Rheumatic Fever

Rheumatic fever is an autoimmune disease that sometimes occurs after strep throat.

Rheumatic fever (acute rheumatic fever or ARF) is an autoimmune disease that may occur after a group A streptococcal throat infection. Such a reaction to strep throat causes inflammatory lesions in connective tissue, the heart, joints, and blood vessels of various organs and subcutaneous tissue. The disease has been around since the 1500s, but the association between throat infection and rheumatic fever symptom development was not described until the 1880s.

The sore throat was later associated with fever and rash (caused by streptococcal exotoxins) in the 1900s. Prior to the broad availability of penicillin, rheumatic fever was a leading cause of death in children and one of the leading causes of acquired heart disease in adults. The disease has many symptoms and can affect different parts of the body, including the heart, joints, skin, and brain.

There is no single diagnostic test for rheumatic fever, so the American Heart Association's modified Jones criteria (first published in 1944 and modified in 1992) guide the physician in making the proper diagnosis.

There is a direct and well-described connection between certain streptococcal infections and rheumatic fever. Most commonly, rheumatic fever is preceded by a throat infection caused by group A beta-hemolytic Streptococcus bacteria (strep throat, GABHS, or GAS). The bacterium causes an autoimmune (antibodies that attack the host's own cells) inflammatory response in some people which leads to the myriad of signs and symptoms described by the revised Jones criteria.

Streptococcal throat infections are contagious, but rheumatic fever is not. The symptoms of rheumatic fever generally develop within two to three weeks following infection with streptococcal bacteria, and usually, the first symptoms are painful joints or arthritis.

It is still not fully understood why some people develop an abnormal immune response to group A streptococcus bacteria, while others do not. However, it is believed that certain factors may increase the risk of developing acute rheumatic fever, including:

• Genetics: Certain genes may make some individuals more susceptible to developing acute rheumatic fever after a streptococcal infection.
• Environmental factors: Environmental factors such as poor sanitation and crowded living conditions may increase the risk of streptococcal infections, which can lead to acute rheumatic fever.
• Age and gender: Acute rheumatic fever is most common in children between the ages of 5 and 15, and it occurs more frequently in girls than in boys.
• Delayed or inadequate treatment of streptococcal infections: The risk of developing acute rheumatic fever increases if streptococcal infections are left untreated or are inadequately treated with antibiotics.

As mentioned above, there are quite a few symptoms associated with rheumatic fever. The symptoms usually develop about two to four weeks after a streptococcal infection (strep throat), and they can persist for several weeks or months.

Major Jones criteria include the following:

1. Carditis (inflammation of the heart), which occurs in 60% of patients, is the most severe symptom of ARF and can result in permanent damage to the heart valves, the heart muscle itself, or the tissue surrounding the heart (pericardium). These effects can be life-threatening.
2. Polyarthritis or migratory polyarthritis (joint inflammation), which is usually the first presenting symptom of ARF, occurs in 45% of patients. Large joints (knees, ankles, elbows, and wrists) are the most commonly affected. The pain may be moderately painful.
3. Some affected people have small, firm, painless lumps beneath the skin that are most common around the wrists, elbows, and knees. These are present in only about 2% of affected people.
4. Erythema marginatum is a characteristic rash that occurs in 5% of patients. The rash is wavy and has a snakelike appearance (serpiginous) that has distinct erythematous (red) borders or "margins." The rash is not itchy or painful, starts on the trunk, and expands to involve the extremities. It does not affect the face.
5. Sydenham's chorea occurs in 30% of patients and is a movement disorder comprising of uncontrollable, purposeless, volatile movements of the face and arms. This was also called St. Vitus' dance, which was named after the patron saint of the "mania dancers" of the middle ages. This movement disorder is characteristic of ARF and may be associated with emotional disturbances and inappropriate behaviors. This movement disorder may appear months following the GAS throat infection.

Minor Jones criteria include the following:

1. Fever is often present during the acute infection with group A strep and is present during the initial phase of rheumatic fever.
2. Arthralgia -- sore joints without evidence of swelling, warmth, or associated skin changes
3. Previous rheumatic fever or rheumatic heart disease
4. Nonspecific laboratory changes of inflammation: elevated white blood cell (WBC) levels, elevated erythrocyte sedimentation rate (ESR), and elevated C-reactive protein (CRP)
5. Characteristic changes on an electrocardiogram (EKG)

Evidence of a preceding GAS infection includes

1. positive throat culture for GAS,
2. positive rapid throat test for GAS,
3. recent scarlet fever, or an
4. increase in anti-strep antibodies -- rising ASO, anti-DNase B, or anti-hyaluronidase titers.

The revised Jones criteria are guidelines decided on by the American Heart Association to help doctors diagnose rheumatic fever. Two major criteria or one major and two minor criteria plus laboratory evidence of a preceding group A streptococcal (GAS) infection are required to make the diagnosis of rheumatic fever.

The major criteria for diagnosis include

1. Migratory arthritis of several joints (polyarthritis): Inflammation of multiple joints, typically involving the knees, ankles, wrists, and elbows.
2. Heart inflammation (carditis: pericarditis or heart valve disease): This can be detected using an echocardiogram or other imaging tests.
3. Subcutaneous nodules under the skin: Small painless, firm bumps, typically located over bony prominences such as the elbows and knees.
4. Chorea: Rapid, jerky movements (Sydenham's chorea, also known as St. Vitus' dance)
5. A characteristic skin rash (erythema marginatum): A distinctive skin rash that appears as red, raised, and ring-shaped patches on the trunk and limbs.

The minor criteria for diagnosis include

• fever,
• elevated ESR (erythrocyte sedimentation rate or CRP [C-reactive protein], nonspecific laboratory signs of inflammation),
• joint pain (arthralgia),
• EKG (electrocardiogram) changes, and
• history of previous acute rheumatic fever or rheumatic heart disease.

Evidence of preceding streptococcal infection includes the following:

• Positive throat culture for GAS infection
• Positive rapid direct GAS throat swab
• Recent scarlet fever
• Supporting blood studies for recent GAS infection. These could include rising ASO titers, anti-DNase titers, or anti-hyaluronidase titers. Measurement of rising ASO titers is the preferred study.

The person must have a history of infection with group A streptococcal bacteria, either by laboratory documentation (for example, a positive rapid strep test) or positive strep culture, and must have two major or one major and two minor revised Jones criteria findings.

During a physical examination, the healthcare professional will look for signs of inflammation in the body, including joint swelling, skin rash, and abnormal heart sounds. They may also look for signs of Sydenham's chorea.

Diagnostic tests that may be used to diagnose rheumatic fever include:

• Blood tests: Blood tests can help detect signs of inflammation and streptococcal infection, such as elevated levels of white blood cells and antibodies to the streptococcus bacteria.
• Echocardiogram: This test uses ultrasound waves to produce images of the heart and can help detect abnormalities in the heart valves or heart muscle.
• Electrocardiogram (ECG): This test measures the electrical activity of the heart and can help detect abnormal heart rhythms or other abnormalities.
• Throat culture: A sample of a throat swab may be taken to check for the presence of streptococcus bacteria.
• Joint fluid analysis: If joint swelling is present, a sample of fluid from the affected joint may be taken and analyzed for signs of inflammation.

Patients with rheumatic fever can survive and recover with appropriate treatment. Early diagnosis and treatment are essential to prevent the development of serious complications. 

With prompt and effective treatment, most people with rheumatic fever recover completely within a few weeks to several months. However, in some cases, the damage to the heart valves caused by rheumatic fever may be permanent, leading to long-term complications such as rheumatic heart disease.

The first step in treating rheumatic fever is to eradicate the bacteria (usually with penicillin) that initially caused the immunologic response. For penicillin-allergic patients, there are other options such as erythromycin azithromycin, or a member of the cephalosporin family. It is important to make sure that patients receive treatment for the acute infection, but such treatment won't necessarily change the course of rheumatic fever once the immunologic response has begun. Your doctor will decide on the best treatment option for you. Aspirin or aspirin-related medications treat joint pains. It may be necessary to use very high doses to decrease the symptoms. (Caution: Do not routinely use aspirin in pediatric patients because of its association with Reye's syndrome.) Consult a pediatric specialist for treatment protocols.

High-dose steroids treat carditis, but it may be necessary to use other cardiac medications to control the inflammation of the heart. Healthcare professionals initially manage this serious condition in a hospital.

The most challenging and unpredictable symptom to treat is the chorea (involuntary movements). It often responds to antipsychotic medications such as haloperidol (Haldol) but may continue for a protracted period. For patients who develop Sydenham's chorea, it can be the most difficult of the symptoms, since it involves involuntary movements and can interfere with daily activities. These individuals must remain on chronic long-term antibiotics to prevent the recurrence of the strep infection, as a recurrent strep infection may cause chorea to recur.

The most concerning complications of ARF include:  

• Cardiac in nature.
• Patients with rheumatic fever who develop carditis may develop long-lasting heart dysfunction. Often the mitral valve or the aortic valve is affected. For patients not responsive to medications, surgical valve replacement may become necessary.
• Atrial fibrillation (irregular fast heart rate) and heart failure can occur.
• Sydenham's chorea can be the most difficult complication to treat, and individuals with this complication may get a recurrence of the movement disorder.
• A few people remain very susceptible to reinfection with GABHS and may require lifetime antibiotic treatment.
• Joint damage: If the joints are affected by rheumatic fever, they can become permanently damaged, leading to chronic pain and limited mobility.
• Skin and eye problems: Rheumatic fever can cause a range of skin and eye problems, including nodules (small, hard bumps under the skin), erythema marginatum (a skin rash), and inflammation of the eyes.
• Other complications: Rheumatic fever can also cause a range of other complications, such as anemia, inflammation of the brain, and inflammation of the lining of the abdomen.

Prevention of rheumatic fever requires the recognition and diagnosis of group A strep throat infections and appropriate antibiotic therapy. In children 5-15 years of age, strep throat infections are very common and appear as a sudden onset of throat pain, fever, headache, and abdominal pain. Generally, patients with strep throat do not have symptoms such as runny nose, nasal congestion, cough, or other symptoms more commonly seen with a routine upper respiratory infection (URI, or the common cold). Most providers either test for a GAS infection with a rapid strep test or throat culture. Most causes of sore throat are not bacterial but are viral, do not carry the risk of rheumatic fever, and cannot be treated with antibiotics. In addition, once an individual develops rheumatic fever after a strep throat infection, that individual remains at risk for subsequent episodes of rheumatic fever during subsequent strep throat infections. These individuals may need to receive chronic long-term prophylaxis (preventive treatment) with antibiotics. Researchers continue to attempt development of a vaccine against group A beta-hemolytic streptococcal infection, but currently no vaccine is available.

Infectious disease specialists emphasize the importance of preventing recurrent episodes of ARF. There are several options varying from a once a month long-acting injection of penicillin to daily oral antibiotics. The guidelines currently recommend a prophylactic (preventative) antibiotic regimen for patients without carditis for five years or to 21 years of age (whichever is longer). For those with carditis but no residual heart disease, prevention should be for 10 years or well into adulthood (whichever is longer). Those who have residual heart disease because of carditis are advised to utilize antibiotic prophylaxis until 40 years of age and some specialists recommend lifelong therapy.