Vasculitis

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Vasculitis

Friday, 18 January 2008 21:00

Gene G Hunder, MD

UpToDate performs a continuous review of over 375 journals and other resources. Updates are added as important new information is published. The literature review for version 15.2 is current through April 2007; this topic was last changed on April 27, 2007. The next version of UpToDate (15.3) will be released in October 2007.

INTRODUCTION — The word vasculitis means inflammation of blood vessels. Blood vessels include the huge network of arteries and veins that deliver blood from the heart to all of the organs and tissues throughout the body, and then return the blood back to the heart.
Vasculitis can affect any blood vessel, although it seldom affects large veins. Inflammation can affect the lining of the vessels (endothelium) or the wall of an artery or vein. This can cause the vessel to become thickened, weakened, narrowed, or scarred (show figure 1). The damaged vessel may not function normally, which can affect blood flow to the tissues that the vessel normally serves. The damage caused by vasculitis may be reversible or it may be permanent. Damaged blood vessels can lead to decreased blood flow, partial or complete organ failure due to lack of blood flow, or bleeding into the skin or other part of the body due to rupture of the blood vessel wall.
Some types of vasculitis resolve without treatment while others require life long medications. Fortunately, treatments can usually control or minimize vessel damage in the short term. However, long-term side effects of these treatments are possible, and regular monitoring is important.

NORMAL BLOOD VESSELS — There are many different types of blood vessels in the body. Vessels are part of the large vascular system that includes large and medium sized arteries and smaller arterial branches (arterioles). The arterioles deliver oxygen and nutrients to a network of tiny vessels called capillaries. The capillaries drain into the venous system (veins) and help to remove waste products. The smallest veins are venules; these connect to form veins.

CAUSES — In most cases, the cause of vasculitis is unknown. A combination of factors likely sets the inflammatory process in motion. Vasculitis can occur in conjunction with another illness, such as lupus erythematosus or rheumatoid arthritis. (See "Patient information: Rheumatoid arthritis symptoms and diagnosis" and see "Patient information: Systemic lupus erythematosus (SLE)"). Sometimes, it is the result of a reaction to a drug or other substance (called hypersensitivity vasculitis). In still other cases, vasculitis occurs in conjunction with a viral illness, such as hepatitis B or C, HIV (the virus that causes AIDS), cytomegalovirus, Epstein-Barr virus, or Parvo B19 virus.

TYPES OF VASCULITIS — There are many different types of vasculitis, each of which is classified according to the type and location of the blood vessels that are involved. Some types of vasculitis are more serious than others. The names and characteristics of the most common types of vasculitis are listed below. These are organized according to the size of the blood vessel affected.

Large vessel vasculitis — Vasculitis that affects large arteries includes Takayasu arteritis and giant cell (temporal) arteritis.

Takayasu arteritis — Takayasu arteritis primarily affects the main artery that receives blood from the heart (the aorta) and its branches. The inflammation may be localized to a portion of the aorta, located in the chest or abdomen. In most cases arteries branching off the aorta are also involved.
In North America, only one to three cases are diagnosed per year per one million people. The disease usually affects women who are between 10 and 40 years old. Common symptoms include pain and weakness with use of the arms or legs (claudication). Other organs can also be affected, such as the intestines, which may cause abdominal pain after eating, and the heart, which may cause chest pain with exertion. (See "Patient information: Claudication").
Diagnosis is based upon testing of the arteries. Testing usually includes magnetic resonance imaging (MRI) or angiography or arteriography, which uses an injection of x-ray contrast dye to view the blood vessels with x-ray.
Giant cell arteritis — Giant cell arteritis can affect the aorta and its branches. Another name for giant cell arteritis is temporal arteritis, based upon the frequent involvement of the arteries of the face and scalp, particularly those near the temples. Giant cell arteritis is a disease that always affects people older than 50 years of age and is the most common form of vasculitis in this age group. Giant cell arteritis is closely linked to polymyalgia rheumatica (See "Patient information: Polymyalgia rheumatica and giant cell (temporal) arteritis").
Approximately 2 in 1000 people who are older than 50 years have giant cell arteritis at any one time. Common symptoms of giant cell arteritis include headache, tiring of jaw muscles during chewing, and visual changes or loss of vision.
The diagnosis is suspected based upon symptoms, a blood test called erythrocyte sedimentation rate or C-reactive protein, and a confirmatory biopsy of an artery (usually one or both temporal arteries).
Medium sized vessel vasculitis — Some types of vasculitis do not affect the aorta, but instead affect medium sized arteries. Polyarteritis is the term for vasculitis in people who do not have an associated condition (eg, lupus).
Medium sized vessel vasculitis can also develop in people with rheumatoid arthritis, systemic lupus, scleroderma (systemic sclerosis), hairy cell leukemia, and infectious forms of hepatitis (hepatitis B and C). (See "Patient information: Rheumatoid arthritis symptoms and diagnosis" and see "Patient information: Systemic lupus erythematosus (SLE)" and see "Patient information: Hepatitis B" and see "Patient information: Hepatitis C").

Polyarteritis nodosa — Polyarteritis nodosa causes inflammation of medium to small arteries. In the skin, the inflammation causes thickened nodular vessels that can be felt or sometimes seen or ulcers of the skin. Symptoms can occur as a result of changes in the blood vessels, eg, bleeding, decreased blood flow (ischemia), or irreversible damage to organs due to the absence of blood flow (infarction). Damage to the nerves of the arms or legs, to the kidneys, the intestines, and the heart may occur.
Polyarteritis nodosa is suspected when several organs of the body are damaged at the same time. Polyarteritis nodosa is an uncommon form of vasculitis. Arteriography or biopsy of an involved blood vessel is often necessary to confirm the diagnosis.

Kawasaki disease — Kawasaki disease is an arteritis of large, medium, and small arteries, particularly the coronary arteries. The disease mainly occurs in young children.
Isolated central nervous system vasculitis — Isolated central nervous system vasculitis (also called primary central nervous system vasculitis) affects medium and small arteries over a diffuse area of the central nervous system. It tends to occur in middle-aged persons. Common symptoms include headache, confusion, and stroke.
Small vessel vasculitis — Several different types of vasculitis can affect small vessels (eg, very small arteries, arterioles, capillaries, and small veins [venules]). These types may appear similar based upon biopsy results, although they can usually be distinguished from one another by other signs and symptoms.
Small vessel vasculitis may also be seen in some patients with rheumatoid arthritis, systemic lupus erythematosus, inflammatory muscle diseases (polymyositis and dermatomyositis), and Sjögren's syndrome. (See "Patient information: Rheumatoid arthritis symptoms and diagnosis" and see "Patient information: Systemic lupus erythematosus (SLE)" and see "Patient information: Myositis and other inflammatory diseases of the muscle" and see "Patient information: Sjögren's syndrome").

Churg-Strauss vasculitis — Churg-Strauss vasculitis occurs almost exclusively in people who have asthma. The condition often causes lung damage. Testing for blood antineurtrophil cytoplasmic antibodies (ANCA) is helpful. A biopsy of the lung or other involved tissue is the best test to confirm the diagnosis.
Wegener's granulomatosis — Wegener's granulomatosis usually affects the nose, sinuses, lungs, and kidneys. Most people with Wegener's granulomatosis have a positive ANCA blood test. A biopsy of the lining of the nose, sinus, part of a lung, or kidney can confirm the diagnosis.
A conditon known as microscopic polyangiitis, which can affect the kidneys, lungs, and other organs, appears to be similar to Wegener's granulomatosis. The two conditions are treated similarly. Patients with this type of vasculitis have a positive ANCA test, although the result is slightly different than that found in people with Wegener's granulomatosis.
Henoch-Schönlein purpura — Henoch-Schönlein purpura usually affects children, although it can occasionally cause disease in adults. Symptoms of this illness include abdominal and joint pain, a skin rash consisting of small, red to purple, slightly raised areas (show picture 1), and kidney involvement that causes the urine to appear bloody or darkly colored, like tea or coffee.
Henoch-Schönlein purpura is diagnosed based upon the symptoms and characteristic skin rash. A skin or kidney biopsy can confirm the diagnosis, especially if there are increased amounts of a specific class of antibody proteins (immunoglobulin A or IgA) in affected blood vessels or within the kidney.

Cryoglobulinemia — Cryoglobulins are a combination of the body's infection fighting proteins (antibodies, immunoglobulins) and their target proteins (antigens). When the serum (liquid part) of the blood is cooled, the complexes become so large that they form visible clumps (precipitates, cryoglobulins).
There are several types of cryoglobulinemia, and the symptoms depend upon the type. Common symptoms include muscle and joint pain, fatigue, and skin lesions. These symptoms may worsen after exposure to cold temperatures because the clumped immunoglobulins plug small blood vessels. People with cryoglobulinemic vasculitis often have chronic infections, the most common of which is caused by the hepatitis C virus. Two features of this type of vasculitis are the appearance of raised red bumps on the legs (show picture 2) and inflammation of the kidneys (glomerulonephritis).
Cryoglobulinemia is diagnosed based upon the results of a blood test for cryoglobulins, the characteristic appearance of the skin, or the results of a kidney biopsy. (See "Patient information: Renal biopsy").

Hypersensitivity vasculitis — Hypersensitivity vasculitis may develop after exposure to a medication. To be diagnosed with hypersensitivity type vasculitis, a person must have the following characteristics: Older than 16 years Recently used a medication that is capable of causing this type of reaction (show table 1) Have a skin reaction (called purpura, show picture 3 and show picture 4) Have a rash (show picture 5) Biopsy of a skin lesion showing a type of white blood cell (neutrophil) around an arteriole or venule

Behcet's disease — Behcet's disease is a chronic, relapsing, inflammatory disease that causes recurrent oral ulcers, and may also cause genital ulcers, eye disease, skin lesions, neurologic disease, vascular disease, and arthritis. It affects both small and large vessels, which can lead to vessel blockage, aneurysm (weakening of the vessel wall), and thrombus (blood clot) formation (show table 2).
The diagnosis of Behcet's disease is based upon a person's signs and symptoms (show table 3). Blood tests may be used, although no test is available to determine for certain if Behcet's is present.
The optimal treatment depends upon the type of organ system involved and the severity of disease within that organ system. Because many patients have more than one organ system involved, treatment is often guided by the degree of disease severity in the most critical organ.

SYMPTOMS — Symptoms vary from one patient to another and depend upon the type of vasculitis. Some common symptoms include: Fatigue Weakness Fever Muscle and joint pain Lack of appetite and weight loss Abdominal pain Kidney problems (bloody urine, dark urine) Nerve problems (numbness, weakness, pain)
Even if the underlying vasculitis resolves, some problems, such as numbness or pain in the fingers and toes, may take months to disappear while other problems may be permanent.

DIAGNOSIS — It can be difficult to diagnose vasculitis because a person's symptoms may suggest a number of other illnesses. The clinician will begin with a careful history and physical examination, which may be able to detect signs of organ problems that suggest vasculitis.
The diagnostic tests that are used to diagnose vasculitis vary widely depending on the type of vasculitis that is suspected. Laboratory tests can help to determine if organs are affected. Tests may include those that examine muscle, liver, or kidney function. Other common tests include blood tests, urinalysis, chest x-ray, and electrocardiogram. Tests of lung function may be needed in some cases. Patients with evidence of nerve or muscle involvement may undergo nerve conduction studies and an electromyogram (a test of muscle function). To perform electromyography, a small needle is inserted through the skin into a muscle in several locations (usually the arms and legs). The needle is connected to a recording device that displays the muscle's electrical activity at rest and in response to contraction. The electrical activity may also be heard as a static-type noise through a speaker. Tissue biopsy is a critical test in the diagnosis of vasculitis. During a biopsy, the clinician removes a small piece of tissue from an area. This tissue is then examined with a microscope. An arteriogram may be used to examine larger vessels. This test involves injecting dye into the arteries, which makes them visible on x-ray. MRI or ultrasound examinations may also be helpful.
TREATMENT — The exact treatment of the other types of vasculitis will depend upon the specific type of vasculitis and the areas/organs that are involved.

General measures — Treatment may include one or more of the following measures. Use of steroids, such as prednisone. Steroids may be taken by mouth in some cases; high doses may be given into a vein. Because there are risks associated with prolonged use of steroids, the smallest possible dose is used for the shortest possible time. The dose is generally decreased slowly over a period of days or weeks. Some people require long-term steroids to control symptoms and prevent worsening of their condition. Close monitoring for possible side effects of steroids (diabetes, weight gain, bone thinning) is needed. For more serious types of vasculitis, a treatment that strongly suppresses the immune system is needed. This type of treatment is known as cytotoxic treatment. One cytotoxic medication, cyclophosphamide, has dramatically improved the outlook for patients with some types of vasculitis. Cytotoxic treatments can be used along with steroids, and may be taken by mouth every day or given into a vein every three to four weeks. Treatment is usually continued until the disease activity is minimal (called remission). Serious side effects (eg, low blood cell counts, cancer) can develop as a result of cytotoxic treatment. As a result, close monitoring is required. Azathioprine and methotrexate are immunosuppressive medications that are not as potent as cytotoxic treatments. These treatments have been used for less severe forms of vasculitis and as maintenance therapy after remission has been induced with cyclophosphamide.
Hypersensitivity vasculitis treatment — In hypersensitivity vasculitis, stopping the medication that caused the vasculitis is usually sufficient to resolve the problem. Some patients may need a short course of steroid therapy. Others benefit from nonsteroidal antiinflammatory drugs such as ibuprofen.

OUTCOME — The limited data available reveal a good outcome for many patients with vasculitis (show table 4). It is important to remember that discussions of outcomes are based upon averages; these averages do not necessarily predict how long an individual patient will survive. Most cases of pure hypersensitivity vasculitis resolve spontaneously when the trigger is identified and eliminated. Patient with giant cell arteritis who receive appropriate treatment have no overall increased risk of death compared to other people of the same age group. Henoch-Schönlein purpura resolves almost universally in all patients, although the course may be more severe in the few adults with this vasculitis. Polyarteritis nodosa, one of the most worrisome types of vasculitis, is associated with a 5-year survival rate of around 80 percent. This means that at 5 years after treatment, approximately 80 percent of people are alive. Survival is better among those with limited organ involvement. Patients with Wegener's granulomatosis who are treated with cyclophosphamide have a 5-year survival of approximately 80 percent; some long term studies show that 88 percent of patients are still alive 12 years after diagnosis. More than 90 percent of people who are treated with cyclophosphamide have remission of their disease.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html) American Academy of Family Physicians
11400 Tomahawk Creek Parkway Leawood, KS 66211-2672 (913) 906-6000 (www.aafp.org) National Institute of Arthritis and Musculoskeletal and Skin Diseases
(www.niams.nih.gov) National Institutes of Health 1 AMS Circle Bethesda, MD 20892-3675 phone: 301-495-4484 American College of Rheumatology
(www.rheumatology.org) 1800 Century Place, Suite 250 Atlanta, GA 30345 phone: 404-633-3777 fax: 404-633-1870
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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Hunder, GG, Arend, WP, Bloch, DA, et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Introduction. Arthritis Rheum 1990; 33:1065. 2. Langford, CA, Klippel, JH, Balow, JE, et al. Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 2: Inflammatory bowel disease, systemic vasculitis, and therapeutic toxicity. Ann Intern Med 1998; 129:49. 3. Schmidt, WA. Use of imaging studies in the diagnosis of vasculitis. Curr Rheumatol Rep 2004; 6:203. 4. Langford, CA. Chronic immunosuppressive therapy for systemic vasculitis. Curr Opin Rheumatol 1997; 9:41. 5. Weyand, CM, Goronzy, JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003; 349:160.