POLYARTERITIS NODOSA AND WEGENER'S GRANULOMATOSIS

WHAT ARE PAN AND WEGENER'S?

PAN and Wegener's are classified as vascular (vessel) diseases because 
they cause severe inflammation of the blood vessel walls, a condition 
called vasculitis.

The inflammation damages the lining of the blood vessels. As a result, 
the inflamed vessels narrow or close completely, causing the blood flow 
to slow down or even stop. Blockage of the blood supply prevents organs 
and tissues from functioning normally, which causes many of the symptoms 
of these diseases.

The symptoms of vasculitis can vary from one person to another, 
depending on which vessels are inflamed. Vessels throughout the body 
often are affected, and the symptoms are numerous.

PAN, Wegener's, and other types of chronic vasculitis are considered to 
be autoimmune diseases - that is, for reasons that are not well 
understood, the blood proteins (antibodies) and white blood cells 
(lymphocytes) of the immune system attack and damage one's own body 
tissues instead of attacking only foreign, infectious organisms.

Both PAN and Wegener's are rare conditions not easily diagnosed in their 
early stages, nor are they simple to treat. These diseases usually are 
chronic, lasting months or years and are characterized by an 
unpredictable course. After several months of feeling well, your 
symptoms may flare up unexpectedly. Repeated check-ups and continued 
vigilance by your doctor is very important.

Because diagnosing and treating PAN and Wegener's can be difficult, your 
doctor usually will consult with another doctor who has training and 
experience in treating vasculitis. A rheumatologist, or specialist in 
arthritis and inflammatory diseases of the body as a whole, can either 
confirm the diagnosis or suggest another and then outline a treatment 
plan. Even though the rheumatologist may not treat you throughout the 
entire course of the illness, he or she will be available for further 
consultation. A kidney specialist (nephrologist) or a lung specialist 
(pulmonologist) also may be consulted.

POLYARTERITIS NODOSA (PAN)

What is PAN?

PAN is a type of vasculitis that affects the small and medium-sized 
arteries throughout the body. Any tissues or organs can be involved, but 
PAN usually affects the kidneys, skin, intestines, joints, and nerves. 
PAN may vary from person to person; some patients have one system 
involved (nerves or skin, for example), and others may have intestinal 
or kidney involvement.

The general symptoms of PAN include fever, muscle aches, muscle 
weakness, weight loss, and general fatigue. Other symptoms depend on 
which organs and tissues are affected. Skin involvement can cause 
rashes, bruising, purplish or blue mottled skin over the lower legs, 
skin ulcers, and gangrene. Involvement of the gastrointestinal system 
can cause severe abdominal pain and even bowel rupture. If the kidneys 
are affected, high blood pressure and severe kidney disease may develop. 
Sudden pain and tingling in the hands, arms, feet, or legs can occur if 
the nerves are affected. Nerve involvement also can cause muscle 
weakness, loss of feeling, or even paralysis of the affected limb. 
Blockage of vital arteries can cause strokes or heart attacks.

Some people have a mild form of PAN that causes only a few problems. 
Other people have severe, widespread disease that causes serious 
problems. Therefore, it is important that PAN be diagnosed early, 
because with the proper treatment it usually can be controlled, and 
widespread damage to organs can be prevented.

Diagnosing PAN

PAN may be difficult to diagnose because it produces many different 
symptoms in different people. Unfortunately, there is no single 
laboratory test or x-ray that can give a definite diagnosis. Your doctor 
will ask questions about your symptoms and give you a physical 
examination. This helps rule out other causes of the symptoms. Next, 
your doctor usually will need to confirm that vasculitis is present.

Vasculitis in a medium-sized artery is detected in two ways: 1) A 
biopsy, or small sample of skin, muscle, kidney, or nerve, is removed 
and examined under a micro- scope. If vasculitis is present, the 
arteries in the sample will contain abnormal cells that appear only when 
inflammation is present. 2) Special x-ray studies of the blood vessels 
(angiogram) can show narrowing, irregularities, or blockages that are 
caused by vasculitis. In this procedure, a dye that shows up on x-rays 
is injected into a blood vessel, and several x-rays are taken as the dye 
flows through the vessels.

Your doctor may need to do both a biopsy and an angiogram to diagnose 
PAN. Other blood tests and x-rays usually are done to rule out other 
diseases that could cause similar symptoms.

Treatment of PAN

The treatment of PAN is directed at stopping the inflammation that is 
narrowing the blood vessels. If treatment is started early enough in the 
disease, normal blood flow can be restored to the involved tissues and 
organs, and irreversible damage often can be prevented.

Corticosteroids, such as cortisone, usually are prescribed first because 
they work quickly and are the most powerful anti-inflammatory drugs 
available. If you have a mild amount of inflammation, low doses of 
corticosteroids may be sufficient, but if the PAN is severe, high doses 
may be needed for several months to control the inflammation. 
Unfortunately, high doses taken over a period of months can produce 
serious side effects such as easy bruising, osteoporosis (thinning of 
the bones that can lead to fractures), cataracts, weight gain, a round 
face, high blood pressure, and susceptibility to infections.

A second type of drug called an immunosuppressive is often prescribed in 
addition to corticosteroids. As the name suggests, immunosuppressive 
drugs suppress the immune system, which controls the inflammation. In 
some situations, immunosuppressive drugs allow the dose of 
corticosteroids to be reduced and eventually stopped once the disease is 
controlled. Cyclophosphamide (Cytoxan) and azathioprine (Imuran) are the 
immunosuppressive drugs most commonly used to treat PAN, but others also 
are prescribed. Like corticosteroids, immunosuppressive drugs can cause 
serious side effects including a susceptibility to infections, anemia 
and other blood abnormalities, nausea and vomiting, hair loss, skin 
rash, kidney and bladder problems, and sterility. If you are taking 
cyclophosphamide, it is important to drink a lot of fluids (at least 
three liters or quarts of water a day) to prevent bladder irritation.

As long as you are taking either corticosteroids or immunosuppressive 
drugs, your doctor will monitor you closely for signs of problems. Blood 
tests will be necessary to detect low blood cell counts if you are 
taking immunosuppressives. It is important that you see your doctor 
regularly. Between these scheduled visits, call your doctor if symptoms 
of infection (such as fever) or other problems occur.

Outlook for People with PAN

Fortunately, most cases of PAN now are diagnosed before severe or 
irreversible organ damage has occurred. High doses of corticosteroids 
can prevent severe organ damage, and immunosuppressive drugs can keep 
the disease under control while the corticosteroids are gradually 
tapered. Corticosteroids may be necessary for only three to six months. 
Immunosuppressive drugs may be needed for several years. Once the 
disease is under control, the dose is tapered very slowly while the 
doctor watches for unexpected flare-ups. If a flare-up occurs, it may be 
necessary to start high doses of corticosteroids again and to increase 
the dose of the immunosuppressive drug.

It is very important for you and your family to be aware of the symptoms 
of PAN as well as the side effects of corticosteroids and 
immunosuppressive drugs. Being well-informed is one of the most 
important factors in controlling your disease.

WEGENER'S GRANULOMATOSIS

What is Wegener's?

Wegener's is a type of inflammation of small and middle-sized blood 
vessels. The inflammation is so destructive that it causes lumps of 
tissue (called granulomas) to form in the sinuses, nose, ears, and 
lungs. Wegener's also can affect small vessels throughout the body. The 
kidneys often are involved, and the skin, eyes, heart, and nervous 
system also can be affected.

Common early symptoms of Wegener's are pain in the sinuses and ears; 
nasal discharge; and nosebleeds. Other early symptoms include fever, 
fatigue, loss of appetite, weight loss, pain in the joints and muscles, 
skin rash, and redness and swelling in the eyes.

Other problems that may occur include a chronic cough (sometimes 
coughing up blood), breathing difficulties, skin ulcers, and weakness 
and numbness in the limbs. Kidney involvement is common, but usually 
causes no symptoms and therefore must be searched for by your doctor.

Diagnosing Wegener's

The doctor will ask questions about your symptoms and perform a physical 
examination. The diagnosis often is confirmed by taking a small sample 
(biopsy) of the inflamed tissue and examining it under a microscope. 
Usually, the biopsy is easy to get from inflamed areas in the 
nose or the skin, but sometimes a sample is needed from a lung or 
kidney. It often is possible to get a sample from the lung or kidney 
through a needle (needle biopsy), but sometimes surgery is necessary to 
get the sample.

In recent years, a new blood test called ANCA has become available to 
help confirm the diagnosis of Wegener's. (ANCA stands for 
Anti-Neutrophil Cytoplasmic Antibody, which is manufactured by the 
body's immune system.) Since most people with Wegener's produce ANCA, 
they usually have a positive ANCA test, especially when the symptoms 
worsen. A positive test is not 100 percent accurate, however, because 
some people with PAN or other types of vasculitis also test positive. 
Even so, the ANCA test is a big breakthrough for diagnosing Wegener's. 
The test also is helpful in monitoring treatment, since the amount of 
ANCA in the blood tends to fall in some patients as the disease gets 
better.

Treatment of Wegener's

Wegener's is treated with a combination of corticosteroids and 
immunosuppressive drugs. The corticosteroids control the inflammation, 
and the immunosuppressives appear to stop the growth of granulomas. The 
immunosuppressive drug most commonly used to treat Wegener's is 
cyclophosphamide (Cytoxan), but azathioprine (Imuran) also is 
prescribed.

When therapy is started, corticosteroids are given in high doses. 
Usually, the dose can be lowered after about two to four months and 
gradually tapered until only the immunosuppressive drug is needed. You 
may need to continue taking the immunosuppressive for several years, 
even after the symptoms disappear.

Both corticosteroids and immunosuppressive drugs can produce serious 
side effects. When a person takes high doses of corticosteroids for 
several months, easy bruising, osteoporosis (tidying of the bones, which 
can lead to fractures), cataracts, weight gain, a round face, high blood 
pressure, and susceptibility to infections can result. 
Immunosuppressives can cause anemia and other blood abnormalities, 
susceptibility to infections, nausea and vomiting, skin rash, sterility, 
and kidney and bladder problems. If you are taking cyclophosphamide, it 
is important to drink a lot of fluids (at least three liters or quarts 
of water a day) to avoid bladder irritation.

Recently, the combination antibiotic trimethoprim/sulfamethoxazole 
(Bactrim or Septra) was given to people with early, mild Wegener's. Some 
researchers reported that this drug worked well for some people, but 
other researchers did not find this drug to be very helpful. If your 
case of Wegener's is mild and in the early stage, your doctor may want 
you to try trimethoprim/sulfamethoxazole first. If you have a good 
response, then you may not need to take corticosteroids and 
immunosuppressives. However, these stronger drugs are necessary if you 
have widespread Wegener's or if your kidneys, lungs, or other organs 
already are damaged.

Outlook for People with Wegener's

Before it was known that cyclophosphamide could bring about dramatic 
improvements in people with Wegener's, this disease sometimes was 
disfiguring and often fatal. The extensive granuloma process in the 
nasal passages and sinuses often caused deformities, such as a collapsed 
bridge of the nose. But cyclophosphamide and other immunosuppressives 
prevent such deformities from occurring by stopping the granuloma 
process. In addition, these drugs save lives. Today, many people who had 
advanced Wegener's appear to be cured after several years of 
cyclophosphamide treatment.

As a routine test for monitoring people with Wegener's, the ANCA test 
may improve the outlook even more. Since an increased amount of ANCA in 
the blood may indicate a disease flare is about to occur, treatment can 
be started immediately to stop the flare before it causes any damage. It 
is important to point out that Wegener's is one disease where physicians 
have been able to improve the outlook greatly in the past 10 years. 

It is very important for you and your family to be aware of the symptoms 
of Wegener's, as well as the side effects of corticosteroids and 
immunosuppressive drugs. Being well-informed is one of the most 
important factors in controlling your disease.

COPING WITH PAN AND WEGENER'S

Because of the pain and unpredictability of PAN and Wegener's, most 
people will have difficulty coping at times. 

Learning to cope with these diseases or any other chronic disease 
requires accepting changes - in your relationships, your work habits, 
your leisure time activities, and sometimes even your appearance. All 
these changes may leave you sad, depressed, or angry.

It is important that you and your family learn as much as possible about 
your disease. Sometimes it helps to talk with a family member, a friend, 
or someone else who has a similar disease. A counselor, psychologist, or 
social worker may also help you develop better coping skills.