Vasculitides

Definition

Vasculitides is the plural of the word vasculitis, which may be used to describe any disorder characterized by inflammation of the blood or lymph vessels. Vasculitis is not a distinctive disease in its own right, but rather a symptom or characteristic of a number of different diseases. It can affect any type or size of blood vessel—large arteries and veins as well as arterioles, venules, or capillaries. The term juvenile vasculitides is sometimes used to refer to a group of disorders that primarily affect children and adolescents. These disorders vary widely in their severity as well as the specific blood vessels and organs affected. Some are mild and may resolve even without treatment, while others are potentially life-threatening. The most common childhood vasculitides are Kawasaki syndrome (sometimes called Kawasaki disease) and Henoch-Schönlein purpura.

The most widely used classification scheme for the vasculitides was first proposed at an international conference in 1994. It classifies these disorders according to the size of the blood vessels involved:

• Large-sized vessel vasculitis. This category includes two disorders, only one of which—Takayasu arteritis (TA)—is found in children and adolescents.
• Medium-sized vessel vasculitis. This category includes infantile polyarteritis nodosa (IPAN) and Kawasaki disease.
• Small-sized vessel vasculitis. The disorders in this category include Henoch-Schönlein purpura (HSP) and Wegener's granulomatosis.

Description

Vasculitis may damage blood vessels in two different ways. In some cases the inflamed tissue becomes weakened and stretches, producing a bulge in the wall of the vessel known as an aneurysm. The aneurysm may eventually rupture or burst, allowing blood to escape into nearby tissues. In other cases, the inflammation causes the blood vessel to narrow, sometimes to the point that blood can no longer flow through the vessel. When enough of the larger vessels supplying a specific organ or other part of the body are closed by inflammation, the tissue that is starved for blood may die. The area of dead tissue is called an infarction or infarct.

The early symptoms of vasculitis frequently include fever , weakness, loss of appetite, weight loss, tiring easily, pains in the muscles or joints, and swollen joints. Some of the childhood vasculitides affect the skin, producing rashes , ulcers, or reddish-purple spots known as purpura. Others affect the lungs, digestive tract, kidneys, liver, nervous system, eyes, or brain, resulting in symptoms ranging from pain in the abdomen, diarrhea , coughing, or high blood pressure to shortness of breath, visual disturbances, headache or fainting, and numbness in the limbs. The specific symptoms of the more common childhood vasculitides are described in more detail below.

Transmission

Some of the childhood vasculitides may be preceded and possibly triggered by infectious diseases. In addition, Kawasaki disease sometimes occurs in epidemics, such as those reported in Japan in 1979, 1982, and 1985. No epidemics, however, have been reported since 1985.

Demographics

Most vasculitides are relatively rare disorders; one source estimates that about 100,000 persons (including adults as well as children and adolescents) are hospitalized each year in the United States for treatment of vasculitis. Although this number is small compared to the number of those treated for cancer or diabetes, the vasculitides can nonetheless have a significant financial and emotional impact on the families of children diagnosed with them.

The demographics of specific childhood vasculitides are as follows:

• Henoch-Schönlein purpura (HSP). HSP most commonly affects children between the ages of three and 12 years. The sex ratio is about 1.5–2 males for every one female. The disease is more common in North America between November and January; it is estimated to affect 14 or 15 children per 100,000. About 50–60 percent of children with HSP were diagnosed with strep throat or another upper respiratory infection two to three weeks before the onset of the vasculitis.
• Kawasaki disease. Kawasaki disease affects between one and three children per 10,000 in the United States each year. It is much more common in Japan, striking one child per thousand below the age of five. In the United States, Kawasaki disease is more common among children of Japanese descent than among children from other racial or ethnic backgrounds. It is also more likely to affect African Americans than Caucasians. The sex ratio is about 1.5 males for every one female. Kawasaki disease is primarily a disease of younger children; the average age at onset is 18 months, with 80 percent of cases found in children younger than five years.
• Infantile polyarteritis nodosa (IPAN). IPAN is a rare disease, and is sometimes described as a severe variant of Kawasaki disease. The incidence of IPAN in the United States is uncertain as of the early 2000s, primarily because of disagreements among doctors about the classification of childhood vasculitides; the most common figure given is 0.7 cases per 100,000 children. The first known case of IPAN was reported in London in 1870, although polyarteritis nodosa in adults was first described in 1852. Like Kawasaki disease, IPAN is more common in children of Asian descent. The male to female ratio is not known for certain, but is thought to be about two to one.
• Takayasu arteritis (TA). TA, which was first described by a Japanese ophthalmologist in 1908, is primarily a disease of adolescent and young adult women, although it has been diagnosed in children as young as six months. TA is relatively rare, affecting about 2.6 individuals per million. In the United States it is most common in young women of Japanese descent, with a male to female ratio of one to eight. In India, however, TA is more commonly associated with tuberculosis , and the sex ratio is two females for every one male.
• Wegener's granulomatosis. Wegener's granulomatosis is also a rare disease, diagnosed in one to three individuals per 100,000, with only 3 percent of these cases found in people below 20 years of age. It is, however, one of the most serious vasculitides. The male to female ratio is two to one.

Causes and symptoms

Causes

There is no single disease process that underlies all the childhood vasculitides. Various causes have been proposed for specific disorders.

• Henoch-Schönlein purpura. Although the ultimate cause of HSP was unknown as of 2004, the disease is preceded by an acute upper respiratory infection in at least half the children diagnosed with it. In other cases HSP appears to be triggered by an immune complex reaction to certain vaccines (most commonly vaccines for typhoid, measles , yellow fever, or cholera) or medications (most commonly penicillin, erythromycin, quinidine, or quinine). A characteristic finding in children diagnosed with HSP is higher levels of immunoglobulin A (IgA) in the blood and deposits of IgA on the walls of the child's blood vessels.
• Kawasaki disease. It is thought that an infectious organism of some kind is the cause of Kawasaki disease, although no specific virus or bacterium has been identified as of 2004. The disease has been linked to a variety of disease agents, including parvovirus B19, HIV infection , measles, influenza viruses, rotaviruses, adenoviruses, Klebsiella pneumoniae, and Mycoplasma pneumoniae. Some doctors think that genetic and immunologic factors are involved as well as an infectious organism.
• Infantile polyarteritis nodosa. As with Kawasaki disease, various infectious organisms have been proposed as the cause of IPAN, including hepatitis B virus, Epstein-Barr virus (EBV), various retroviruses, streptococci, and even a virus usually found in cats. None of these viruses or bacteria has been found in all patients with IPAN, however. Another theory is that IPAN is an immune complex disease, but its trigger had not been identified as of 2004.
• Takayasu arteritis. The cause of TA is unknown as of the early 2000s but may involve genetic factors, as the disease has been reported in identical twins.
• Wegener's granulomatosis. The cause of Wegener's granulomatosis was not known as of 2004. As with other childhood vasculitides, various disease organisms (including fungi as well as bacteria or viruses) have been suggested as the cause, but none have been definitely identified. A genetic cause seems unlikely, as it is unusual for two people in the same family to develop the disease.

Symptoms

The early symptoms of the childhood vasculitides are often difficult to distinguish from those of other illnesses. This section will focus on the symptoms specific to each disease.

• Henoch-Schönlein purpura (HSP). HSP is an acute but self-limited illness characterized by a low-grade fever (around 100.4°F[38°C]), purpura, joint pains (usually in the ankles and knees), abdominal pain, bleeding in the digestive tract, and inflammation of the kidneys. Boys with HSP often have inflammation of the testicles.
• Kawasaki disease. Kawasaki disease has three stages: an acute stage lasting about 11 days, characterized by a high fever (over 104°F [40°C]), strawberry tongue and cracked lips, conjunctivitis , involvement of the liver, kidneys, and digestive tract, and inflammation of the heart muscle; a subacute phase lasting about three weeks, characterized by irritability, loss of appetite, the peeling of skin from the finger tips, and the development (in about 20 percent of patients) of aneurysms in the coronary artery; and a convalescent phase marked by expansion of the aneurysms and possible heart attack. As of the early 2000s, Kawasaki disease is the leading cause of acquired heart problems for children in the developed countries.
• Infantile polyarteritis nodosa. The early symptoms of IPAN are nonspecific, usually including fever, loss of appetite, weight loss, and pain in the abdomen. The disease is most likely to affect the kidneys, heart, or liver. Depending on the organ(s) involved, the child may develop aneurysms in the arteries supplying the kidneys, kidney failure, aneurysms in the coronary artery, congestive heart failure, massive bleeding in the digestive tract, aneurysms in the arteries supplying the brain, and stroke . About half of patients with IPAN develop pains in the joints or skin rashes; boys frequently have pain in the testicles.
• Takayasu arteritis. Takayasu arteritis is a chronic inflammatory disorder that affects the aorta (the large artery that leaves the heart) and its major branches. Its early symptoms include fever, weight loss, and a general feeling of tiredness. The disease may not be diagnosed for months or even years, however. The inflammation of the aorta eventually leads either to the formation of aneurysms or the narrowing or complete blocking of the blood vessels. The patient may feel aching or pain in parts of the body affected by inadequate blood supply, such as aching in the legs while walking or cramping sensations in the abdomen after meals. In rare cases, the patient may suffer a heart attack or stroke. The patient may develop high blood pressure if the blood supply to the kidneys is affected. TA is sometimes called pulseless disease because the doctor may not be able to detect the pulse on one side of the patient's body. Another diagnostic clue is a significant difference (greater than 30 mm Hg) in the blood pressure on the right and left sides of the body.
• Wegener's granulomatosis. Wegener's most commonly affects the upper respiratory tract, the eyes, ears, kidneys, and skin. The disease is called a granulomatosis because it is characterized by the formation of granulomas, which are small lumps or nodules of inflammatory cells in the patient's tissues. The patient may have recurrent ear infections that are slow to heal, inflammation of the tissues inside the eye, inflamed sinuses, nosebleeds, coughing up blood, narrowing of the windpipe, and saddle nose, which is a deformity caused by the collapse of cartilage inside the nose. The patient may also have joint pains, loss of appetite, skin lesions, and fever. Vasculitis associated with Wegener's may lead to a heart attack. If untreated, the disease eventually progresses to kidney failure and death.

When to call the doctor

Although not all children who are eventually diagnosed with vasculitis will have all of the following signs and symptoms, parents should consult the doctor if most are present:

• The child's symptoms are constitutional; that is, they affect his or her overall physical health on a basic level. Malaise (a general feeling of physical discomfort), loss of appetite, fever, and loss of energy are examples of constitutional symptoms.
• The symptoms involve more than one organ or organ system.
• The child has noticeable purpura.
• The child has tingling or other unusual sensations followed by numbness in certain parts of the body.

Diagnosis

The diagnosis of vasculitis is complicated by several factors. To begin with, many of the early symptoms of the childhood vasculitides are not specific to these disorders and may have a wide range of other possible causes. In many cases the doctor may not be able to make the diagnosis until specific organs or organ systems are affected. The doctor will begin by ruling out such other possible diagnoses as bacterial or viral infections, collagen vascular disease, hypersensitivity reactions, and malignant tumors.

Another factor that complicates diagnosis is that the various childhood vasculitides have overlapping symptom profiles. Although lists of diagnostic criteria have been drawn up for the various disorders in this group, some patients do not meet the full criteria of any one disorder.

The first step in diagnosis is taking a careful history. The child's doctor may be able to narrow the diagnostic possibilities on the basis of the patient's age, sex, ethnicity, and a history of recent vaccinations or upper respiratory infections. The doctor will also ask whether the child is experiencing fever, abdominal cramping, diarrhea, or pains in the muscles and joints. The second step is a general physical examination. Several of these disorders affect the circulation or eyes as well as the skin. For example, Takayasu arteritis affects the patient's pulse and blood pressure, as well as producing small hemorrhages in the retina of the eye, while Kawasaki disease is characterized by conjunctivitis (inflammation of the tissues lining the eyelids). The doctor will examine the child's skin for purpura, other skin rashes or ulcers, reddening or swelling of the skin, and will note the locations of these abnormalities. In most cases the doctor will refer the child to a specialist for further evaluation. The specialist may be a pediatric rheumatologist, cardiologist, neurologist, or specialist in infectious diseases.

Laboratory tests for vasculitis include blood and urine tests. The blood tests include a complete blood count, a blood serum chemistry panel, erythrocyte sedimentation rate (ESR), tests for rheumatoid factor and circulating immune complexes, and tests for antineutrophil cytoplasmic antibodies (c-ANCA and p-ANCA). Urinalysis is done to evaluate kidney function. The doctor may also order skin, muscle, lung, or sinus biopsies in order to distinguish among the various childhood vasculitides.

Imaging studies that are used to diagnose the various childhood vasculitides include chest x rays or CT scans of the sinuses (Wegener's granulomatosis); CT scan of the aorta, angiography or ultrasonography (Takayasu's arteritis); arteriography or echocardiography (IPAN); chest x ray and echocardiography (Kawasaki disease); chest x ray, abdominal ultrasound, or barium contrast study of the digestive tract (Henoch-Schönlein purpura).

Treatment

The treatment of children with one of these disorders is highly individualized; it is tailored to the specific organs affected and the child's overall condition. Henoch-Schönlein purpura usually resolves on its own without any specific therapy. The general goals of treatment for vasculitis are to reduce inflammation in the affected blood vessels; maintain an adequate blood supply to the vital organs and skin; and monitor the side effects of the medications given to treat vasculitis.

Medications

Most patients with vasculitis will be given corticosteroids (usually prednisone) to reduce joint pain if present and inflammation in the blood vessels. Other types of drugs that are commonly used are the immunosuppressants (usually cyclophosphamide, methotrexate, azathioprine, or etanercept) and anticoagulants (usually heparin). Immunosuppressants are drugs that are given to treat inflammation by lowering the intensity of the body's reaction to allergens and other triggers, while anticoagulants are given to prevent blood clots from forming and blocking blood vessels that have already been narrowed by inflammation. Children with muscle or joint pain may be given nonsteroidal anti-inflammatory drugs , or NSAIDs, many of which are available without a prescription. An antibiotic (usually trimethoprim-sulfamethoxazole) is sometimes given to children with Wegener's granulomatosis to control flares, or recurrences of the disease.

Surgery

Patients with Takayasu arteritis often require surgical repair of damaged arteries. The most common procedures used are balloon angioplasty or stenting. Stents are small metal tubes or wires that are inserted into damaged blood vessels to hold them open. In severe cases, the damaged section of the artery may have to be removed completely and replaced with a graft made from an artificial material.

Alternative treatment

There is little information about the use of alternative treatments for vasculitides in children, most likely because the disorders in this category are relatively uncommon and vary widely with regard to the organ systems affected, symptom severity, and prognosis. One Chinese medical journal has reported on the benefits of treating children with Henoch-Schönlein purpura with a remedy made from colquhounia root, while a team of Dutch researchers has observed that acupuncture appears to be effective in reducing the inflammation associated with vasculitis. The researchers noted, however, that large randomized trials comparing acupuncture with mainstream treatments had not been undertaken as of 2004.

Some herbal preparations have been associated with harmful effects on the heart and circulatory system; however, the cases that have been reported mostly involve either contaminated or adulterated herbal products, or interactions between prescription medications and herbal preparations. The herbs most frequently mentioned in these case reports are aconite, ephedra, and licorice. The extent of the problem is not known as of the early 2000s because no large-scale analyses have been done. In any event, however, parents should never give a child a herbal remedy without first consulting the child's doctor, whether or not the child is taking prescription drugs.

Nutritional concerns

Children who develop high blood pressure with one of these disorders are usually placed on a low-sodium diet.

Prognosis

The prognoses for the childhood vasculitides vary widely depending on the disease and the extent of organ involvement. In general, children whose lungs or kidneys are affected have poorer outcomes.

• Henoch-Schönlein purpura. The prognosis for children with HSP is generally good, as the disease usually goes away by itself even without treatment; however, about a third of patients have recurrences.
• Kawasaki disease. Patients who are treated promptly have a good prognosis. The mortality rate in the early 2000s is estimated at 0.1–2 percent.
• Infantile polyarteritis nodosa. IPAN has a poor prognosis even when treated aggressively; the 10-year survival rate for this vasculitis is only 20 percent.
• Takayasu arteritis. TA is a chronic disorder with a high rate of relapse; the 15-year survival rate is about 95 percent.
• Wegener's granulomatosis. Untreated Wegener's is fatal, usually within five months. With treatment, about 87 percent of patients have a remission of the disease, but 53 percent have recurrences.

Prevention

Apart from minimizing a child's exposure to strep throat and similar upper respiratory infections, there is nothing that parents can do to prevent vasculitis in children, in that the cause(s) of these disorders are still unknown.

Parental concerns

The impact of childhood vasculitis on a child's family varies widely, depending on the child's age at onset, the specific symptoms of the disorder, its severity, the types of medications or other treatments that are needed, and the prognosis. Parents should work closely with the child's pediatrician and other specialists who may be involved to monitor the child's progress through regular follow-up appointments. The child's primary doctor can usually provide advice regarding such concerns as medication side effects, limitations on the child's activities if any, and explaining the disease to the child and other family members.

See also Conjunctivitis; Kawasaki syndrome.

KEY TERMS

Aneurysm —A weakened area in the wall of a blood vessel which causes an outpouching or bulge. Aneurysms may be fatal if these weak areas burst, resulting in uncontrollable bleeding.

Aorta —The main artery located above the heart that pumps oxygenated blood out into the body. The aorta is the largest artery in the body.

Conjunctivitis —Inflammation of the conjunctiva, the mucous membrane covering the white part of the eye (sclera) and lining the inside of the eyelids also called pinkeye.

Flare —A sudden worsening or recurrence of a disease.

Granuloma —An inflammatory swelling or growth composed of granulation tissue

Henoch-Schönlein purpura —A syndrome sometimes classified as a hypersensitivity vasculitis, associated with a variety of digestive symptoms, pain in the joints, and kidney involvement. Purpura comes from the Latin word for "purple" and refers to the reddish-purple spots on the skin caused by leakage of blood from inflamed capillaries.

Infarct —An area of dead tissue caused by inadequate blood supply.

Kawasaki syndrome —A syndrome of unknown origin that affects the skin, mucous membranes, and the immune system of infants and young children. It is named for the Japanese pediatrician who first identified it in 1967.

Malaise —The medical term for a general condition of unease, discomfort, or weakness.

Rheumatologist —A doctor who specializes in the diagnosis and treatment of disorders affecting the joints and connective tissues of the body.

Saddle nose —A sunken nasal bridge.

Stent —A slender hollow catheter or rod placed within a vessel or duct to provide support or to keep it open.

Strawberry tongue —A sign of scarlet fever in which the tongue appears to have a red coating with large raised bumps.

Takayasu arteritis —A disease in which the aorta and its major branches become inflamed. It is often accompanied by high blood pressure, an abnormal pulse, and visual symptoms.

Vasculopathy —Any disease or disorder that affects the blood vessels.

Resources

BOOKS

"Vasculitis." Section 5, Chapter 50 inThe Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

"Wegener's Granulomatosis." Section 5, Chapter 50 inThe Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

PERIODICALS

Burns, J. C., and M. P. Glode. "Kawasaki Syndrome." Lancet 364 (August 7, 2004): 533–544.

Ernst, E. "Cardiovascular Adverse Effects of Herbal Medicines: A Systematic Review of the Recent Literature." Canadian Journal of Cardiology 19 (June 2003): 818–827.

Miyata, T., O. Sato, H. Koyama, et al. "Long-Term Survival After Surgical Treatment of Patients with Takayasu's Arteritis." Circulation 108 (September 23, 2003): 1474–1480.

Zhou, J. H., A. X. Huang, and T. L. Liu. "Clinical Study on Treatment of Childhood Henoch-Schonlein Purpura Nephritis with Colquhounia Root Tablet." Zhongguo Zhong Xi Yi Jie He Za Zhi 24 (May 2004): 418–421.

Zijlstra, F. J., I. van den Berg-de Lange, F. J. Huygen, and J. Klein. "Anti-Inflammatory Actions of Acupuncture." Mediators of Inflammation 12 (April 2003): 59–69.

ORGANIZATIONS

American College of Rheumatology (ACR). 1800 Century Placce, Suite 250, Atlanta, GA 30345-4300. (404) 633-3777. Fax: (404) 633-1870. <http://www.rheumatology.org>.

Arthritis Foundation. P. O. Box 7669, Atlanta, GA 30357-0669. (800) 283-7800. Web site: <http://www.arthritis.org>.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). 1 AMS Circle, Bethesda, MD 20892-3675. (301) 495-4484 or (877) 22-NIAMS. Fax: (301) 718-6366. Web site: <http://www.niams.nih.gov>.

National Institute of Neurological Disorders and Stroke (NINDS). National Institutes of Health. 9000 Rockville Pike, Bethesda, MD 20892. (301) 496-5751. Web site: <http://www.ninds.nih.gov>.

WEB SITES

Cleveland Clinic. Vasculitis: What You Need to Know. April 18, 2003. [cited August 17, 2004]. Available online at: <http://www.clevelandclinic.org/health/health-info/docs/0700/0746.asp?index=4969>.

Hom, Christine, MD. "Takayasu Arteritis." eMedicine. December 23, 2003 [cited August 18, 2004]. Available online at: <http://www.emedicine.com/ped/topic1956.htm>.

Hom, Christine, MD. "Vasculitis and Thrombophlebitis." eMedicine. February 14, 2003 [cited August 17, 2004]. Available online at: <http://www.emedicine.com/ped/topic2390.htm>.

Johns Hopkins Vasculitis Center. What is Vasculitis? 1998–2004. [cited August 18, 2004]. Available online at: <http://vasculitis.med.jhu.edu/whatis/whatis.html>.

Matteson, Eric L., MD. A Puzzler Among Rheumatic Diseases. American College of Rheumatology, 2004. [cited August 18, 2004]. Available online at: <http://www.rheumatology.org/public/usatoday/vasculitis.asp>.

Person, Donald A., MD. "Infantile Polyarteritis Nodosa." eMedicine. May 22, 2002 [cited August 18, 2004]. Available online at: <http://www.emedicine.com/ped/topic1180.htm>.

Scheinfeld, Noah S., MD, Elena L. Jones, MD, and Nanette Silverberg, MD. "Henoch-Schoenlein Purpura." eMedicine. May 19, 2004 [cited August 18, 2004]. Available online at: <http://www.emedicine.com/ped/topic3020.htm>.

Scheinfeld, Noah S., MD, and Nanette Silverberg, MD. "Kawasaki Disease." eMedicine. June 6, 2003. [cited August 23, 2004]. Available online at: <http://www.emedicine.com/ped/topic1236.htm>.

OTHER

National Institute of Arthritis and Musculoskeletal and Skin Disorders (NIAMS). NIH Pediatric Rheumatology Clinic. NIH Publication No. 03-5156. Bethesda, MD: NIAMS, 2003.

National Institute of Neurological Disorders and Stroke (NINDS). NINDS Vasculitis Including Temporal Arteritis Information Page. Bethesda, MD: NINDS, 2001.

Rebecca Frey, PhD

Vasculitis

Definition

Vasculitis refers to a varied group of disorders which all share a common underlying problem of inflammation of a blood vessel or blood vessels. The inflammation may affect any size blood vessel, anywhere in the body. It may affect either arteries and/or veins. The inflammation may be focal, meaning that it affects a single location within a vessel; or it may be widespread, with areas of inflammation scattered throughout a particular organ or tissue, or even affecting more than one organ system in the body.

Description

Inflammation is a process which occurs when the immune system of the body responds to either an injury or a foreign invader (virus, bacteria, or fungi). The immune system response involves sending a variety of cells and chemicals to the area in question. Inflammation causes blood vessels in the area to leak, causing swelling. The inflamed area becomes red, hot to the touch, and tender.

Antibodies are immune cells which recognize and bind to specific markers (called antigens) on other cells (including bacteria and viruses). These antibody-antigen complexes can then stimulate the immune system to send a variety of other cells and chemicals involved in inflammation to their specific location.

Some researchers believe that the damaging process of vasculitis is kicked off by such antibody-antigen complexes. These complexes are deposited along the walls of the blood vessels. The resulting inflow of immune cells and chemicals causes inflammation within the blood vessels.

The type of disease caused by vasculitis varies depending on a number of factors:

• the organ system or tissue in which the vasculitis occurs
• the specific type of inflammatory response provoked
• whether the affected vessels are veins (which bring blood to the heart) or arteries (which carry blood and oxygen from the heart to the organs and tissues)
• the degree to which blood flow within the affected vessel is reduced

Causes and symptoms

Some types of vasculitis appear to be due to a type of allergic response to a specific substance (for example, a drug). Other types of vasculitis have no identifiable initiating event. Furthermore, researchers have not been able to consistently identify antibody-antigen complexes in all of the types of diseases caused by vasculitis. The types of antigens responsible for the initial immune response have often gone unidentified as well. Furthermore, not all people with such complexes deposited along the blood vessels go on to develop vasculitis. Some researchers believe that, in addition to the presence of immune complexes, an individual must have some other characteristics which make him or her susceptible to vasculitis. Many questions have yet to be answered to totally explain the development these diseases.

Symptoms

Symptoms of vasculitis depend on the severity of the inflammation and the organ system or systems affected. Some types of vasculitis are so mild that the only symptoms noted are small reddish-purple dots (called petechiae) on the skin due to tiny amounts of blood seeping out of leaky blood vessels. In more widespread types of vasculitis, the patient may have general symptoms of illness, including fever, achy muscles and joints, decreased appetite, weight loss, and loss of energy. The organ systems affected by vasculitis may include:

• The skin. Rashes, bumps under the skin, petechiae, larger reddish-purple circles (purpura), or bruising (ecchymoses) may appear. Areas of skin totally deprived of blood flow, and therefore of oxygen, may die, resulting in blackened areas of gangrene.
• The joints. In addition to joint pain, the joints themselves may become inflamed, resulting in arthritis.
• Brain and nervous system. Inflammation of the blood vessels in the brain can cause headaches, changes in personality, confusion, and seizures. If an area of the brain becomes totally deprived of oxygen, a stroke occurs. A stroke means that an area of brain tissue is either severely injured or completely dead from lack of oxygen. This may leave the individual with a permanent disability. If the vessels that lead to the eyes are affected, vision may become seriously disturbed. Nerves in the arms and legs may result in painful tingling sensations, loss of feeling, and weakness.
• Gastrointestinal system. Patients may have significant abdominal pain, vomiting, and diarrhea. If blood flow is completely cut off to an area of intestine, that part of the intestine will die off. The liver may be affected.
• Heart. This is an extremely serious type of vasculitis. The arteries of the heart (coronary arteries) may develop weakened areas, called aneurysms. The heart muscle itself may become inflamed and enlarged. With oxygen deprivation of the heart muscle, the individual may suffer a heart attack.
• Lungs. The patient may experience shortness of breath with chest pain, and may cough up blood. There may be wheezing.
• Kidney. Changes in the arteries of the kidney may result in high blood pressure. The kidneys may become increasingly unable to appropriately filter the blood, and kidney failure may occur.

Specific diseases

Multiple types of disease are associated with vasculitis. Many autoimmune diseases have vasculitis as one of their complications. These include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and polymyositis. Other types of diseases which have vasculitis as their major manifestations include:

• Polyarteritis nodosa. This is an extremely serious, systemic (affecting systems throughout the body) form of vasculitis. Small and medium arteries are involved, and the inflammation is so severe that the walls of the arteries may be destroyed. Any organ system, or multiple organ systems, may be affected. The most serious effects include kidney failure, complications involving the heart, gastrointestinal problems, and high blood pressure.
• Kawasaki's disease is an acute disease which primarily strikes young children. Fever and skin manifestations occur in all patients. While most patients recover completely, a few patients suffer from vasculitis in the heart. This is frequently fatal.
• Henoch-Schonlein purpura. While this frequently occurs in children, adults may also be affected. This disease tends to affect the skin, joints, gastrointestinal tract, and kidneys.
• Serum sickness occurs when an individual reacts to a component of a drug, for example penicillin. Symptoms of this are often confined to the skin, although fevers, joint pain, and swelling of lymph nodes may also occur.
• Temporal arteritis (also called giant cell arteritis) tends to involve arteries which branch off the major artery that leads to the head, called the carotid. An artery which feeds tissues in the area of the temple (the temporal artery) is often affected. Severe headaches are the most classic symptom. Other symptoms include fatigue, loss of appetite and then weight, fever, heavy sweating, joint pain, and pain in the muscles of the neck, shoulders, and back. If the vasculitis includes arteries which supply the eye, serious visual disturbance or even blindness may result.
• Takayasu's arteritis affects the aorta (the very large main artery that exits the heart and receives all of the blood to be delivered throughout the body), and arteries which branch off of the aorta. Initial symptoms include fatigue, fever, sweating at night, joint pain, and loss of appetite and weight. Every organ may be affected by this disease. A common sign of this disease is the inability to feel the pulse in any of the usual locations (the pulse is the regular, rhythmic sensation one can feel with a finger over an artery, for example in the wrist, which represents the beating of the heart and the regular flow of blood).
• Wegener's granulomatosis: This disease exerts its most serious effects on the respiratory tract. The vasculitis produced by this disease includes the formation of fibrous, scarring nodules called granulomas. Symptoms include nose bleeds, ear infections, cough, shortness of breath, and chest pain. There may be bleeding in the lungs, and a patient may cough up blood. The kidneys, eyes, and skin are also frequently involved.

Diagnosis

Diagnosis of any type of vasculitis involves demonstrating the presence of a strong inflammatory process. Tests which reveal inflammation throughout the body include erythrocyte sedimentation rate, blood tests which may reveal anemia and increased white blood cells, and tests to demonstrate the presence of immune complexes and/or antibodies circulating in the blood. An x-ray procedure, called angiography, involves injecting dye into a major artery, and then taking x-ray pictures to examine the blood vessels, in order to demonstrate the presence of inflammation of the vessel walls. Tissue samples (biopsies) may be taken from affected organs to demonstrate inflammation.

KEY TERMS

Aneurysm— A weakened area in the wall of a blood vessel which causes an outpouching or bulge. Aneurysms may be fatal if these weak areas burst, resulting in uncontrollable bleeding.

Antibody— Specialized cells of the immune system which can recognize organisms that invade the body (such as bacteria, viruses, and fungi). The antibodies are then able to set off a complex chain of events designed to kill these foreign invaders.

Antigen— A special, identifying marker on the outside of cells.

Autoimmune disorder— A disorder in which the body's antibodies mistake the body's own tissues for foreign invaders. The immune system therefore attacks and causes damage to these tissues.

Immune system— The system of specialized organs, lymph nodes, and blood cells throughout the body which work together to prevent foreign invaders (bacteria, viruses, fungi, etc.) from taking hold and growing.

Inflammation— The body's response to tissue damage. Includes hotness, swelling, redness, and pain in the affected part.

Petechia— A tiny, purplish-red spot on the skin. Caused by the leakage of a bit of blood out of a vessel and under the skin.

Purpura— A large, purplish-red circle on the skin. Caused by the leakage of blood out of a vessel and under the skin.

Treatment

Even though there are many different types of vasculitis, with many different symptoms based on the organ system affected, treatments are essentially the same. They all involve trying to decrease the activity of the immune system. Steroid medications (like prednisone) are usually the first types of drugs used. Steroids work by interfering with the chemicals involved in the inflammatory process. More potent drugs for severe cases of vasculitis have more serious side effects. These include drugs like cyclophosphamide. Cyclophosphamide works by actually killing cells of the patient's immune system.

Prognosis

The prognosis for vasculitis is quite variable. Some mild forms of vasculitis, such as those brought on by reactions to medications, may resolve totally on their own and not even require treatment. Temporal arteritis, serum sickness, Henoch-Schonlein purpura, and Kawasaki's disease usually have excellent prognoses, although when Kawasaki's affects the heart, there is a high death rate. Other types of vasculitis were always fatal, prior to the availability of prednisone and cyclophosphamide, and continue to have high rates of fatal complications. These include polyarteritis nodosa and Wegener's granulomatosis.

Prevention

Because so little is known about what causes a particular individual to develop vasculitis, there are no known ways to prevent it.

Resources

ORGANIZATIONS

Lupus Foundation of America. 1300 Piccard Dr., Suite 200, Rockville, MD 20850. (800) 558-0121. 〈http://www.lupus.org〉.

Wegener's Foundation, Inc. 3705 South George Mason Drive, Suite 1813 South, Falls Church, VA 22041. (703) 931-5852.

Vasculitis

Definition

Vasculitis refers to a condition that causes inflammation of blood vessels (arteries, capillaries, and/or veins). When the blood vessels become inflamed, scarring, thickening of the vessel walls, and narrowing of the vessel caliber decrease the amount of blood flow through the blood vessels. When there is less blood flow, the organs or tissues that should be receiving blood flow are deprived of oxygen, causing damage to them. Because blood vessels anywhere in the body can be affected by vasculitis, organs and tissues anywhere in the body can be damaged by its consequences. Vasculitis can occur very focally (in a relatively small, circumscribed area) or diffusely (a widespread network of blood vessels are inflamed).

Description

Vasculitis describes a large number of conditions. Vasculitis can be primary (the vessel inflammation occurs spontaneously, with no other associated disease process) or secondary (the vessel inflammation occurs due to some other preexisting disease). Secondary vasculitis can be a manifestation of a large number of disease processes, including a variety of connective tissue or autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, Raynaud's phenomenon, Sjogren's syndrome, sclerodactyly, polymyositis , and dermatomyositis , as well as sarcoidosis, malignancy, hepatitis B and hepatitis C infections, allergic reactions to antibiotics and/or diuretics, and severe bacterial infections such as endocarditis, pneumonia, meningitis, gonorrhea, or syphilis.

Normally, inflammation is an immune system response to the presence of either an injury or an infection with an invading organism such as a virus, bacteria, or fungi. When faced with either of these threats, the immune system produces a variety of cells and chemicals that cause blood vessels in the injured or infected area to dilate and then become leaky. Fluid, protein, and blood cells leak out of the blood vessels and into the surrounding tissues, causing swelling. The affected area turns red, warm, and painful.

Inflammation causes a cascade of effects, both in the tissues adjacent to the initial area of inflammation and at distant sites throughout the body. Locally, the process of inflammation causes various chemicals of inflammation to leak out into the neighboring tissues, prompting the same cycle of vessel dilatation and leakiness, resulting in swelling of those neighboring tissues. Chemicals of inflammation traveling through the bloodstream can precipitate the cycle of inflammation in tissues and/or organs at a distance from the initial site of inflammation.

In vasculitis, the inflammation response has gone awry: it may be kicked off initially by the presence of an invader such as vasculitis secondary to a severe bacterial infection; it may be part of an overall immune system over-reactiveness as occurs when vasculitis occurs secondary to an autoimmune disease such as systemic lupus erythematosus and rheumatoid arthritis; or it may erupt spontaneously as in cases of primary vasculitis. The end results, however, are inflammation and destruction of blood vessel walls, blood clot blockages within blood vessels, aneurysms (weakened bulging areas of blood vessel walls which can rupture, causing catastrophic bleeding),

and oxygen deprivation of the affected organs and/or tissues, leading to damage and destruction of various tissue or organs throughout the body.

A variety of classification systems have been developed to describe and organize the various types of vasculitis. These include systems that are based on the specific organs affected, and systems that are based on the size and type of vessels affected, and the kinds of microscopic, cellular changes seen within those vessels. One of the most popular systems for classification of vasculitis is called the Chapel Hill system, named for the creators at the University of North Carolina-Chapel Hill. This system divides the types of vasculitis into three categories: large-vessel vasculitis (including giant cell or temporal arteritis and Takayasu's arteritis); medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki's disease); and small-vessel vasculitis (including Wegener's granulomatosis, Churg-Strauss syndrome, microsopic polynagiitis, Henoch-Schonlein purpura, essential cryoglobulinemic vasculitis, and cutaneous leukocytoclastic angiitis).

Demographics

Each type of vasculitis has its own primary demographic. Those that tend to strike older individuals include polyarteritis nodosa, giant cell or temporal arteritis, and Wegener's granulomatosis. Takayasu's arteritis tends to strike individuals in middle age. Henoch-Schonlein pupura and Kawaskai disease tend to strike children.

Causes and symptoms

Some researchers believe that vasculitis is prompted by the deposition of antibody-antigen complexes along the inside of blood vessel walls. Antibodies are immune cells that recognize and attach to specific markers (antigens) on foreign cells such as bacteria, viruses, and fungi. The presence of antibody-antigen complexes serves to jumpstart the immune cell response, prompting it to produce a variety of other cells and chemicals in an effort to rid the body of a foreign invader. Sometimes, however, the body accidentally produces antibodies that accidentally identify antigens on the body's own cells as foreign. When these antibodies bind to the body's antigens, the same immune response is provoked, but instead of being directed against a foreign invader, it is directed against the body itself.

Some researchers believe that the immune system is prompted into action by the presence of an actual threat (in the case of secondary vasculitis due to a bacterial infection), or is already overreacting (in the case of secondary vasculitis due to a preexisting autoimmune disease), or spontaneously swings into an overreactive state (in the case of primary vasculitis).

Symptoms of vasculitis depend on the specific organs or tissues affected. Affected body systems and potential symptoms include:

• Skin. Vasculitis of the skin may lead to a variety of rashes, bumps, bruises, or areas of subtle bleeding suchas petechia (tiny red dots), pupura (larger reddish purple spots), or ecchymoses (large, complexly colored areas of bruising). When areas of skin are completely deprived of any blood flow, and therefore of any oxygen delivery, the skin may die and turn black (gangrene).
• Joints. Vasculitis-induced arthritis occurs when the lining of the joints is affected by vasculitis, causing swelling, pain , decreased range of motion, and reduced functioning.
• Brain and nervous system. When vasculitis affects the nervous system, a variety of symptoms may result. Vasculitis of blood vessels in the brain can lead to headaches, confusion, personality changes, seizures , and coma. Depending on the area of the brain affected, other senses may suffer, including vision, hearing, and/or balance. Vasculitis of the nerves that provide sensation to the arms or legs can lead to pain and paresthesias (odd sensations of tingling, burning, pinpricks, lightning-flashes of pain, or numbness). A stroke occurs when an area of the brain tissue is completely deprived of oxygen, causing severe damage or destruction. The results of a stroke may be temporary or permanent, and the specific types of potential disability depend on what functions are normally controlled by the area of brain injured by the stroke.
• Gastrointestinal system. Any part of the gastrointestinal system can be affected by vasculitis, including the liver. Symptoms referable to the gastrointestinal system include pain, diarrhea, constipation, and vomiting. When blood flow is cut off to an area of the intestine, that area will become gangrenous or necrotic and die. This is a medical emergency.
• Heart. Vasculitis of the coronary arteries, which normally feed the heart muscle, can result in weakening of the heart muscle with compensatory enlargement, heart attack, or myocardial infarcation. When the walls of the arteries or the aorta undergo serious destruction due to vasculitis, weakened bulges called aneurysms may develop. If these aneurysms rupture, hemorrhage may occur.
• Lungs. Vasculitis of the complex network of blood vessels throughout the lungs can result in severe shortness of breath, cough, chest pain, and wheezing.
• Kidneys. When the kidney or renal arteries are damaged by vasculitis, high blood pressure results. The kidneys may fall behind in their normal role of filtering the blood, and kidney or renal failure may occur.

Diagnosis

Initial attempts to diagnosis vasculitis will depend on the area of the body affected and the kinds of symptoms exhibited. Blood tests that can demonstrate the presence of a strong inflammatory process include erythrocyte sedimentation rate, C-reactive protein, increased white blood cell count, and a variety of tests that can identify the presence of immune complexes or antibodies circulating within the blood. A variety of imaging techniques may reveal blood vessel inflammation, including ultrasound, echocardiography, computed tomography (CT ), and magnetic resonance imaging (MRI) scanning. When the kidneys are involved, urine tests may reveal abnormalities. An x-ray procedure called angiography involves the injection of dye into a major artery to allow the detection of inflammation in the walls of blood vessels. Biopsies (tissue samples) may be taken from the blood vessels that serve affected organs or tissues to look for the presence of inflammation or scarring.

Treatment team

While rheumatologists specialize in the treatment of various autoimmune diseases (including various forms of vasculitis), patients may also be treated by specialists who concentrate on diseases that affect specific organs or tissues. For example, a patient may need to consult a cardiologist if the heart is affected; a nephrologist if the kidneys are affected; a neurologist if the nervous system is affected; a pulmonologist if the lungs are affected; a gastroenterologist if the gastrointestinal tract is affected; an ophthomologist if the eyes are affected; an otorhinolaryngologist if the ear, nose, and/or throat are affected; or a dermatologist if the skin is affected.

Treatment

Medications that calm the immune system and decrease inflammation are the mainstay of treatment for the various types of vasculitis. These include nonsteroidal anti-inflammatory medications (such as ibuprofen or aspirin) and corticosteroids (such as prednisone). More severe cases of vasculitis may require potent immunosuppressant drugs (such as cyclophosphamide or azathioprine).

Prognosis

The prognosis of vasculitis depends on the specific organ system affected and the severity of the particular case. In general, most people who receive appropriate treatment have a good recovery from vasculitis. However, when the disease causes kidney failure or affects the heart, the prognosis may be worse. Basic prognosis statistics of treated vasculitis include:

• Polyarteritis nodosa: about 90% of cases go into long-term remission.
• Hypersensitivity vasculitis: Most people recover completely, even without treatment.
• Giant cell arteritis: May require one to two years of steroid treatment, but most people recover completely.
• Wegener's granulomatosis: With treatment, 90% can expect symptom relief, and 75% go into complete remission.
• Takayasu's arteritis: 90% survive, with some spontaneous remission.
• Kawasaki disease: Under 3% of patients suffer fatal complications; most children recover uneventfully.

Resources

BOOKS

Fauci, Anthony S. "The Vasculitis Syndromes." In Harrison's Principles of Internal Medicine, edited by Eugene Braunwald, et al. New York: McGraw-Hill Professional, 2001.

Cercomb, Clare T. "Systemic Lupus Erythematosus and the Vasculitides." In Rosen's Emergency Medicine: Concepts and Clinical Practice, 5th ed., edited by Lee Goldman, et al. St. Louis: Mosby, Inc., 2002.

Sergent, John S. "Vasculitic Syndromes." In Kelley's Textbook of Rheumatology, edited by Shaun Ruddy, et al. Philadelphia: W. B. Saunders Company, 2001.

PERIODICALS

González-Gay, M. A. "Epidemiology of the Vasculitides." Rheumatic Disease Clinics of North America 27, no. 4 (1 November 2001): 729–749.

Langford, C. A. "Vasculitis." Journal of Allergy and Clinical Immunology 111, no. 2 (1 February 2003): 602–612.

Naides, Stanley. "Known Infectious Causes of Vasculitis in Man." Cleveland Clinic Journal of Medicine 69, no. 2.

ORGANIZATIONS

Johns Hopkins Vasculitis Center. Bayview Medical Center, 5501 Hopkins Bayview Circle, JHAAC, Room 1B.1A, Baltimore, MD 21224. (410) 550-6825. <http://vasculitis.med.jhu.edu/index.html>.

Rosalyn Carson-DeWitt, MD

vasculitis (vas-kew-ly-tis) n. see angiitis.

angiitis (vasculitis) (an-ji-I-tis) n. a patchy inflammation of the walls of small blood vessels.