Rheumatic fever: what it is and how it manifests itself

Rheumatic fever is a systemic inflammatory disease that occurs 1-5 weeks after an infection with group A β-hemolytic streptococcus (most commonly pharyngitis in children). The primary risk is damage to the heart valves, leading to rheumatic heart disease: it is the leading preventable cause of valvular defects and heart failure in adolescents and young adults worldwide. Diagnosis is based on a clinical "pattern"—a combination of symptoms and laboratory findings—established in the Jones criteria (the most recent major revision of the American Heart Association, 2015, with an emphasis on Doppler echo and adjustments for high-risk groups). [1]

The modern approach differs from the "classical" one: greater attention has been paid to echocardiographic signs of carditis, even in cases of "silent" progression, and to population risk stratification. In regions with intermediate/high risk, the diagnostic threshold is lower, and Doppler echo is a mandatory part of the assessment. At the same time, the World Health Organization and the World Heart Federation have updated guidelines for the prevention, diagnosis, and screening of latent RHD to detect the disease earlier and prevent progression. [2]

Treatment is based on three goals: (1) eliminate and suppress the streptococcus, (2) control inflammation and symptoms (joints, heart, nervous system), (3) provide long-term secondary prophylaxis with regular injections of benzathine benzylpenicillin to prevent relapses and worsening of valve damage. New data have strengthened the evidence base: penicillin prophylaxis significantly reduces relapses of LC and slows the progression of latent RHD. [3]

On the horizon are improved echo screening algorithms according to the WHF-2023 criteria, a focus on increasing adherence to prevention (organization of injection programs, adherence to 3-4 week intervals), and standards for care during the transition from pediatric to adult cardiologist. All of this is already changing the prognosis for patients and entire communities. [4]

Epidemiology

The global burden of RHD remains high: the Global Burden of Disease Study (GBD-2019) estimates that >40 million people live with RHD, with approximately 0.3 million deaths and >10 million healthy life-years lost annually. Although standardized mortality rates have been declining for decades, the absolute number of cases remains high due to demographics and unequal access to prevention. Low- and middle-income regions are most affected. [5]

Rheumatic fever is a disease predominantly affecting children and adolescents (5-15 years old), but its long-term consequences—rheumatic heart disease—occur in adulthood. Women often contribute more to mortality and the burden of rheumatic heart disease, partly due to pregnancy and the strain on the healthcare system. Screening schoolchildren with portable echocardiography increases the detection rate of "latent" rheumatic heart disease, changing the early diagnosis curve. [6]

The incidence of LC is closely linked to housing overcrowding, access to primary care and antibiotics for sore throat, education, and poverty. Regular secondary prevention programs in communities can dramatically reduce recurrences and valve defects in young people. In 2024, the WHO released updated recommendations for the prevention and diagnosis of LC/RHD to scale up such programs. [7]

Despite progress, the "epidemiology of inequality" persists: in high-income countries, LC has become rare, while in vulnerable populations, it remains a common diagnosis in cardiac hospitals. Therefore, clinical criteria and prevention tactics have been adapted to the risk population, as reflected in the revision of the Jones criteria (2015). [8]

Reasons

The underlying cause is an immune response to Streptococcus pyogenes (group A) infection, most commonly pharyngitis. In response to bacterial antigens, the body produces antibodies that cross-react with host tissues (myocardium, endocardium, synovium, basal ganglia), triggering autoimmune inflammation. This is accompanied by an increase in antistreptolysin O and/or anti-DNase B in the blood, and a history of acute tonsillitis (confirmed by tests or clinical examination). [9]

Not every streptococcal pharyngitis develops into rheumatoid arthritis—a genetic predisposition and, possibly, "rheumatogenic" strains are necessary. Repeated throat infections without prompt treatment increase the likelihood of a first episode of rheumatoid arthritis. The role of cutaneous streptococcal infections in certain regions is also being discussed, but pharyngitis remains the key trigger. [10]

Delayed treatment is also important: timely antibiotic therapy for confirmed pharyngitis (penicillin) significantly reduces the risk of subsequent pharyngitis, which emphasizes the role of accessible pediatric testing and adherence to antibiotic regimens. In outpatient practice, rapid antigen tests and culture/sowing are used when rapid tests are negative in children. [11]

Classic RL develops 2-5 weeks after infection, when the bacteria have already disappeared and the immune system is "working by inertia" against its own body. This explains why antibiotics at the onset of RL no longer relieve arthritis or carditis, but are critical for secondary prevention of relapses. [12]

Risk factors

Key population factors include overcrowding, poverty, limited access to primary care, and low adherence to pharyngitis treatment and secondary prevention. Family crowding increases the circulation of streptococci and the risk of recurrent infections. School-clinic-family programs with rapid tests and a single visit for penicillin injection reduce the risk. [13]

Individual factors include age 5-15 years, recent streptococcal pharyngitis, a family history of rheumatoid arthritis/rheumatoid arthritis, recurrent sore throats, and a genetic predisposition. In adolescents and young adults, symptoms may be "faded," and echocardiography helps detect carditis. In high-risk regions (according to the AHA, 2015), diagnostic thresholds are relaxed. [14]

Low adherence to secondary prophylaxis (missed benzathine benzylpenicillin injections) is an independent risk factor for relapses of LC and progression of RHD. Organizational measures such as reminders, patient "catch-up" by school nurses, and mobile teams are effective. [15]

Finally, social determinants (education, transportation, cultural barriers) and comorbid conditions (eg, pregnancy in women with RHD) increase the risks of adverse outcomes and require a team approach.[16]

Pathogenesis

The immunopathogenesis of RL is an example of molecular mimicry: antibodies and T cells, "trained" by streptococcal antigens, recognize similar structures in the heart valves, myocardium, synovium, and nervous tissue. Inflammation develops with edema and tissue infiltration, and in the heart, pancarditis, especially endocarditis involving the mitral (most commonly) and aortic valves. The result is thickening of the valve leaflets, chordal changes, and regurgitation. [17]

In the joints, a volatile polyarthritis of large joints is typical: immune complexes and inflammatory mediators create a pronounced but reversible inflammatory response. In the skin and subcutaneous tissue, annular erythema and subcutaneous nodules are rare but highly specific manifestations. [18]

The nervous system is affected by chorea minor (Sydenham's disease): an autoimmune attack on the basal ganglia causes involuntary movements, emotional instability, and impairments in handwriting and fine motor skills. Chorea may appear later than other symptoms, sometimes as the only major symptom. [19]

The severity of inflammation correlates with laboratory markers (C-reactive protein, ESR), but the key to cardiac damage is Doppler echocardiography. It visualizes early mitral/aortic regurgitation and "subclinical" carditis, which previously went undetected. [20]

Symptoms

The classic onset is 2-5 weeks after a sore throat: fever, severe pain, and swelling of the joints (usually the knees, ankles, and elbows), often with a "fleeting" character—one joint "heals" and another immediately becomes affected. The pain is severe and responds well to anti-inflammatory medications. This is the most common major symptom. [21]

Carditis can present with shortness of breath, tachycardia, chest pain, regurgitant murmurs, and, in children, decreased exercise tolerance. Sometimes carditis is "silent" and only detected by echocardiography—today, this is also considered a significant criterion. In severe cases, heart failure rapidly develops. [22]

Chorea minor – involuntary twitching, "sloppy" writing, clumsiness, dropping objects, emotional instability; in schoolchildren – declining academic performance. Often without fever or arthritis, which hinders recognition. This is a separate, major criterion, even if no others are present. [23]

Skin and subcutaneous tissue: annular erythema (pale pink rings on the trunk, easily missed) and subcutaneous nodules (dense, painless, over tendons and bony prominences) are rare but very specific signs of active LC. They are almost always accompanied by carditis. [24]

Forms and stages

A distinction is made between the first episode of pulmonary valve disease and a relapse (a repeated attack following a previous episode of pulmonary valve disease/RHD). Relapses are particularly dangerous for the valves: each repeated episode "layers" damage to the leaflets and accelerates the development of the defect. Therefore, secondary prevention is the cornerstone of the strategy. [25]

Based on the activity of the process, they speak of acute rheumatoid arthritis and a protracted/recurrent form. The acute episode lasts several weeks, arthritis and fever resolve, but valve damage can progress. Delayed diagnosis and lack of prevention "transfer" the patient to chronic rheumatoid arthritis. [26]

Rheumatic heart disease (RHD) is a chronic consequence of rheumatic heart disease with valvular defects (most often mitral regurgitation/stenosis, then aortic regurgitation). Today, it is increasingly being diagnosed at the latent stage of RHD according to the WHF-2012/2023 criteria, when clinical symptoms are absent but echocardiography already reveals characteristic changes. This provides an opportunity for preventative intervention. [27]

The neurobehavioral variant (chorea) is characterized by solitary chorea without other signs of active RL. The diagnosis is made clinically, and confirmation of recent GAS exposure is noted retrospectively. This form requires special treatment and monitoring strategies. [28]

Table 1. Major and minor Jones criteria (AHA, 2015) - simplified

Category	Criteria
Big ones	Carditis (including "subclinical" by Doppler echo); polyarthritis; chorea minor; erythema annulare; subcutaneous nodules
Small	Arthralgia/monoarthritis (depending on risk population); fever; elevated CRP/ESR; prolonged PQ on ECG
Plus is a must	Evidence of recent GAS infection (positive test/culture, elevated ASO/anti-DNase B, recent scarlet fever)
Notes	For populations with intermediate/high risk, some exceptions are made (e.g., monoarthritis as major; polyarthralgia as minor). Doppler echo is the standard for assessing carditis. [29]

Complications and consequences

The main consequence is rheumatic heart disease: chronic valvular defects leading to heart failure, arrhythmias (including atrial fibrillation), thromboembolism, and the need for valve surgery at a young age. Prevention of relapses and early diagnosis of latent RHD reduce these risks. [30]

In some patients, acute carditis can progress to severe regurgitation and heart failure, requiring intensive care and sometimes early valve intervention. This is not a rule, but the likelihood is higher with late presentation, repeated attacks, and high inflammatory activity. [31]

The neurological consequences of chorea are reversible in most cases, but during the active symptomatic phase they impair quality of life and learning; relapse prevention strategies are sometimes required if the chorea persists. Psychosocial support from family and school is an important part of the treatment. [32]

Pregnancy associated with RHD increases the burden on the heart: mitral valve defects and pulmonary hypertension worsen the prognosis for both mother and fetus. Planning the pregnancy, correction of the defect before gestation, and strict secondary prophylaxis with penicillin are the standard for safe management. [33]

Diagnostics

If rheumatic fever is suspected, the doctor will order the following tests:

• Blood tests: complete blood count (leukocytosis, thrombocytosis), C-reactive protein and erythrocyte sedimentation rate (inflammatory activity), antistreptolysin O and/or anti-DNase B (recent GAS infection), biochemistry.
• Throat swab/rapid GAS antigen test; in children, if the rapid test is negative, culture (according to algorithms).
• Electrocardiography (looking for prolongation of PQ, arrhythmia), chest x-ray (as indicated).
• Echocardiography with Doppler is mandatory for everyone with suspected carditis, even without murmurs.

Doppler echo is performed using a standard chest transducer (for children, a phased array/pediatric transducer is used). This method allows for the visualization of mitral and/or aortic regurgitation, leaflet thickening, limited mobility, prolonged jets, and abnormal Doppler profiles. The 2015 AHA criteria recognize "subclinical carditis" by echo as a major criterion, even in the absence of clinical murmur. [34]

Rheumatic fever manifests on echo as regurgitation with specific Doppler signs (e.g., high-velocity and duration of mitral jet, abnormal closing click), sometimes without significant thickening at onset. As the disease progresses to RHD, thickening and "hairiness" of the leaflets, shortening of the chords, and signs of stenosis/calcification in older patients appear. WHF-2012/2023 regulates the criteria for "definite" and "borderline" RHD, applicable for screening. [35]

Additional instrumental diagnostics:

• Cardiomagnetic tomography - for complex indications (assessment of myocarditis, in case of doubts based on echo).
• Focal "pocket" echo (FOCUS) - used by trained professionals for field screening; positive findings are verified by standard echo.
• Neuroassessment in chorea: clinical scale, if necessary - exclusion of other causes of hyperkinesis.
• Throat diagnostics in contacts - to identify GAS carriers and "family sanitation" in outbreaks.

If a child complains of severe joint pain and fever 2-4 weeks after a sore throat, pulmonary leukemia (RL) is the first diagnosis considered. Elevated C-reactive protein/ESR, antistreptococcal antibody titers, and evidence of recent GAS pharyngitis are diagnostic. If carditis is suspected, Doppler echo plays a crucial role—it detects "silent" regurgitation even in the absence of murmur. WHO/CDC algorithms emphasize that antibiotics in confirmed GAS pharyngitis reduce the risk of RL; in children, a negative rapid test is confirmed by culture. [36]

Table 2. What suggests a RL on echo (simplified)

Sign	Comment
Pathological mitral regurgitation	Long-lasting, high-speed, non-physiological
Aortic regurgitation	In combination with early thickening of the valves
Thickening/decreased mobility of the valves	An early sign of a transition to RBS
Absence of pronounced clinical noises	Doesn't rule out carditis - Doppler decides
"Subclinical" carditis as a major criterion	Recognized by AHA-2015 for the diagnosis of LC [37]

Differential diagnosis

What is rheumatic fever most often confused with?

• Juvenile idiopathic arthritis: long-term (>6 weeks) inflammatory joint syndrome without volatility, morning stiffness. In rheumatoid arthritis, there is a "volatile" polyarthritis, a rapid response to NSAIDs, and a history of recent tonsillitis.
• Viral arthritis (parvovirus, adenovirus): joint pain after acute respiratory viral infection, but without the characteristic set of Jones criteria and without evidence of GAS infection.
• Infective endocarditis: fever, murmurs, elevated markers - but often positive blood cultures, vegetations on echo and a different time profile.
• Neurogenic hyperkinesias (tic disorders, chorea in other diseases): in RL - Sydenham's chorea with characteristic clinical features and often traces of recent GAS contact.

How to distinguish in practice:

• Time from sore throat to symptoms (2-5 weeks for RL), evidence of GAS (ASO/anti-DNase B test/culture), Jones criteria, echo signs of carditis.
• In endocarditis - blood cultures, vegetations on echo, signs of sepsis; in juvenile arthritis - chronic course and lack of "volatility".
• Chorea in RL is a self-sufficient major criterion; a neurologist evaluates the phenomenology of movements and excludes metabolic and other autoimmune causes.
• If in doubt, a multidisciplinary consultation and re-evaluation in 1-2 weeks with the dynamics of markers and echo. [38]

Table 3. RL vs. "mimics": quick differences

Situation	For RL	For an alternative
"My joints hurt after an acute respiratory viral infection"	Volatile polyarthritis, high CRP/ESR, association with angina, ASL-O↑	Monotonous pain, viral markers, no GAS evidence
Heart murmur in a teenager	Doppler signs of regurgitation + Jones criteria	Vegetations/bacteremia (endocarditis)
Chorea	Characteristic hyperkinesis + traces of GAS	Tics/metabolic, no association with GAS
Long-term arthritis	Rapid response to NSAIDs, "volatility"	JIA: chronic, morning stiffness [39]

Treatment

1) Treatment of streptococcal infection and inflammation control. If the patient has active GAS pharyngitis, penicillin is recommended (a single intramuscular dose of benzathine-benzylpenicillin or oral regimens), which reduces the risk of RL and prevents transmission. At the onset of RL, antibiotics eliminate carriage but do not treat inflammation; NSAIDs (ibuprofen/aspirin) and bed rest for carditis are prescribed for symptoms. Glucocorticoids are prescribed for severe carditis/heart failure. [40]

2) Heart and chorea. In case of carditis, echocardiographic monitoring and standard heart failure therapy are recommended; in case of severe mitral regurgitation and decompensation, early cardiac surgery is considered (rarely in the acute phase). Minor chorea is treated symptomatically (e.g., valproate/carbamazepine); in severe cases, short courses of steroids/immunomodulators are recommended as indicated. [41]

3) Secondary prevention is the foundation of outcome. Benzathine-benzylpenicillin intramuscularly every 4 weeks (in some regions, every 3 weeks for high-risk individuals) for at least 5-10 years or up to 21-25 years (longer for carditis/RHD). New data confirm that intramuscular penicillin is approximately 10 times more effective than oral regimens in preventing relapses and also reduces the progression of latent RHD. The key is adherence, reminders, and convenient injection sites. [42]

4) Screening and treatment of latent RHD. According to the WHF-2012/2023 criteria, echo screening of schoolchildren/adolescents in endemic regions is being conducted. If "latent" RHD is detected, secondary prophylaxis with penicillin reduces the risk of progression (demonstrated in a randomized trial, NEJM). WHO-2024 has issued practical guidelines for the implementation of such programs in healthcare systems. [43]

Table 4. Secondary prophylaxis with penicillin: what is important

Parameter	Recommendations/facts
Preparation	Benzathine-benzylpenicillin intramuscularly
Interval	Every 4 weeks (every 3 weeks for high-risk patients)
Duration	≥5-10 years or up to 21-25 years; longer with carditis/RHD
Effect	Significant reduction in LC relapses; inhibition of latent RBS progression
Oral alternatives	Less effective; used when injections are not possible [44]

Table 5. When to refer to a cardiac surgeon (simplified)

Scenario	Arguments
Severe mitral/aortic regurgitation with heart failure	Low probability of reversibility, risk of remodeling
Mitral valve stenosis in an adolescent/young adult	Symptoms: Increased pulmonary artery pressure
Recurrent decompensations against the background of RBS	Change in quality of life, prognosis
Pregnancy plans with a severe defect	Planning for correction before gestation [45]

Prevention

Primary prevention involves prompt diagnosis and treatment of GAS pharyngitis: access to rapid tests and/or culture, penicillin as a first-line drug, and informing parents that antibiotics reduce the risk of pharyngitis. In schools and clinics, simple algorithms are in place: "sore throat + fever" → test → if confirmed, treatment according to the regimen. [46]

Secondary prevention involves regularly scheduled injections of benzathine benzylpenicillin. Systematic measures increase adherence: telephone reminders, a one-stop shop for injections, training for nurses, and outreach to families and schools. WHO-2024 provides practical recommendations for organizing programs at the regional level. [47]

Forecast

With early recognition of LC, adequate anti-inflammatory therapy, and strict secondary prevention, children and adolescents live without disabling consequences; the risk of RHD is minimal. Even with "silent" carditis, systematic echocardiographic monitoring allows for timely adjustments to management. [48]

If diagnosis is late and preventive measures are not taken regularly, the risk of RHD and valve surgery at a young age increases significantly. Modern echo criteria (WHF-2023) and latent screening programs help change the trajectory of the disease at an early stage. [49]

Table 6. Algorithm for managing a patient with suspected LC (briefly)

Step	Action
1	Assess Jones criteria; take inflammatory markers and GAS antibodies
2	Conduct an echo with Doppler (for everyone!) to look for “silent” carditis
3	If GAS pharyngitis is confirmed, penicillin (elimination of carriage)
4	Symptomatic therapy: NSAIDs; in severe carditis - steroids
5	Prescribe and organize secondary prophylaxis with penicillin
6	Observation plan: echo control, family training, route to the RBS center [50]

FAQ

• Is rheumatic fever an infection? Are antibiotics needed to treat the fever?

RL is an autoimmune inflammation following GAS pharyngitis. Antibiotics in the acute episode are needed to eradicate streptococci and prevent transmission, but symptoms (arthritis, carditis) are treated with NSAIDs/steroids as indicated. The key is regular secondary prevention. [51]

• How long does secondary prevention last and why injections?

Usually 5-10 years or up to 21-25 years; in carditis/RHD - longer. Intramuscular benzathine penicillin is more effective than oral regimens (approximately 10 times in preventing relapses) and reduces the progression of latent RHD. [52]

• Can valve disease be detected before symptoms occur?

Yes. The WHF-2012/2023 criteria allow for the detection of latent RHD on echocardiography. This is important: patients receive prevention and monitoring, which reduces the risk of defects. [53]

• What should parents do if their child often has a sore throat?

Consult a doctor if you have a sore throat and fever, get a rapid test/culture, and if GAS is confirmed, treat with penicillin. This reduces the risk of RL. Do not prescribe antibiotics "as a last resort" without testing. [54]

Table 7. Where to look for official recommendations and “what to take on board”

Organization/document	What is useful?
AHA, 2015: Revision of the Jones Criteria	Modern diagnostic thresholds, Doppler echo as a major criterion
WHO, 2024: guidelines for the prevention/diagnosis of RL/RHD	Policies and clinical algorithms for health systems
WHF, 2023: RBS echo criteria	Screening for "latent" RBS, unified definitions
NEJM 2022 (prevention of latent RHD)	Randomized evidence on the benefits of penicillin
Cochrane 2024 (secondary prevention)	Evidence of superiority of intramuscular penicillin over oral regimens [55]