What is Churg Strauss Syndrome?

Churg Strauss Syndrome is a rare systemic autoimmune disease characterized by inflammation of small to medium sized arteries, arterioles and venules. This inflammatory process of blood vessels is more commonly known as vasculitis. Churg Strauss vasculitis is characterized by the invasion and abnormal increase of a white blood cell known as an eosinophil. The eosinophils cluster together and release harmful granules that collect in different parts of the body as inflammatory nodule lesions. This is called granulomatosis. This eosinophilic inflammation, along with asthma, are the hallmarks of Churg Strauss Syndrome. The inflammatory process can cause impaired blood flow to various organ systems. The resultant damage to different organs may be temporary or permanent.

Churg Strauss Syndrome should be considered when there is late onset asthma, or worsening asthma, along with either numbness or pain in the extremities, sinus problems, a lingering cough, a rash, stomach problems, or symptoms of cardiac involvement.

The American College of Rheumatology established the following criteria for diagnosing CSS:

Asthma
Eosinophilia >10%
Neuropathy, mono or poly
Pulmonary infiltrates, non-fixed
Paranasal sinus abnormality
Extravascular eosinophils

For classification purposes, a patient is said to have Churg Strauss syndrome if at least 4 of these 6 criteria are positive. Some researchers believe that early cases of CSS may consist of asthma and tissue eosinophilia without detectable vasculitis. If caught early, CSS is more responsive to corticosteroids, while cases with full-blown vasculitis may require the addition of more powerful immunosuppressive drugs. Unfortunately, early stage CSS is often under-diagnosed.

Churg Strauss is a baffling disorder that is difficult to diagnose and one whose effects vary widely from patient to patient. Some people have mild symptoms which barely affect day to day living while others suffer from a wide variety of problems including sinus problems, rashes, lung involvement, peripheral neuropathy, gastrointestinal problems and heart involvement. CSS is not contagious and is not inherited. Its cause is unknown. There is no cure, but many people achieve long term remissions. It affects men slightly more than women. It can affect people of all ages with the average age at diagnosis being 35 to 45. Estimates about the incidence of CSS vary widely and range from 2.4 to 10 cases per 1 million people, or roughly from 720 to 3,000 people in the United States.

CSS was almost always a fatal disease until the discovery of effective drug therapy. Treatment consists of quieting the inflammation of the blood vessels and suppressing the immune system. Corticosteroids are usually the initial therapy. For those with more severe, life threatening complications, or those who fail to respond to steroids alone, cytotoxic drugs may be added. Side effects and drug toxicity need to be carefully monitored during treatment. The chief causes of mortality are severe asthma, cardiopulmonary failure, or gastrointestinal complications. With prompt diagnosis and treatment many people achieve at least medically maintained remission, although some may experience occasional flares.

Because there is no cure for CSS and relapses, or flares, are common it is very important that the disease be carefully monitored by a physician with regularly scheduled lab tests even while in remission. CSS may present differently during a flare than when first diagnosed, so any new symptoms should be reported promptly. CSS is a chronic and sometimes life threatening disease, but with diligence and effective medical care most patients enjoy a very good quality of life.

Terms

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Symptoms

CSS is a progressive disease consisting of three distinct phases: the allergic stage, the hypereosinophilic stage and the vasculitic stage. With early diagnosis and effective treatment, not everyone diagnosed with Churg Strauss Syndrome experiences all three phases, or experiences them sequentially.

The first stage is often called the prodromal phase. Prodromal simply means symptoms that occur at the onset of a disease. This first, allergic phase, is almost always characterized by asthma. Often the individual develops asthma late in life. This is called late onset asthma. Some people who have had asthma throughout their lives experience a worsening of symptoms that become more difficult to treat. Sinus disease, which is characterized by facial pain from sinusitis, nasal polyps, allergic rhinitis (inflammation of the mucous membranes of the nose causing sneezing, itching, runny nose) and recurrent pneumonia and/or bronchitis are also typical of this prodromal phase. This phase can last from 4 to 27 months, although some patients stay in this phase for many years.

The next phase is called the hypereosinophilic phase. Hypereosinophilia means there is an overabundance of a certain white blood cell called an eosinophil. This overabundance of eosinophils can occur either in the blood or in the tissues. Often during this phase, patients suffer from chronic eosinophilic pneumonia and eosinophilic gastroenteritis (inflammation of the esophagus, stomach or intestines). The symptoms during this phase can include feeling generally unwell with weight loss, fever, and night sweats. In addition if the lungs are affected, the patient may experience shortness of breath, a feeling of heaviness in the chest and a constant cough. If the gastrointestinal tract is involved people may experience abdominal pain, bloating, vomiting, diarrhea, and nausea. Inflammation of the esophagus may cause dysphagia, or difficulty swallowing. Many people with eosinophilic gastroenteritis find it very difficult to eat. They often experience increasing and sometimes very severe pain after meals. After eating they may experience bouts of vomiting and/or diarrhea, sometimes resulting in weight loss and even anorexia. Some patients get ulcers. Patients may stay in the this second phase for months or years. During this time, their symptoms may become less severe and may even go away, only to recur. Some people experience the second and third phases simultaneously. With treatment and medication some folks never even get to the third phase which is:

The systemic vasculitis phase. Systemic vasculitis means that there may be inflammation and damage to blood vessels throughout the body. This, in turn, may cause damage to many different organs. Because CSS can affect so many different organs at this stage, symptoms vary widely depending on the organ affected. General symptoms include fever, weight loss and adenopathy (enlargement of the glands, especially the lymph glands). Common organs affected by CSS include the skin, the heart, the lungs, the central nervous system, the peripheral nervous system, the gastrointestinal tract and less commonly, the kidneys, the eyes and the musculoskeletal system.

CSS involving the skin can manifest itself in many way. Rashes, purpura (purplish discolorations caused by bleeding vessels near the surface of the skin) or nodules (solid raised bumps of more than 10 millimeters in diameter) are common. In addition, livedo reticularis (a blotchy mottling of the skin), urticaria (raised red welts) and vesicles (small fluid filled blisters) might occur.

If the lungs are involved the following symptoms might be present: cough, shortness of breath, hemoptysis (coughing up blood stained sputum), rales (small clicking, bubbling or rattling sounds in the lung), rhonchi (chest sounds that sound like snoring) and a feeling of pressure in the chest.

If the disease progresses to the heart the CSS patient might experience fatigue, dyspnea (shortness of breath), chest pain, irregular heartbeat, increased blood pressure, difficulty in breathing except when upright, swollen legs, appetite loss and fainting episodes. Some of these symptoms are related to pericarditis, which is inflammation of the sac-like covering of the heart, where others are related to congestive heart failure. Heart problems are a leading cause of death in Churg Strauss Syndrome.

Involvement of the central nervous system, or the brain, might cause intellectual or motor disturbances, seizures, confusion, difficulty in speaking and headaches. Cerebral hemorrhage is a cause of death in Churg Strauss Syndrome and usually occurs in patients who also have hypertension.

Patients more commonly have problems associated with the peripheral nervous system, such as peripheral neuropathy, including mononeuritis multiplex. Symptoms occur in the limbs and include feelings of numbness or hypoesthesia, and hyperesthesia , which is an increased sensitivity to any stimulation and can be experienced as tingling or a burning pain. Other symptoms include abnormal sensations, and difficulty in moving a part of the body. Some people experience foot drop. Patients with foot drop cannot lift up the ankle, straighten or extend the toes, or turn the foot outward.

Gastrointestinal problems occur in approximately 40% to 60% of patients whose disease progresses to the vasculitic phase. The main symptoms are severe abdominal pain, bloody diarrhea, vomiting and nausea. The symptoms may be the same or similar to those of eosinophilic gastroenteritis. Some patients may develop obstructions or perforated intestines.

Involvement of the musculoskeletal system may result in swelling of the joints, muscle pain and arthritis.

Kidney involvement is not common in CSS. If the kidneys themselves are damaged there might not be any symptoms at all. Tests, however might show there to be blood or protein in the urine. Sometimes kidneys can be damaged by obstructive uropathy which occurs when urine cannot drain through a ureter because of a blockage, causing urine to back up into the kidney. Symptoms of kidney involvement include fever, urinary tract infection, nausea, edema (swelling), and difficulty or pain while urinating.

Although not common, the optic nerve can be affected by vasculits causing eye pain and vision problems.

During the vasculitic phase patients may be anemic or have low platelet counts, resulting in weakness and fatigue.

In addition to all the possible symptoms caused by Churg Strauss Syndrome in any of the three phases, patients might also experience the general effects of anyone who has a a chronic illness, such as depression, fatigue and general malaise. In addition, the medications used to treat the disease may also cause side effects. Treatment sometimes causes the immune system to be suppressed leading to a greater vulnerability to all sort of illnesses, including a greater susceptibility to pneumonia. CSS is a type of vasculitis and people with vasculitis have an increased risk of blood clots. Because it is often hard to sort out what is disease, what are the effects of medications, and what is something else all together, it is helpful to keep a medical journal to keep track of symptoms, problems and concerns for discussion with your doctors.

It is easy to feel overwhelmed and discouraged after reading about all the possible problems associated with having Churg Strauss Syndrome, but it is essential to remember that: 1) with early diagnosis and treatment, many people never experience the vasculitic phase of the disease, 2) with effective treatment most of the symptoms in any of the three phases can be relieved, and 3) researchers are working to achieve a greater understanding of the disease which will lead to better treatment and possibly, a cure.

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Diagnosis and Tests

In 1990 The American College of Rheumatology (ACR) established criteria
that distinguished Churg Strauss Syndrome from other vasculitic diseases. Criteria for the classification of Churg Strauss Syndrome was developed by comparing 20 patients who had this diagnosis with 787 control patients with other forms of vasculitis. Six disease features were selected as being those that best distinguished it from other vasculitic diseases. The six criteria are:

History of Asthma

Eosinophilia-eosinophilia >10% on a white blood cell differential count

Mononeuropathy or polyneuropathy-development of mononeuropathy, multiple mononeuropathies, or polyneuropathy (i.e. glove/stocking distribution) attributable to a systemic vasculitis

Pulmonary infiltrates- non fixed migratory or transitory pulmonary infiltrates on radiographs (not including fixed infiltrates), attributable to a systemic vasculitis

Paranasal sinus abnormality-history of acute or chronic paranasal sinus pain or tenderness or radiographic opacification of the paranasal sinuses

Extravascular eosinophils-biopsy including artery, arteriole, or venule, showing accumulations of eosinophils in extravascular areas

The presence of four or more of these six criteria yielded a sensitivity of 85% and a specificity of 99.7%. Sensitivity of 85% means that the presence of 4 or more of the six criteria will correctly pick up the disease 85 out of 100 times. A specificity of 99.9% means that when CSS is diagnosed using those standards, 99.9% of those people will actually have the disease. Many doctors feel comfortable diagnosing CSS when only two or three of these criteria are present, but for purposes of being in a trial or study, four out of six have to be met.

A classification tree was also constructed with 3 selected criteria: asthma, eosinophilia greater than 10% on differential white blood cell count, and history of documented allergy other than asthma or drug sensitivity. If a subject has eosinophilia and a documented history of either asthma or allergy, then that subject is classified as having CSS. For the tree classification, the sensitivity was 95% and the specificity was 99.2%.
Although the classification tree criteria are very simple and might be advantageous in patients who are known to have systemic vasculitis, they are not generally considered to be helpful in the diagnosis of individual patients.

When CSS is diagnosed early, patients may have asthma and tissue eosinophilia without detectable vasculitis. They may have eosinophilic pneumonia and/or lymph node involvement. The disease at this early stage can often be treated with steroids instead of more damaging chemotherapy. That is why early diagnosis is so important.

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Treatment of Churg Strauss Syndrome

Once diagnosed with Churg-Strauss Syndrome (CSS), systemic steroids are usually the initial therapy. Prednisone, and Medrol are the most commonly used steroids for treatment. Initially, high doses of oral steroids (e.g. 40-80mg) are given in an attempt to get the disease into remission as quickly as possible. Once improvement is seen, the steroids are very slowly tapered down to a lower dose for maintenance. Much of the literature on CSS states that most people are able to completely wean off steroids. However, in our experience that seems to be more the exception than the rule. Most people seem to require a maintence level of steroids indefinitely.

For those who have more severe, life-threatening complications or who fail to respond to steroids alone, an additional immunosuppressant drug such as Cyclophosphamide (Cytoxan) may be added. High doses of IV steroids (e.g. Solumedrol) may also be used for more severe cases. Other immunosupressant drugs, that are usually less toxic can be used and can help you be able to reduce your steroid dose to avoid some of the steroid side effects. These drugs include Methotrexate, Azathioprine, Cellcept, and Cyclosporin.

Other treatments that have been known to work in some cases of CSS are IVIG and interferon alpha. IVIG is an infusion of immune globulins. It is a very costly treatment, with fewer side effects than the other traditional treatments. Reports show it to be effective for some especially initially, but some are not able to maintain a good response. Interferon alpha is a man made substance that is part of your immune system. It is given either by IV or injection. The literature on interferon alpha used in treating CSS is mostly encouraging, with most showing some improvement.

Unfortunately, most of the treatments for CSS have significant side effects. The key is to try and be maintained on as low a dose of medication as possible to avoid side effects. Many find they can be maintained on fairly low doses of steroids alone after the initial therapy. With any flares of disease a high dose of steroids will again be given and then tapered when symptoms improve. If steroids alone can control the disease they are often the best option. If you continue to have symptoms or “flare” then many times that is when an additional immunosuppressive drug is added. The nature of CSS tends to be one where symptoms go up and down, and you will find that your dosage of medications will also go up and down. It is our hope that more and more research will be done for CSS, and that new medications with fewer side effects will become available. There are a few promising studies researching new medications for CSS. One such study is on the anti-IL-5 drug. In the promising studies so far, it has shown to greatly reduce eosinophil counts and symptoms, with very few side effects. More research is needed and our organization is committed to supporting all research into CSS and the treatments of this disease.

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Medications and Side Effects

Prednisone

Prednisone is by far the most common of all drugs used to treat CSS. Almost all CSS patients are on this drug. There is currently no other drug that can quickly stop the activity of disease, and in this sense it is truly a miracle drug to those who suffer from inflammatory diseases.

As with other powerful drugs, the success of Prednisone comes at a price. There is a long list of side effects associated with Prednisone, and most people do experience some side effects. As would be expected, the higher the dose and the longer the duration of treatment, the more likely you are to have more troublesome side effects. The most common side effects that most patients report are:

There are many things you can do to help minimize these side effects. For instance, anyone on steroids should also take calcium or Fosamax to help prevent osteoporosis. Engaging in weight bearing exercises will also help keep bones strong. Taking a drug such as Prilosec, Previcid, or Nexium can help to lessen the stomach upset associated with steroids. A balanced diet and plenty of exercise are important to keep the weight gain to a minimum and are vital to help maintain your physical abilities, especially when one is afflicted with neuropathy.

When you are on long term high dose steroids, as in severe disease, these side effects are magnified and there are additional side effects to look out for. High dose steroids, (and even lower dose) are associated with failure of the adrenal glands. Your adrenal glands are vital to help you when your body is in a trauma, such as in an accident, surgery, or serious infection. While you are on steroids, should one of these things occur you must tell any physican caring for you of your steroid use. When a person is on systemic steroids for a long period of time they stop producing natural steroids or cortisol, which is vital any time the body is in trauma. Without cortisol or an added “stress” dose of steroids in a time of crisis to your body, you could go into shock with potentially fatal consequences. High dose, long term steroids are also associated with necrosis of the joints, particularly the hip. Taking additional calcium or Fosamax can help with this, but unfortunately sometimes even these steps are not enough to prevent it, and joint replacement may be neccessary. In rare instances even damage to vital organs such as the heart or kidneys can occur from long term steroid use. Chloesterol levels, both your LDL and Triglycerides, can go up while on steroids, and hypertension can develop as well, which increases your risk of developing cardiovascular disease. More commonly, patients on steroids develop glucose intolerance, insulin resistance, or even full blown diabetes. Anyone on long term steroids should frequently have their blood pressure, glucose levels, HGA1C and lipid levels checked to monitor for these conditions. Making the most of your health by not smoking, and maintaining a healthy lifestyle will help to minimize these rare, but serious, side effects. Anyone who is on long term steroids will be closely monitored by their physican who will be vigilant to any serious side effects. Your doctor will have you undergo yearly bone scans and eye exams as well, to catch problems as early as possible. It is possible to reverse many of the side effects associated with steroids by either reducing your dose, or getting off steroids completely.

Cytoxan (cyclophosphamide)

Cytoxan is a very powerful immunosuppressive drug and is one of the most powerful drugs used to treat CSS. Even though there are some very serious side effects associated with Cytoxan, most people tolerate it well. The most common side effects are stomach upset, which can be helped with drugs like Phenegren or Zofran, and hair thinning or hair loss. Usually, once the medication is discontinued any hair you may have lost will grow back.

Cytoxan works by going after rapidly dividing cells in the immune system, and suppressing them. In doing so it reduces the activity of disease. It helps reduce symptoms and damage to vital organs, and can help to get the disease into remission more quickly. Cytoxan can be given in oral or IV form. The IV form is usually given as pulsed therapy, perhaps once a month. Cytoxan was originally used in treating cancer. When used in treatment of autoimmune diseases the dosages are usually anywhere from 10-50% of what is prescribed for treating cancers. At these lower doses the side effects are rarer.

The white blood cell count, platelet count, and red blood cell count can all become decreased while on Cytoxan and can create an increased risk for bleeding, serious infections, and shingles. Lowering or discontinuing the drug for a while will allow your blood counts to come up, usually returning to normal. While you are on Cytoxan this will need to be monitored through monthly blood counts. Use of Cytoxan can also cause bleeding from the bladder and can even cause bladder cancer, although this is rare. Taking the drug in the morning and drinking plenty of water is essential in helping to flush the drug out of your system, thereby reducing your risk of developing these conditions. Cytoxan can cause sterility in both men and women, and should not be taken by women who are pregnant. All immunosuppressive drugs are associated with an increased risk of developing a malignancy. The higher the dose of Cytoxan and the longer the treatment, the greater the risks. In general these very serious side effects are rare, but the risks are there, so the decision to use these drugs should not taken lightly.

Imuran (Azathioprine), Methotrexate (Folex), Cyclosporin (Sandimmune) and Cellcept

These others are all immunosuppressive drugs used to treat CSS. They are used when the disease does not respond to steroids alone and when the disease is not causing life threatening organ damage. These drugs are less potent than Cytoxan. Like Cytoxan, they too can cause serious side effects, but the risk is much lower. These drugs can cause a decrease of white blood cells, platelet counts and red blood cell counts. Monthly blood tests are important to be sure that counts don’t get too low.

Imuran and Methotrexate are known as antimetabolites. They are both very commonly used immunosuppressive drugs for treatment of various autoimmune diseases. Many doctors will try to use one of these drugs if your disease can only be controlled by high doses of steroids. The addition of one of these drugs is known as "steroid sparing" therapy, with the hope that this combination of drugs will allow for lowered steroid doses thereby reducing the risk of developing the serious steroid complications caused by high doses and/or long term use.

Cyclosporin and Cellcept are commonly used to prevent organ rejection in transplant patients. Their ability to effectively suppress an overactive immune system response while sparing serious toxicities have made these drugs very useful in the treatment of immune system disorders.

The side effects of all these drugs can include a lowering of the white blood cell count which in turn causes an increased susceptibility to infection, easy bruising or bleeding, as well as liver problems and a small increased risk of developing certain cancers. These risks are rare and happen much less often than they do with the more powerful immunosuppressive drugs used in high doses. The more common side effects of these drugs are nausea, vomiting, diarrhea, headaches, insomnia, fatigue, dizziness, blurred vision, skin rashes, drowsiness, acne, and thinning of hair. Most people tolerate these drugs quite well, with little to no side effects. Others may experience side effects in the beginning which go away once their bodies adjust to treatment. Some patients may be able to wean off steroids completely by using these drugs. Even if they cannot get off steroids completely, they often allow patients to be maintained on much lower doses of steroids.

Interferon alpha

Interferon is a protein that is naturally produced when you have a
virus and is considered a biological drug. Biological drugs are simply drugs made from natural substances produced by the body. Interferon alpha is one of the many more recently discovered biological drugs used in the treatment of a variety of different diseases. Interferon is becoming more widely used due to the fact it usually has less toxic side effects than some of the more commonly used drugs. Even though it can cause lowered white blood cell and platelet counts, it is not as likely to cause these side effects compared to some of the other immunosuppressive drugs used for CSS.

Interferon is known to cause flu-like symptoms, such as fever, aches,
chills, fatigue, nausea and vomiting. The likelihood of more debilitating side effects from these flu-like symptoms is higher with Interferon alpha than with other drugs. Some do tolerate Interferon very well, although this varies from person to person as it does with any drug.

IVIG (intravenous immunoglobulin)

IVIG is the most benign of all treatments used in treatment CSS. It may take some adjustments of infusion time and products, but most tolerate IVIG very well. The most common side effects of headaches and flu-like symptoms usually only last for 24 hours after an infusion and then go away. Most people will get 1 infusion per month.

IVIG is usually used in the treatment of immune deficiencies, but it is now being used more frequently in other immune diseases. The biggest draw back of IVIG is the cost as each infusion is anywhere from $10,000-$20,000. The studies using IVIG in treatment of CSS show varying degrees of response. Some have shown dramatic improvement, while others have shown no improvement at all. At this point it is not a mainstay of treatment but may be a consideration before trying other, more toxic therapies.

There may be other drugs used in the treatment of Churg Strauss Syndrome that are not listed here. Those drugs will be added as more is known about them. More information on the medications used to treat CSS can be found in the Helpful Links as well as the Research pages of this website.

DISCLAIMER:

The material provided by the Churg Strauss Syndrome Association is for information only and should not take the place of advice or guidance from your own healthcare providers. Be sure to check with your doctor about all aspects of your medical care, including all decisions about medication.

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