Rheumatic fever

Definition

Rheumatic fever (RF) is an illness that occurs as a complication of untreated or inadequately treated strep throat infection. Rheumatic fever causes inflammation of tissues and organs and can result in serious damage to the heart valves, joints, central nervous system and skin.

Rheumatic fever is rare in the United States, though there were outbreaks in both New York City and in Utah in the 1990s. The disease is more prevalent in the developing world, where rheumatic fever is the leading cause of heart disease . In some countries, as many as one to two percent of children are afflicted with the disease.

Description

Though the exact cause of rheumatic fever is unknown, the disease usually follows the contraction of a throat infection caused by a member of the Group A streptococcus (strep) bacteria (called strep throat). The streptococcus A bacteria has also been linked to many serious diseases, including "flesh-eating" disease and toxic shock syndrome . About 9,700 cases of invasive diseases linked to strep A were reported in the United States in 1997. Rheumatic fever may occur in people of any age, but is most common in children between the ages of five and 15. Poverty, overcrowded living conditions, and inadequate access to medical care increase the likelihood of contracting the disease.

The initial strep throat is easily treated with a 10-day course of antibiotics taken orally. However, when a throat infection occurs without symptoms, or when a patient neglects to take the prescribed medication for the full 10-day course of treatment, there is up to an estimated 3% chance that he or she will develop rheumatic fever. Other types of strep infections (such as of the skin) do not put the patient at risk for RF.

Causes & symptoms

Two different theories exist as to how a bacterial throat infection can result in rheumatic fever. One theory, less supported by research evidence, suggests that the bacteria produce some kind of poisonous chemical (toxin). This toxin is sent into circulation throughout the bloodstream, thus affecting other systems of the body. Research more strongly supports the theory that the disease is caused by an interaction between antibodies produced to fight the group A streptococcus bacteria and the heart tissue. The body produces immune cells (antibodies), that are specifically designed to recognize and destroy invading agents. The antibodies are able to recognize the bacteria because the bacteria contain special markers called antigens on their surface. Due to a resemblance between Group A streptococcus bacteria's antigens and antigens present on the body's own cells, the antibodies mistakenly attack the body itself, specifically heart muscle.

In 2002, a report announced that scientists had mapped the genome (genetic material) of an A streptococcus bacterium responsible for acute rheumatic fever. The discovery will help researchers map the factors in the strain of bacterium that help it overcome the body's defenses.

It is interesting to note that members of certain families seem to have a greater tendency to develop rheumatic fever than do others. This could be related to the above theory, in that these families may have cell antigens that more closely resemble streptococcal antigens than do members of other families.

Symptoms of rheumatic fever usually begin one to six weeks after a sore throat . Symptoms may include fatigue and fever, stomach pain, and vomiting . In about 75% of all cases of RF one of the first symptoms is arthritis. The joints (especially those of the ankles, knees, elbows, and wrists) become red, hot, swollen, shiny, and extremely painful. Unlike many other forms of arthritis, symptoms may not occur symmetrically (affecting a particular joint on both the right and left sides, simultaneously). Rather, pain may move from joint to joint. The arthritis of RF rarely strikes the fingers, toes, or spine. The joints become so tender that even the touch of bed sheets or clothing is terribly painful.

A peculiar type of involuntary movement, coupled with emotional instability, occurs in about 10% of all RF patients (the figure used to be about 50%). The patient begins experiencing a change in coordination, often first noted by changes in handwriting. The arms or legs may flail or jerk uncontrollably. The patient seems to develop a low threshold for anger and sadness. This feature of RF is called Sydenham's chorea or St. Vitus' dance.

A number of skin changes are common in rheumatic fever patients. A rash called erythema marginatum develops (especially in those patients who will develop heart problems from their illness), which takes the form of pink splotches that may eventually spread into each other. The rash does not itch. Bumps the size of peas or larger may occur under the skin. These are called subcutaneous nodules; they are hard to the touch, but not painful. These nodules most commonly occur over the knee and elbow joint, as well as over the spine.

The most serious result of RF is called pancarditis (pan means total; carditis refers to inflammation of the heart). Pancarditis is an inflammation that affects all aspects of the heart, including the lining of the heart (endocardium), the sac containing the heart (pericardium), and the heart muscle itself (myocardium). Heart damage caused by RF has the most serious long-term effects. The valves within the heart (structures that allow the blood to flow only in the correct direction, and only at the correct time in the heart's pumping cycle) are frequently damaged, which may result in blood leaking back in the wrong direction, or being unable to pass a stiff, poorly moving valve. Damage to a valve can result in the heart having to work very hard in order to circulate the blood. The heart may not be able to "work around" the damaged valve, which may result in a consistently inadequate amount of blood entering the circulation. About 40-80% of all RF patients develop a form of carditis. Heart damage, however, may not be apparent until months or years after a bout with rheumatic fever. The effect of the disease on the heart also depends on the avoidance of recurrences. The severity of heart damage is often related to the number of attacks of RF a patient experiences.

Diagnosis

The initial description of diagnostic criteria for RF were created by William Cheadle in 1889, during a virulent outbreak of the disease in London. In the 1950s, T. Duckett Jones created a list of both major and minor diagnostics for RF. According to the "Jones Criteria," a patient

can be diagnosed with RF if he or she exhibits either two major criteria (conditions), or one major and two minor criteria. In either case, it must also be proven that the individual has had a previous infection with streptococcus.

The major criteria include:

• carditis
• arthritis
• chorea
• subcutaneous nodules
• erythema marginatum

The minor criteria include:

• fever
• joint pain (without actual arthritis)
• evidence of electrical changes in the heart (determined by measuring electrical characteristics of the heart's functioning during a test called an electrocardiogram, or EKG)
• evidence (through a blood test) of the presence in the blood of certain proteins, which are produced early in an inflammatory/infectious disease

Tests are also performed to provide evidence of recent infection with group A streptococcal bacteria. The doctor may swab the throat and grow a culture to see if the bacteria will grow and multiply. The culture will be processed and examined to identify streptococcal bacteria. Blood tests can be performed to see if the patient is producing antibodies only made in response to a recent strep infection. A doctor may also do an electrocardiogram in order to check for abnormalities in the heartbeat. An echocardiogram, or ultrasound test, may be ordered to check the heart vales, cardiac function and the heart's structure.

Treatment

Though there are no proven effective alternative remedies for rheumatic fever itself, alternative methods may help patients with the results and symptoms of the disease, such as pain relief and improved cardiac function. Rheumatoid arthritis can be treated with a number of alternative therapies:

• Massage: A massage therapist uses gentle strokes to stimulate circulation in and around the joints.
• Aromatherapy: Often combined with massage, the essential oils of rosemary , benzoin, German chamomile , camphor, juniper , or lavender are used to help relieve pain. Oils of cypress, fennel , lemon, and wintergreen may be used to detoxify or reduce inflammation.
• Acupuncture: Uses small needles to stimulate appropriate acupoints for pain relief.
• Osteopathy: Recommends stretching and trigger point therapy to improve mobility, as well as craniofacial massage.

Allopathic treatment

Penicillin is still the most effective treatment for rheumatic fever. A 10-day course of penicillin by mouth, or a single injection of penicillin G is the first line of treatment for RF. Patients will need to remain on some regular dose of penicillin to prevent recurrence of RF. This can mean a small daily dose of penicillin by mouth, or an injection every three weeks. Some practitioners keep patients on this regimen for five years, or until they reach 18 years of age (whichever comes first). Other practitioners prefer to continue treating those patients who will be regularly exposed to streptococcal bacteria (teachers, medical workers), as well as those patients with known RF heart disease.

Of major concern to medical professionals is compliance in taking oral penicillin. A full course of penicillin must be taken to prevent rheumatic fever. However, it is not always easy for patients to follow such a strict regimen. Researchers have found that the time-honored practice of thrice-daily dosing may be unnecessary. Research has shown that twice-daily dosing is just as effective as more frequent doses, and compliance may be improved, since both doses can be administered at home.

Arthritis typically improves quickly when the patient is given a preparation containing aspirin, or some other anti-inflammatory agent (ibuprofen). Mild carditis will also improve with such anti-inflammatory agents; although more severe cases of carditis will require steroid medications. A number of medications are available to treat the involuntary movements of chorea, including diazepam for mild cases, and haloperidol for more severe cases.

Expected results

The long-term prognosis of an RF patient depends primarily on whether he or she develops carditis. This is the only manifestation of RF that can have permanent effects. Those patients with mild or no carditis have an excellent prognosis. Those with more severe carditis have a risk of heart failure, as well as a risk of future heart problems, which may lead to the need for valve replacement surgery.

Prevention

Initial prevention of rheumatic fever depends upon prompt medical attention. Patients should see a physician if they have sore throat that lasts for more than 24 hours and is accompanied by fever. Treatment of a streptococcal throat infection with an appropriate antibiotic will usually prevent the development of rheumatic fever. Prevention of RF recurrence requires continued antibiotic treatment, perhaps for life. Prevention of complications of already-existing RF heart disease require that the patient always take a special course of antibiotics when he or she undergoes any kind of procedure (even dental cleanings) that might allow bacteria to gain access to the bloodstream.

Because of the prevalence of the Strep A bacteria, it is difficult to completely eradicate rheumatic fever. However, progress in identifying a genetic marker for predisposition to the disease and in mapping the virulence (ability to overcome the body's defenses) or the bacteria that lead to rheumatic fever may help lead to a vaccine. Researchers are also seeking to develop a rapid test for strep which would mean earlier detection and more prompt treatment of strep. In addition, in 1999, testing began on a vaccine against group A streptococcus. The development of such a vaccine was halted in the 1970s after children who received the experimental vaccine developed rheumatic fever. In 1979, the Food and Drug Administration (FDA) prohibited group A strep vaccines from ever being licensed for use, the only vaccine to carry such a prohibition. Clinical trials have been approved by the FDA, however, it will be several years before a vaccine is approved. Doctors at the National Institute of Allergy and Infectious Diseases remain hopeful that a vaccine will someday be available.

Resources

BOOKS

Kaplan, Edward L. "Rheumatic Fever." In Harrison's Principles of Internal Medicine. edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

Ryan, Kenneth. "Streptococci." In Sherris Medical Microbiology: An Introduction to Infectious Diseases. Norwalk, CT: Appleton and Lange, 1994.

Stoffman, Phyllis. The Family Guide to Preventing and Treating 100 Infectious Diseases. New York: John Wiley and Sons, Inc., 1995.

Todd, James. "Rheumatic Fever." In Nelson Textbook of Pediatrics. edited by Richard Behrman. Philadelphia: W.B. Saunders Co., 1996.

Woodham, Anne and Dr. David Peters. Dorling Kindersley Encyclopedia of Healing Therapies. New York: Dorling Kindersley, 1997.

PERIODICALS

Albert, Daniel A., et al. "The Treatment of Rheumatic Carditis: A Review and Meta-Analysis." Medicine 74, no. 1 (January 1995): 1+.

Bass, James W., Donald A. Person, and Debora S. Chan. "Twice Daily Oral Penicillin for Treatment of Streptococcal Pharyngitis: Less is Best." Pediatrics 2000 105 (February, 2000): 423-424.

Capizzi, Stephen A., et al. "Rheumatic Fever Revisited: Keep This Diagnosis on Your List of Suspects." Postgraduate Medicine 102, no. 6 (December 1997): 65+.

Eichbaum, Q.G., et al. "Rheumatic Fever: Autoantibodies Against a Variety of Cardiac, Nuclear, and Streptococcal Antigens." Annals of the Rheumatic Diseases 54, no. 9 (September 1995): 740+.

Harder, B. "Deciphering Virulence: Heart-Harming Bacteria Flaunt Unique Viral Genes." Science News 161, no. 13 (March 30, 2002): 197.

Markowitz, Milton. "Rheumatic Fever: A Half-Century Perspective." Pediatrics (July, 1998): 272-275.

Pollack, Andrew. "In the Works: Tests on Strep Vaccine Restart, Gingerly." The New York Times (July 20, 1999): Section F, Page 7, Column 1.

"Rheumatic Fever." In Clinical Reference Systems (July 1, 1999): 1264.

Stollerman, Gene H. "Rheumatic Carditis." Lancet 346, no. 8972 (August 12, 1995): 390+.

Stollerman, Gene H. "Rheumatic Fever." Lancet (March 29, 1997) : 935 - 943.

ORGANIZATIONS

Centers for Disease Control and Prevention. (404) 332-4559. http://www.cdc.gov.

Amy Cooper

Teresa G. Odle

Rheumatic Fever

History

Causesa

Signs and symptoms

Major signs

Minor signs

Treatment and prevention

Resources

Rheumatic fever is an acute inflammatory disease that involves fever and pain, swelling of joints, and redness. In its severe form, rheumatic fever causes inflammation of the heart and can eventually damage the heart valves. it is a rare complication that occurs after an infection with Streptococcus pyogenes bacteria. The most common type of S. pyogenes infection is “strep throat,” in which the tissues that line the pharynx become infected with the bacteria. Rheumatic fever does not occur if the initial strep infection is treated with antibiotics. Major symptoms of rheumatic fever include infection of the protective layers of the heart, arthritis (an inflammation of the joints), skin rashes, and chorea (a condition characterized by abrupt, purposeless movements of the face, hands, and feet). Rheumatic fever is treated with antibiotics, but recurrences are common. To prevent recurrences, preventive antibiotic therapy is administered for at least three years after an initial occurrence.

Rheumatic fever occurs most frequently among the poor in large cities, perhaps because this segment of the population does not have access to health care and is not treated promptly for strep infections. Rheumatic fever is also common in developing countries without access to antibiotics. It is a disease that usually affects young people aged five to 15 years, and girls more frequently than boys. Symptoms often manifest themselves in late summer or early fall if a child has had a throat infection in the spring or early summer. Once common in the United States, since the beginning of the twentieth century there have only been a few outbreaks of the illness. However, when it does occur, the illness is serious. Rheumatic fever has a mortality rate of about from 2 to 5 percent in the United States.

History

Much of what is known about the bacteria that cause rheumatic fever was from initial work performed by American bacteriologist Rebecca Craighill Lancefield (1895–1981) of the Rockefeller Institute (New York). Lancefield was a pioneer in classifying the chains of round bacteria known as streptococci. In her laboratory during the 1920s, she identified many types of streptococci and saw the connection between rheumatic fever and Group A streptococcus. However, she was frustrated in her efforts to discover how the bacteria cause the disease. Why they prompt such a destructive immune system response still remains a mystery.

After Lancefield’s work, and with the coming of the age of antibiotics, penicillin was used to effectively treat rheumatic fever, and still is today. If the initial strep throat infection is treated with antibiotics (such as sulfadizine, penicillin, or erythromycin), the disease cannot progress; however, without treatment, perhaps 1% of cases will develop into rheumatic fever. In conjunction with antibiotics, anti-inflammatory medications are recommended (such as aspirin, except for children, or corticosteroids). Both therapies help to counteract joint pain and minimize heart damage. Sometimes a child with rheumatic fever continues to take low doses of penicillin over a long period of time to prevent recurrence.

Rheumatic fever had almost disappeared in the United States by the early 1980s—only 88 cases were recorded in 1983 as compared to 10,000 in 1961. However, in 1985, two hospitals in Utah alone reported 150 new cases, and outbreaks have since been reported in several other states. In addition, the current strain appears to be more likely to cause heart damage because strep symptoms are much less severe, often being mistaken for a simple cold or other respiratory infection. As of 2005, rheumatic fever and rheumatic heart disease killed over 3,500 people in the United States each year, with about twice the number being women over men. In the developing countries of Asia and Africa, the disease is more common. There is no vaccine to prevent rheumatic fever, nor is there a cure once it develops.

Causesa

Rheumatic fever occurs as a result of a primary infection with Streptococcus pyogenes. If the infection is not treated, the body’s immune system starts to overreact to the presence of the bacteria in the body. Illnesses caused by such overreactions of the immune system are called hypersensitive reactions. Some of the symptoms of rheumatic fever, particularly the involvement of the heart, are thought to be caused by the hypersensitive reactions. Other symptoms may be caused by the release of toxins from the S. pyogenes bacteria that are spread to other parts of the body through the bloodstream.

Not all strains of S. pyogenes cause rheumatic fever; only certain strains of S. pyogenes, called the M strains, have been implicated in cases of rheumatic fever. In addition, not everyone infected with these strains of S. pyogenes will progress to rheumatic fever. Individuals with a specific type of antigen (an immune protein) on their immune cells, called the human leukocyte antigen (HLA), are predisposed to develop rheumatic fever following an untreated strep infection. The specific type of HLA antigen that pre-disposes a person to develop rheumatic fever is called the class II HLA. These individuals develop their susceptibility during early childhood. Children under two years of age rarely contract rheumatic fever; the incidence of the disease increases during childhood from ages five to 15 and then decreases again in early adulthood. Researchers are not sure about the exact mechanism that leads to susceptibility or the role that the class II antigen plays in susceptibility to rheumatic fever.

Signs and symptoms

Rheumatic fever can be difficult to diagnose because the signs and symptoms are diverse. In order to simplify diagnosis, rheumatic fever is indicated if a person has two major manifestations of rheumatic fever, or one major manifestation and two minor manifestations. In both cases, evidence of strep infection is also necessary.

Major signs

The most common sign of rheumatic fever is arthritis, or inflammation of the joints. Arthritis occurs in 75% of rheumatic fever patients. The arthritis is extremely painful and involves the larger joints of the body, such as the knee, elbow, wrist, and ankle. Symptoms include tenderness, warmth, severe pain, and redness. The inflammation resolves by itself in two to three weeks with no lasting effects.

Another common sign of rheumatic fever is carditis, or infection of the linings of the heart. Carditis occurs in 40-50% of patients. Often, the aortic (the valve that connects the left ventricle of the heart to the aorta) and mitral (the valve that connects the left atrium and left ventricle) valves become scarred, leading to a condition called stenosis. In stenosis, the delicate leaflets that make up the valve weld together. The valve is essentially frozen shut, obstructing the flow of blood through the heart. Carditis and stenosis cause few symptoms but are serious manifestations of rheumatic fever. If the carditis is severe, it may lead to heart failure. Congestive heart failure, in which the heart gradually loses its ability to pump blood, occurs in 5-10% of patients with rheumatic fever.

The third most common sign of rheumatic fever occurring in 15% of patients is chorea, in which the face, hands, and feet move in a rapid, non-purposeful way. Patients with chorea may also laugh or cry at unexpected moments. Chorea disappears within a few weeks or months, but is a particularly distressing sign of rheumatic fever.

The least common sign of rheumatic fever occurring in less than 10% of patients is the appearance of subcutaneous (under the skin) nodules. These nodules are painless and localize over the bones and joints. Nodules may last about a month before they disappear. A skin rash called erythema marginatum is also a sign of rheumatic fever. The rash is ring-shaped and painless, and may persist for hours or days and then recur.

Minor signs

Typical minor signs of rheumatic fever include fever, joint pain, prior history of rheumatic fever, and laboratory evidence of a hypersensitive immune response to strep bacteria.

Treatment and prevention

Rheumatic fever is treated primarily with antibiotics. In severe cases of carditis, corticosteroids may be used to reduce inflammation. Because rheumatic fever tends to recur, patients must continue antibiotic therapy in order to prevent subsequent strep infections. Typically, this preventive antibiotic therapy should last for three to five years after the initial infection. Some researchers recommend that preventive antibiotics be administered until early adulthood.

Aspirin is useful in treating arthritis caused by rheumatic fever. In fact, if arthritic symptoms respond particularly well to aspirin, the diagnosis of rheumatic fever is strengthened.

Rheumatic fever can be prevented entirely if strep infections are diagnosed correctly and antibiotic treatment is initiated within ten days of onset. A severe sore throat that is red and swollen, accompanied by fever and general fatigue, should be examined by a physician, and tested for the presence of strep bacteria. Patients diagnosed with strep throat must be sure to take their full course of antibiotics, as incompletely healed infections may also lead to rheumatic fever.

KEY TERMS

Antibiotic— A drug that targets and kills bacteria.

Antigen— A molecule, usually a protein, that the body identifies as foreign and toward which it directs an immune response.

Aortic stenosis— The welding of the leaflets of the valve that connects the left ventricle to the aorta.

Arthritis— Inflammation of the joints.

Carditis— Infection of the protective layers of the heart.

Chorea— Rapid, random movements of the face, hands, and feet.

Human leukocyte antigen (HLA)— A type of antigen present on white blood cells; divided into several distinct classes; each individual has one of these distinct classes present on their white blood cells.

Hypersensitive reaction— An immune reaction in which the body’s immune system overreacts to the presence of antigens in the body; may lead to disease.

Mitral stenosis— The welding of the leaflets that make up the mitral valve of the heart.

Resources

BOOKS

Editors of the World Health Organization. Braunwald’s Rheumatic Fever and Rheumatic Heart Disease: Report of a WHO Expert Consultation. Geneva, Switzerland: World Health Organization, 2004.

Fuster, Valentin, ed. Hurst’s The Heart. New York: McGraw-Hill, Medical Publications Division, 2004.

Rosendorff, Clive, ed. Essential Cardiology: Principles and Practice. Totowa, NJ: Humana Press, 2005.

Zipes, Douglas, ed. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. Philadelphia, PA: W.B. Saunders, 2005.

Kathleen Scogna

Rheumatic fever

Definition

Rheumatic fever (RF) is an illness that arises as a complication of untreated or inadequately treated strep throat infection. Rheumatic fever can seriously damage the valves of the heart.

Description

Throat infection with a member of the Group A streptococcus (strep) bacteria is a common problem among school-aged children. It is easily treated with a 10-day course of antibiotics by mouth. However, when such a throat infection occurs without symptoms, or when a course of medication is not taken for the full ten days, there is a 3 percent chance the person will develop rheumatic fever. Other types of strep infections (such as of the skin) do not put the patient at risk for RF.

Demographics

Children between the ages of five and 15 are most susceptible to strep throat, and therefore most susceptible to rheumatic fever. Other risk factors include poverty, overcrowding (as in military camps), and lack of access to good medical care. Just as strep throat occurs most frequently in fall, winter, and early spring, so does rheumatic fever. Rheumatic fever used to be a leading cause of death and disability in children. Since 1960, it has become much less common in the United States, partially because of increasingly accurate and swift diagnosis of strep throat. It is still a large problem in many developing countries. Moreover, children who have family members who have had rheumatic fever are more likely to get rheumatic fever themselves.

Causes and symptoms

Two different theories exist about how a bacterial throat infection can develop into rheumatic fever. One theory suggests that the bacteria produce some kind of poisonous chemical (toxin). This toxin is sent into circulation throughout the bloodstream, thus affecting other systems of the body.

Research seems to point to a different theory, however. The second theory suggests that the disease is caused by the body's immune system acting inappropriately. The body produces immune cells (called antibodies), that are specifically designed to recognize and destroy invading agent—in this case, streptococcal bacteria. The antibodies are able to recognize the bacteria because the bacteria contain special markers called antigens. Due to a resemblance between Group A streptococcus bacteria's antigens and antigens present on the body's own cells, the antibodies may mistakenly attack the body itself.

It is interesting to note that members of certain families seem to have a greater tendency to develop rheumatic fever than do others. This statistical fact could be related to the above theory, in that these families may have cell antigens that more closely resemble streptococcal antigens than do members of other families.

In addition to fever, in about 75 percent of all cases of RF one of the first symptoms is arthritis. The joints (especially those of the ankles, knees, elbows, and wrists) become red, hot, swollen, shiny, and extraordinarily painful. Unlike many other forms of arthritis, this arthritis may not occur symmetrically (affecting a particular joint on both the right and left sides, simultaneously). The arthritis of RF rarely strikes the fingers, toes, or spine. The joints become so tender that even the touch of bed sheets or clothing is terribly painful.

A particular type of involuntary movement, coupled with emotional instability, occurs in about 10 percent of all RF patients. The patient begins experiencing a change in coordination, often first noted by changes in handwriting. The arms or legs may flail or jerk uncontrollably. The patient seems to develop a low threshold for anger and sadness. This feature of RF is called Sydenham's chorea or St. Vitus' dance.

A number of skin changes are common to RF. A rash called erythema marginatum often develops (especially in those patients who will develop heart problems from their illness), composed of pink splotches that may eventually spread into each other. The rash does not itch. Bumps the size of peas may occur under the skin. These are called subcutaneous nodules. They are hard to the touch, but not painful. These nodules most commonly occur over the knee and elbow joint, as well as over the spine.

The most serious problem occurring in RF is called pancarditis ("pan" means total; "carditis" refers to inflammation of the heart). Pancarditis is an inflammation that affects all aspects of the heart, including the lining of the heart (endocardium), the sac containing the heart (pericardium), and the heart muscle itself (myocardium). About 40 to 80 percent of all RF patients develop pancarditis. This RF complication has the most serious, long-term effects. The valves within the heart (structures that allow the blood to flow only in the correct direction and only at the correct time in the heart's pumping cycle) are frequently damaged during the course of pancarditis. This effect may result in blood that either leaks back in the wrong direction or has a difficult time passing a stiff, poorly moving valve. Either way, damage to a valve can result in the heart having to work very hard in order to move the blood properly. The heart may not be able to "work around" the damaged valve, which may result in a consistently inadequate amount of blood entering the circulation.

When to call the doctor

The doctor should be contacted if the child is displaying any of the signs or symptoms of rheumatic fever. If they are not indications of rheumatic fever, they could be indicative of another disease or disorder. The doctor should also be contacted if the child has had a sore throat and fever for more than 24 hours. The doctor will do a strep test, and if the child does have strep throat the doctor can administer antibiotics that will help prevent rheumatic fever.

Diagnosis

There are no laboratory tests that can determine with complete certainty if a child has rheumatic fever. Some laboratory tests may be used in conjunction with careful examination of the patient to determine if the child has RF. A list of diagnostic criteria has been created. These "Jones Criteria" are divided into major and minor criteria. A patient can be diagnosed with RF if he or she has either two major criteria (conditions) or one major and two minor criteria. In either case, it must also be proved that the individual has had a previous infection with streptococcus.

The major criteria include:

• carditis
• arthritis
• chorea
• subcutaneous nodules
• erythema marginatum

The minor criteria include:

• fever
• joint pain (without actual arthritis)
• evidence of electrical changes in the heart (determined by measuring electrical characteristics of the heart's functioning during a test called an electrocardiogram, or EKG)
• evidence (through a blood test) of the presence in the blood of certain proteins that are produced early in an inflammatory/infectious disease

Tests are also performed to provide evidence of recent infection with group A streptococcal bacteria. A swab of the throat can be taken and smeared on a gel-like substance in a petri dish to see if bacteria will multiply and grow over 24 to 72 hours. These bacteria can then be specially processed and examined under a microscope to identify streptococcal bacteria. Other tests can be performed to see if the patient is producing specific antibodies that are only made in response to a recent strep infection.

Treatment

A 10-day course of penicillin by mouth or a single injection of penicillin G is usually the first line of treatment for RF. If the child does not tolerate or is allergic to penicillin, other antibiotics can be used effectively. These antibiotics are given to help cure a strep infection, if the child still has one. Patients will need to remain on some regular dose of antibiotic to prevent recurrence of RF. This can mean a small daily dose of antibiotic by mouth or an injection every three to four weeks. Some practitioners keep patients on this regimen for five years or until they reach 18 years of age whichever comes first. Other practitioners prefer to continue treating those patients who will be regularly exposed to streptococcal bacteria (teachers, medical workers), as well as those patients with known RF heart disease.

Arthritis quickly improves when the patient is given a preparation containing aspirin or some other anti-inflammatory agent (e.g. ibuprofen). Mild carditis also improves with such anti-inflammatory agents, although more severe cases of carditis require steroid medications. A number of medications are available to treat the involuntary movements of chorea, including diazepam for mild cases and haloperidol for more severe cases.

Prognosis

The long-term prognosis of an RF patient depends primarily on whether he or she develops carditis. This manifestation of RF is the only one that can have permanent effects. Those patients with no or mild carditis have an excellent prognosis. Those with more severe carditis have a risk of heart failure, as well as a risk of future heart problems that may lead to the need for valve replacement surgery. Patients who have had rheumatic fever are at an increased risk of getting it again.

KEY TERMS

Antibody —A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.

Antigen —A substance (usually a protein) identified as foreign by the body's immune system, triggering the release of antibodies as part of the body's immune response.

Arthritis —A painful condition that involves inflammation of one or more joints.

Autoimmune disorder —One of a group of disorders, like rheumatoid arthritis and systemic lupus erythematosus, in which the immune system is overactive and has lost the ability to distinguish between self and non-self. The body's immune cells turn on the body, attacking various tissues and organs.

Chorea —Involuntary movements in which the arms or legs may jerk or flail uncontrollably.

Immune system —The system of specialized organs, lymph nodes, and blood cells throughout the body that work together to defend the body against foreign invaders (bacteria, viruses, fungi, etc.).

Inflammation —Pain, redness, swelling, and heat that develop in response to tissue irritation or injury. It usually is caused by the immune system's response to the body's contact with a foreign substance, such as an allergen or pathogen.

Pancarditis —Inflammation of the lining of the heart, the sac around the heart, and the muscle of the heart.

Prevention

Prevention of the development of RF involves proper diagnosis of initial strep throat infections and adequate treatment within 10 days with an appropriate antibiotic. Prevention of RF recurrence requires continued antibiotic treatment, perhaps for life. Prevention of complications of already-existing RF heart disease requires that the patient always take a special course of antibiotics when he or she undergoes any kind of procedure (even dental cleanings) that might allow bacteria to gain access to the bloodstream.

Parental concerns

Rheumatic fever can be life-threatening if not treated. It can also lead to lifelong heart problems. The best way for parents to prevent rheumatic fever is to take seriously sore throats that are accompanied with fever and to take the child to a doctor to test for strep throat. Children who have had rheumatic fever need to take extra precautions to ensure they do not have repeat attacks triggered by strep infections.

See also Strep throat.

Resources

BOOKS

Margulies, Phillip. Everything You Need to Know about Rheumatic Fever. New York: Rosen Publishing Group, 2004.

PERIODICALS

Mercadante, Marcos T., et al. "The Psychiatric Symptoms of Rheumatic Fever." American Journal of Psychiatry 157, i.12 (December 2000): 2036.

Steeg, Carl N., et al. "Rheumatic Fever: No Cause for Complacence." Patient Care 34, i.14 (July 30, 2000): 40.

Stollerman, Gene H. "Rheumatic Fever in the 21st Century." Clinical Infectious Diseases 33, no. 16 (September 15, 2001): 806.

ORGANIZATIONS

American Heart Association. 7272 Greenville Ave., Dallas, TX 75231. Web site: <www.americanheart.org>.

Tish Davidson, A.M.
Rosalyn Carson-DeWitt, MD

Rheumatic Fever

Definition

Rheumatic fever (RF) is an illness which arises as a complication of untreated or inadequately treated strep throat infection. Rheumatic fever can seriously damage the valves of the heart.

Description

Throat infection with a member of the Group A streptococcus (strep) bacteria is a common problem among school-aged children. It is easily treated with a ten-day course of antibiotics by mouth. However, when such a throat infection occurs without symptoms, or when a course of medication is not taken for the full ten days, there is a 3% chance of that person developing rheumatic fever. Other types of strep infections (such as of the skin) do not put the patient at risk for RF.

Children between the ages of five and fifteen are most susceptible to strep throat, and therefore most susceptible to rheumatic fever. Other risk factors include poverty, overcrowding (as in military camps), and lack of access to good medical care. Just as strep throat occurs most frequently in fall, winter, and early spring, so does rheumatic fever.

Causes and symptoms

Two different theories exist as to how a bacterial throat infection can develop into the disease called rheumatic fever. One theory, less supported by research evidence, suggests that the bacteria produce some kind of poisonous chemical (toxin). This toxin is sent into circulation throughout the bloodstream, thus affecting other systems of the body.

Research seems to point to a different theory, however. This theory suggests that the disease is caused by the body's immune system acting inappropriately. The body produces immune cells (called antibodies), which are specifically designed to recognize and destroy invading agents; in this case, streptococcal bacteria. The antibodies are able to recognize the bacteria because the bacteria contain special markers called antigens. Due to a resemblance between Group A streptococcus bacteria's antigens and antigens present on the body's own cells, the antibodies mistakenly attack the body itself.

It is interesting to note that members of certain families seem to have a greater tendency to develop rheumatic fever than do others. This could be related to the above theory, in that these families may have cell antigens which more closely resemble streptococcal antigens than do members of other families.

In addition to fever, in about 75% of all cases of RF one of the first symptoms is arthritis. The joints (especially those of the ankles, knees, elbows, and wrists) become red, hot, swollen, shiny, and extraordinarily painful. Unlike many other forms of arthritis, the arthritis may not occur symmetrically (affecting a particular joint on both the right and left sides, simultaneously). The arthritis of RF rarely strikes the fingers, toes, or spine. The joints become so tender that even the touch of bedsheets or clothing is terribly painful.

A peculiar type of involuntary movement, coupled with emotional instability, occurs in about 10% of all RF patients (the figure used to be about 50%). The patient begins experiencing a change in coordination, often first noted by changes in handwriting. The arms or legs may flail or jerk uncontrollably. The patient seems to develop a low threshold for anger and sadness. This feature of RF is called Sydenham's chorea or St. Vitus' Dance.

A number of skin changes are common to RF. A rash called erythema marginatum develops (especially in those patients who will develop heart problems from their illness), composed of pink splotches, which may eventually spread into each other. It does not itch. Bumps the size of peas may occur under the skin. These are called subcutaneous nodules; they are hard to the touch, but not painful. These nodules most commonly occur over the knee and elbow joint, as well as over the spine.

The most serious problem occurring in RF is called pancarditis ("pan" means total; "carditis" refers to inflammation of the heart). Pancarditis is an inflammation that affects all aspects of the heart, including the lining of the heart (endocardium), the sac containing the heart (pericardium), and the heart muscle itself (myocardium). About 40-80% of all RF patients develop pancarditis. This RF complication has the most serious, long-term effects. The valves within the heart (structures which allow the blood to flow only in the correct direction, and only at the correct time in the heart's pumping cycle) are frequently damaged during the course of pancarditis. This may result in blood which either leaks back in the wrong direction, or has a difficult time passing a stiff, poorly moving valve. Either way, damage to a valve can result in the heart having to work very hard in order to move the blood properly. The heart may not be able to "work around" the damaged valve, which may result in a consistently inadequate amount of blood entering the circulation.

Diagnosis

Diagnosis of RF is done by carefully examining the patient. A list of diagnostic criteria has been created. These "Jones Criteria" are divided into major and minor criteria. A patient can be diagnosed with RF if he or she has either two major criteria (conditions), or one major and two minor criteria. In either case, it must also be proved that the individual has had a previous infection with streptococcus.

The major criteria include:

• carditis
• arthritis
• chorea
• subcutaneous nodules
• erythema marginatum

The minor criteria include:

• fever
• joint pain (without actual arthritis)
• evidence of electrical changes in the heart (determined by measuring electrical characteristics of the heart's functioning during a test called an electrocardiogram, or EKG)
• evidence (through a blood test) of the presence in the blood of certain proteins, which are produced early in an inflammatory/infectious disease.

Tests are also performed to provide evidence of recent infection with group A streptococcal bacteria. A swab of the throat can be taken, and smeared on a substance in a petri dish, to see if bacteria will multiply and grow over 24-72 hours. These bacteria can then be specially processed, and examined under a microscope, to identify streptococcal bacteria. Other tests can be performed to see if the patient is producing specific antibodies; that are only made in response to a recent strep infection.

Treatment

A 10-day course of penicillin by mouth, or a single injection of penicillin G-is the first line of treatment for RF. Patients will need to remain on some regular dose of penicillin to prevent recurrence of RF. This can mean a small daily dose of penicillin by mouth, or an injection every three weeks. Some practitioners keep patients on this regimen for five years, or until they reach 18 years of age (whichever comes first). Other practitioners prefer to continue treating those patients who will be regularly exposed to streptococcal bacteria (teachers, medical workers), as well as those patients with known RF heart disease.

Arthritis quickly improves when the patient is given a preparation containing aspirin, or some other anti-inflammatory agent (ibuprofen). Mild carditis will also improve with such anti-inflammatory agents, although more severe cases of carditis will require steroid medications. A number of medications are available to treat the involuntary movements of chorea, including diazepam for mild cases, and haloperidol for more severe cases.

Prognosis

The long-term prognosis of an RF patient depends primarily on whether he or she develops carditis. This is the only manifestation of RF which can have permanent effects. Those patients with no or mild carditis have an excellent prognosis. Those with more severe carditis have a risk of heart failure, as well as a risk of future heart problems, which may lead to the need for valve replacement surgery.

Prevention

Prevention of the development of RF involves proper diagnosis of initial strep throat infections, and adequate treatment within 10 days with an appropriate antibiotic. Prevention of RF recurrence requires continued antibiotic treatment, perhaps for life. Prevention of complications of already-existing RF heart disease requires that the patient always take a special course of antibiotics when he or she undergoes any kind of procedure (even dental cleanings) that might allow bacteria to gain access to the bloodstream.

Resources

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. 〈http://www.cdc.gov〉.

KEY TERMS

Antibodies— 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.

Arthritis— Inflammation of the joints.

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.

Chorea— Involuntary movements in which the arms or legs may jerk or flail uncontrollably.

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.

Pancarditis— Inflammation of the lining of the heart, the sac around the heart, and the muscle of the heart.

RHEUMATIC FEVER

DEFINITION

Rheumatic fever (RF; pronounced roo-MAT-ic FEE-ver) is a disease caused by a group of bacteria known as Group A streptococcus (pronounced STREP-tuh-cac-us). The exact conditions that lead to rheumatic fever are not well understood. However, the condition often follows a case of strep throat that was not treated or not treated correctly. Rheumatic fever can seriously damage the valves of the heart.

DESCRIPTION

Streptococcal infections of the throat and ear are common in young children. These infections can be treated efficiently with antibiotics. When so treated, the infections clear up in about a week. Patients seldom experience complications.

Some streptococcal infections are very mild, however. Children may experience no symptoms, so their parents do not seek medical advice. Also, patients sometimes do not take their full course of medication. They stop taking pills when their symptoms are gone. But streptococcal bacteria may still be present. In either of these cases, complications may develop. One of the most serious complications is rheumatic fever.

Children between the ages of five and fifteen are at greatest risk for RF. The rate of RF in the United States has dropped dramatically. Today, it is rarely seen in this country. It continues to be widespread in developing nations, however. Poverty, overcrowding, and lack of access to proper medical care contribute to the high rate of RF in these areas.

CAUSES

There is still some debate as to how rheumatic fever develops. The most popular theory is that the condition is caused by the body's own immune system. The immune system consists of organs, tissues, cells, and chemicals designed to attack foreign invaders, such as bacteria or viruses. One way the immune system protects the body is with antibodies. Antibodies are chemicals produced to fight off specific foreign agents. There is a specific type of antibody, for example, for every bacterium and virus that can invade the human body.

But the immune system sometimes makes mistakes and produces antibodies that attack the body's own cells. The antibodies kill cells and cause a type of disease known as an autoimmune ("against itself") disorder. Rheumatic fever is thought to be an autoimmune disorder (see autoimmune disorder entry).

SYMPTOMS

In addition to fever, there are five main symptoms of RF. One symptom is arthritis (see arthritis entry). Arthritis is an inflammation of the joints that causes severe pain and swelling. In the case of RF, arthritis produces red, hot, swollen, shiny, and very painful joints of the ankles, knees, elbows, and wrists. The joints may become so sore that even the touch of bed sheets or clothing is too painful to endure.

A second symptom of RF is chorea (pronounced co-REE-uh). Chorea is a disorder of the nervous system. It causes a patient to lose coordination and develop jerky movements of the arms and legs. The patient may also develop emotional problems. He or she may become angry or sad for no reason at all. The chorea that occurs as a result of RF is called Syndenham's chorea. At one time, the condition was known as St. Vitus's Dance.

A third symptom of RF is a rash. The rash consists of pink splotches on the body that are not itchy. The medical term for this rash is erythema marginatum (pronounced air-uh-THEE-muh MAR-gin-ay-tum). Along with the rash there may be small bumps just under the skin. The bumps are hard to the touch but not painful. They occur most commonly over the knee and elbow joints. The bumps constitute the fourth symptom of RF. They are also known as subcutaneous nodules (pronounced sub-CYOO-taynee-us NOD-yools).

Rheumatic Fever: Words to Know

Antibodies:

Chemicals produced by the body's immune system to fight off very specific foreign invaders, such as bacteria and viruses.

Arthritis:

Inflammation of the joints.

Autoimmune disorder:

A medical condition in which the body's immune system mistakes the body's own tissues for foreign invaders and attempts to destroy those tissues.

Carditis:

Inflammation of the heart.

Chorea:

Involuntary movements that may cause the arms or legs to jerk about uncontrollably.

Immune system:

A system of organs, tissues, cells, and chemicals that work together to fight off foreign invaders, such as bacteria and viruses.

Inflammation:

The body's response to tissue damage that includes heat, swelling, redness, and pain.

The fifth and most serious symptom of rheumatic fever is called carditis (pronounced car-DIE-tis). The term "carditis" means an inflammation of the heart. About 40 percent to 80 percent of all patients with rheumatic fever develop carditis. It is the most serious complication associated with RF.

One common effect of carditis is damage to the heart valves. The heart valves are flaps of tissue that control the flow of blood in the heart. They ensure that blood always flows in the right direction as it passes through the heart.

If heart valves are damaged, one of two things can happen. First, the flow of blood reverses direction. Second, the valves become so stiff that it is difficult for blood to get through them. Either way, the heart has to work unusually hard to keep blood moving properly. In some cases, the heart has to work so hard that it becomes weakened or fails. The patient develops chronic (long-term) heart disease or dies of a heart attack.

DIAGNOSIS

Diagnosis of rheumatic fever can be difficult because patients may have one, two, or more of the five symptoms listed above. The five symptoms for which a doctor looks include arthritis, chorea, carditis, erythema marginatum, and subcutaneous nodules. Fever is also present. However, fever by itself is not of much use in making a diagnosis. Many kinds of medical disorders have fever as a symptom.

GERHARD DOMAGK

Gerhard Domagk was a German biochemist who was born on October 30, 1895. He earned his medical degree in 1921 and then took a job with a large company, Farbenindustrie. Farbenindustrie manufactured industrial dyes.

Domagk was interested in finding out whether any of the dyes produced by Farbenindustrie had biological effects on animals. In one study, he injected a dye called Prontosil Red into a group of experimental mice. The mice had been given a streptococcus infection. Domagk was amazed to discover that the mice were cured of their disease by the dye.

That discovery might have lead nowhere except for a terrible event in Domagk's life. His daughter Hildegarde pricked herself with a knitting needle and developed a streptococcal infection herself. In desperation, Domagk injected Prontosil Red into his daughter. Again, the dye seemed to work miracles. Hildegarde quickly recovered from the disease.

Shortly after these events, the French chemist Daniele Bovet explained how Prontosil Red works. He showed that only one part of the compound was involved in killing bacteria. That part was a molecule called sulfanilamide. Sulfanilamide was the first of a large group of related compounds, called sulfanamides (or "sulfa drugs") to be used against bacterial infections.

A number of laboratory tests are also used to diagnose RF. For example, a throat smear can be taken to look for the presence of streptococcal bacteria. In a throat smear, a cotton swab is rubbed across the back of the patient's

throat. The material collected on the swab is then placed in a warm, moist environment for twenty-four to seventy-two hours. Any bacteria present in the material begin to grow during that period. If streptococcal bacteria are present, they can be seen with a microscope.

Laboratory tests can also be used to look for antibodies to the streptococcal bacteria. Blood taken from the patient's arm can be treated with chemicals that make these antibodies show up. The presence of the antibodies means that the patient has been infected with the streptococcal bacteria.

An electrocardiogram (ECG; pronounced ih-LEK-tro-KAR-dee-o-gram) can also be used to diagnose RF. An electrocardiogram is a test that measures the electrical activity of the heart. If the heart has been damaged by carditis, its electrical rhythms will be different from those of a healthy heart.

All of these symptoms and tests taken together can provide a diagnosis of rheumatic fever.

TREATMENT

Rheumatic fever is usually treated with penicillin. The patient usually receives a single injection or a ten-day course of pills. Doctors often prescribe a regular dose of penicillin after the symptoms of RF disappear. This program helps prevent the return of RF. Other patients who continue to receive regular doses of penicillin are those individuals who may come into contact with the streptococcal bacterium. This group includes teachers and medical workers, as well as patients with known RF heart disease.

The symptoms of arthritis can be treated with aspirin, acetaminophen (Tylenol), or ibuprofen (Motrin, Advil). These same drugs can be used to treat mild cases of carditis. Aspirin should not be given to children with a fever because it may cause the serious illness Reye's syndrome (see Reye's syndrome entry). More severe cases of carditis are treated with steroid medications. Chorea is treated with a variety of sedatives and tranquilizers that help relax the patient.

PROGNOSIS

RF patients who do not develop carditis have an excellent prognosis. Other symptoms of the disease eventually disappear without complications. Even patients who have mild cases of carditis are likely to experience a full recovery. Severe cases of carditis are another matter. In this case, patients are likely to develop a variety of heart problems that may lead to heart failure. Serious heart problems can often be treated by surgery.

PREVENTION

Rheumatic fever can be prevented with early and proper diagnosis of streptococcal infections of the throat and ears. If antibiotics are given within ten days, the risk of the infection's developing into rheumatic fever is very low.

People who have had rheumatic fever are at risk for contracting the disease again. To prevent the condition from returning, a patient may have to stay on antibiotics for a long time—perhaps for life. People who already have heart damage resulting from RF can prevent further complications. The usual procedure is for the patient to take antibiotics any time he or she might be exposed to the streptococcal bacterium.

FOR MORE INFORMATION

Books

Stoffman, Phyllis. The Family Guide to Preventing and Treating 100 Infectious Diseases. New York: John Wiley and Sons, Inc. 1995.

Web sites

"Rheumatic Fever." Yahoo! Health. [Online] http://dir.yahoo.com/Health/Diseases_and_Conditions/Rheumatic_Fever (accessed on November 5, 1999).

"Rheumatic fever." HealthAnswers Medical Reference Library. [Online] http://www.healthanswers.com/adam/top/view.asp?filename=003940.htm&rdir (accessed on November 5, 1999).