, the American College of Rheumatology revised their classification criteria for EGPA. Among patients who have been shown to have vasculitis, an individual can be classified as having EGPA rather than another small- or medium-vessel vasculitis) if they have a score of six or more points from the following seven items:
1) obstructive airway disease (+3)
2) nasal polyps (+3)
3) mononeuritis multiplex (+1)
4) elevated blood eosinophil levels (โฅ1 ร 109/liter) (+5)
5) extravascular eosinophilic-predominant inflammation on biopsy (+2)
6) positive test for cytoplasmic ANCAs (cANCAs) or antiproteinase 3 (anti-PR3) antibodies (-3)
7) hematuria (-1) (Hematuria refers to the presence of blood in urine. Hematuria and cANCAs or anti-PR3 antibodies are associated with other types of vasculitis and make the diagnosis of EGPA less likely.)
Diagnostic procedures that can aid in a diagnosis include surgical removal (biopsy) and microscopic examination of tissue samples from affected organs (e.g., the skin, kidney, peripheral nerve, lung) to see if they demonstrate inflammation of blood vessels and other associated changes. Chest X-rays and other specialized imaging techniques, such as computerized tomography (CT) scanning, typically reveal abnormalities in the sinuses (e.g. mucosal thickening, sinusitis, polyposis) and lungs (i.e., pulmonary infiltrates, and fluid around the lungs called pleural effusions). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of an organโs tissue structure. In addition, laboratory tests may be conducted, including tests that demonstrate elevated levels of eosinophils (especially when levels are greater than (โฅ1 ร 109/liter or 10 percent of the total white blood cell count) and elevated levels of IgE, which are antibodies involved in allergies and inflammatory processes. Although present in only 30 to 50 percent of patients, ANCAs can help with the diagnosis as well.
Treatment
Eosinophilic granulomatosis with polyangiitis (EGPA) can be effectively managed with proper treatment, but without it, the disease can lead to severe and life-threatening complications. Corticosteroids, such as prednisone or methylprednisolone, are typically the first line of treatment. These drugs are immunosuppressive and reduce inflammation. They are usually administered at high doses initially, then tapered down once improvement is seen. For many people, particularly those with non-severe EGPA, corticosteroids alone (monotherapy) may be sufficient to achieve remission. Long-term, low-dose corticosteroids may be required to control respiratory symptoms.
In cases of severe EGPA or when patients do not get better with corticosteroids alone, additional therapies are often needed. For patients with organ involvement, such as kidney or neurological disease, a combination of corticosteroids and other immunosuppressive or biologic therapies may be necessary. These therapies help prevent the harmful effects of long-term, high-dose corticosteroid use. Treatment typically depends on whether the EGPA is classified as severe or non-severe.
For people experiencing relapses, treatment strategies depend on the severity of the relapse:
Mepolizumab (Nucala) is an anti-interleukin-5 (anti-IL-5) agent, meaning it blocks the effects of IL-5, an immune protein that is important for eosinophils development and activation. It is recommended for helping EGPA patients with non-severe disease to maintain remission and may be used in place of cyclophosphamide, rituximab or methotrexate in these patients. Mepolizumab was shown to reduce EGPA relapses and improve duration of time patients stay in remission in clinical trials which led to the first FDA-approved drug for EGPA.
In 2024, the U.S. Food and Drug Administration (FDA) approved an expanded use of benralizumab (Fasenra), other biologic agent, an anti-IL-5 receptor blocker that have shown similar efficacy as Mepolizumab, for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). Benralizumab not only helps in achieving remission but also aids in tapering off steroid therapy, which has been a challenge for many EGPA patients.
Studies are exploring other treatment options. These advancements offer new hope for EGPA patients, providing effective options to maintain remission, prevent relapses, and minimize the side effects of traditional corticosteroid therapies.
Studies are exploring other treatment options. These advancements offer new hope for EGPA patients, providing effective options to maintain remission, prevent relapses, and minimize the side effects of traditional corticosteroid therapies.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
TEXTBOOKS
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JOURNAL ARTICLES
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INTERNET
Khoury P. Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). UpToDate.Last updated: Mar 29, 2024. Available at: https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss?search=eosinophilic%20granulomatosis%20with%20polyangiitis&source=search_result&selectedTitle=2%7E98&usage_type=default&display_rank=2#topicContent Accessed April 26, 2024.
King Jr TE. Epidemiology, pathogenesis, and pathology of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). UpToDate. Last updated: Jan 31, 2022. Available at: https://www.uptodate.com/contents/epidemiology-pathogenesis-and-pathology-of-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss?search=eosinophilic%20granulomatosis%20with%20polyangiitis&source=search_result&selectedTitle=3%7E98&usage_type=default&display_rank=3#topicContentAccessed April 26, 2024.
King Jr TE, Khoury P. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Treatment and prognosis. UpToDate. Last updated: Apr 01, 2024. Available at: https://www.uptodate.com/contents/eosinophilic-granulomatosis-with-polyangiitis-churg-strauss-treatment-and-prognosis?search=eosinophilic%20granulomatosis%20with%20polyangiitis&source=search_result&selectedTitle=1%7E98&usage_type=default&display_rank=1#topicContent Accessed April 26, 2024.
Mikhail ES, Ghatol A. Hypereosinophilic Syndrome. [Updated 2024 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK599558/ Accessed April 30, 2024.
Chakraborty RK, Aeddula NR. Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss Syndrome) [Updated 2023 Mar 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537099/ Accessed April 30, 2024.
Lowe ST. Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome). Medscape. Updated: Aug 06, 2022. Available at: https://www.emedicine.com/med/topic2926.htm Accessed April 30, 2024.
Eosinophilic Granulomatosis with Polyangiitis Orphanet. October 2020. Available at: https://www.orpha.net/en/disease/detail/183?name=Eosinophilic%20Granulomatosis%20with%20Polyangiitis&mode=name Accessed April 30, 2024.
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