Rheumatic fever: symptoms, diagnosis, treatment

Rheumatic fever (Sydenham's chorea) is an autoimmune neurological complication of a previous infection with group A β-hemolytic streptococcus. It is characterized by rapid, arrhythmic involuntary movements, muscle hypotonia, impaired coordination, and typical signs of a "milk grip," "shooting tongue," and "spooning" of the hands. It most often affects children aged 5 to 15 years, but the disease also occurs in adolescents and, less commonly, in adults; relapses are possible in some patients, including during pregnancy ("chorea of pregnancy"). [1]

Chorea may occur as the sole manifestation of rheumatic fever or be associated with carditis and arthritis. Due to the long latency period between the onset of chorea and the onset of chorea, laboratory signs of a previous streptococcal infection often subside by the time of examination, and throat cultures are often negative; therefore, diagnosis relies on clinical examination in combination with echocardiography and serological markers of recent infection. [2]

The current understanding of pathogenesis links chorea to "molecular mimicry": antibodies produced against streptococci cross-react with neuronal antigens of the striatum (including tubulin, GM1 lysoganglioside, and dopamine receptors), activating calcium-calmodulin-dependent protein kinase II and disrupting dopaminergic transmission. These mechanisms explain both motor and behavioral symptoms. [3]

Treatment combines three approaches: eradication of streptococci, control of chorea symptoms, and relapse prevention. A new data summary from 2024 showed that the use of corticosteroids for at least 1 month, antibiotics, and valproic acid is associated with a shorter duration of chorea and a lower rate of relapses. Updated 2024 World Health Organization guidelines also detail secondary prophylaxis with benzathine benzylpenicillin. [4]

Code according to ICD-10 and ICD-11

The primary coding for rheumatic fever in the International Classification of Diseases, Tenth Revision, is under the category "Acute Rheumatic Fever." ICD-10 uses the category I02 "Rheumatic Chorea" with subdivision by cardiac involvement: I02.0 "with cardiac involvement" and I02.9 "without cardiac involvement." This is important for medical statistics, patient routing, and the rationale for secondary prevention. [5]

In the eleventh revision of the classification (ICD-11), rheumatic fever is included in the block of acute rheumatic fevers with code 1B42. In the Mortality and Morbidity Standards (MMS), 1B40 "Acute rheumatic fever without mention of cardiac involvement" and 1B41 "...with cardiac involvement" are located nearby. When coding according to ICD-11, it is important to take into account the current version of the MMS (e.g., 2025-01) and national adaptations. [6]

Table 1. Codes and formulations (ICD-10 vs ICD-11)

Classification	Code	Formulation
ICD-10	I02	Rheumatic chorea
ICD-10	I02.0	Rheumatic chorea with cardiac damage
ICD-10	I02.9	Rheumatic fever without cardiac involvement
ICD-11 MMS	1B42	Rheumatic chorea
ICD-11 MMS	1B40-1B41	Acute rheumatic fevers with/without cardiac involvement (adjacent categories)

Epidemiology

Rheumatic fever remains the most common acquired form of chorea in children worldwide. According to various sources, chorea occurs in 20-40 percent of patients with rheumatic fever; in some cohorts, it is approximately 25-30 percent. Prevalence is higher in regions with a high incidence of streptococcal infections and rheumatic fever. [7]

Global rates of acute rheumatic fever in schoolchildren range from approximately 8 to 51 cases per 100,000 per year, with average estimates of about 19 per 100,000. In high-income countries, rates are significantly lower, while in some indigenous or socially disadvantaged communities, rates can reach tens of cases per 100,000. [8]

The peak age is 8-10 years; girls are affected somewhat more frequently. In a significant proportion of cases, chorea is the only manifestation and debuts 1-7 months after pharyngitis, which differs from arthritis and carditis, which typically occur 2-4 weeks later. Relapses are described in 16-42 percent of patients, most often in the first years after onset. [9]

Despite a long-term decline in incidence in developed countries, Sydenham's chorea remains highly prevalent in middle- and low-income regions. Increasing availability of echocardiography and secondary prevention registries is key to reducing the incidence of severe outcomes, including chronic valve defects. [10]

Table 2. Epidemiology: Estimate ranges

Indicator	Grade
The prevalence of chorea among patients with rheumatic fever	20-40% (often ≈25-30%)
Global annual incidence of rheumatic fever (children)	~19 per 100,000 (range 8-51)
Peak age of onset of chorea	8-10 years
Latent period after pharyngitis	1-7 months
Frequency of chorea recurrence	16-42%

Reasons

The triggering factor is a previous infection with group A β-hemolytic streptococcus, most often pharyngitis or scarlet fever. The onset of chorea is typically delayed after infection, compared to arthritis or carditis, due to the characteristics of the central nervous system's immune response. [11]

Genetic predisposition probably influences risk, but no single gene modifier uniquely determines the development of chorea; more important are a combination of immunogenetic factors and exposure to streptococci in crowded conditions with poor access to primary care. [12]

Immunological mechanisms include the formation of antibodies that cross-react with basal ganglia antigens (tubulin, GM1 lysoganglioside, dopamine D1/D2 receptors), which disrupts neuromodulation and causes motor and neurobehavioral symptoms. [13]

Repeated streptococcal infections increase the risk of relapse; adequate secondary prophylaxis reduces the frequency of recurrent episodes and the severity of valve damage. [14]

Risk factors

Social determinants of health - overcrowded housing, limited access to health care, irregular treatment of sore throat - are directly associated with a higher incidence of rheumatic fever and, consequently, chorea.[15]

Age 5–15 years and female gender are associated with an increased risk of chorea; onset is possible in adolescents and adults, but less frequently. [16]

Unresolved or frequently recurring throat infections, lack of primary prophylaxis, and failure to adhere to secondary prophylaxis increase the likelihood of relapse.[17]

Special situations—pregnancy and the postpartum period—can trigger a relapse of previously experienced chorea ("chorea of pregnancy"). Health Network

Table 3. Risk factors (by modifiability)

Category	Examples
Non-modifiable	Age 5-15 years; female; history of rheumatic fever
Semi-modifiable	Pregnancy (risk of recurrence); family crowding
Modifiable	Untreated or frequently recurring streptococcal pharyngitis; low adherence to secondary prophylaxis; limited access to primary care

Pathogenesis

The key to pathogenesis is molecular mimicry between streptococcal antigens and neuronal structures. Antibodies to the streptococcal carbohydrate antigen recognize tubulin and GM1 lysoganglioside, as well as dopamine receptors, which activates calcium-calmodulin-dependent protein kinase II and alters synaptic transmission. [18]

There is evidence of elevated levels of anti-D1R and anti-D2R antibodies in some patients and their association with the severity of motor and behavioral symptoms; however, these markers have not yet become routine clinical tests due to variability in results and methodological limitations. [19]

Neuroimaging in chorea is often non-specific, but transient changes in the basal ganglia have been described in some patients; pathologically, an immune-inflammatory lesion of the corpus striatum without necrosis is suggested. [20]

Thus, Sydenham's chorea is a model of post-infectious autoimmune encephalitis of the basal ganglia, in which an imbalance of dopaminergic pathways leads to hyperkinesias and emotional lability. [21]

Symptoms

Motor manifestations include arrhythmic "dancing" movements, motor impersistence (the "milk grip" sign), "shooting" tongue, dysarthria, gait and handwriting disturbances. The movements intensify with excitement and disappear during sleep; some patients experience severe hypotonia ("chorea paralytica"). [22]

Neuropsychiatric symptoms - emotional lability, anxiety, irritability, sleep disturbances, attention deficit, exacerbation of obsessive-compulsive manifestations - often accompany motor disorders and can dominate the picture. [23]

The symptomatic pattern is usually generalized, but hemichorea is possible. In children, symptoms may develop gradually, often misinterpreted as "clumsiness" and deteriorating academic performance before overt hyperkinesis develops. [24]

When combined with rheumatic carditis, fatigue, shortness of breath, and tachycardia are observed; it is important to actively search for asymptomatic valve disease using Doppler echocardiography. [25]

Table 4. Common symptoms and clinical signs

Group	Examples
Motor	Choreic movements, milk grip, spooning of hands, protruding tongue, dysmetria, handwriting disturbances
Tone/strength	Hypotension, weakness; in severe cases - "chorea paralytica"
Speech/gait	Dysarthria, explosive speech; unsteadiness of gait
Neurobehavioral	Emotional lability, anxiety, irritability, sleep disturbances, attention deficit/obsessions
Cardiac (if there is carditis)	Heart murmurs, tachycardia, shortness of breath, fatigue

Classification, forms and stages

Clinically, a distinction is made between "pure" chorea (without signs of heart or joint damage) and chorea associated with typical rheumatic fever (with carditis and/or arthritis). This gradation influences monitoring tactics and the duration of secondary prevention. [26]

According to the severity of movement and hypotonia - from mild to severe form of "chorea paralytica", when the child cannot sit and walk independently; this condition requires hospitalization and active therapy. [27]

Depending on the course of the disease, a distinction is made between the first episode and a relapse; relapses often occur in the first years and are sometimes provoked by pregnancy or hormonal changes. [28]

In ICD-10, for statistical purposes, forms are distinguished with heart damage (I02.0) and without it (I02.9); in ICD-11, there is an independent heading 1B42 in the block of acute rheumatic fevers. [29]

Complications and consequences

The main long-term consequence of the rheumatic process is chronic valve pathology (most often mitral regurgitation). Even with "pure" chorea, the risk of subclinical carditis justifies active echocardiographic screening. [30]

Neurologically, symptoms may persist for months in some patients; relapses and residual mild disturbances of fine motor skills, attention, or mood are possible. Current observational data show that long-term corticosteroid therapy and secondary prophylaxis are associated with a shorter duration of symptoms and a lower incidence of relapses. [31]

In severe hypotension, falls, aspiration, and dehydration are possible; supportive care, nutritional correction, and injury prevention are necessary. [32]

The psychosocial burden on the family is high; follow-up programs and secondary prevention registries improve adherence and outcomes. [33]

When to see a doctor

Immediately – if a child suddenly develops jerky movements, speech or handwriting impairments, or unsteady gait, especially after a sore throat in the last 1-7 months. This helps quickly rule out emergency conditions and begin appropriate treatment. [34]

Urgently - if there are signs of severe hypotension ("chorea paralytica"): inability to sit or stand, difficulty eating, episodes of aspiration. Hospitalization and supportive therapy are required. [35]

Planned but not delayed - if palpitations, shortness of breath, fatigue or new heart murmurs develop: this may indicate carditis, requiring echocardiography and adjustment of monitoring. [36]

And it is imperative that – whenever you miss an injection of benzathine-benzylpenicillin or have doubts about tolerability – the doctor will select an alternative regimen and help maintain adherence to prevention. [37]

Diagnostics

Step 1. Clinical verification of chorea. Assessment of motor signs (milk grip, "shooting" tongue, motor impersistence), neurobehavioral symptoms, and the degree of hypotonia. Medication and metabolic causes are excluded. [38]

Step 2. Confirmation of a connection with a recent streptococcal infection. Serology: antibodies to streptolysin O and deoxyribonuclease B. Keep in mind that titers may decrease by the time of the onset of chorea; a negative result does not exclude the diagnosis. Throat culture is less informative. [39]

Step 3. Search for carditis. All patients should have electrocardiography (sometimes prolongation of the PR interval) and Doppler echocardiography to detect subclinical valvular disease; Doppler echo is included in the diagnostic criteria for rheumatic fever (Jones revision 2015). [40]

Step 4. Basic laboratories. Complete blood count, C-reactive protein and erythrocyte sedimentation rate (may be normal in isolated chorea), biochemistry; if indicated, pregnancy test in adolescents. [41]

Step 5. Neuroimaging and additional tests - as indicated. Magnetic resonance imaging to exclude other causes of chorea (vasculitis, tumor, stroke, Wilson's disease), especially in cases of atypical age, focal symptoms, or atypical evolution. Tests for copper/ceruloplasmin, thyroid hormones, and antineuronal antibodies - as indicated; the latter remain research-based and are not included in the standard. [42]

Table 5. Diagnostic methods and expected findings

Method	What are we looking for?	Comments
Clinic	Chorea, hypotonia, behavioral symptoms	Clinical diagnosis
Serology	Antibodies to streptolysin O, anti-DNase B	May be normal in isolated chorea
ECG	PR extension	Non-specific
Echocardiography with Doppler	Subclinical regurgitation	Included in the Jones 2015 criteria
MRI	Elimination of alternatives	Often without specifics

Differential diagnosis

In children, rheumatic fever must be differentiated from systemic lupus erythematosus with chorea, Wilson's disease, benign hereditary chorea (NKX2-1 mutations), infectious and postinfectious choreic syndromes, thyrotoxicosis, and drug-induced dyskinesias. Age of onset, family history, ophthalmologic features (Kayser-Fleischer rings), copper/ceruloplasmin assays, autoantibody profiles, and neuroimaging help narrow the diagnosis.

For adolescents and adults, chorea of pregnancy, onset of Huntington's disease, and vascular causes are added. In cases of drug-induced etiology (neuroleptics, levodopa, antiepileptic drugs), rheumatic markers are absent, and the association with the start of therapy is clear.

Poststreptococcal neuropsychiatric syndromes (PANDAS) are discussed separately. Although they share some immune mechanisms with Sydenham's chorea, the diagnostic criteria differ; PANDAS is dominated by obsessions/tics, whereas chorea is characterized by hyperkinesias and hypotonia. [43]

And finally, it is important not to miss the “masking” severe hypotension (chorea paralytica), when there are almost no motor outputs, and the patient is immobilized by weakness - this is a severe form of rheumatic chorea itself, and not a separate diagnosis. [44]

Table 6. Differential series (briefly)

State	Distinguishing features
Rheumatic chorea	Chorea + hypotension; associated with recent angina; often subclinical carditis
SLE chorea	Autoimmune markers, systemic manifestations, no association with streptococcus
Wilson's disease	Kayser-Fleischer rings, low ceruloplasmin, liver signs
Benign hereditary chorea	Early onset, family history, stable course
Drug-induced dyskinesias	Association with the use of neuroleptics/dopaminomimetics
Thyrotoxicosis	Tachycardia, weight loss, elevated thyroid hormones
PANDAS	OCD/tics are prominent, no signs of carditis

Treatment

The goals of therapy are to suppress the activity of the post-streptococcal process, control hyperkinesis and behavioral disturbances, and prevent relapses and valve damage. In practice, this means: antibiotics for streptococcal eradication, symptomatic treatment of chorea, and long-term secondary prophylaxis. [45]

Primary eradication of streptococci is performed with a single intramuscular dose of benzathine benzylpenicillin or a ten-day course of phenoxymethylpenicillin. In patients with a true allergy to beta-lactams, macrolides (e.g., erythromycin) are acceptable. This step is important even with negative cultures, as it reduces bacterial colonization and the risk of transmission. [46]

Symptomatic therapy for hyperkinesias traditionally includes dopamine antagonists (haloperidol, risperidone) and antiepileptic drugs (valproic acid, carbamazepine). According to a 2024 individual meta-analysis, long-term (at least 1 month) administration of corticosteroids reduced the median duration of chorea from approximately 2.8 to 1.2 months; valproic acid and antibiotics were associated with a lower risk of relapse. This confirms the rationale for a combination strategy. [47]

Corticosteroids (eg, prednisolone tapered over 4–6 weeks) are used for moderate to severe forms, particularly those with paralytic chorea or severe behavioral disturbances. The choice is made based on concomitant carditis. Observational data suggest clinical benefit, but randomized trials of optimal regimens are scarce; monitoring for adverse effects is important. [48]

For refractory chorea, second-line immunotherapies—intravenous immunoglobulin and plasmapheresis—are possible. These methods are considered in severe cases and those with an inadequate response to steroids and symptomatic medications; the evidence base is limited, and decisions are made by a multidisciplinary team. [49]

Among new and "crossover" approaches, the use of levetiracetam or tetrabenazine is being discussed as alternatives in cases of intolerance to standard agents; evidence is somewhat less available, but individual case series describe efficacy. Safety and individual dose titration are particularly important here. [50]

Supportive care for chorea paralytica includes fall and aspiration prevention, nutritional support, physical therapy, and occupational therapy. The goal is to maintain functional independence while immune activity subsides. Speech therapy and psychology are consulted if necessary. [51]

Secondary prevention is the cornerstone. Benzathine benzylpenicillin intramuscularly every 4 weeks (in some high-risk settings, every 3 weeks) reduces the risk of relapse and progression of valve disease. Duration according to American recommendations: without carditis - at least 5 years or up to 21 years (whichever is longer); with carditis without residual defect - 10 years or up to 21 years; with persistent valve damage - 10 years or up to 40 years and longer, sometimes for life. In 2024, the World Health Organization separately emphasizes the importance of measures to improve adherence and allows the addition of lidocaine to the injection to reduce pain. [52]

Pregnancy and the postpartum period require coordination with a neurologist, cardiologist, and obstetrician. Most symptoms of chorea respond to the same approaches, but the choice of drugs (e.g., avoidance of valproate) and prophylaxis regimens should take into account the risks to the fetus; secondary prophylaxis with penicillin remains a priority. [53]

Finally, educational and organizational measures—maintaining registries, appointment reminders, and teaching families the "painful injection" technique with anesthesia—increase the percentage of completed injections to over 80 percent and are associated with better outcomes. This is as important as the choice of specific medication. [54]

Table 7. Symptomatic therapy of chorea (brief chart)

Class	Examples	Comments on effectiveness
Dopamine antagonists	Haloperidol, risperidone	Traditional choice, monitor for extrapyramidal effects
Antiepileptic drugs	Valproic acid, carbamazepine	Data on relapse reduction (valproate)
Corticosteroids	Prednisolone (course ≥1 month)	Reduction in chorea duration in observational data
Immunotherapy	Intravenous immunoglobulin, plasmapheresis	In refractory severe cases
Alternatives	Levetiracetam, tetrabenazine	According to individual indications

Prevention

Primary prevention—timely diagnosis and treatment of streptococcal throat infections, public health education, reduced overcrowding, and improved access to primary care—reduces the risk of both rheumatic fever and chorea. [55]

Secondary prophylaxis involves regular injections of benzathine benzylpenicillin every 4 weeks (or 3 weeks in high-risk individuals) for all those who have had rheumatic fever. The choice of alternatives in case of allergy should take into account the local sensitivity of streptococci to macrolides. [56]

Improving adherence—adding a local anesthetic to the injection, organizing reminders, educating and supporting families, and maintaining registries—has been shown to increase the proportion of injections completed and is associated with a reduction in mortality from rheumatic heart disease. [57]

Valve screening - Doppler echocardiography is recommended for any episode of chorea to allow early detection of valve disease and determine the duration of prophylaxis.[58]

Table 8. Prevention of rheumatic fever

Level	Measures
Primary	Early treatment of sore throat; reduction of crowding; access to primary health care
Secondary	Benzathine benzylpenicillin once every 4 weeks (or once every 3 weeks if risk is high)
Adjuvant	Anesthesia injections, reminders, family education, registries
Cardiac screening	Echocardiography with Doppler in all patients with chorea

Forecast

In most patients, symptoms resolve within 6-9 months; with adequate therapy and secondary prevention, the risk of relapse and severe neurological sequelae is reduced. However, some children still experience mild impairments of fine motor skills and attention. [59]

Relapses are possible, especially in the early years, and more often with poor adherence to prophylaxis. Pregnancy and hormonal factors can trigger a recurrence of symptoms in women with a history of chorea in childhood. [60]

Cardiac prognosis is determined by early detection and management of carditis. Regular echocardiographic monitoring allows for early detection of valvular disease progression and prompt adjustment of preventive measures or consideration of cardiac surgical options. [61]

At the population level, educational programs, registries, and sustainable supplies of benzathine penicillin are proven tools for reducing the burden of rheumatic heart disease and its consequences. [62]

FAQ

Is it necessarily rheumatic chorea if a child's hands are twitching?
No. There are many causes of chorea in children, ranging from drug-induced dyskinesias and thyrotoxicosis to Wilson's disease and systemic lupus erythematosus. Rheumatic chorea is confirmed by clinical examination, serological markers of a recent streptococcal infection, and echocardiography.

Is it possible to cure the condition without antibiotics if the throat no longer hurts?
It's still necessary to eradicate the streptococcus and then carry out secondary prophylaxis. This isn't so much for the throat itself, but to reduce the risk of relapse and valve damage. [63]

When are hormones and immunoglobulin prescribed?
Corticosteroids are indicated for moderate to severe cases: they accelerate clinical improvement. Intravenous immunoglobulin and plasmapheresis are used for refractory severe cases, as determined by a multidisciplinary team. [64]

How long is penicillin prophylaxis necessary?
This is a key element. Typical recommendations include: without carditis – at least 5 years or up to age 21; with carditis – longer; with persistent valve disease – up to age 40 and sometimes lifelong. National adaptations are in place in some countries. [65]

Is chorea dangerous during pregnancy?
It most often represents a relapse of a previous episode. A joint approach involving a neurologist, cardiologist, and obstetrician is necessary; secondary prophylaxis with penicillin is continued, and symptomatic treatment is selected individually, taking into account fetal safety. [66]

Additional table: Duration of secondary prophylaxis

Clinical situation	Recommended duration
Rheumatic fever without carditis	≥5 years or up to 21 years (whichever is longer)
Rheumatic fever with carditis, without residual defect	10 years or up to 21 years (whichever is longer)
Persistent valvular disease	10 years or up to 40 years (whichever is longer), sometimes for life
After valve replacement	As a rule, for life