CHAPTER 98
Vasculitic Disorders
Vasculitic disorders are characterized by inflammation of the blood vessels (vasculitis).
Usually, what triggers vasculitis is unknown, but sometimes certain viruses or drugs trigger it.
People may have general symptoms, such as fever or fatigue, followed by other symptoms depending on which organs are affected.
Typically, a biopsy of an affected blood vessel is needed to confirm the diagnosis.
Corticosteroids and other drugs that suppress the immune system are used to reduce inflammation and relieve symptoms.
Vasculitis can affect people of all ages, but some types are more common among certain age groups.
Usually, what triggers vasculitis is unknown. However, certain viruses, especially hepatitis viruses, and drugs sometimes trigger it. Presumably, the inflammation occurs when the immune system mistakenly identifies blood vessels or parts of a blood vessel as foreign and attacks them. Cells of the immune system, which cause inflammation, surround and infiltrate the affected blood vessels, damaging them. The damaged blood vessels may become leaky, narrow, or clogged. As a result, blood flow to the tissues supplied by the damaged vessels is disrupted. The tissues deprived of blood (ischemic areas) can be permanently damaged or die.
Vasculitis may affect arteries (large, medium-sized, or small), capillaries, veins, or a combination. It may affect a whole blood vessel or only part of it. It may affect blood vessels that supply one part of the body, such as the head or skin, or blood vessels that supply several different organs (called systemic vasculitis). Any organ system can be affected.
Did You Know…
Blood vessels can become inflamed.
Symptoms
Symptoms may result from direct damage to the blood vessels or from indirect damage to tissues (such as nerves or organs) whose blood supply has been disrupted or reduced.
Symptoms vary, depending on the size of the affected blood vessels and the organs whose blood supply is disrupted or reduced. For example, the following may occur:
SOME DISORDERS CHARACTERIZED BY VASCULITIS
| DISORDER | DEFINITION | SYMPTOMS* |
| Behçet’s syndrome | Chronic inflammation of arteries and veins, characterized by recurring mouth sores | Recurring mouth sores Sores on the genital organs Red, painful eyes Rashes Swollen, painful joints Sometimes blood clots in arteries and veins |
| Churg-Strauss syndrome | Inflammation of small blood vessels (often in the lungs, sinuses, skin, nerves, and kidneys) that occurs in people with asthma or a nasal allergy | Various symptoms depending on the organ affected Cough, which sometimes brings up blood Facial pain Shortness of breath Rashes Numbness, tingling, or weakness in a limb Muscle and joint aches and pains Abdominal pain |
| Giant cell arteritis | Inflammation of large and medium-sized arteries in the head, neck, and upper body, especially the temporal arteries (which run through the temples) | Headaches Pain in the scalp Pain in the jaws or tongue during chewing Double or blurred vision Without treatment, possibly irreversible vision loss |
| Henoch-Schönlein purpura | Inflammation of small blood vessels, often in the skin, intestine, and kidneys | Hard, purple spots or blotches on the skin of the lower legs Joint pains Nausea Abdominal pain Blood in the stool or urine |
| Microscopic polyangiitis | Inflammation of small blood vessels, usually starting in the lungs and kidneys | Shortness of breath Swelling in the legs Purplish bumps or spots on the skin Numbness, tingling, or weakness in a limb |
| Polyarteritis nodosa | Inflammation of medium-sized arteries | Various symptoms depending on the organ affected Muscle and joint pain Abdominal pain High blood pressure Numbness, tingling, or weakness in a limb |
| Takayasu’s arteritis | Inflammation of the aorta, the arteries that branch off from the aorta, and the pulmonary arteries, usually in young women | Pain and fatigue in the arms or legs when they are used Dizziness Strokes High blood pressure |
| Wegener’s granulomatosis | Inflammation of small and medium-sized blood vessels, usually in the sinuses, nose, lungs, and kidneys | Various symptoms depending on the affected organ Nosebleeds Ear infections Chronic sinusitis Cough, which sometimes brings up blood Shortness of breath Chest pain Joint and muscle aches and pain Rashes |
| Many of these disorders also cause general symptoms, such as fever, fatigue, loss of appetite, and weight loss. | ||
Skin: A rash of bluish purple spots (hemorrhages) or blotches (purpura), small bumps (nodules), or sores (ulcers) on the lower legs
Peripheral nerves: Numbness, tingling, or weakness in the affected limb
Brain: Changes in personality, confusion, seizures, and strokes
Digestive tract: Abdominal pain, diarrhea, nausea, and vomiting
Heart: Angina and heart attacks
Kidneys: Sometimes no symptoms or high blood pressure, retention of fluid (edema), and kidney dysfunction
Joints: Joint pain or swelling
Inflammation can also cause general symptoms such as fever, night sweats, fatigue, muscle and joint aches, loss of appetite, and weight loss.
Vasculitis can also cause serious complications that require immediate treatment. For example, damaged blood vessels in the lungs, brain, or other organs may bleed (hemorrhage). Effects on the kidneys may progress rapidly, leading to kidney failure. Eye problems may result in blindness.
Diagnosis
Vasculitis is usually not suspected when symptoms first develop. Vasculitis is uncommon, and most of its symptoms are caused much more often by other disorders. Nonetheless, certain combinations of symptoms or the persistence of symptoms eventually lead doctors to suspect vasculitis. Blood and urine tests, including the following, are usually done:
A complete blood cell count is done. If blood contains too few red blood cells (anemia), too many platelets, too many white blood cells, or a high proportion of certain kinds of white blood cells, vasculitis may be the cause. Vasculitis may cause anemia by decreasing the body’s production of red blood cells or by causing internal bleeding.
Blood is analyzed for substances produced by the body when inflammation is present. These substances include certain antibodies (such as antineutrophil cytoplasmic antibodies) and complement proteins. Antineutrophil cytoplasmic antibodies attack certain white blood cells and occur in several types of vasculitis.
Blood tests may be done to check for infections (such as hepatitis) that may have triggered the vasculitis.
Blood tests are done to estimate the degree of inflammation, which vasculitis usually causes. For example, how quickly red blood cells (erythrocytes) drop to the bottom of a test tube (erythrocyte sedimentation rate) is measured. A fast rate suggests inflammation. Levels of C-reactive protein (which the liver produces in response to bodywide inflammation) may be measured instead or in addition. However, inflammation has many causes other than vasculitis.
A sample of urine is tested for red blood cells and protein. This information can help doctors determine whether the kidneys are affected.
Blood tests may be done to measure levels of proteins that can change when vasculitis develops (total protein and albumin)
Blood and urine tests results may help in making the diagnosis but are usually not conclusive. For confirmation, a sample of the affected blood vessel is usually removed and examined under a microscope (biopsy) for signs of vasculitis. A local anesthetic is used, and the test may be done on an outpatient basis.
Other tests may be needed. For example, if the lungs seem to be affected, a chest x-ray is done. Imaging tests, such as magnetic resonance angiography, may be done to determine which blood vessels are affected. If the kidneys may be affected, blood levels of substances that increase when the kidneys are damaged (blood urea nitrogen and creatinine) are measured. Some tests may be done to rule out other disorders that can cause similar symptoms.
Prognosis
The prognosis depends on the type and severity of vasculitis and the organs that are affected. If the kidneys or heart is affected, the prognosis tends to be worse.
Treatment
Treatment depends on the type and severity of the vasculitis and the organs that are affected. But generally, treatment aims to stop the immune system from continuing to damage blood vessels.
If vital organs, such as the lungs, heart, brain, or kidneys, are affected, emergency treatment in a hospital is often necessary. Sometimes a team of specialists (experts in such fields as inflammation, lung disorders, or kidney disorders) is needed to provide care.
Mild types of vasculitis, such as those that affect only the skin, may require little treatment, possibly only close monitoring or antihistamines.
For most types of vasculitis, a corticosteroid (usually prednisone) is typically used first to reduce inflammation. Sometimes another drug that suppresses the immune system (immunosuppressant), such as azathioprine, cyclophosphamide, or methotrexate, is used with the corticosteroid (see page 567). Drugs used to treat vasculitis can have side effects. Thus, as the inflammation is being controlled, the dose of the drugs may be slowly reduced, the corticosteroid may be stopped, and less strong immunosuppressants are used. The lowest dose that can control symptoms is used. Once inflammation is controlled (called remission), all drugs may be stopped. Some people remain in remission indefinitely. In others, symptoms recur one or more times (called a relapse). If relapses occur often, people may need to take an immunosuppressant indefinitely. Some people have to take corticosteroids for a long time.
Side effects, such as decreased bone density, an increased risk of infections, cataracts, high blood pressure, weight gain, and diabetes, are more likely to occur when corticosteroids are taken for a long time. To help prevent decreased bone density, people are advised to take calcium and vitamin D supplements and are given a bisphosphonate, such as alendronate or risedronate, which help increase bone density. Bone density is measured periodically.
Immunosuppressants weaken the immune system, so the risk of developing serious infections is increased. Cyclophosphamide, one potent immunosuppressant drug, can cause bladder irritation and sometimes even bladder cancer. A complete blood count is done frequently, sometimes as often as once a week for patients who take strong immunosuppressants. Immunosuppressants may cause the number of blood cells to decrease.
People should learn as much as they can about their disorder so that they can report any important symptoms to their doctor promptly. Learning about the side effects of the drugs being used is also important. People, even when in remission, should keep in touch with their doctor because how long remission will last cannot be predicted.
Polyarteritis Nodosa
Polyarteritis nodosa is inflammation of medium-sized arteries that damages the arteries and impairs blood flow through them.
Any organ (except the lungs) can be affected.
Polyarteritis nodosa can be rapidly fatal or develop gradually.
Symptoms vary depending on which organ is affected.
Biopsy of an affected artery can confirm the diagnosis.
Prompt treatment with a corticosteroid, another drug that suppresses the immune system, or both can delay or prevent death.
Polyarteritis nodosa most often develops during middle age, usually when people are in their 50s, but it can occur at any age. It is rare.
The cause is unknown, but it sometimes appears to be triggered by certain viral infections (such as hepatitis B) or drugs. About 1 of 5 people with polyarteritis nodosa has hepatitis B. Most often, no trigger can be identified.
Symptoms
The disorder can be mild at first but can worsen rapidly and be fatal within several months, or it can develop gradually as a chronic debilitating disease. Any organ (except the lungs) or combination of organs can be affected. Symptoms depend on which organs are affected. Occasionally, only one organ, such as the intestine or skin, is affected.
People may have general symptoms at first. They may feel generally ill and tired and have a fever. They may lose their appetite and lose weight.
Other symptoms occur when the arteries that carry blood to an organ are damaged, and the organ does not receive enough blood to function normally. Thus, symptoms vary depending on the organ that is affected:
Joints: Muscle and joint pain (common) and joint inflammation (arthritis)
Kidneys: High blood pressure, swelling due to water retention (edema), and decreased production of urine
Digestive tract: Abdominal infection (peritonitis), severe pain, bloody diarrhea, nausea, vomiting, and tears (perforations) in the intestine
Heart: Chest pain (angina) and heart attacks
Brain: Headaches, seizures, and strokes
Nerves: Patchy numbness, tingling, weakness, or paralysis in a hand or foot
Liver: Liver damage
Skin: Blue or red discoloration of the fingers or toes, rashes that are usually bumpy, purplish blotches, and occasionally skin sores
Sometimes damage to an organ is irreversible. Such organs cannot function normally. A weakened artery may rupture, causing internal bleeding. Problems, such as a heart attack, can occur long after the inflammation has been treated.
Diagnosis
Doctors suspect polyarteritis nodosa when people have a certain combination of symptoms and blood test results. For example, they may suspect it if a previously healthy middle-aged man has a fever and evidence of a certain pattern of nerve damage, such as patchy numbness, tingling, or paralysis.
To confirm the diagnosis, doctors may take a small sample of an affected blood vessel and examine it under a microscope (biopsy). If the skin, liver, or kidneys appear to be affected by vasculitis, these organs may also be biopsied. Arteriography (angiography of arteries) may be done to check for bulges (aneurysms) in the wall of affected arteries. For this test, x-rays are taken after a dye that is visible on x-rays (radiopaque dye) is injected into the arteries.
Treatment
Without treatment, polyarteritis nodosa can result in death. Prompt, appropriate treatment can delay or prevent death from this disorder. However, treatment cannot always reverse the damage already done.
Treatment depends on the severity of the disorder. Any drugs that may have triggered the disorder are stopped.
High doses of a corticosteroid, such as prednisone, can prevent polyarteritis nodosa from worsening and help people feel better. The goal is a symptom-free period (remission). Because most people need long-term treatment with a corticosteroid and because long-term treatment can have significant side effects, doctors reduce the dose once symptoms have subsided.
If the corticosteroid does not reduce the inflammation adequately, drugs that suppress the immune system (immunosuppressants), such as cyclophosphamide, may be given with the corticosteroid. Taking a corticosteroid or another immunosuppressant for a long time reduces the body’s ability to fight infections. Thus, people so treated have an increased risk of infections, which may be serious or fatal if not recognized and treated promptly.
Other treatments, such as those used to control high blood pressure, are often needed to prevent damage to internal organs. Hepatitis B, if present, is treated after the inflammation has been controlled.
Giant Cell Arteritis
Giant cell (temporal) arteritis is chronic inflammation of large arteries of the head, neck, and upper body. Typically affected are the temporal arteries, which run through the temples and provide blood to part of the scalp, the jaw muscles, and salivary glands.
The cause is unknown.
Typically, people have a severe and often throbbing headache, pain in the scalp when they brush their hair, and pain when they chew.
Without treatment, blindness can result.
Symptoms and results of a physical examination suggest the diagnosis, but biopsy of the temporal artery is done to confirm it.
Prednisone, a corticosteroid, is effective.
Giant cell arteritis typically affects people over 55. About 40 to 60% of people with giant cell arteritis also have polymyalgia rheumatica. The cause of these disorders is unknown.
Symptoms
Symptoms vary, depending on which arteries are affected. Typically, the large arteries to the head are affected, causing a severe, sometimes throbbing headache at the temples or back of the head to develop for the first time. Arteries in the temple may be tender to the touch and feel swollen and bumpy. The scalp may feel painful when the hair is brushed. Double or blurred vision, large blind spots, blindness in one eye, or other eye problems may develop. The greatest danger is permanent blindness, which can occur suddenly if the blood supply to the optic nerve is blocked. Without treatment, giant cell arteritis causes blindness in 20% of people.
Typically, the jaw and its muscles hurt and become tired soon after beginning chewing. The tongue may also hurt when eating or speaking. People may also feel tired and generally unwell. They may lose weight unintentionally and sweat more than usual.
Did You Know…
Combing the hair and chewing often hurt when people have giant cell arteritis.
Occasionally, blood flow to the brain is blocked, and a stroke occurs. Sometimes inflammation damages the aorta, causing its lining to tear (dissection) or a bulge (aneurysm) to form in its wall.
If polymyalgia rheumatica is also present, severe pain may occur in the neck, shoulders, and hip. These muscles may feel stiff, particularly in the early morning.
Diagnosis
Doctors suspect the diagnosis based on symptoms and results of a physical examination. Doctors feel the temples to see whether the temporal arteries feel hard, bumpy, or tender. Blood tests are done. Results can support the diagnosis. For example, anemia, a very high erythrocyte sedimentation rate (ESR), and a high level of C-reactive protein indicate inflammation. A biopsy of the temporal artery (in the temple) is done to confirm the diagnosis.
Biopsy of the Temporal Artery
A biopsy of the temporal artery is the definitive procedure for diagnosing temporal arteritis. Doppler ultrasonography is occasionally used to locate the part of the temporal artery to be biopsied. After a local anesthetic is injected, a shallow incision is made directly over the artery, and a segment of the artery at least 1 inch long is removed. The incision is then stitched up.
If giant cell arteritis is suspected in arteries other than the temporal artery, magnetic resonance angiography may be done to confirm the diagnosis.
Treatment
Treatment is started as soon as giant cell arteritis is suspected because without treatment, blindness can develop. Treatment is usually started even before a biopsy is done. Treatment does not affect the biopsy results as long as the biopsy is done within weeks after starting treatment. Prednisone, a corticosteroid, is effective. Initially, the dose is high—to stop the inflammation in the blood vessels. After several weeks, doctors gradually reduce the dose if people are improving. Some people can stop taking prednisone within a year, but many need to take very low doses for many years to control symptoms and prevent blindness.
People should take a low dose of aspirin every day to help prevent strokes.
With treatment, most people recover fully, but the disorder may recur.
POLYMYALGIA RHEUMATICA
Polymyalgia rheumatica involves inflammation of the lining of joints, causing severe pain and stiffness in the muscles of the neck, shoulders, and hips.
The cause is unknown.
The neck, shoulders, and hips feel stiff and painful.
Blood tests and sometimes biopsy of a muscle help doctors make the diagnosis.
Most people improve dramatically when they take prednisone, a corticosteroid.
Polymyalgia rheumatica occurs in people over 55. Its cause is unknown. Polymyalgia rheumatica may occur with giant cell (temporal) arteritis. Some experts think that the two disorders are variations of the same abnormal process.
Symptoms
Symptoms may develop suddenly or gradually. Severe pain and stiffness occur in the neck, shoulders, and hips. The stiffness is worse in the morning and after periods of inactivity. But muscles are not damaged or weak. People may also have a fever, feel generally unwell or depressed, and lose weight unintentionally.
Some people with polymyalgia rheumatica also have symptoms of giant cell arteritis, which can lead to blindness. Some people have mild arthritis, but if the arthritis is severe or is the main symptom, the diagnosis is more likely to be rheumatoid arthritis (see page 563).
SPOTLIGHT ON AGING
Giant cell (temporal) arteritis and polymyalgia rheumatica, which often occur together, affect people over age 55 almost exclusively. These disorders become more common as people age. They are 10 times more common among people over 80 than among those aged 50 to 59.
Giant cell arteritis typically causes a throbbing headache and problems with vision (including pain in and around the eyes). Polymyalgia rheumatica makes muscles painful and stiff. Without treatment, the pain these disorders cause, whether they occur together or separately, can make everyday living miserably difficult. Also, without prompt treatment, giant cell arteritis can cause blindness.
The main treatment of these disorders, corticosteroids, may be problematic in older people. These drugs can cause dramatic improvement and are essential for preventing blindness. However, they are more likely to have side effects in older people. People may retain fluids, their appetite may increase, and they may become confused. Blood sugar may increase, sometimes causing diabetes, and bone density may decrease. Blood pressure may increase. To reduce the risk of these effects, doctors reduce the dose of the corticosteroid and stop the drug as soon as possible.
Older people who take corticosteroids are encouraged to take measures to help maintain bone density. They can do weight-bearing exercise and take calcium and vitamin D supplements. Taking bisphosphonates (such as alendronate or risedronate) can help increase bone density.
Faithfully continuing treatment as instructed results in complete recovery for many people.
Diagnosis
Doctors base the diagnosis on symptoms and results of a physical examination and blood tests. Blood tests usually include the following:
Erythrocyte sedimentation rate (ESR), C-reactive protein levels, or both: In people with polymyalgia rheumatica, results of both tests are usually very high, indicating active inflammation.
Blood count: This test is done to check for anemia.
Thyroid-stimulating hormone: This test is done to rule out hypothyroidism, which can cause weakness and sometimes pain of the shoulder and hip muscles.
Creatine kinase: This test is done to check for muscle tissue damage (myopathy), which can cause weakness and pain of the shoulder and hip muscles.
Rheumatoid factor: This antibody occurs in people with rheumatoid arthritis but not in those with polymyalgia rheumatica. This test helps doctors distinguish between the two.
If the diagnosis is unclear, a sample of muscle tissue may be removed and examined under a microscope (biopsy), or electromyography (see page 636) may be done to locate the source of muscle symptoms. If the cause is polymyalgia rheumatica, these test results are normal.
Treatment
Taking a low dose of prednisone, a corticosteroid, usually causes dramatic improvement. If people also have giant cell arteritis, a higher dose is needed to reduce the risk of blindness. As the symptoms subside, the dose is gradually reduced to the lowest effective one. Many people can stop taking prednisone in 1 to 4 years, although some people need to take a low dose longer.
Aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) can help relieve pain but usually less effectively than prednisone.
Wegener’s Granulomatosis
Wegener’s granulomatosis often begins with inflammation of small and medium-sized blood vessels and tissues in the nose, sinuses, throat, or lungs. It may progress to inflammation of blood vessels throughout the body (generalized vasculitis).
The cause is unknown.
The disorder usually begins with nosebleeds, nasal congestion with crusting, sinusitis, hoarseness, wheezing, and coughing.
Other organs may be affected, sometimes with serious complications, such as kidney failure.
Symptoms and other findings suggest the diagnosis, but a biopsy is usually needed to confirm it.
A corticosteroid and usually another drug that suppresses the immune system are needed to control inflammation.
Wegener’s granulomatosis can occur at any age. Its cause is unknown. It resembles an infection, but no infecting organism has been identified. Collections of immune cells that cause inflammation (called granulomas) form nodules and ultimately destroy normal tissue. Various organs in the body are damaged and malfunction because the arteries that supply them with blood are damaged. Wegener’s granulomatosis is often life threatening.
Symptoms
The disorder may begin suddenly or gradually. Usually, the first symptoms involve the upper respiratory tract—the nose, sinuses, ears, and windpipe (trachea). They may include the following:
Nosebleeds, sometimes severe
Nasal congestion with crusting in and around the nose
Collapse of the bridge of the nose, causing it to sag
A hole in the nasal cartilage that separates one side of the nose from the other (nasal septum)
Sinusitis
Hoarseness
Middle ear infections (otitis media)
Difficulty breathing
Coughing (sometimes with blood)
Sometimes only the upper respiratory tract is affected for many years. People may also have a fever, feel generally unwell, and lose their appetite. Inflammation can affect the eyes, which may become swollen, red, and painful.
The disorder may progress to affect other areas of the body or may affect several organs from the beginning:
Lungs: The lungs are usually affected at some point. People may feel short of breath and cough. Difficulty breathing may result from bleeding in the lungs, which requires immediate medical attention.
Joints: Joints may become swollen and ache.
Nerves: A limb may feel numb, tingly, or weak, or vision may be impaired. People may see double and, without treatment, may become blind.
Skin: A rash or sores may appear on the skin.
Kidneys: The kidneys are often affected. Kidney function may be slightly or severely impaired. Severe kidney damage causes high blood pressure and swelling due to fluid retention (edema). Life-threatening kidney failure may occur.
Anemia is common and can be severe.
Diagnosis
Wegener’s granulomatosis must be diagnosed and treated early to prevent complications, including kidney disorders, lung disorders, and heart attacks.
Doctors usually suspect the diagnosis based on the distinctive pattern of symptoms. A chest x-ray is done because the lungs are usually affected. However, symptoms and chest x-rays can resemble those of several lung disorders, making the diagnosis difficult. For example, a chest x-ray may show cavities or dense areas in the lungs that look like cancer.
Although blood test results cannot specifically identify Wegener’s granulomatosis, they can strongly support the diagnosis. One such test can detect antineutrophil cytoplasmic antibodies in the blood. These antibodies attack certain white blood cells and occur in several types of vasculitis. Urine tests also help support the diagnosis. People with this disorder may have blood or too much protein in their urine.
Doctors can confirm the diagnosis only by examining a small piece of tissue under a microscope (biopsy). The tissue sample may be taken from an affected area, such as the nasal passages, airways, or lungs. Skin and kidney biopsies may also be helpful.
Treatment
With treatment, symptoms usually disappear (called remission). However, in about half of treated people, symptoms return (called a relapse). Relapses may occur when treatment is stopped or many years later.
Corticosteroids are almost always used to suppress inflammation. Most people also need drugs that suppress the immune system (immunosuppressants), such as cyclophosphamide (usually used when the disorder is severe), methotrexate, or azathioprine. Most people feel better within days to weeks. But for some, improvement may take months.
During remission, the dose of the drugs is reduced. Treatment is usually continued for at least a year after the symptoms disappear. The dose of a corticosteroid can usually be gradually decreased and eventually stopped. Doses may need to be adjusted throughout the course of treatment. If symptoms worsen or recur, the dose is increased, or if drugs have been stopped, they are started again.
Because immunosuppressants weaken the immune system, the risk of developing serious infections is increased. Taking prednisone for a long time can result in weight gain, cataracts, high blood pressure, decreased bone density, diabetes, changes in mood, and difficulty sleeping. Cyclophosphamide can cause bladder irritation and sometimes bladder cancer. A complete blood count is done frequently, sometimes as often as once a week for patients who take strong immunosuppressants. Immunosuppressants may cause the number of blood cells to decrease.
People with Wegener’s granulomatosis need to be closely monitored by their doctor to check whether the dose of the drugs is appropriate, whether they are having side effects from the drugs, whether they could have an infection, and, during remission, whether there is any indication of a relapse.
People should also learn as much as they can about the disorder. Thus, they can recognize signs of a relapse early. People can also learn to test their urine for blood and protein so that they can notify their doctor at the first sign of any new abnormality.
Behçet’s Syndrome
Behçet’s syndrome is chronic inflammation that can cause painful mouth sores, skin blisters, genital sores, and swollen joints. The eyes, blood vessels, nervous system, and digestive tract may also become inflamed.
Typically, sores appear, disappear, and reappear in the mouth and on the genitals and skin.
Doctors base the diagnosis on symptoms and results of a physical examination.
Corticosteroids, other drugs that suppress the immune system, thalidomide, and colchicine are used to relieve symptoms.
Behçet’s syndrome occurs worldwide but is most common in the area along the silk route from the Mediterranean to China. It is uncommon in the United States. It occurs nearly equally in men and women, typically beginning during their 20s. But it can develop at any age. The cause is unknown.
Symptoms
Almost everyone with this syndrome has recurring, painful mouth sores, similar to canker sores. Sores may appear on the tongue, gums, and lining of the mouth. Sores may also appear on the genital organs. Those on the penis, scrotum, or vulva tend to be painful. Those in the vagina may be painless.
Other symptoms appear days to years later:
Eyes: Part of the eye becomes inflamed intermittently. This inflammation (relapsing iridocyclitis or uveitis—see page 1447) causes eye pain, redness, sensitivity to light, and hazy vision. Several other eye problems can occur. If untreated, blindness can develop.
Skin: Skin blisters and pus-filled pimples develop in about 80% of people. A slight injury, even a puncture from a hypodermic needle, can cause small red or pus-filled bumps to form.
Joints: In about half of affected people, the knees and other large joints become painful. This relatively mild inflammation (arthritis) does not progress or damage tissue.
Blood vessels: Inflammation of blood vessels (vasculitis) throughout the body can cause blood clots to form and bulges (aneurysms) to develop in weakened blood vessel walls. Vasculitis can result in strokes if arteries to the brain are affected. It can cause kidney damage if arteries to the kidneys are affected. If arteries in the lungs are affected, bleeding may occur, and people may cough up blood.
Digestive tract: Symptoms may range from mild discomfort to severe cramping and diarrhea.
Central nervous system: Inflammation of the brain or spinal cord is less common but has serious consequences. People may have a headache first. Other symptoms include a fever and stiff neck (symptoms of meningitis), confusion, and loss of coordination. Changes in personality and memory loss may develop years later.
Symptoms can come and go unpredictably, becoming very disruptive. Symptoms or symptom-free periods (remissions) may last weeks, years, or decades. Many people eventually go into remission. Occasionally, damage to the nervous system, digestive tract, or blood vessels is fatal.
Diagnosis
The diagnosis is based on symptoms and results of a physical examination. No laboratory tests can confirm Behçet’s syndrome. Doctors suspect the disorder in people, particularly young adults, who have the following:
Recurrent mouth and genital sores
Characteristic eye problems
Skin bumps triggered by a slight injury
However, symptoms may resemble those of many other disorders, including reactive arthritis (previously called Reiter’s syndrome), lupus (systemic lupus erythematosus), Crohn’s disease, herpes, and ulcerative colitis. The diagnosis may take months to make because doctors look for a pattern of symptoms that subside and recur (remissions and relapses) to help identify the syndrome.
Blood and urine tests are done. They cannot identify the syndrome but can confirm that inflammation is present.
Treatment
There is no cure, but treatment can usually relieve specific symptoms. Which drugs are used depends on which organ is affected and how severe the disease is. For example, the following may be used:
For inflamed eyes and skin sores: A corticosteroid (used to reduce inflammation) can be applied to the eyes or skin.
For severe inflammation of the eyes or nervous system: Cyclosporine or azathioprine, which are drugs that suppress the immune system (immunosuppressants), may be used when eye inflammation is severe or when prednisone does not adequately control symptoms.
For mouth and genital sores and joint pain: Colchicine (used to treat gout) can be taken by mouth to prevent new sores. Thalidomide may help mouth, genital, and skin sores heal, but the sores may recur when the drug is stopped. Etanercept, which is a tumor necrosis factor inhibitor (and thus suppresses the immune system), helps prevent new mouth and genital sores. It is given by injection.
Azathioprine may also reduce the number of mouth and genital sores, help sores heal, and reduce joint pain. Cyclophosphamide and chlorambucil are used when other drugs are ineffective or when life-threatening complications develop.
Takayasu’s Arteritis
Takayasu’s arteritis causes chronic inflammation, mainly of the aorta (the artery that connects directly with the heart), the arteries that branch off from it, and the pulmonary arteries.
The cause is unknown.
People may have general symptoms, such as fever or muscle or joint aches, followed by various symptoms, depending on which organs are affected.
Imaging tests of the aorta, such as angiography, are done to confirm the diagnosis.
A corticosteroid and sometimes another drug that suppresses the immune system can usually control the inflammation.
Takayasu’s arteritis is rare. It affects mostly women aged 15 to 30. Its cause is unknown.
The aorta and its branches, including arteries that take blood to the head and the kidneys, become inflamed. In about half of people, the pulmonary arteries are also affected. Inflammation may cause sections of these arteries to become narrow or blocked. The walls may weaken and stretch, resulting in a bulge (aneurysm). The affected vessels cannot provide enough blood to the tissues they supply.
Symptoms
Takayasu’s arteritis is a chronic disorder with symptoms that fluctuate in severity.
Sometimes the disorder begins with fevers, muscle and joint aches, loss of appetite, weight loss, and night sweats. But usually, symptoms occur when an artery narrows, reducing blood flow to part of the body, as in the following:
Arms or legs: The arms and legs ache and tire easily when they are used. When walking, people may feel pain, usually in the calves—a symptom called claudication.
Head: People may feel dizzy or have problems with vision. Less often, a stroke results.
Heart: Sometimes blood flow to the heart is reduced, and angina or a heart attack results.
Kidneys: The kidneys may malfunction, resulting in high blood pressure. High blood pressure increases the risk of kidney failure, strokes, and heart attacks.
Lungs: Blood pressure in the lungs becomes very high. People feel short of breath, tire easily, and may have chest pain.
Some people do not have any symptoms. In other people, the disorder progresses, causing serious complications such as strokes, heart failure, heart attacks, kidney failure, and aneurysms.
Diagnosis
Doctors suspect the disorder based on the following, especially in young women:
Blood pressure cannot be measured in one or both arms.
Blood pressure is much higher or pulse is much stronger in one arm or leg than in the other.
Blood pressure is unexpectedly high.
A person has a disorder such as stroke, angina, heart attack, or kidney damage that has no apparent explanation and that is unexpected.
Doctors ask about symptoms, review the person’s medical history, and do a complete physical examination to exclude other disorders that may cause similar symptoms.
Blood and urine tests are done. They cannot identify the disorder but may confirm that inflammation is present.
To confirm the diagnosis, doctors may use angiography—conventional, magnetic resonance, or computed tomography (CT) angiography—to evaluate the aorta and its branches. For conventional or CT angiography, a dye that can be seen on x-rays (radiopaque dye) is injected into blood vessels to outline them. Then x-rays are taken. Magnetic resonance angiography does not require the injection of a dye. These procedures can detect aneurysms and show where the arteries are narrowed.
After Takayasu’s arteritis is diagnosed, regular doctor visits should be scheduled so that the doctor can check whether the disorder is progressing.
Treatment
Corticosteroids (such as prednisone) are usually used. They effectively reduce inflammation in most people. Sometimes another drug that suppresses the immune system (immunosuppressant), such as azathioprine, cyclophosphamide, mycophenolate mofetil, or methotrexate, is also used. Tumor necrosis factor inhibitors, such as infliximab and etanercept, may also be effective. However, drugs cannot control symptoms in about one fourth of people.
How long drugs should be given has not been determined. The dose of the corticosteroid is gradually reduced, and the drug is eventually stopped because these drugs, especially when used for a long time, can have serious side effects. When drugs are stopped, symptoms return in about one half of people, so the drugs may need to be restarted.
High blood pressure must be controlled to prevent complications (see page 339). Angiotensin-converting enzyme (ACE) inhibitors are often used. Taking a low dose of aspirin is usually recommended to help decrease the risk of clotting in the inflamed artery, which can lead to blockages. If an artery that supplies the heart is blocked, a heart attack can result.
If people have difficulty using their arms or walking, bypass surgery may be done to restore the blood flow to the affected limb. Other procedures to restore blood flow (such as coronary artery bypass surgery or percutaneous transluminal coronary angioplasty) may be needed, depending on the symptoms.
Churg-Strauss Syndrome
Churg-Strauss syndrome is inflammation of small blood vessels that damages organs and that usually occurs in people with a history of asthma, nasal allergies, or both.
The cause is unknown.
At first, people may have a runny nose or asthma for months or years or have facial pain, followed by various symptoms, depending on which organs are affected.
Doctors base the diagnosis on symptoms and results of a physical examination, blood tests, a chest x-ray, and biopsy.
Corticosteroids are usually effective, but if a vital organ is affected, another drug that suppresses the immune system may be used.
Churg-Strauss syndrome can occur in people of all ages. The average age at the time of diagnosis is 45 to 50. Almost all affected people have a history of asthma, nasal allergies, or both. The cause is unknown.
Inflammation may affect any organ. The nerves, sinuses, skin, joints, lungs, digestive tract, heart, and kidneys are most commonly affected. Collections of immune cells that cause inflammation (called granulomas) may form nodules in affected tissue. Granulomas can destroy normal tissue and interfere with functioning. They may also cause lumps to form under the skin.
Symptoms
At first, asthma, nasal allergies, or both may develop or worsen. People may sneeze and have a persistently runny nose and itchy eyes. Inflammation of the sinuses may cause facial pain, and polyps may develop in the nose.
People may feel generally ill and tired. They may have fevers or night sweats or lose their appetite and lose weight. Other symptoms depend on which organs are affected and may include the following:
Muscle and joint pain
Shortness of breath
Cough, sometimes bringing up blood
Chest pain
Rashes
Abdominal pain
Blood in the stool
Abnormal sensations, numbness, or weakness in a limb
Any combination of these symptoms may occur. Symptoms may occur in episodes. In subsequent episodes, people may have the same symptoms as the first episode or different ones.
Inflammation of the kidneys may not cause symptoms until the kidneys malfunction and kidney failure develops. Other complications include heart failure, heart attacks, and heart valve disorders.
Diagnosis
Early diagnosis and treatment help prevent severe organ damage.
No single test can confirm the diagnosis. The diagnosis is made by recognizing the combination of typical symptoms and results of the physical examination and other tests.
Blood tests are done. Doctors determine how many eosinophils are in the blood. These white blood cells are produced during allergic reactions, and their number increases when Churg-Strauss syndrome is present. Doctors also look for certain antibodies (antineutrophil cytoplasmic antibodies) that may be present. A chest x-ray is done to look for inflammation in the lungs. Urine tests are done to determine whether the kidneys are affected.
A sample of inflamed tissue is taken and examined under a microscope (biopsy). A biopsy can show whether the tissue contains eosinophils or granulomas. If possible, a sample is taken from the skin or muscle because the biopsy can then be done as an outpatient procedure with only a local anesthetic. Sometimes a biopsy of lung tissue is necessary. It may require hospitalization.
Treatment
Corticosteroids (such as prednisone) are usually used. These drugs can reduce inflammation. If a vital organ is affected, another drug that suppresses the immune system (immunosuppressant) is also used. Azathioprine or methotrexate may be used. Cyclophosphamide is used when the symptoms are severe.
After symptoms resolve, the dose of the drugs is gradually reduced, and after a while, the drugs may be stopped. If necessary, they can be started again. These drugs, especially when taken for a long time, can have serious side effects.
People with Churg-Strauss syndrome should learn about their disorder. Then they can recognize any new symptoms and report them immediately to the doctor.
Henoch-Schönlein Purpura
Henoch-Schönlein purpura is inflammation mainly of small vessels, usually occurring in children.
A rash of reddish purple bumps and spots on the lower legs is usually the first symptom, followed by joint aches, digestive upset, and kidney malfunction.
Biopsy of the affected skin can confirm the diagnosis.
Corticosteroids can relieve joint aches and digestive upset, but occasionally, other drugs that suppress the immune system are also needed.
Henoch-Schönlein purpura usually affects children aged 3 to 15 but can occur at any age. It may develop when the immune system responds abnormally to an infection or something else. It may be triggered by upper respiratory infections, drugs, or insect bites. Blood vessels in the intestine and kidney may become inflamed.
Symptoms
A rash of small spots that look like bruises or reddish purple bumps (purpura) appear on the arms, legs, buttocks, and top of the feet. After a few days or weeks, more spots and bumps may appear, sometimes on the face or trunk. Most children also have a fever and achy, tender, and swollen joints, including the ankles, knees, hips, wrists, and elbows.
Crampy abdominal pain, nausea, vomiting, and diarrhea are common. Stools or urine may contain blood. Rarely, the intestine slides into itself, like a collapsible telescope. This complication, called intussusception, can cause sudden stomach pain and vomiting because the intestine is blocked.
Symptoms usually resolve after about 4 weeks but often recur at least once after a few weeks. Most people recover completely. Rarely, chronic kidney failure develops.
Diagnosis
Doctors suspect the disorder when the characteristic rash occurs in children. If the diagnosis is not clear, a sample from the affected skin is taken and examined under a microscope (biopsy) to look for abnormalities that can confirm the diagnosis. Urine tests are done to check for blood and excess protein, which indicate that the kidneys are affected. Blood tests are usually done to measure kidney function.
If kidney malfunction worsens, a kidney biopsy is done. It can help doctors determine how severe the problem is and what kind of recovery can be expected.
Treatment
If a drug is contributing to the disorder, it is stopped. Otherwise, treatment focuses on relieving symptoms.
It may include nonsteroidal anti-inflammatory drugs (NSAIDs) and bed rest.
Corticosteroids or other drugs, taken by mouth, may help control abdominal pain and are occasionally needed to help control severe joint pain or swelling. If the kidneys or digestive organs are severely affected, methylprednisolone (a corticosteroid), given intravenously, and cyclophosphamide (which suppresses the immune system), taken by mouth, may be used.
Microscopic Polyangiitis
Microscopic polyangiitis is inflammation of mainly small vessels throughout the body.
People have a fever, lose weight, and have achy muscles and joints, as well as various other symptoms depending on the organs affected.
Biopsy is done to confirm the diagnosis.
Treatment depends on disease severity but includes corticosteroids and drugs that suppress the immune system (immunosuppressants).
Microscopic polyangiitis is rare. It can occur at any age. The cause is unknown. People with this disorder usually have abnormal antibodies called antineutrophil cytoplasmic antibodies in their blood. Some people also have hepatitis B or C.
Symptoms
Most people have a fever and lose weight. Muscles and joints often ache.
Various organs may be affected:
Kidneys: The kidneys are affected in up to 90% of people. Blood may appear in the urine, but often there is no sign of kidney malfunction until it is severe. Kidney failure may develop rapidly unless diagnosis and treatment are prompt.
Respiratory tract: People may have nosebleeds or facial pain due to sinusitis. If the lungs are affected, bleeding in the lungs may occur, causing people to cough up blood. The lungs may fill with fluid, and scar tissue may eventually develop. Either problem causes difficulty breathing. Bleeding in the lungs, which may occur early in the disorder, requires immediate medical attention.
Skin: About one third of people have a rash of reddish purple spots and bumps, usually on the legs, feet, or buttocks. The nails may contain thin purplish lines, indicating bleeding (called splinter hemorrhages).
Digestive tract: Abdominal pain, nausea, vomiting, and diarrhea may occur. Stools may contain blood.
Nerves: People may have tingling, numbness, or weakness in a limb.
Brain: Headache may result if the arteries to the brain are affected. Less often, bleeding in the brain (cerebral hemorrhage), stroke, or seizures occur.
Other organs are affected less often.
Diagnosis
Doctors suspect the diagnosis based on symptoms. Blood and urine tests are done. These tests cannot identify the disorder but can confirm that inflammation is present. Blood tests can also help doctors detect bleeding in the digestive tract. Blood is tested for abnormal antibodies, such as antineutrophil cytoplasmic antibodies, which attack certain white blood cells. A sample of urine is tested for red blood cells and protein. This information can help doctors determine whether the kidneys are affected.
A chest x-ray is done to determine whether the lungs are affected. The x-ray can also help doctors determine whether there is bleeding in the lungs. If there are signs of bleeding, a flexible viewing tube is inserted through the nose or mouth into the airways to directly view the lungs (bronchoscopy). This procedure can confirm the presence of bleeding.
A biopsy of affected tissue (usually the skin, lungs, or kidneys) is done to confirm the diagnosis.
Treatment
If symptoms are mild, a corticosteroid plus another drug that suppresses the immune system (immunosuppressant), such as azathioprine or methotrexate, is used. If vital organs are affected, cyclophosphamide, a stronger immunosuppressant, and a corticosteroid are used. Sometimes plasma exchange (plasmapheresis) or methylprednisolone, given intravenously, is used.