Brief overview
- What is polyarteritis nodosa? Autoimmune disease in which inflammation of the small and medium-sized arteries occurs. If the blood vessels become blocked by a blood clot, serious complications such as a heart attack or stroke are imminent.
- Causes: Unknown
- Risk factors: viral infections such as hepatitis B or C.
- Symptoms: Fever, fatigue, weight loss, damage to skin and internal organs.
- Diagnosis: Tissue sample (biopsy), vascular examination (arterial angiography)
- Treatment: cortisone (corticosteroids) and drugs that suppress the immune system (immunosuppressants)
- Prevention: Hepatitis vaccination
What is PAN?
Polyarteritis nodosa (periarteritis nodosa, panarteritis nodosa, PAN) is a disease associated with inflammation of the small and medium-sized arteries. It can affect numerous organs and cause various symptoms. The name “Kussmaul-Maier disease” comes from the names of the physicians who first described the disease in 1866.
In PAN, mainly small and medium-sized arteries are affected: The inflammation affects all wall layers of the blood vessels and destroys them over time. As a result, bulges (aneurysms) and narrowing of the vessels (stenoses) form. If blood clots (thromboses) form in this area, the tissue behind the focus of inflammation is poorly supplied with blood and may die.
In principle, polyarteritis nodosa affects every organ, sometimes even several organs at the same time. However, PAN typically causes damage primarily to the arteries of the gastrointestinal tract, the musculature and the nervous system. If the change occurs in the skin vessels, inflammatory nodules strung together become visible, usually on the lower leg and forearms. A characteristic feature of PAN is that the pulmonary vessels are spared.
Without treatment, the disease is life-threatening. However, with appropriate therapy, most patients live permanently without symptoms.
Frequency
PAN is a very rare disease: out of one million people, about 1.6 develop polyarteritis nodosa each year. PAN diseases associated with hepatitis infections have decreased significantly in recent years. The reason for this is that hepatitis is becoming increasingly treatable.
Causes and risk factors
The cause of PAN is not yet fully understood. Doctors assume that several factors interact in the development of the disease.
In about 20 percent of all PAN patients, doctors find evidence of a previous infection with the hepatitis B virus, and much less frequently with hepatitis C. As a result of this infection, so-called “immune complexes” are formed. As a result of this infection, so-called “immune complexes” (compounds of viral components and antibodies) are formed, which are deposited in the vascular wall of small and medium-sized vessels, where they trigger an inflammation (immune complex vasculitis).
As a result, the tissue is severely damaged, leading to constriction or bulging of the vessel walls. If the affected vessel closes completely, the tissue behind it is no longer supplied with blood and dies (infarction).
Other – very rare – triggers for the formation of such immune complexes are the HI virus (HIV) and the parvovirus B19.
Even more rarely, the disease is associated with the use of certain medications or with congenital immunodeficiencies (weakened or absent immune defenses).
In most patients, however, the cause remains unclear. Doctors then speak of idiopathic polyarteritis nodosa (formerly also referred to as classic PAN or cPAN).
Symptoms
The further symptoms depend on which blood vessels are affected and which organs are damaged as a result. Since panarteritis can basically occur anywhere in the body, infarctions are possible in all regions of the body or organs.
Nervous system: Damage to the nerves causes pain and paralysis. This is the case in 50 to 70 percent of all PAN patients. Signs of a circulatory disorder of the brain are paralysis, speech disorders, dizziness, headaches, vomiting, seizures (epilepsy) or psychoses. If blood vessels of the brain are affected, a stroke may occur.
Musculature and skin: In 50 percent of cases, the musculature and skin are also affected. On the skin, small to pea-sized, bluish-reddish nodules (nodi) are usually palpable in the area of the elbows as well as the lower legs and ankles. These give polyarteritis nodosa its name.
Circulatory disturbances may cause severe tissue damage in the affected section (sores, dying fingers or toes). Another characteristic is a reticular, light purple discoloration of the skin (livedo racemosa).
Heart: In the majority of patients, the coronary arteries, which supply the heart with blood, are affected by the disease. Narrowing of the arteries causes symptoms such as chest pain or arrhythmia. In the event of a complete blockage, a heart attack is imminent.
Gastrointestinal tract: If PAN affects the gastrointestinal tract, the most common complaints are abdominal pain, diarrhea, bleeding in the intestines or jaundice (icterus).
Lungs: It is typical for polyarteritis nodosa that the lungs are rarely affected. However, blood clots may become lodged in the lungs and cause obstruction of pulmonary vessels (pulmonary infarction, pulmonary embolism).
Genitals: Men with PAN often suffer from testicular pain.
Diagnosis
Polyarteritis nodosa is a very rare disease that causes various symptoms. For this reason, the diagnosis is often made late. The first contact person when PAN is suspected is the internist or rheumatologist.
In a detailed initial consultation, the physician inquires about the current symptoms (medical history) and examines the patient for physical signs of the disease. If periarteritis nodosa is suspected, the physician performs further examinations.
These include:
Blood test
To rule out or confirm an infection with hepatitis viruses, the physician has the blood tested for corresponding antibodies.
Examination of the blood vessels (angiography)
With the help of an angiography, it is possible to visualize damage to the blood vessels, such as bulges or constrictions. For this purpose, the physician injects the patient with a contrast medium. The changes become visible during a subsequent X-ray examination. However, the disease cannot be definitively ruled out even if no aneurysms are visible.
Tissue sample (biopsy)
If changes are found in organs, the physician performs a biopsy. This involves taking a tissue sample from the affected organ and examining it under the microscope for typical changes.
ACR criteria for the classification of polyarteritis nodosa
All of the above examinations give the physician initial indications that PAN may be involved. However, specific tests that enable the physician to make a definite diagnosis of the disease do not exist. If other diseases that cause similar symptoms (such as rheumatoid arthritis or systemic lupus erythematosus) have been ruled out, the suspicion of PAN is confirmed.
- Weight loss since onset of disease over four kilograms not due to other diseases
- Typical changes in the skin (livedo racemosa)
- Testicular pain or swelling with unknown cause
- Muscle pain (myalgia), feeling of heaviness in the legs
- Nerve pain
- Diastolic blood pressure elevation > 90 mm Hg
- Serum creatinine elevation > 1.5 mg/dl
- Detection of hepatitis virus in serum
- Abnormalities in angiogram (aneurysm, occlusions)
- Typical changes in tissue sample (biopsy)
Treatment
How polyarteritis nodosa is treated depends on which organ is affected.
In acute disease, treatment is initially with high-dose cortisone (has a strong anti-inflammatory effect) and so-called immunosuppressants such as cyclophosphamide. They slow down the excessively working immune system. In severe cases, plasma exchange treatment is sometimes necessary. This involves filtering the immune complexes from the patient’s blood.
After acute therapy, patients receive somewhat milder drugs such as azathioprine or methotrexate (MTX), which also suppress the excessive immune system.
If an infection with hepatitis viruses is present at the same time, patients receive low-dose cortisone and antivirals such as interferon-alpha, vidarabine, lamivudine or famciclovir to inhibit viral replication.
Prognosis
Without therapy, polyarteritis nodosa is usually severe, and the prognosis in these cases is poor.
The prognosis has – with appropriate therapy – improved significantly in recent years. While the disease was usually fatal until about 25 years ago, the survival rate after five years is currently about 90 percent. The prognosis of PAN depends primarily on which organ is affected. If the kidneys, heart, gastrointestinal tract or nervous system are affected, the prognosis is somewhat worse.
In general, the earlier PAN is diagnosed and treated, the better organ damage can be prevented. In many cases, the symptoms even disappear completely.
Prevention
Since the causes of polyarteritis nodosa are not fully understood, no specific prevention is possible. However, vaccination against hepatitis B can reduce the risk of developing PAN.
