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 .

Resources

BOOKS

"Vasculitis." Section 5, Chapter 50 in The 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 in The 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