Asthma Subgroups: Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic Granulomatosis with Polyangiitis, formerly known as Churg Strauss Syndrome, is a very rare subgroup of asthma where severe asthma is combined with a combination of other medical conditions. Here is what you need to know.

What is it?

It’s a combination of eosinophilic, granulomatosis with polyangiitis, and airway inflammation. Okay, allow me to put this into terms you can understand.

• Eosinophilia. This is a high eosinophil level in blood or tissues. Eosinophils are white blood cells involved in the inflammatory response. When they come into contact with tissues they cause prolonged inflammation. This leads to vasculitis and airway inflammation.
• Granulomatosis with Polyangiitis This is fancy term for inflammation of blood vessels (vasculitis) leading to organs. The most common organs affected are the lungs and skin, although the nervous system, gastrointestinal tract, kidneys and heart may also be affected.
• Airway Inflammation This may lead to severe asthma, rhinitis, and sinusitis.

What causes it?

No one knows the exact cause, although it’s believed to be caused by some form of genetic flaws. Here is what is presently known.

• Human Leukocyte Antigens (HLA) Researchers believe it is caused by a flaw or flaws on the Human leukocyte antigens (HLA) family of genes. HLA genes are genes that hold the recipes for making proteins that help your immune system know the difference between proteins on healthy tissue and proteins on foreign invaders like viruses and bacteria.^3,4
• T-helper 2 (TH2) Dominant Response Dendritic cells roaming your bloodstream are responsible for recognizing proteins on foreign invaders, binding to them, and carrying them to Th2 cells.  Chemicals are then released by Th2 cells telling B-cells to create IgE antibodies. During subsequent exposures to that specific antigen, IgE antibodies recognize them and release chemicals to initiate an immune response to trap, kill, and remove them from your body.
• Theory A respected explanation postulates that this asthma subgroup is caused by a flaw on genes HLA-DRB1*04 and HLA-DRB1*07. These genes may become activated due to repeated exposure to allergens or some other antigen. Once activated, they may have an impact on a glycoprotein called CD4.³
• CD4 Another gene is called the CD4 gene. It produces CD4, which attaches to dendritic and Th2 cells, helping them distinguish between proteins on healthy tissue and proteins on foreign invaders. A flaw on the HLA genes may cause CD4 to tell dendritic and Th2 cells to recognize proteins on healthy tissue as foreign, namely cells lining airways and blood vessels.³

What are the symptoms?

Researchers have broken the disease into three stages, each of which can be recognized by various signs and symptoms. Not every person experiences all stages, and they do not always present in this order. The stages include.⁵

Prodromal (allergic)

This phase can last from a few months to up to eight years.

• Severe Asthma If you have asthma, it becomes worse and probably requires corticosteroids to control it. If you do not have asthma, you are diagnosed with late onset asthma, as onset is after the age of 21.  Asthma symptoms include coughing and shortness of breath that is difficult to control with corticosteroids.
• Rhinitis Nasal allergies develop, resulting in nasal congestion, runny nose, nasal itchiness, and sneezing.
• Sinusitis. Sinus infections develops, resulting in facial pain and headaches.
• Nasal Polyps They may also develop, further complicating matters.^1,5

Eosinophilic

This is high eosinophil levels in blood and tissue.

• Abnormally high eosinophil levels are found in blood and tissues.
• The tissues affected may become inflamed.
• Prolonged inflammation may cause tissue to become scarred or damaged.
• Depending on the organs affected, symptoms may be fever, fatigue, stomach pain, gastrointestinal bleeding, joint pain, night sweats.^1,5

Vasculitis

This is when blood vessel inflammation becomes very severe and persistent (chronic), causing the passages inside them to narrow, impeding the flow of blood to the affected organ. Chronically inflamed vessels may also become thin, and easily rupture or form bulges called aneurysms.

• Skin The skin is affected in about 50%, causing purplish skin, rashes and hives.
• Neurologic Neurological symptoms include neuropathy (numbness of hands and feet).
• Gastrointestinal (GI) GI symptoms include stomach pain, nausea, vomiting, and gastrointestinal bleeding.
• Heart If the heart is affected, it may cause chest pain, abnormal heart beats, and severe dyspnea due to congestive heart failure.
• Kidney Kidney involvement may cause bloody urine.^1,5

How is it diagnosed?

It is most often diagnosed between the ages of 30 and 50. Early diagnosis is essential to slowing the progression of the disease and improve asthma control. It usually involves adult onset, severe asthma combined with any four of the following.

• Eosinophilia (need blood sample)
• Chronic sinusitis (sinus infections)
• Neuropathy (numbness of hands and feet)
• Lesions on x-ray that appear to migrate (need chest x-ray)
• White blood cells in tissue (need tissue biopsy)¹

What is the history and future outlook?

The first 13 cases were described in 1951 by Dr. Jacob Churg and Dr. Lotte Strauss as symptoms caused by the combination of vasculitis, eosinophilia, fever, and severe asthma. Two of these cases survived, although 11 were diagnosed on autopsy.

Today, the life expectancy is about 80% in five years, so the prognosis has greatly improved. This is mainly because it responds very well to corticosteroids and immune-suppressing drugs.^{2, 6, 7}