Can't stop dancing: Could it be St. Vitus' dance?

Keywords

Sydenham's chorea; acute rheumatic fever; Jones criteria; streptococcal pharyngitis.

Abstract

Purpose: To inform providers of one of the rare but significant consequences that result from not diagnosing and treating streptococcal pharyngitis: Sydenham's chorea (St. Vitus' dance).

Data sources: Current Internet sources including review articles, informational articles, online medical textbooks, and professional organization Web sites.

Conclusion: It is vital that each case of streptococcal pharyngitis be treated with appropriate antibiotic therapy. Doing so will help prevent the sequelae associated with streptococcal infections, such as acute rheumatic fever (ARF) and Sydenham's chorea.

Implications for practice: Streptococcal pharyngitis is a common illness that has the potential to cause very serious consequences. The consequences may be life altering, such as suffering permanent heart damage. With appropriate diagnosis and treatment with antibiotics, the sequelae of ARF and Sydenham's chorea can be prevented.

Introduction

Sydenham's chorea, also known as St. Vitus' dance, is a neurological movement disorder caused by an inflammatory response to a group A beta-hemolytic streptococcal (GABHS) infection. Following a GABHS infection, 2%-3% of patients will develop acute rheumatic fever (ARF) (Luckstead, 2005). Of these individuals, 10%-26% will develop Sydenham's chorea, a late symptom of rheumatic fever (Beers & Berkow, 2006; Leffler, 2004).

Sydenham's chorea is predominantly a self-resolving childhood disorder characterized by rapid, involuntary, irregular movements of the muscles (National Institute of Neurological Disorders and Stroke [NINDS], 2006). All but the ocular muscles are typically involved.

The development of Sydenham's chorea follows a particular sequence. The sequence begins when an individual is infected with GABHS. The GABHS infection proceeds to incubate over the next 2-5 days, culminating with a significant sore throat, fever, pharyngeal exudate, and adenopathy, a condition commonly known as bacterial pharyngitis or "strep throat" (Discolo, Darrow, & Koltai, 2003). The symptoms typically resolve in 3-5 days, and the individual enters a temporary asymptomatic period. This asymptomatic period may last as little as a few weeks or continue for months before the individual becomes sick again, typically with symptoms of fever and joint pain (arthritis), classic for ARF. In conjunction with or independent of previous symptoms, individuals may complain of uncontrollable abnormal body movements or Sydenham's chorea, an uncommon but potentially serious complication of a GABHS infection and ARF.

Pathophysiology

The exact mechanism for the development of Sydenham's chorea is unknown, but many theories exist. Sydenham's chorea is believed to be an autoimmune inflammatory disorder in which streptococcal infection causes the body to make antibodies against itself in specific brain regions (NINDS, 2006). Known as the autoimmune mimicry theory, it is thought that the invading bacteria contain proteins that are so similar to the body's own cells that when an immune reaction is started, the body cannot detect a difference between its own cells and the invading bacteria; therefore, the body inappropriately attacks itself. Researchers have reported finding antibodies in children with Sydenham's chorea that interact with cellular proteins within the basal ganglia (Leffler, 2004). The basal ganglia is a portion of the brain partially responsible for initiating and controlling body movement, in addition to regulation of attention and cognition (Leffler; Marieb, 2001). The interaction between GABHS antibodies and neuronal cells (cellular proteins) leads to inflammation within the basal ganglia causing abnormal body movements, but also symptoms of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) (Anderson & Savage, 2004; Miller & Laxer, 2003).

Researchers have found, with use of positron emission tomography (PET), patients with Sydenham's chorea have certain regions in their brain that become hypermetabolic, metabolizing increased amounts of glucose. This finding helps differentiate Sydenham's chorea from Huntington's chorea, which would have areas of hypometabolic activity on PET scan. Last, examination of the brain using magnetic resonance imaging (MRI) has shown increased size of the basal ganglia in patients with Sydenham's chorea, further supporting the theory of an inflammatory process (Luckstead, 2005).

Epidemiology

Since the 1980s, the incidence of ARF has been on the decline in civilized countries such as the United States. The decrease is attributable to the increased use of antibiotics for acute streptococcal infections. However, there has been a recent resurgence of ARF in civilized countries, believed to be related to more virulent rare forms of streptococci. In underdeveloped countries, rheumatic fever remains a major health concern because of lack of adequate health care (Leffler, 2004).

Of all patients with ARF, up to 26% will develop Sydenham's chorea. Sydenham's chorea is most prevalent in children and adolescents between the ages 5 and 15 (NINDS, 2006). Although females are more commonly affected than males during early childhood, during adolescence, the ratio increases further, with Sydenham's chorea typically affecting girls two to one (Beers & Berkow, 2006; Leffler, 2004). Sydenham's chorea occurs primarily in the summer and early fall, after the peak incidence of ARF (Beers & Berkow).

Although patients are usually left with no residual symptoms, the reoccurrence rate is about 20% within 2 years' time (Leffler, 2004). Patients are at increased risk for reoccurrence while pregnant or taking certain medications such as estrogen-containing oral contraceptives and phenytoin, leading researchers to believe that there is a link between Sydenham's chorea and the female sex hormone estrogen (Leffler). Researchers have also identified B cell marker D8/17 in 90% of people with ARF. This marker proves that some individuals are genetically susceptible to ARF and its sequelae (Miller & Laxer, 2003).

Signs and symptoms

Initially, patients present with a complaint of a sore throat or pharyngitis. After the pharyngitis resolves, the individual will have a symptom-free period that lasts up to 6 weeks before the symptoms of ARF and Sydenham's chorea appear (Leffler, 2004). This time period, seemingly free of symptoms, is referred to as the latent period.

The latent period ends with onset of symptoms associated with ARF, so in order to identify and diagnose Sydenham's chorea, providers must be familiar with ARF. The characteristic symptoms of ARF include the following: fever, arthritis, carditis, erythema marginatum, and subcutaneous nodules. The most common initial symptom is fever followed by redness, warmth, tenderness, and arthralgia of the affected joints (Luckstead, 2005). This arthritis is called "migratory polyarthritis" because it will progress from joint to joint. It primarily affects the knees and ankles but may affect additional joints as well (Leffler, 2004). On exam, the patient is often found to have hyperreflexive deep tendon reflexes.

Carditis is a symptom of ARF that may go unnoticed for a prolonged period of time as it can be asymptomatic. Carditis may involve any region of the heart. It is believed that 80% of individuals with ARF carditis will develop cardiac lesions (Leffler, 2004). Symptoms of carditis include arrhythmias, cardiomegaly, and new onset murmurs. The patient might also develop heart failure characterized by dyspnea, nausea and vomiting, a nonproductive cough, and epigastric discomfort (Luckstead, 2005). The majority of cases of rheumatic carditis resolve within 5 months; however, some individuals will suffer permanent effects. Damage to the mitral valve is the most common effect; however, the aortic and tricuspid valves may also be affected. The greatest risk associated with ARF carditis is the development of cardiac effusion ending in cardiac tamponade (Luckstead). Signs of pericardial effusion may include distant heart sounds, friction rub, chest pain, and electrocardiogram (EKG) changes.

Other symptoms commonly associated with carditis are erythema marginatum and subcutaneous nodules (Leffler, 2004). This rash is characterized as being a nonpruritic, pink or red macule that fades in the middle with time, most commonly located on the trunk. Erythema marginatum blanches with pressure and increases in size with heat (Luckstead, 2005). Subcutaneous nodules are typically found on the joint extensor surface of the elbows, knees, and wrists and possibly over the spine. These nodules are typically firm, nontender, and are freely mobile. This symptom, like erythema marginatum, is less common and is usually not present unless associated with carditis.

Sydenham's chorea is usually a late sign of ARF, but in 20% of cases, it may be the only manifestation (Leffler, 2004). Sydenham's chorea patients often present with bilateral rapid, nonpurposeful, irregular, involuntary movements (Beers & Berkow, 2006). Voluntary movements are also affected, becoming abrupt, which causes the individual to look clumsy or uncoordinated (Beers & Berkow). The individual may develop difficulty dressing and feeding as Sydenham's chorea may affect muscles of the legs, arms, trunk, face, and neck (Beers & Berkow; Leffler). Symptoms may not develop until 6 months after the fever and infection has cleared, but the average time is about 8 weeks (Leffler; NINDS, 2006) (see Table 1 for list of symptoms). At this point, all other symptoms of ARF may be resolved. Murmurs and migratory polyarthritis may be the only remaining evidence of ARF.

The severity of Sydenham's chorea varies. A mild case may only cause difficulty performing activities of daily living or school activities. A severe case, however, may totally disable the individual, causing confinement to bed and the need for medications to prevent harm from flailing limbs. Choreic movements tend to disappear with sleep but typically increase with stress, excitement, or fatigue.

Other symptoms suspected to be specific to Sydenham's chorea and not ARF are emotional and behavioral disturbances such as OCD and ADHD (Maia, Teixeira, Cunningham, & Cardoso, 2005). It is estimated that over 70% of children with Sydenham's chorea develop obsessivecompulsive behaviors (Miller & Laxer, 2003). Weeks before the child develops Sydenham's chorea, parents complain that the child has become restless, aggressive, or excessively emotional (Leffler, 2004). The child may be described as irritable, moody, anxious, impulsive, confused, or easily distractible (Maia et al.). Outbursts of uncontrollable crying or increased motor activity are common. Some children may even suffer from transient psychosis.

In rare situations (only 1.5% of patients with Sydenham's chorea), the individual may develop "paralytic chorea" (Leffler, 2004). The symptoms of paralytic chorea include decreased muscle tone, muscular rigidity, or increasing muscle stiffness and resistance to movement. Paralytic chorea can be disabling without appropriate treatment.

Diagnostics

There is no definitive diagnostic test for Sydenham's chorea. As a result, the diagnosis is made primarily on the patient's history and physical examination. History and physical examination should include investigation as to whether the individual has had a fairly recent GABHS infection. As mentioned previously, there may be a latent period before the patient develops symptoms of ARF. Therefore, if the patient does not recall a recent infection, some initial lab work should be performed to determine if the patient has had a recent GABHS infection. Lab work may include an antistreptolysin O (ASO) titer, throat culture, and erythrocyte sedimentation rate (ESR) (Leffler, 2004).

The ASO is used as an indicator of a recent GABHS infection. ASO titers typically elevate 1 week following a GABHS infection, peak in approximately 3-6 weeks, and then gradually decline (Discolo et al., 2003). The first limitation of this test is that chronic GABHS carriers will not have elevated titers. A second limitation is that while the ASO is elevated in about 80% of individuals with ARF, it may be negative in patients with Sydenham's chorea because of the latent period (Discolo et al.; Leffler, 2004).

Throat cultures are another widely used method for detecting GABHS. However, like the ASO titer, throat cultures are not a reliable indicator of ARF because by the time the testing is done, the latent period is over and frequently the results come back negative. Further complicating the effectiveness of the test, 60%-80% of asymptomatic teenagers will have a positive culture (Leffler, 2004).

The ESR is not indicative of ARF or Sydenham's chorea either, as it is only a nonspecific indicator of inflammation. Its value comes into play when providers are adjusting anti-inflammatory medication dosages (Leffler, 2004). Like the ASO and throat culture, the ESR may be normal by the time Sydenham's chorea begins. When looking at inflammation, a provider might consider adding a C-reactive protein, another inflammation marker, to the list of labs. Other diagnostic tests that may be of value when evaluating chorea of unknown origin include: complete blood count, urine toxin screen, electrolytes, thyroid function tests, and genetic testing (Anderson, 2005).

All the previously mentioned tests aid in diagnosing ARF, as does the Jones criteria, a set of guidelines created by the American Heart Association (Table 2). The Jones criteria divide symptoms into major and minor criteria. In order to be diagnosed with ARF, the patient must have evidence of recent GABHS infection and either two major criteria or one major criterion and two minor criteria. Erythema marginatum and subcutaneous nodules may not be used as the single major criteria (Luckstead, 2005 ). There are two exceptions to the Jones criteria where a patient may be diagnosed with ARF. The first exception is when a patient has chorea (Sydenham's chorea), which is determined to be unrelated to other disorders. The second exception occurs if the patient has late onset or insidious carditis unrelated to another cause (Leffler, 2004).

Imaging studies to include when diagnosing Sydenham's chorea are MRI of the brain, electroencephalography (EEG), chest x-ray, EKG, and echocardiogram (ECG). The MRI is used to detect enlarged areas in the basal ganglia (Beers & Berkow, 2006). Increased volume is primarily located in the caudate nucleus, putamen, and/or globus pallidus (Miller & Laxer, 2003). An EEG may provide evidence of nonspecific dysrhythmias, slowing of brain wave patterns (Beers & Berkow; Leffler, 2004). Chest x-ray is used to determine if there is any cardiomegaly associated with carditis. The ECG and EKG evaluate heart function and electrical conduction, looking for dysrhythmias and decreased function also related to carditis.

Diagnosing ARF and Sydenham's chorea is not based on diagnostic studies alone. A good physical exam is also vital in evaluating and treating these patients. Providers must pay particular attention to the cardiac, respiratory, musculoskeletal, and neurological systems. The cardiac exams should focus on listening for new onset murmurs related to valvular stenosis or r�gurgitation. Because cardiac function may be compromised, the provider must carefully assess lung sounds to determine if there is evidence of heart failure, such as wheezes or crackles.

Chorea may be caused by several factors other than ARF. Listed in Table 3 are some of the differentials and how they differ from Sydenham's chorea.

Treatment

Treatment for Sydenham's chorea is symptomatic. Medication and joint padding may be necessary to protect the individual from injury during involuntary, choreic movements. As shown in Table 4, medications commonly used to modify movements include benzodiazepines and antipsychotics (Beers & Berkow, 2006).

Anticonvulsant medication, such as valproate sodium, is also used to reduce the choreic movements (Leffler, 2004). A provider may choose an anticonvulsant medication over an antipsychotic because of the increased risk for tardive dyskinesia when taking antipsychotics such as haloperidol. In extreme situations, such as chorea paralytica, pimozide is recommended. When these options fail, the provider may turn to immunomodulatory treatment, steroids, intravenous (IV) IgG, or plasmapheresis (Leffler).

Once the patient is no longer in danger of injury from choreic movements, the provider can address the ARF. Bedrest and antibiotic therapy are standard treatments for patients with ARF (Leffler, 2004). Penicillin is the antibiotic of choice, given either orally or intramuscularly (IM). In the case of allergy to penicillin, appropriate alternative antibiotics targeted at gram-positive organisms like streptococcus may also be given.

Pain and inflammation also need to be addressed in cases of ARF involving arthritis and carditis. Salicylates, nonsteroidal anti-inflammatory drugs, and codeine are all drugs of choice. However, when dealing with children, salicylates are not recommended because they may lead to Reye syndrome. In addition, a provider would not want to give salicylates before deciding on the diagnosis of Sydenham's chorea. Salicylates given prior to diagnosis may confuse the situation by masking any associated migratory polyarthritis (Leffler, 2004).

Patients with ARF carditis showing signs of heart failure may benefit from corticosteroids. Experts believe that corticosteroids, such as prednisone, may accelerate improvement in patients with ARF carditis (Beers & Berkow, 2006). In a recent research study, complete resolution of all symptoms was achieved within 7-12 days, with marked improvement in 24-48 h, in all patients receiving corticosteroid therapy (Barash, Margalith, & Matitiau, 2005). In this study, the patients received prednisone 2 mg/kg/day for 3 weeks and then gradually tapered off the prednisone over the next 3 weeks. They were also treated prophylactically with penicillin. Over an average of 26 months of monitoring, none of the participants had a relapse of ARF carditis (Barash et al.).

In addition, patients with ARF carditis may benefit from the use of diuretics and cardiac glycosides (digitalis) to remove excess fluid and strengthen cardiac contractions (Leffler, 2004). Depending on the extensiveness of cardiac damage, surgery may be necessary to repair or replace stenosed or weak heart valves.

After Sydenham's chorea and ARF have resolved, the individual should be treated prophylactically to prevent recurrence. Experts vary on the recommended length of prophylactic therapy. Some experts recommend that treatment continue for 5 years after occurrence or until the age of 18, which ever comes first, while others say prophylaxis should be a life-long therapy (Leffler, 2004). No matter the length of treatment, penicillin is the drug of choice given IM every 21 days or orally daily. Sulfadiazine or erythromycin may be used instead of penicillin for individuals with penicillin sensitivities (Leffler).

Providers ideally have the ability to help control the occurrences of ARF and Sydenham's chorea by treating all streptococcal infections with adequate antibiotics, a 10-day course of penicillin V (Discolo et al., 2003). It is reported that treatment is most beneficial when antibiotics are started within 1 week after onset of streptococcal pharyngitis (Leffler, 2004). Antibiotics started early in the course of pharyngitis will quickly suppress the infection and lower the risk of transmission within 24 h. When compliance is an issue, providers may use IM benzathine penicillin G as an alternative. In cases involving GABHS carriers, penicillin will not eliminate the bacteria. In this situation and in a case where the organism has been nonresponsive to prior antibiotics, the patient should be given clindamycin (Discolo et al.).

Prognosis

The prognosis for individuals with Sydenham's chorea is good. Symptoms typically resolve completely, but the rate of resolution varies from individual to individual. Sydenham's chorea may resolve in as little as 3-6 weeks, but in 50% of cases, it takes up to 2 years for symptoms to resolve completely (Beers & Berkow, 2006; Leffler, 2004; NINDS, 2006). Providers need to educate patients that this is a transitory disorder and that Sydenham's chorea typically resolves without residual effects. However, patients should also be educated that the reoccurrence rate is as high as 20%, typically occurring within 2 years of initial episode (Leffler).

Summary

Sydenham's chorea is a serious consequence of an untreated case of GABHS, a common infection among young children and adolescents. Following a latent period, untreated children may develop fever, arthritis, and unexplained choreic movements. The symptoms are characteristic of ARF and Sydenham's chorea. The most serious condition is carditis. Asymptomatic carditis can lead to a variety of cardiac complications, the most common being valvular dysfunction and the most serious being cardiac tamponade.

Providers have the potential to decrease the patient's risk of developing Sydenham's chorea and associated symptoms by treating GABHS infections at the time of diagnosis. Penicillin remains the current antibiotic of choice although alternative antibiotics are appropriate in specific situations. All providers need to consistently treat all cases of GABHS. Failure to treat could leave the patient doing St. Vitus' dance.

[Sidebar]

Conflict of interest disclosure

No relationship exists between the author/myself and any commercial entity or product mentioned in this article that might represent a conflict of interest. No inducements have been made by any commercial entity to submit the manuscript for publication.

[Reference]

References

Anderson, K. E. (2005). Huntington's disease and related disorders. Psychiatric Clinics of North America, 28. Retrieved March 31, 2006, from http:// home.mdconsult.eom/das/clinics/view/63047154-2/N/ 15350891?sid=522818143&source=MI&summaryresults=true&SEQNO= 1

Anderson, K. E., & Savage, C. R. (2004). Cognitive and neurobiological findings in obsessive-compulsive disorder. Psychiatric Clinics of North America, 27. Retrieved March 31, 2006, from http://home.mdconsult.com/das/clinics/view/ 59714987-2/N/14945873?ja=406315&PAGE=1.html&sid=492908418&source= MI&SEQNO=1

Barash, J., Margalith, D., & Matitiau, A. (2005). Corticosteroid treatment in patients with Sydenham's chorea. Pediatric Neurology, 32, 205-207. Retrieved March 31, 2006, from http://www.child-neuro.org.uk/content/uploads/journal-scan/ steroids-sydenhams-chorea.pdf#search='corticosteroid%20treatment %20in%20patients%20with%20sydenhams%20chorea'

Beers, M. H., & Berkow, R. (2006). Neurologic disorders. In Merck Manual. Whitehouse Station, NJ: Merck. Retrieved March 31, 2006, from http:// www.merck.com/mrkshared/mmanual/section19/chapter271/271a.jsp

Discolo, C. M., Darrow, D. H., & Koltai, P. J. (2003). Infectious indications for tonsillectomy. Pediatric Clinics of North America, 50, 445-458. Retrieved March 31, 2006, from http://www.medscape.com/medline/abstract/12809333

Leffler. J. B. (2004). Sydenham's chorea. In We Move. Retrieved March 31, 2006, from http://www.wemove.org/syd/syd.html

Luckstead, E. F. (2005). Cardiovascular disorders in the college student. Pediatric Clinics of North America, 52. Retrieved March 31, 2006, from http:// home.mdconsult.com/das/clinics/view/59714987-2/N/15379557?sid= 492908043&source= MI&summaryresults=true&SEQNO=1

Maia, D. P., Teixeira, A. L., Cunningham, M. C., & Cardoso, F. (2005). Obsessive compulsive behavior, hyperactivity, and attention deficit disorder in Sydenham chorea. Neurology, 64, 1799-1801. Retrieved March 31, 2006, from http:// www.neurology.org/cgi/content/abstract/64/10/1799

Marieb, E. N. (2001). The central nervous system. Human anatomy and physiology (5th ed., pp. 440). San Francisco: Addison Wesley Longman.

Miller, D., & Laxer, R. M. (2003). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Pediatric Rheumatology Online Journal. Retrieved March 31, 2006, from http:// www.pedrheumonlinejoumal.org/April/reviewarti.htm

National Institute of Neurological Disorders and Stroke. (2006). Sydenham Chorea Information Page. National Institute of Health. Retrieved March 31, 2006, from http://www.ninds.nih.gov/disorders/sydenham/ sydenham.htm

[Author Affiliation]

Corrie Rogness, RN, MS, FNP

Nursing Division, University of Mary, Bismarck, North Dakota

[Author Affiliation]

Correspondence

Corrie Rogness, RN, MS, FNP,

1131 Deapolis Drive, Hazen, ND 58545.

Tel: 701-748-3546;

E-mail: corrie@beu.midco.net

Received: March 2007; accepted: September 2007

doi:10.1111/j.1745-7599.2008.00331.x