History
Rheumatic fever manifests as various signs and symptoms that may occur alone or in various combinations.
Sore throat
Although estimates vary, only 35%-60% of patients with rheumatic fever recall having any upper respiratory symptoms in the preceding several weeks. Many symptomatic individuals do not seek medical attention, go undiagnosed, or do not take the prescribed antibiotic for acute rheumatic fever (ARF) prevention. [6, 14] If a course of penicillin or another appropriate antibiotic is taken at this time, the risk for ARF is reduced by approximately 80%. [22]
Arthritis
Overall, arthritis occurs in approximately 75% of first attacks of ARF. The likelihood increases with the age of the patient, and arthritis is a major manifestation of ARF in 92% of adults. [14] The arthritis is typically polyarticular, but monoarthritis may occur with ARF in select high-risk populations.
The arthritis of ARF is usually symmetrical and involves large joints, such as the knees, ankles, elbows, and wrists. Tenosynovitis is common in adults and may be severe enough to suggest a diagnosis of disseminated gonococcal disease. [14] Aseptic monoarticular arthritis is seen in a substantial minority of cases from higher-risk areas, especially South Asia and Oceania, and can occur when NSAIDs are used early in the course. [23, 24]
The evolution of polyarthritis in individual joints tends to overlap; therefore, multiple joints may be inflamed simultaneously, causing more of an additive than a migratory pattern. [14]
In most instances, the entire bout of arthritis subsides within 4-6 weeks without any permanent damage. If not, a different diagnosis should be entertained.
Carditis
Of first attacks of ARF, carditis occurs in 30%-60% of cases. It is more common in younger children but does occur in adults. [14]
Severe inflammation can cause congestive heart failure (CHF).
Patients with carditis may present with shortness of breath, dyspnea upon exertion, cough, paroxysmal nocturnal dyspnea, chest pain, and/or orthopnea. Carditis may also be asymptomatic and may be diagnosed solely via auscultation or echocardiography. [6, 24, 20]
Sydenham chorea
This occurs in up to 25% of ARF cases in children but is very rare in adults. It is more common in girls. Sydenham chorea in ARF is likely due to molecular mimicry, with autoantibodies reacting with brain ganglioside. [25]
Sydenham chorea may occur with other symptoms or as an isolated finding. It typically presents 1-6 months after the precipitating streptococcal infection and usually has both neurologic and psychological features. [25]
In the isolated form, laboratory evidence of a preceding streptococcal infection may be lacking.
Like the arthritis, Sydenham chorea usually resolves without permanent damage but occasionally lasts 2-3 years and be a major problem for the patient and her family. [6]
Erythema marginatum
In first attacks of ARF in children, erythema marginatum occurs in approximately 10%. Like chorea, it is very rare in adults.
Patients or parents may report a nonpruritic, painless, serpiginous, erythematous eruption on the trunk. It is usually noted only in fair–skinned patients. [2]
The lesions may persist intermittently for weeks to months.
Subcutaneous nodules
Subcutaneous nodules are rarely noticed by the patient.
Other symptoms
Other symptoms may include fever, abdominal pain, arthralgia, malaise, and epistaxis.
Physical
Arthritis
Joint involvement in ARF may range from arthralgia to frank arthritis characterized by swelling, redness, warmth, and joint tenderness. Monoarticular arthritis may occur if anti-inflammatory agents are used early in the course [23] and is increasingly seen in areas of medium-high endemicity. [24]
The joints frequently involved include the knees, ankles, elbows, and wrists. The small joints of the hands and the spine are rarely involved. Hand involvement tends to occur in poststreptococcal arthritis, a controversial related syndrome with a lower but apparently nonzero risk of carditis. [6, 24]
Inflammation begins to subside within a few days to a week and disappears within 2-6 weeks.
The arthritis is classically described as migratory, but, in many cases, new joints are affected before the previously involved joints improve, leaving the appearance of an additive arthritis. [14] Monoarthritis can also occur.
In most cases, the process does not leave any residual damage. On very rare occasions, periarticular fibrosis occurs after rheumatic arthritis, the so-called Jaccoud joint.
Carditis
Carditis is the only manifestation of ARF with significant potential to cause long-term disability and/or death. It is usually a pancarditis involving the pericardium, myocardium, and endocardium.
The signs of carditis include the development of new murmurs, cardiac enlargement, CHF, pericardial friction rub, and/or pericardial effusion.
Characteristic murmurs of acute carditis include the high-pitched, blowing, holosystolic, apical murmur of mitral regurgitation; the low-pitched, apical, mid-diastolic, flow murmur (Carey-Coombs murmur); and a high-pitched, decrescendo, diastolic murmur of aortic regurgitation heard at the aortic area. Murmurs of mitral and aortic stenosis are observed in chronic valvular heart disease. Isolated aortic disease is distinctly unusual.
The features of CHF include tachycardia, a third heart sound, rales, and edema.
Pericarditis presents as a pericardial rub or effusion.
The use of echocardiography to detect carditis often reveals "subclinical" rheumatic cardiac disease (both acute and chronic) not appreciated by the standard examination. [24, 26, 27, 28, 29, 20] Subclinical carditis has been a controversial topic in rheumatic fever diagnosis, [30, 31, 32] but the 2015 revision of Jones Criteria now includes echocardiographically diagnosed subclinical endocarditis as a major criterion and recommends echocardiography in all proven and suspected cases.
Subcutaneous nodules
Subcutaneous nodules are uncommon and are usually associated with severe carditis. They tend to occur several weeks after illness onset, are usually painless, and usually go unnoticed by the patient.
They are found primarily over the bony surfaces or prominences and in tendon sheaths. The common sites include the elbows, knees, wrists, ankles, over the Achilles tendon, the back of the scalp, and the spinous process of the vertebrae. [2]
They usually persist for 1-2 weeks. The main differential diagnosis is the nodules of rheumatoid arthritis. [14]
Erythema marginatum
The individual lesions of erythema marginatum are evanescent, moving over the skin in serpiginous patterns. Likened to smoke rings, they have a tendency to advance at the margins while clearing in the center.
The lesions may be macular and can develop and disappear in minutes, appearing to change shape while being examined.
They are found on the trunk and proximal aspects of the extremities and often go unnoticed by patients and parents, as they are usually covered by clothing. [2]
Sydenham chorea
This is a neurological disorder characterized by emotional lability, personality change, muscular weakness, and uncoordinated, involuntary, purposeless movements.
The classic weakness is characterized by the inability to sustain a tetanic contraction. Patients are unable to maintain a clenched fist when attempting to grip the examiner's hand. Other findings include dysarthric speech, gait problems, and poor fine-motor skills. [25]
The motor symptoms usually disappear during sleep and may be partially suppressed by sedation.
They can involve the face, hands, and feet.
Untreated rheumatic fever/chronic rheumatic fever
The average duration of an untreated ARF attack is 3 months. Chronic rheumatic fever, generally defined as disease persisting for longer than 6 months, occurs in less than 5% of cases.
Causes
Group A beta-hemolytic streptococcal infection may lead to rheumatic fever. The overall attack rate after streptococcal pharyngitis 0.3-3%, but certain genetically predisposed individuals, comprising perhaps 3%-6% of the population, account for those who develop rheumatic fever. [6] Ongoing research using genome-wide association studies may uncover more specifics of the gnetic suscepibilty patterns. [21]
Studies in developed countries have established that rheumatic fever followed only pharyngeal infections and that not all of the 230 serotypes of group A streptococci could cause rheumatic fever. The classic rheumatogenic strains include emm types 1, 3, 5, 6, 14, 18, 19,24,27 and 29. [2, 9] More recent data, largely from studies of the indigenous peoples of Australia, suggest that streptococcal skin infections (pyoderma) can predispose to ARF and that many other group A emm types may be involved. [5, 9] Some data also indicate that group C and G streptococci may precipiate acute rheumatic fever. [5, 7, 12]
Two basic theories have been postulated to explain the development of ARF and its sequelae following group A streptococcal infection: (1) a toxic effect produced by an extracellular toxin of group A streptococci on target organs such as the myocardium, valves, synovium, and brain and (2) an abnormal immune response to streptococcal components. Increasing and compelling evidence now strongly favors the autoimmune explanation. It seems clear that an exaggerated immune response in a susceptible individual leads to rheumatic fever. This probably occurs through molecular mimicry, in which the immune response fails to differentiate between epitopes of the streptococcal pathogen and certain host tissues. [6, 10, 29, 20]
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Clinical manifestations and time course.
