Wegener's Granulomatosis Causes, Symptoms, Diagnosis, Treatment, Prevention

Wegener's Granulomatosis Causes, Symptoms, Diagnosis, Treatment, Prevention


What is Wegener's Granulomatosis?


Wegener's granulomatosis is an uncommon disease, in which the blood vessels are inflamed (vasculitis). This inflammation damages important organs of the body by limiting blood flow to those organs and destroying normal tissue.

Although the disease can involve any organ system, Wegener's granulomatosis mainly affects the respiratory tract (sinuses, nose, trachea [windpipe], and lungs) and the kidneys. This disorder can affect people at any age and strikes men and women equally. It is rare in African Americans compared to Caucasians. Health experts do not know what causes Wegener's granulomatosis.

Wegener's granulomatosis also produces a type of inflammatory tissue known as a granuloma that's found around the blood vessels. Granulomas can destroy normal tissue. There is no known cause for Wegener's granulomatosis.

Early diagnosis and treatment of Wegener's granulomatosis may lead to a full recovery. Without treatment, Wegener's granulomatosis can be fatal, most commonly from kidney failure.

Cause of Wegener's granulomatosis


The cause for Wegener's granulomatosis is unknown. Since inflammation is usually the result of immune system activity, researchers believe the cause may be that the immune system cells begin to attack the blood vessel walls in the body. However, the cause of the immune system attack is not clear.

Risk factors of Wegener's Granulomatosis


Wegener's granulomatosis can begin at any age, but it most often starts in middle age, with an average onset between 40 and 65. Whites are more likely than blacks to develop Wegener's granulomatosis.

What are the Symptoms of Wegener's Granulomatosis?


The first symptoms of Wegener's granulomatosis are often vague and frequently include upper respiratory tract symptoms, joint pains, weakness, and tiredness.

Upper respiratory tract


The most common sign of Wegener's granulomatosis is involvement of the upper respiratory tract, which occurs in nearly all patients. Symptoms include sinus pain, discolored or bloody fluid from the nose, and, occasionally, nasal ulcers. A common sign of the disease is almost constant rhinorrhea ("runny nose") or other cold symptoms that do not respond to usual treatment or that become increasingly worse.

Rhinorrhea can result from nasal inflammation or sinus drainage and can cause pain. A hole may develop in the cartilage of the nose, which may lead to collapse (called saddle-nose deformity). The eustachian tubes, which are important for normal ear function, may become blocked, causing chronic ear problems and hearing loss. Bacterial infection can cause Wegener's-related sinusitis (inflammation of the sinuses) with congestion and chronic sinus pain.

Lungs


The lungs are affected in most patients with Wegener's granulomatosis, although no symptoms may be present. If symptoms are present, they include cough, hemoptysis (coughing up blood), shortness of breath, and chest discomfort.

Kidneys


Kidney involvement, which occurs in more than three-fourths of patients, usually does not cause symptoms. If detected by blood and urine tests, the doctor can start proper treatment, preventing long-term damage to the kidneys.

Musculoskeletal system


Pain in the muscles and joints or, occasionally, joint swelling affects two-thirds of patients with Wegener's granulomatosis. Although joint pain can be very uncomfortable, it does not lead to permanent joint damage or deformities.

Eyes


Wegener's granulomatosis can affect the eyes in several ways. Patients may develop

  • Conjunctivitis (inflammation of the conjunctiva, the inner lining of the eyelid)
  • Scleritis (inflammation of the scleral layer, the white part of the eyeball)
  • Episcleritis (inflammation of the episcleral layer, the outer surface of the sclera)
  • Mass lesion behind the eye globe
Symptoms in the eye include redness, burning or pain. Double vision or a decrease in vision are serious symptoms requiring immediate medical attention.

Skin lesions


Nearly half of people with Wegener's granulomatosis develop skin lesions. These often have the appearance of small red or purple raised areas or blister-like lesions, ulcers, or nodules that may or may not be painful.

Other symptoms of Wegener's Granulomatosis


Some patients experience narrowing of the trachea. The symptoms can include voice change, hoarseness, shortness of breath, or cough.

The nervous system and heart occasionally may be affected. Fever and night sweats may occur. Fever also may signal an infection, often of the upper respiratory tract.

How is Wegener's Granulomatosis Diagnosed?


To treat people with Wegener's granulomatosis most effectively, doctors must diagnose the disease early. There are no blood tests that a doctor can use to diagnose Wegener's granulomatosis, but blood tests are important to rule out other causes of illness and to determine which organ sites may be affected. Most blood tests can only suggest that a person has inflammation somewhere in the body. Anemia (low red blood cell count), elevated white blood cell count and platelet count, and an elevated sedimentation rate are commonly found in people with Wegener's granulomatosis. If the kidneys are involved, a health professional can see red blood cells and structures called red blood cell casts in the urine when viewed under a microscope, and the blood tests measuring kidney function may show abnormalities.

X-ray results can be very helpful in diagnosing Wegener's granulomatosis. People with lung problems will have abnormal chest x-rays. Computed tomography (CT) scans in people with sinus problems may show thickening of the sinus lining.

Many patients with active Wegener's granulomatosis have a blood test that shows the presence of a specific type of antibody called antineutrophil cytoplasmic antibodies (ANCA) (an antibody is a disease-fighting protein). Although a positive ANCA test is useful to support a suspected diagnosis of Wegener's granulomatosis, in most instances health professionals do not use it by itself to diagnose this disorder. The ANCA test may be negative in some patients with active Wegener's granulomatosis.

Currently, the only clear-cut way to diagnose Wegener's granulomatosis is by performing a biopsy (removing a tiny piece of tissue) of an involved organ (usually the sinuses, lung, or kidney). A health professional will examine tissue from the organ under the microscope to confirm the presence of vasculitis and granulomas (a specific type of inflammation), which together are features of Wegener's granulomatosis. A biopsy is very important both to confirm the presence of the disease and also to make sure other disorders that may have similar signs and symptoms are not present.

How is Wegener's Granulomatosis Treated?


With the appropriate treatment, the outlook is good for patients with Wegener's granulomatosis. In a study of 158 patients who were treated with prednisone and cyclophosphamide at the National Institutes of Health (NIH), 91 percent of them markedly improved. After 6 months to 24 years of follow-up, 80 percent of the patients survived.

In most cases, treatment consists of a combination of a glucocorticoid (a steroid) and a cytotoxic medicine. Although these medicines are helpful in treating Wegener's granulomatosis, patients and their doctors should be aware that they potentially have serious side effects. In many instances these can be minimized or prevented by careful monitoring by both the physician and patient.

Approximately half of people with Wegener's granulomatosis may experience a return of their disease. This occurs most frequently within two years of stopping medication, but can occur at any point both during treatment or after stopping treatment. Thus, it is extremely important that patients continue to see their doctors regularly, both while they are on these medicines, as well as after the medicines have been stopped.

Prednisone


Prednisone is the most common glucocorticoid that doctors use. Prednisone is similar to cortisol, the natural glucocorticoid hormone produced by the body. It is chemically different from the anabolic steroids that have been used by athletes and is given in doses much higher than the body normally produces. Doctors usually give prednisone as a single morning dose to try to imitate how the body normally secretes cortisol.

When the person's illness improves, the prednisone dose is gradually decreased and converted to an every other day dosing schedule, usually over a period of 3 to 4 months. With further improvement in the disease, prednisone is gradually decreased and discontinued completely after approximately 6 to 12 months.

When prednisone is taken by mouth, the body stops making its own natural cortisol. As the prednisone dose is gradually reduced, the body will resume making cortisol again. It is extremely important that prednisone never be stopped suddenly because the body requires prednisone (or cortisol) to function and may not be able to immediately make what it needs.

Prednisone can affect the body's ability to fight off infection. Patients should report immediately any symptoms of infection and, specifically, any fever to their doctors. Prednisone can also cause weight gain, cataracts, brittle bones, diabetes, and changes in mood and personality.

Cyclophosphamide


Cyclophosphamide (Cytoxan) is the most commonly used cytotoxic drug used to treat Wegener's granulomatosis. Patients take cyclophosphamide once a day by mouth and must take the drug all at once in the morning followed by drinking a large amount of liquid. Although the first dose of cyclophosphamide is based on the patient's weight and kidney function, the doctor may adjust the dosage based on blood counts, which are monitored closely to be sure that the white blood cell count is maintained at a safe level. In the original regimen, cyclophosphamide was continued for a full year beyond that point at which the disease is in remission. The dose of cyclophosphamide is then decreased gradually and eventually stopped. In more recent treatment approaches, cyclophosphamide is given until remission and then switched to another medicine such as methotrexate or azathioprine (discussed below).

Cyclophosphamide is a powerful medicine that keeps the immune system from working normally. The doctor must monitor patients carefully and perform blood tests frequently. Cyclophosphamide can cause an increased risk of infection, bone marrow suppression (lowering of blood counts), sterility, hemorrhagic cystitis (bleeding from the bladder), bladder cancer, as well as other serious side effects.

Methotrexate


Methotrexate has been studied at the NIH for the treatment of Wegener's granulomatosis since 1990. In people with active, but not immediately threatening, Wegener's granulomatosis, methotrexate has been used in combination with prednisone to bring about remission. Another way that it has been used is to maintain remission after a patient has initially received cyclophosphamide. Methotrexate is usually given for 1-2 years, after which time if people stay in remission, it is decreased and stopped.

Methotrexate is given once a week usually by mouth, but occasionally as an injection under the skin or in the muscle. People taking methotrexate need to have regular blood work to monitor their response and to watch for side effects.

The side effects of methotrexate include infection, lowering of the blood counts, nausea, soreness and ulceration of the mouth lining, irritation of the lungs (pneumonitis), and inflammation and scarring of the liver. People taking methotrexate cannot consume alcoholic beverages. Methotrexate cannot be given to people who have poor kidney function or who have underlying liver disease such as hepatitis.

Azathioprine


Azathioprine (also called imuran) is primarily used to maintain remission in people who have initially been treated and gone into remission with cyclophosphamide. It is taken once a day by mouth. Similar to methotrexate, it is usually given for 1-2 years after which time the dosage is lowered until it is stopped.

The side effects of azathioprine include infection, lowering of the blood counts, and rarely an allergic type reaction. In patients who receive azathioprine to prevent rejection of a transplanted organ, there has been a suggestion of an increased risk of blood cancers (leukemia and lymphoma) but it is not clear whether this risk exists in other situations. Azathioprine can be given to people with poor kidney function or liver disease.

Other medications for Wegener's Granulomatosis


During the course of treating Wegener's granulomatosis, other medications are often given to prevent medication side effects. These include

  • Trimethoprim/sulfamethoxazole (also called bactrim or septra) given three times a week to prevent Pneumocystis carinii infection (a lung infection)
  • A medication regimen is often given to prevent prednisone-related bone loss (osteoporosis)
  • Folic acid or folinic acid (also called leucovorin) are often given to patients taking methotrexate.

How to Prevent Wegener's Granulomatosis


Because the cause of this condition is unknown, it is not yet clear what you can do to prevent it.

Side effects of treatment for Wegener's granulomatosis


While taking medication, a patient with Wegener's granulomatosis needs careful and regular medical monitoring to maintain the best possible health. This is because the treatment may cause a wide range of unwanted side effects, including:
  • nausea
  • mouth ulcers
  • hair loss
  • oedema (fluid retention)
  • insomnia
  • unwanted weight gain
  • increased susceptibility to infection
  • cystitis (bladder inflammation)
  • easily broken bones
  • diabetes
  • cognitive changes such as mood swings
  • sterility
  • cancer of the bladder.
It is important to discuss potential side effects of your medication with the doctor. See your doctor immediately if you suspect that your medications may be causing adverse reactions. Your doctor may alter the dose of particular medications, usually over a period of time to reduce the risk of withdrawal symptoms, such as low blood pressure and dizziness.

Long-term outlook for Wegener's granulomatosis


There is no cure for Wegener's granulomatosis, but the long-term outlook, with appropriate medical treatment, is very good. In many cases, prompt treatment can bring about a remission, which means the person has no signs or symptoms of the disease. 

Relapses may occur after the end of medical treatment. In most cases, relapses occur some two years after treatment is stopped. Regular check-ups are important.