What Is Wegener's Granulomatosis? What Causes Wegener's Granulomatosis?

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Main Category: Blood / Hematology
Also Included In: Vascular;  Immune System / Vaccines
Article Date: 06 May 2010 - 0:00 PDT


Wegener's granulomatosis, also known as Wegener granulomatosis is a type of inflammation and injury to blood vessels (vasculitis) that affects several organs, including the lungs, kidneys and upper respiratory tract. It is a life-threatening disorder that requires long-term immunosuppression. Some patients die due to toxicity of treatment.

Wegener's granulomatosis is a rare disorder which restricts the blood flow to several organs. According to the Vasculitis Foundation, Kansas City, USA, it affects about 1 in 20,000 to 1 in 30,000 people. Although individuals of any age may be affected, initial symptoms and diagnosis usually occurs in patients in their 40s and 50s. Males and females are equally affected. Caucasians seem to be significantly more commonly affected than other ethnic groups.

As well as causing inflammation to the blood vessels, Wegener's granulomatosis produces granuloma around the blood vessels. A granuloma is one of several forms of localized nodular inflammation found in tissues - put simply; a granuloma is a type of inflammatory tissue.

Experts do not know what causes Wegener's granulomatosis. We do know it is not a type of cancer or infection.

If treated and diagnosed early enough, a patient with Wegener's granulomatosis can make a full recovery. If left untreated there is a risk of kidney failure and death.

Wegener's granulomatosis is part of a larger group of vasculitic syndromes. All of which feature an autoimmune attack by an abnormal type of circulating antibody called antineutrophil cytoplasmic antibodies (ANCAs) against small and medium-sized blood vessels. Examples of vasculitic syndromes include:

• Wegener's granulomatosis
• Churg-Strauss syndrome
• Microscopic polyangiitis

Wegener's granulomatosis is formally classified as one of the small blood vessel vasculitides in the Chapel Hill system, even though it affects both small and medium-sized vessels.

According to Medilexicon's medical dictionary:

Wegener granulomatosis is "a disease occurring mainly in the fourth and fifth decades that is characterized by necrotizing granulomas, vasculitis, and ulceration of the upper respiratory tract, with purulent rhinorrhea and nasal obstruction, and sometimes with otorrhea, hemoptysis, pulmonary infiltration and cavitation, and fever. Exophthalmos, involvement of the larynx and pharynx, and glomerulonephritis may occur. The underlying condition, a vasculitis affecting small vessels, is possibly caused by an immune disorder. Cases in which only the lungs are involved have been seen; isolated tracheal stenosis is increasingly recognized."

What are the signs and symptoms of Wegener's granulomatosis?

A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.

Wegener's granulomatosis signs and symptoms can develop either gradually or suddenly. Initial symptoms can vary widely, and diagnosis may sometimes be delayed because of their non-specific nature. The first symptom in most patients is rhinitis - runny and stuffy nose. Signs and symptoms may include:

• Persistent runny nose
• Cough - sometimes this may include blood
• Ear infections
• Joint aches
• Loss of appetite
• Malaise - a general feeling of being unwell
• Nosebleeds
• Shortness of breath
• Sinusitis
• Skin sores
• Swelling of joints - often initially diagnosed as rheumatoid arthritis; but is usually arthritis
• Eye pain
• Burning sensation in the eyes
• Eye redness
• Vision problems
• Fever
• Weakness, which is often due to anemia
• Rapidly progressive glomerulonephritis - a syndrome of the kidney that, if left untreated, rapidly progresses into acute renal (kidney) failure.

What are the causes of Wegener's granulomatosis?

Experts do not know what causes Wegener's granulomatosis. Most agree that it develops as a result of an initial inflammation-causing event that provokes an abnormal immune system reaction, leading to inflamed and constricted blood vessels and granulomas (inflammatory tissue masses).

Many scientists tend to believe that an initial infection may be the start of the whole event. Studies have shown that about 50% of patients with Wegener's granulomatosis had an infection. Some people believe that there may be other contributory factors, such as:

• Environmental toxins
• A genetic predisposition
• A combination of both

How is Wegener's granulomatosis diagnosed?

A doctor will usually only suspect Wegener's granulomatosis when the patient has had unexplained symptoms for an extended period. The doctor, initially usually a GP (general practitioner, primary care physician) will ask the patient about the signs and symptoms, as well as conducting a physical exam and studying his/her medical history.

The following diagnostic tests may be ordered:

• Blood tests - may detect ANCAs (anti-neutrophil cytoplasmic autoantibodies), antibodies which are present in 80% to 95% of patients with active Wegener's granulomatosis. ANCAs in blood cannot by themselves confirm a diagnosis of Wegener's granulomatosis, but they will provide helpful data towards one.
  
  A blood test can also measure the patient's sed rate (erythrocyte sedimentation rate). In this test, the speed at which red blood cells fall to the bottom of a tube is measured - this usually takes about an hour. A sed rate test can help determine whether there is inflammation in the body, and if so, how severe it is. When there is inflammation the red blood cells fall to the bottom faster.
  
  A blood test may also check for anemia, a common problem among patients with Wegener's granulomatosis.
  
  A blood test may also show whether the kidneys are working properly.
  
  
• Urine test - usually done to determine whether the kidneys have been affected.
  
  
• Chest X-ray - this imaging test can sometimes help the doctor decide whether the patient has Wegener's granulomatosis or some other lung disease.
  
  
• Biopsy - a small piece of tissue is removed from an affected organ and examined under a microscope. This is the only way of being 100% certain whether the patient has the disease. Tissue samples might be taken from the airways, nasal passages or lungs to rule out or confirm the presence of granulomas and vasculitis. Sample may also be taken from the skin or kidneys if the patient has renal (kidney) failure or cutaneous vasculitis.

What are the treatment options for Wegener's granulomatosis?

Wegener's granulomatosis treatment is usually divided into two stages:

• The induction of disease remission - getting rid of all the signs and symptoms
• Maintenance of disease remission - preventing a recurrence

If Wegener's granulomatosis is diagnosed and treated early on there is a good chance the patient can make a full recovery within months. Some patients may require longer. It is important to monitor the individual after signs and symptoms have gone away (remission) because the disease can recur.

Before the availability of steroid treatment, 90% of patients died within one year, with average survival being 5 months. Steroids increased average survival to 8 months. Cyclophosphamide (CYC), which became available in the 1970s, was a major breakthrough, after which five-year survival has reached 87%.

Medications:

• Corticosteroids - such as prednisone may be prescribed for initial signs and symptoms. In a few cases this is the only medication needed.
  
  
• Other immunosuppressive drugs - such as cyclophosphamide (Cytoxan), azathioprine (Imuran) or methotrexate (Rheumatrex) is prescribed as well in most cases. The aim is to stop the body's immune system from overreacting.
  
  
• Rituximab (Rituxan) - this medication, which was originally designed to treat non-Hodgkin's lymphoma (a type of cancer), was later approved for rheumatoid arthritis treatment. Rituximab reduces the number of B cells in the body - B cells are involved with inflammation. If standard treatments are not effective some doctors may prescribe Rituximab.

As many drugs used for Wegener's granulomatosis treatment weaken the patient's immune system, it is important to monitor his/her condition - a lower immune system is less able to fight off infection. The following medications may be prescribed:

• Trimethoprim-sulfamethoxazole (Bactrim, Septra) - help protect from lung infections
• Bisphosphonates (Fosamax) to prevent osteoporosis. Corticosteroids can cause bone loss (osteoporosis).
• Folic acid - to prevent sores and other problems that can occur when folate levels are low. Methotrexate can deplete folate levels.

Surgery - if the Wegener's granulomatosis patient has suffered kidney failure the doctor may recommend a kidney transplant.

What are the possible complications of Wegener's granulomatosis?

Complications usually result from lack of treatment.

Deafness - granulated tissue in the middle ear can become inflamed, leading to deafness.

Skin scarring - sores can develop on the skin, which may result in severe scarring.

Heart attack - if the arteries of the heart are affected.

Renal (kidney) damage - the disease, if left untreated, will usually eventually affect the kidneys. Glomerulonephritis may develop, in which the kidneys cannot filter out waste and excess fluids from the body properly, resulting in an accumulation of waste products in the bloodstream. Most patients who die from Wegener's granulomatosis do so as a result of kidney failure.

Written by Christian Nordqvist


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