Predominately small vessel

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

  • What is it?
    • Eosinophilic Granulomatosis with Polyangiitis (EGPA), previously referred to as Churg-Strauss syndrome (CSS), is a rare type of vasculitis that affects the small and medium blood vessels in the body and is a part of the group of ANCA-associated vasculitides. This group of disease also includes Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Like these two diseases, EGPA also involves ANCAs (anti-neutrophil cytoplasmic antibodies), though they are only present in around 40-60% of patients of all ages.
    • EGPA is mainly described as involving allergic rhinitis (swelling/irritation or the lining inside the nose), asthma, and an increase in the number of particular immune cells called eosinophils in the blood (eosinophilia).
    • The main organs involved in EGPA include the lungs, followed by the skin. However, any organ system can actually become involved in EGPA, though this is rarer.
    • The term “Eosinophilic Granulomatosis with Polyangiitis” can be broken down to help understand this disease better.
      • The term “eosinophilic” refers to a type of white blood cell called eosinophils which are often present in a larger than normal amount in this disease. These white blood cells are normally involved in destroying germs like viruses and bacteria, and in causing an inflammatory response (cause swelling).
      • The term “granulomatosis” describes granulomas forming, which are organized collections of immune cells (called histiocytes) which form after the body’s immune system attacks substances it thinks are foreign. These granulomas can contribute to inflammation (swelling) and narrowing of the blood vessels, leading to problems in blood flow.
      • Lastly, “polyangiitis” refers to inflammation (swelling) of the walls of many blood vessels.
    • Other names for this disease include allergic granulomatosis and angiitis.
  • How does it happen?
    • It is not known exactly how a patient may develop EGPA. However, it is thought that it has to do with the irregular functioning of the immune system that could involve the role of ANCAs and specific immune cells called eosinophils. This could involve the immune system attacks the walls of the blood vessels in parts of the body, and leading to swelling (inflammation) and narrowing of vessels in various organs.
  • Though the true cause of EGPA is unknown, there are certain factors that are being discussed and considered. Genetic factors and use of specific medications are often considered as possible causes. Also, the use of cocaine has been related to the appearance of an EGPA-like vasculitis.
  • A great majority of patients with EGPA are adults, with a mean age of 40 years old. There is therefore less data available on the childhood population with EPGA. When EGPA does occur in children, the cases are more serious and involve problems with the lungs and the heart. In the adult population, EGPA is seen in both males and females, and 10% of vasculitis patients are found to have EGPA.
  • Click here for more detailed information on classifying and diagnosing EGPA.
    • Click here for more detailed information on suggested treatment protocols
  • Classification:
    • Note that unlike many of the major forms of systemic vasculitis, such as Kawasaki Disease and Takayasu arteritis, EGPA does not have specific classification criteria for the childhood population. Since there are no EULAR/PRINTO/PRES criteria, the American College of Rheumatology (ACR) criteria is used most commonly. However, there are other types of criteria for EGPA that exist.
    • According to the ACR criteria, the presence of 4 or more of the following criteria point towards Hypersensitivity Vasculitis:
    • Asthma (a history of wheezing or the finding of diffuse high pitched wheezes on expiration)
    • Greater than 10 percent eosinophils on the differential leukocyte count
    • Mononeuropathy (including multiplex) or polyneuropathy
    • Migratory or transient pulmonary opacities detected radiographically
    • Paranasal sinus abnormality
    • Biopsy containing a blood vessel showing the accumulation of eosinophils in extravascular areas

    Diagnosis:

    In order to reach a diagnosis, it is important to consider a combination of clinical features, laboratory tests, along with biopsy results. For more details view the diagnostic algorithm for EGPA.

  • The most common symptom in patients with EGPA is asthma (lungs), but other organs and parts of the body can also be affected.
    • Asthma
      • This symptom is the defining feature of EGPA, and is present in approximately 90% of EPGA patients of all ages.
      • This often occurs 8-10 years prior to the actual vasculitis occurring in adults.
      • Many patients that are diagnosed with EGPA often take glucocorticoids (drugs like prednisone) to control their asthma.
        • In these cases, the diagnosis of EGPA might become clearer when the patient stops taking the glucocorticoid medication.
      • Other lung problems have also been noted in 50-70% of adults with EPGA
    • Ear, Nose and Throat
      • In studies involving adult patients with EGPA, it was found that around 48% of patients showed the involvement of the ear, nose and throat.
      • Some of the types of ear/nose/throat involvement include:
        • Otitis media (when fluid collects in the middle ear)
        • Allergic rhinitis (usually called “hay fever”, involves reacting to allergens in the air, inflammation in the nose)
          • Symptoms of this occurrence include runny/stuffy nose, itchy and water eyes, sneezing and swelling around the eyes.
        • Nasal obstruction (something in the nose that blocks air flow)
        • Recurrent sinusitis (the nasal passages become inflamed and swell up
        • Nasal polyposis (growths that occur in the lining of the passage of the nose)
      • Skin
        • This is one of the most common symptoms in EGPA, seen in around half of patients of all ages.
        • In patients with EPGA, skin lesions can form. The affected areas usually are the arms (elbows and hands), and legs.
        • A biopsy of the skin can be done to reveal granulomas (collections of immune cells)
      • Heart and Circulatory System
        • These are one of the more serious cases in patients with EGPA.
        • Sign of this level of involvement in patients with EGPA include heart failure, pericarditis (swelling of the outer layer of the heart) and heart rhythm issues.
        • In two adult studies, it was found that a higher count of eosinophils is related to more involvement of the heart.
      • Kidney
        • Across the adult populations, a couple studies found that about a quarter to a half of adults patients with EGPA showed kidney (renal) involvement.
        • There is another study that looks at adult patients with EGPA that develop glomerulonephritis (inflammation/swelling of the small units of the kidney).
          • In this study, they found that all patients that developed glomerulonephritis were found to be positive for ANCAs.
        • Other organs that can also be involved:
          • Gastrointestinal tract
          • Muscles and skeletal system
          • Lymphadenopathy (swelling/inflammation of the lymph nodes)
  • Diagnostic Purposes
    • The following are findings that are often seen in patients with this illness:
      • Eosinophilia – an increased number of eosinophils (immune cells)
        • This finding is important in hinting towards EGPA
        • Though this finding is usually found in the blood, it can also be tested in the tissues
      • Antineutrophil cytoplasmic antibodies (ANCAs)
        • Across a few studies, it has been found that around 40-60% of patients of all ages with EPGA are found to have ANCAs.
        • There are a couple of studies that have found that the symptoms of patients with EGPA may be different depending on whether they do or do not have ANCAs.
  • Chest radiography
    • This imaging test is done to test for the involvement of the lungs
    • It is often done after an asthma flare or to test for peripheral eosinophilia.
  • Spirometry
    • This is a test for the lungs which helps show whether there is a limited amount of flow of air, which points towards asthma.
    • Through this test, the lung volumes, which measure amounts of air, can be decreased.
    • Also, the amount of gas that can be transferred in the lungs can also be decreased in patients with EGPA.
  • Bronchoalveolar Lavage (BAL)
    • This test is used with pateints who show interstitial opacities on radiograph images of the lungs.
    • It helps test for signs of infection, eosinophilia (increased number of immune cells called eosinophils), alveolar hemorrhage, or malignancy.
  • These tests such as echocardiograms, electrocardiograms, and cardiovascular MRIs (CMRs) are usually done in the beginning before a patient is actually diagnosed with EGPA.
  • It is found that even though patients with EGPA may not have any signs that point to heart problems, these issues with the heart can still be present.
    • Echocardiogram
      • In the adult population, the most common findings are issues related to the motion of the heart walls.
    • CMR = Cardiovascular MRI (Magnetic Resonance Imaging)
      • This test is only done if certain issues are seen in the results of an electrocardiogram of an echocardiogram.
  • The use of a biopsy can be very useful in diagnosing a patient with EGPA. The various types are discussed below:
    • Lungs
      • Surgical lung biopsy is the most accurate and useful tool in figuring out if a patient has EGPA.
      • However, this procedure isn’t available all the time because it is more invasive.
      • Lung biopsies can show inflammation of lung airways, granulomas (collections of immune cells), or vasculitis (inflammation of blood vessels).
    • Skin Biopsy / Peripheral Nerve Biopsy
      • These types of biopsies are less invasive and can be used to help make a diagnosis of EGPA.
    • Heart Biopsy (Endomyocardial)
      • A biopsy of the heart muscle is only done is EGPA is already being considered, and if inflammation of the heart muscle is suspected (endomyocarditis). Also, the most important factor in doing this test is whether or not the results of this test will actually help determine whether certain drugs, such as immunosuppressants, will be used in the patient’s treatment.

Types of Treatments

  • The main treatment for patients with EGPA is the use of glucocorticoids, which is sometimes combined with a type of immunosuppressant in more serious cases. The treatment of EGPA is very similar to the treatment of another ANCA-associated vasculitis called Granulomatosis with polyangiitis (GPA). Other features of EGPA like asthma and hypertension (high blood pressure) are treated normally as if they were seen separate from EGPA.

Corticosteroids

  • Glucocorticoids (ex. prednisone) are usually used in the treatment of EGPA in order to suppress the systemic symptoms and arrest the progression of EGPA. More specifically, these medications suppress the immune system and help reduce the amount of inflammation of the blood vessels. Also, if there is involvement of the heart, kidneys, digestive tract or the central nervous system (brain or spinal cord), then a higher dose of corticosteroids are usually given in combination with immunosuppressants.

Traditional immunosuppressants

  • Cyclophosphamide (CYC)
    • This drug is usually used in combination with steroids (corticosteroids) in mostly severe cases of EPGA involving many organs.
  • Azathioprine (AZA) and Methotrexate (MTX)
    • In milder cases, corticosteroids can be used in combination with either MTX or AZA. However, AZA is often preferred because it is easier to monitor for drug side effects.
  • Mycophenolate mofetil (MMF)
    • This drug has been used in the past for the treatment of patients with GPA. Though less commonly, there have also been reports of MMF being used for patients with EGPA as well.

It is important to note that different combinations of medications are used at different phases in the treatment of EGPA. For example, initially, corticosteroids and cyclophosphamide are used together to begin treatment (induction therapy). Later on, maintenance therapy (see below) consists of drugs such as azathioprine (AZA). Also note that AZA and MTX are often used in milder cases of EGPA, in conjunction with corticosteroids instead of cyclophosphamide.

Biological therapy

  • Rituximab

Refractory diseases, which do not respond to medications such as steroids and immunosupressants, can be treated using biological therapies. This drug has been used in the treatment of the other ANCA-associated vasculitides such as GPA and MPA. However, there is little research on the use of this drug in children with EGPA.

 

Plasmapheresis

  • A technique that removes the liquid portion of the patient’s blood (called plasma) which may contain disease-related substances. After this, the body is given an infusion of fresh protein or plasma which allows the body to produce new plasma. This has been done in patients with EGPA and kidney involvement, however the results are not very reliable and there may be no real benefit of this treatment.

Refractory Disease

  • Refractory disease describes cases in which patients do not respond optimally to the initial treatment. In these cases, there have been some studies which have used intravenous immune globulin (IVIG) in combination with glucocorticoids.
  • Birmingham Vasculitis Activity Score (BVAS)
    • This tool helps monitor disease activity
    • It considers different patient symptoms and signs to come up with specific score
    • This score then reflects the disease activity and helps doctors make decisions about patient treatments
  • Five Factor Score (FFS)
    • This tool for monitoring vasculitis is not specific for EGPA or for children
    • The FFS can help physicians consider what type of treatment to follow for patients with EGPA
  • Specific to the paediatric population
    • Paediatric Vasculitis Activity Score (PVAS)
      • A paediatric vasculitis assessment tool that is based off of BVAS
      • 64 active items with 9 organ sub-systems
      • This tool reports an overall score which reflects disease activity
    • Paediatric Vasculitis Damage Index (PVDI)
      • This is a modified version of the original Vasculitis Damage Index (VDI)
      • Contains 72 items across 10 systems in the body
      • Contains a separate page which reports school absence.
      • Each item receives one point, and reports an overall score.

Below you can find downloadable PDF files of suggested treatment protocols for patients with Hypersensitivity Vasculitis.

Suggested Treatment Protocols:

  1. (These numbers depend on the types of treatment protocols provided for Eosinophilic Granulomatosis with Polyangiitis (EGPA) / Churg-Strauss Syndrome (CSS))
  2. (These numbers depend on the types of treatment protocols provided for Eosinophilic Granulomatosis with Polyangiitis (EGPA) / Churg-Strauss Syndrome (CSS))
  3. (These numbers depend on the types of treatment protocols provided for Eosinophilic Granulomatosis with Polyangiitis (EGPA) / Churg-Strauss Syndrome (CSS))