What is polyarteritis nodosa (PAN)?
Polyarteritis nodosa (PAN) is a rare disease that results from blood vessel inflammation ("vasculitis") causing injury to organ systems. The areas most commonly affected by PAN include the nerves, intestinal tract, heart, and joints. PAN can also affect the blood vessels to the kidney resulting in high blood pressure and damage to kidney function.
What is vasculitis?
Vasculitis is a general term that refers to inflammation of the blood vessels. When inflamed, the blood vessel may become weakened and stretch in size, which can lead to aneurysms, or become so thin that they rupture resulting in bleeding into the tissue. Vasculitis can also cause blood vessel narrowing to the point of closing off entirely so that organs become damaged from loss of oxygen and nutrients that were being supplied by the blood.
PAN exclusively affects medium sized blood vessels.
Who is affected by PAN?
PAN can occur in people of all ages, from children to the elderly and appears to affect men and women equally.
Symptoms and Causes
What causes polyarteritis nodosa (PAN)?
The cause of PAN is unknown. PAN is not a form of cancer, it is not contagious, and it does not usually occur within families. Evidence from research laboratories strongly supports that the immune system plays a critical role in PAN, causing blood vessel and tissue inflammation and damage. PAN is highly associated with hepatitis B infection. Since the hepatitis B vaccine was established, the rates of PAN have decreased significantly.
What are the symptoms of polyarteritis nodosa (PAN)?
Because many different organ systems may be involved, a wide range of symptoms are possible in PAN. Patients who have PAN may feel generally ill and fatigued, have fevers, or have loss of appetite and weight. They may have symptoms related to areas of involvement such as pain in the muscles and/or joints, skin sores that may appear as hard tender nodules or ulcers, abdominal pain or blood in the stools occurring as a result of intestinal tract involvement, or shortness of breath or chest pain from disease affecting the heart. High blood pressure is common in PAN and usually due to vasculitis decreasing blood flow to the kidneys. PAN may affect nerves and cause abnormal sensations, numbness or loss of strength. Any combination of these symptoms may be present.
Diagnosis and Tests
How is polyarteritis nodosa (PAN) diagnosed?
A doctor may suspect PAN based on information gathered from a variety of sources, including:
- Medical history to look for the presence of PAN symptoms.
- Physical examination to detect sites of organ involvement and to exclude other illnesses that may have a similar appearance.
- Blood tests and urinalysis to look for features that may suggest inflammation or sites of organ involvement.
- Imaging tests such as X-rays, computed tomography (CT) or magnetic resonance (MR) scans may show abnormalities in affected areas.
Once the diagnosis of PAN is suspected, confirmation of the diagnosis is usually pursued by obtaining an arteriogram or a biopsy. An arteriogram involves the injection of a dye into the blood stream that allows visualization of the blood vessels and may show aneurysms or blood vessel narrowing suggestive of vasculitis. Depending on the site of involvement, a biopsy of an affected area may be performed to try to confirm the presence of vasculitis within the tissue. Biopsies and arteriograms are only recommended for organ sites in which there are abnormal findings present by examination, laboratory tests, or other types of imaging studies.
Management and Treatment
How is polyarteritis nodosa (PAN) treated?
Medications that suppress the immune system form the foundation of treatment for PAN. There are a variety of immunosuppressive medications that are used in PAN, each of which has individual side effects.
People with PAN who have critical organ system involvement are generally treated with a corticosteroid such as prednisone or prednisolone combined with another immunosuppressive medication such as cyclophosphamide (Cytoxan®). Cyclophosphamide is given at high doses as a treatment for certain types of cancer and therefore is sometimes referred to as "chemotherapy." In cancer treatment, cyclophosphamide works by killing or slowing the growth of rapidly multiplying cancer cells. In vasculitis, cyclophosphamide is given at doses that are 10 to 100 times lower than those used to treat cancer. In this setting, its primary effect is to influence the behavior of the immune system in a manner that results in immunosuppression. In rare instances, people who do not have manifestations affecting the nervous system, heart, kidneys, intestinal tract or other features of severe disease might do well with corticosteroid therapy alone.
All immunosuppressive medications can have side effects. Monitoring for side effects plays a critical role in preventing or minimizing their occurrence. Each medication has a unique side effect profile that forms the basis for the monitoring plan. The fact that someone with PAN may initially tolerate treatment does not guarantee that the person will have the same degree of tolerance over time. This makes ongoing monitoring essential, and in some instances, monitoring for long-term effects may be important even after the medication is stopped.
The goal of treatment is to eliminate features of inflammation due to PAN. When that is achieved it is referred to as "remission." Once it is apparent that the disease is improving, doctors slowly reduce the corticosteroid dose and eventually hope to discontinue it completely. When cyclophosphamide is used, it is often only given until the time of remission (usually around 3-6 months), after which time it may be switched to another immunosuppressive agent such as methotrexate or azathioprine (Imuran®) to maintain remission. The treatment duration of the maintenance immunosuppressive medication may vary between individuals. In most instances, it is given for a minimum of 1 to 2 years before consideration is given for whether it would be appropriate to slowly reduce the dosage to discontinuation.
In people who have a PAN-like vasculitis that is associated with hepatitis B, antiviral medications used to treat the hepatitis form an important part of care. Immunosuppressive agents are often given initially to control the vasculitis but may be withdrawn more quickly than in other settings so as to allow the anti-viral medications a better chance to control the infection.
Outlook / Prognosis
What is the outlook for patients with polyarteritis nodosa (PAN)?
Because PAN is a rare disease, accurate statistics on overall outcome are only approximate. On average, after 5 years of illness, over 80% of people have survived the effects of PAN. How people with PAN do is strongly related to the severity of their illness. Although PAN can be a sudden and serious illness, many people with PAN do extremely well.
The best opportunity to minimize damage comes when treatment has been promptly initiated and is carefully monitored by a physician who is knowledgeable about PAN. Even patients who have the most severe PAN can achieve remission when treated promptly and followed closely.
After achieving remission, it is possible for the PAN to recur (referred to as a "relapse"). Estimates of the rate of relapse for PAN vary widely but range from 10 to 40%. Such relapses may be similar to what the person experienced at the time of their diagnosis or they may be different. The likelihood of experiencing a severe relapse can be minimized by promptly reporting any new symptoms to a physician, regular physician follow-up, and ongoing monitoring with laboratory tests. The treatment approach for relapses is similar to that of newly diagnosed disease, remission again being possible for most people with PAN.