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Acute rheumatic fever: Clinical manifestations and diagnosis

Acute rheumatic fever: Clinical manifestations and diagnosis
Literature review current through: Aug 2023.
This topic last updated: Mar 10, 2022.

INTRODUCTION — Acute rheumatic fever (ARF) is a nonsuppurative sequela that occurs two to four weeks following group A Streptococcus (GAS) pharyngitis and may consist of arthritis, carditis, chorea, erythema marginatum, and subcutaneous nodules. Damage to cardiac valves may be chronic and progressive, resulting in cardiac decompensation.

The clinical manifestations and diagnosis of ARF are reviewed here. The epidemiology, pathogenesis, treatment, and prevention of this disorder are presented separately. (See "Acute rheumatic fever: Epidemiology and pathogenesis" and "Acute rheumatic fever: Treatment and prevention".)

CLINICAL MANIFESTATIONS

Acute illness — ARF can present with several different clinical findings within one to five weeks (usually two to three weeks) of a group A streptococcal (GAS) tonsillopharyngitis (or streptococcal pyoderma in patients from tropical regions) [1-3]. The possible major and minor manifestations are reviewed here. These manifestations are used for diagnosis (Revised Jones Criteria) (table 1) [4]. The diagnostic criteria are reviewed below. (See 'Diagnosis' below.)

The five major manifestations (and percent of patients with each) are [4]:

Arthritis (usually migratory polyarthritis predominantly involving the large joints) – 60 to 80 percent

Carditis and valvulitis (eg, pancarditis) that is clinical or subclinical – 50 to 80 percent

Central nervous system involvement (eg, Sydenham chorea) – 10 to 30 percent

Subcutaneous nodules – 0 to 10 percent

Erythema marginatum – <6 percent

The four minor manifestations are:

Arthralgia

Fever

Elevated acute phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP])

Prolonged PR interval on electrocardiogram

There are two primary forms of presentation for ARF (table 2). The more common form (approximately 70 to 75 percent of patients) is an acute febrile illness with joint manifestations and often carditis. The less common form is a neurologic/behavioral disorder with Sydenham chorea. Joint manifestations are usually absent, and carditis, when present, is often subclinical. There are also other atypical presentations of ARF. In resource-limited settings, patients may present for the first time with a complication of established rheumatic heart disease (RHD) rather than ARF because of a lack of awareness of the symptoms of ARF or lack of access to care [5].

Major manifestations — The major manifestations of ARF include arthritis, carditis, Sydenham chorea, subcutaneous nodules, and erythema marginatum.

Arthritis — Arthritis usually is the earliest symptomatic manifestation of ARF, generally presenting within 21 days of GAS infection, although asymptomatic carditis may develop first. It is more common and more severe in teenagers (approximately 80 percent) and young adults than in children (approximately 65 percent) [6]. Joint pain typically is more prominent than objective signs of inflammation and is almost always transient. However, the arthritis may be severe enough to severely limit movement.

Generally, the inflammation affects several joints in quick succession, and each joint is inflamed for a day or two to a week [7]. The knees, ankles, elbows, and wrists are most commonly affected, with the leg joints typically involved first. The onset of arthritis in different joints usually overlaps, giving the appearance that the disease "migrates" from joint to joint. Thus, the terms "migrating" or "migratory" are used to describe the polyarthritis of ARF, and it is also regarded as an "additive" polyarthritis. The arthritis resolves without treatment in approximately four weeks, and there is no long-term joint deformity [4].

The natural history of arthritis in ARF is altered by empiric treatment with nonsteroidal antiinflammatory drugs (NSAIDs) or glucocorticoids. In such cases, arthritis subsides quickly in the joint(s) affected and does not "migrate" to new joints. The diagnosis of ARF should be reconsidered if joint symptoms do not respond to NSAID treatment within 48 hours.

Patients treated with NSAIDs early in the course of ARF, particularly before the other signs and symptoms of ARF become distinct, may appear to have monoarthritis rather than polyarthritis. As an example, involvement of a single large joint was common in one series of patients with ARF who were treated for associated arthritis [7]. In another series including 555 Aboriginal Australians, aseptic monoarticular arthritis was also described in 17 percent of cases [8]. The presence of monoarthritis rather than polyarthritis can make it difficult to establish the diagnosis of ARF and determine the need for secondary ARF prophylaxis. Commencement of NSAID therapy can be delayed if the diagnosis of ARF is suspected but only a single joint is involved, with acetaminophen used for analgesia in the meantime, since there is no evidence that temporarily withholding such therapy has any adverse effects. NSAIDs may be commenced once a second joint is involved and the diagnosis is clear.

Radiography of an affected joint may demonstrate a slight effusion but is usually unremarkable. Thus, radiographic evaluation of affected joints is not routinely performed. Joint aspiration and synovial fluid evaluation, including culture, is indicated if there is significant effusion of one joint or septic arthritis is suspected. Analysis of the synovial fluid generally demonstrates sterile inflammatory fluid in patients with ARF.

Carditis — The carditis associated with ARF is classically considered to be a pancarditis that can involve the pericardium, epicardium, myocardium, and endocardium [4]. While myocarditis and pericarditis may occur in ARF, the predominant manifestation of carditis is involvement of the endocardium presenting as a valvulitis, especially of the mitral and aortic valves. It usually presents within three weeks of GAS infection. The presence of valvulitis is established by auscultatory findings together with echocardiographic evidence of mitral or aortic regurgitation. If valvulitis is severe, acute heart failure may occur.

Mitral regurgitation is the most typical form of valvulitis in ARF, characterized by a pansystolic murmur heard loudest at the apex and radiating to the left axilla. The Carey Coombs murmur, a short mid-diastolic murmur heard loudest at the apex, is an indicator of moderate-severe mitral regurgitation as a result of increased blood flow across the mitral valve during left ventricular filling. Aortic regurgitation is characterized by an early diastolic murmur heard at the base of the heart, made louder by the patient sitting forward in forced expiration.

Pericarditis occurs in up to 10 percent of patients with ARF but vary rarely in the absence of valvulitis. Chest pain may be present, and a pericardial friction rub may be heard on auscultation.

Subclinical carditis can be diagnosed by echocardiography/Doppler studies that reveal mitral or aortic regurgitation in the absence of ausculatory findings (either because the clinical exam findings are absent or are not recognized). Damage to cardiac valves may be progressive and chronic, resulting in cardiac decompensation. Clinical manifestations and diagnosis of carditis are discussed separately. (See "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Rheumatic carditis' and "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Diagnosis of rheumatic carditis' and "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Transition from acute to chronic disease' and "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Chronic valve disease'.)

Sydenham chorea — Sydenham chorea (also known as chorea minor or "St. Vitus dance") is a neurologic disorder consisting of abrupt, nonrhythmic, involuntary movements, muscular weakness, and emotional disturbances [9]. Chorea has a longer latent period than other rheumatic manifestations, typically presenting one to eight months after a GAS infection [10], and may occur as an isolated finding. It is more common in girls and may present as refusal to go to school and self-isolation due to shame and embarrassment. Recurrence of rheumatic chorea is not uncommon, sometimes associated with pregnancy or the oral contraceptive pill. Most patients with Sydenham chorea recover fully within six weeks and nearly all within six months, with only rare cases described lasting longer than that. (See "Sydenham chorea".)

The choreiform movements frequently are more marked on one side, are occasionally unilateral (hemichorea), and cease during sleep. The movements may be subtle and intermittent, sometimes only seen after a 10- to 15-minute period of quiet observation. Muscle weakness is best demonstrated by asking the patient to squeeze the examiner's hands. The pressure of the patient's grip increases and decreases capriciously, a phenomenon known as relapsing grip or "milk maid's sign." The head is often involved, with erratic movements of the face that resemble grimaces, grins, and frowns. The tongue, if affected, can resemble a "bag of worms" when protruded, and protrusion cannot be maintained. Chorea disappears with sleep and is made more pronounced by purposeful movements. Diffuse hypotonia may be present. Neurologic examination fails to reveal sensory losses or involvement of the pyramidal tract.

Emotional changes manifest with outbursts of inappropriate behavior including crying and restlessness. Some patients have features of obsessive-compulsive disorder (OCD). Halting and jerky speech patterns are also sometimes seen. In rare cases, psychologic manifestations are severe and may result in transient psychosis.

Erythema marginatum — Erythema marginatum is an evanescent, pink or faintly red, nonpruritic rash involving the trunk and sometimes the limbs but not the face [11]. When present, it usually occurs early in the course of ARF, but, in some cases, the lesions are first noticed late in the illness or even during convalescence [12]. In some instances, it persists or recurs after all other manifestations have resolved. Erythema marginatum most commonly occurs in patients with acute carditis but has been reported in patients with chronic carditis [7]. It rarely occurs as the sole manifestation of ARF.

The lesion extends centrifugally, with return of the skin in the center to a normal appearance. The outer edge of the lesion is sharp; the inner edge is diffuse. The lesion is also known as "erythema annulare" since the margin of the lesion is usually continuous, making a ring (picture 1 and picture 2). Individual lesions may appear, disappear, and reappear in a matter of hours. A hot bath or shower may make them more evident.

Subcutaneous nodules — Subcutaneous nodules in ARF are firm, painless lesions ranging from a few millimeters to 2 cm in size. They are smaller and shorter lived than the nodules of rheumatoid arthritis. Subcutaneous nodules associated with ARF generally appear after the first weeks of illness, usually in patients with relatively severe carditis. They rarely appear as the only manifestation of ARF. Typically, nodules are present for one or more weeks, but they rarely persist for more than a month.

The nodules are usually located over a bony surface or prominence or near tendons (usually extensor surfaces) and are usually symmetric. The elbows are involved most frequently in both ARF and rheumatoid arthritis. However, ARF nodules occur most commonly on the olecranon, whereas rheumatoid nodules are usually found 3 to 4 cm distally. The overlying skin is not inflamed and usually can be moved over the nodules (picture 3) [13]. The number of nodules varies from a single lesion to a few dozen; the average number is three to four.

Minor manifestations — The minor manifestations of ARF include fever, arthralgia, elevated ESR and CRP, and prolonged PR interval on electrocardiogram [4].

Fever – Fever associated with ARF is usually ≥38.5°C orally (101.3°F). However, low-grade fever (≥38°C [100.4°F]) is more common in high-risk groups and is accepted as a minor criterion in high-risk groups.

Arthralgia – Arthralgia usually involves several joints (polyarthralgia) when it occurs in patients with ARF. However, it is a common manifestation in many other rheumatologic disorders and therefore is highly nonspecific.

Elevated acute phase reactants – Acute phase reactants are almost always elevated in patients with ARF, except in some patients with isolated chorea or in those treated with antirheumatic drugs [14]. Typical elevations of acute phase reactants seen in ARF include an ESR ≥60 mm/hour and CRP ≥3 mg/dL (≥30 mg/L). As with fever, lower levels (ie, ESR ≥30 mm/hour) can be seen in high-risk groups.

Prolonged PR interval on electrocardiogram – Interpretation of PR prolongation depends upon age and heart rate and is >0.2 seconds in adults. It is important to note that up to one-third of children with uncomplicated streptococcal infections have a prolonged PR interval [15]. Abnormal atrioventricular conduction is common in ARF, with first-degree block the most common abnormality observed [16]. Severe first-degree block can occasionally lead to a junctional rhythm, and second-degree and complete heart block can occur (waveform 1) [17,18].

Additional features

Family history – A family history of ARF should heighten the suspicion for ARF in the setting of suggestive features.

Other findings – Other clinical features seen in patients with ARF include abdominal pain, precordial pain, malaise, epistaxis, rapid sleeping pulse rate, and tachycardia out of proportion to fever. Laboratory findings include leukocytosis and mild normochromic, normocytic anemia of chronic inflammation. Complement levels are usually normal in ARF. In contrast, hypocomplementemia is typically observed in the setting of poststreptococcal glomerulonephritis.

Late sequelae — RHD is the most common and severe sequela of ARF. Jaccoud arthropathy is a rare complication associated with recurrent episodes of ARF with polyarthritis.

Rheumatic heart disease — RHD usually occurs 10 to 20 years after the original illness, although it may present earlier after a severe or recurrent episode of ARF. It is the most common cause of acquired valvular disease in the world [19,20]. The mitral valve is more commonly involved than the aortic valve, and mitral regurgitation is the most common finding of RHD. This may progress to mitral stenosis in severe cases due to fibrosis and calcification of the mitral valve. In general, valvular damage manifesting as a murmur later in life occurs in approximately 50 percent of patients who had carditis during the initial episode of ARF [21,22]. RHD is discussed in greater detail separately. (See "Clinical manifestations and diagnosis of rheumatic heart disease".)

Jaccoud arthropathy — Jaccoud arthropathy is a benign, chronic arthropathy that involves loosening and lengthening of periarticular structures and tendons in the hands and/or feet (picture 4) [23]. The deformities are painless, "correctable" with manipulation, and do not cause functional impairment. The arthropathy is not associated with active joint inflammation.

DIAGNOSIS — ARF is characterized by group A streptococcal (GAS) infection followed by the clinical manifestations outlined above (see 'Acute illness' above). The diagnosis of ARF is established on clinical grounds using the 2015 Jones Criteria (table 1), which are stratified based upon whether the patient is from a low-risk or a moderate- to high-risk population [4]. The diagnostic evaluation includes studies to establish the diagnosis of GAS infection, evaluate acute phase reactants, and assess cardiac function.

Diagnostic criteria — The initial description of clinical manifestations in 1944, known as the Jones Criteria [24,25], was used by the American Heart Association (AHA) to establish guidelines for the diagnosis of ARF. These guidelines have been modified over time, most recently in 2015 [4,26,27].

The 2015 revision of the criteria provides two different sets of criteria: one for low-risk populations (ie, those with a rheumatic fever incidence ≤2 per 100,000 school-aged children per year or all-age rheumatic heart disease [RHD] prevalence ≤1 per 1000 population) and one for moderate- to high-risk populations (table 1).

The major and minor manifestations included in the Jones Criteria are reviewed above (see 'Acute illness' above). Joint (arthritis or arthralgia) and cardiac (carditis or prolonged PR interval) manifestations can only be counted once, not twice, as either a major or a minor criterion.

Diagnosis of an initial episode of ARF – Two major manifestations or one major plus two minor are sufficient for diagnosis of an initial episode of ARF in a patient with evidence of a preceding GAS infection.

Diagnosis of a recurrent episode of ARF – Patients with a history of ARF are at risk of subsequent episodes of ARF with GAS reinfection, and repeat episodes are associated with a greater likelihood of severe cardiac involvement. In these patients, two major, one major plus two minor, or three minor manifestations are sufficient for diagnosis of recurrent ARF.

In patients with a history of ARF-associated carditis or RHD, it may be difficult to establish a diagnosis of acute carditis during an acute attack in the absence of pericarditis or involvement of a new valve. Thus, a presumptive diagnosis of recurrent ARF may be made with one major or two minor criteria if there is evidence of a recent GAS infection. Caution against using a single clinical finding (eg, monoarthritis, fever, arthralgia) as a criterion for the diagnosis of recurrent disease is suggested [27].

All patients undergo cardiac evaluation, even if they do not present with clinical evidence of carditis. (See 'Cardiac evaluation' below.)

Exceptions — There are two circumstances in which a presumptive diagnosis of ARF can be made without strict adherence to the above criteria [26]:

Chorea as the only manifestation. These patients should undergo evaluation for carditis with echocardiogram. (See "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Rheumatic carditis'.)

Indolent carditis as the only manifestation in patients who come to medical attention months after acute GAS infection. An echocardiogram should be performed in these patients to look for evidence of carditis.

Moderate/high-risk populations — Strict adherence to the Jones Criteria in areas of higher prevalence (defined as ARF incidence >2 per 100,000 school-aged children per year or all-age RHD prevalence of >1 per 1000 population) may result in under-diagnosis. This was illustrated in a report of 555 cases of confirmed ARF among Aboriginal Australians in whom monoarthritis and low-grade fever were important manifestations [8]. Thus, the criteria are slightly modified for moderate- to high-risk populations as follows [4]:

The major criterion of arthritis includes monoarthritis or polyarthralgia in addition to polyarthritis. Polyarthralgia should only be considered as a major manifestation after exclusion of other causes.

The minor criterion for joint involvement is monoarthralgia rather than polyarthralgia.

A lower cutoff for fever is used (≥38°C [100.4°F] rather than ≥38.5°C [101.3°F]).

A lower cutoff for erythrocyte sedimentation rate (ESR) is used (≥30 mm/hour rather than ≥60 mm/hour), although the C-reactive protein (CRP) cutoff is unchanged (≥3 mg/dL [≥30 mg/L]).

Evidence of preceding GAS infection — Confirmation of group A streptococcal (GAS) infection is helpful but not necessary to make the diagnosis of ARF. A high index of suspicion of ARF is important, particularly in children or young adults presenting with signs of arthritis and/or carditis, even in the absence of a documented episode of pharyngitis. Laboratory confirmation is required because the clinical documentation of an antecedent pharyngitis is unreliable and has an age-related variability. One study, for example, noted that the recollection of pharyngitis approached 70 percent in older children and young adults versus only 20 percent in younger children [28].

Therefore, evidence of prior GAS infection may be sought in one of the following ways:

Positive throat culture for group A beta-hemolytic streptococci

Positive rapid streptococcal antigen test

Elevated or rising antistreptococcal antibody titer – Either antistreptolysin O (ASO) or antideoxyribonuclease B (ADB)

Streptococcal serology is most helpful in the diagnosis of ARF because of the delayed nature of the disease following GAS infection. Antibody titers are elevated, while culture or detection of the organism is usually no longer possible by the time ARF presents. Throat cultures are negative in approximately 75 percent of patients by the time manifestations of ARF appear [26]. The rapid streptococcal antigen test is also commonly negative.

During an infection with GAS, there is a broad immune response to multiple cellular antigens. However, measurement of the antibody response to streptolysin O and/or deoxyribonuclease B is used most in clinical practice.

Antistreptococcal antibodies have a high sensitivity for the documentation of streptococcal infection in the setting of ARF [29]. Titers vary with age, season, and geography [30], but published normal values are available for children in the US and children in tropical settings (table 3 and table 4) [31-34]. Healthy children of elementary school age often have titers of 200 to 300 Todd units/mL because GAS tonsillopharyngitis is common in this age group, whereas older children and adults who are asymptomatic pharyngeal GAS carriers tend to have low titers [35].

ASO and ADB titers may be interpreted either by comparison of acute with convalescent titers or against a reference upper limit of normal (ULN). An increase in titer from acute to convalescent (at least two weeks apart) is considered the best evidence of antecedent GAS infection [36]. The antibody response of ASO peaks at approximately three to five weeks following GAS pharyngitis, which usually is during the first to third week of ARF, while ADB titers peak at six to eight weeks [37,38]. Antibody titers fall off rapidly in the next several months and, after six months, have a slower decline. For these reasons, it may be useful to collect one specimen when the diagnosis of ARF is first suspected and another two weeks later.

Approximately 80 percent of patients with documented ARF demonstrate a rise in ASO titer above the ULN value for age, defined by the 80th centile, although this cannot be used as a measure of rheumatic activity. In a study in Australia, diagnosis of poststreptococcal syndromes using an ULN value for ASO had a sensitivity of 73 percent, but the sensitivity increased to >95 percent when ADB was added to ASO [39]. At the center of one author (AS), an ASO titer is measured first, and, if negative, measurement of ADB is added.

There is ongoing research into improved assays for streptococcal serology, including the addition of a novel antigen (SpnA) to ASO and ADB using a bead-based cytometric immunoassay [40].

Laboratory studies — In addition to streptococcal serology, laboratory studies obtained during the initial evaluation include measurement of CRP or ESR to seek evidence of systemic inflammation and a complete blood count with differential to look for anemia and leukocytosis. A throat culture should also be performed and rapid streptococcal antigen test if available.

Cardiac evaluation — A chest radiograph, electrocardiogram, and echocardiogram are performed as part of the initial diagnostic work-up. Portable, handheld echocardiography is a lower-cost option than standard echocardiography in resource-limited settings but must have appropriate capacity to provide high-quality 2D images, accurate color Doppler, and accurate pulse-wave Doppler measurements [41,42]. The findings are discussed in brief above and in greater detail separately, as is the diagnostic approach. (See 'Carditis' above and "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Rheumatic carditis' and "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Diagnosis of rheumatic carditis'.)

DIFFERENTIAL DIAGNOSIS — The approach to and differential diagnosis of polyarticular joint pain in children (table 5) and adults (table 6) are discussed separately. (See "Evaluation of the child with joint pain and/or swelling" and "Evaluation of the adult with polyarticular pain".)

Additional manifestations of ARF generally can be distinguished from similar findings in other conditions, although the differences may be subtle (eg, subcutaneous nodules versus rheumatoid nodules, Sydenham chorea versus other types of chorea, or erythema marginatum versus erythema annulare). (See "Rheumatoid nodules" and "Overview of chorea" and "Approach to the patient with annular skin lesions".)

Poststreptococcal reactive arthritis — Several investigators have speculated that some cases of arthritis occurring after a streptococcal infection may not be caused by ARF. This disorder has been called poststreptococcal reactive arthritis (PSRA) [43-48]. However, an unusual clinical course should not be sufficient to exclude the diagnosis of ARF. Migratory arthritis without evidence of other major Jones Criteria, if supported by two minor manifestations, must still be considered ARF, especially in children. Defining this reactive arthritis as an ARF variant has important implications for secondary prophylactic treatment. (See "Reactive arthritis", section on 'Differential diagnosis'.)

The following observations have been used to support the notion that PSRA is a separate disorder [49,50]:

The latent period between the antecedent streptococcal infection and the onset of migratory arthritis is shorter (one to two weeks) than the two to three weeks usually seen in classic ARF.

The response of the arthritis to aspirin and other nonsteroidal medications is poor in comparison to the dramatic response seen in classic ARF.

Evidence of carditis is not seen in these patients, and the severity of the arthritis is quite marked.

Extraarticular manifestations, such as tenosynovitis and renal abnormalities, often are seen in these patients.

Acute phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) tend to be lower than in the setting of ARF.

However, these patients may actually have ARF, with the above observations being explained by other genetic or environmental factors. As an example, variations in the response to aspirin in affected adults may be caused by variations in salicylate levels. Even when patients with PSRA do not fulfill the Jones Criteria, some investigators regard it as a forme fruste of rheumatic fever requiring similar secondary prophylaxis [51]. On the other hand, some investigators argue that PSRA is a benign condition without need for prophylaxis [45]. Both the 1992 guidelines and the 2002 update reached the following conclusions [25,30]:

Although the relationship between PSRA and ARF remains unresolved, patients who fulfill the Jones Criteria should be considered to have ARF.

Among patients who do not fulfill the Jones Criteria, the diagnosis of PSRA should be made only after excluding other rheumatic diseases such as Lyme disease and rheumatoid arthritis.

Treatment of poststreptococcal reactive arthritis is discussed separately. (See "Acute rheumatic fever: Treatment and prevention", section on 'Poststreptococcal reactive arthritis'.)

REFERRAL — The diagnosis of rheumatic fever can be challenging. Thus, there should be a low threshold to seek opinion from a pediatric infectious disease specialist and/or pediatric rheumatologist with expertise in ARF. In addition, pediatric cardiology is consulted for clinical review and an echocardiogram. The pediatric patient with suspected ARF is usually admitted to the hospital for this evaluation.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute rheumatic fever and rheumatic heart disease".)

SUMMARY

Definition – Acute rheumatic fever (ARF) is a nonsuppurative sequela of group A Streptococcus (GAS) pharyngitis that occurs two to four weeks following infection. (See 'Introduction' above.)

Major manifestations of acute illness – The five major manifestations (major Jones Criteria) of ARF are migratory arthritis (predominantly involving the large joints), carditis and valvulitis (eg, pancarditis), central nervous system involvement (eg, Sydenham chorea), erythema marginatum, and subcutaneous nodules (table 1). The four minor manifestations (minor Jones Criteria) are arthralgia, fever, elevated acute phase reactants, and prolonged PR interval on electrocardiogram. (See 'Acute illness' above.)

Arthritis – Arthritis usually is the earliest symptomatic manifestation of ARF. The natural history consists of inflammation affecting several joints in quick succession with overlapping onset, giving the appearance that the disease "migrates" from joint to joint. Joint pain usually is more prominent than objective signs of inflammation and is almost always transient. (See 'Arthritis' above.)

Carditis – ARF causes a pancarditis, affecting the pericardium, epicardium, myocardium, and endocardium, with valvulitis being the most common clinical presentation. However, the carditis can be subclinical. (See 'Carditis' above.)

Sydenham chorea – Sydenham chorea (also known as chorea minor or "St. Vitus dance") is a neurologic disorder consisting of abrupt, nonrhythmic, involuntary movements; muscular weakness; and emotional disturbances. (See 'Sydenham chorea' above.)

Erythema marginatum – Erythema marginatum is an evanescent, pink or faintly red, nonpruritic rash involving the trunk and sometimes the limbs but not the face (picture 1 and picture 2). The lesion extends centrifugally, with return of the skin in the center to a normal appearance. (See 'Erythema marginatum' above.)

Subcutaneous nodules – Subcutaneous nodules are firm, painless lesions ranging from a few millimeters to 2 cm in size (picture 3). The nodules are usually located over a bony surface or prominence or near tendons (usually extensor surfaces) and are usually symmetric. (See 'Subcutaneous nodules' above.)

Diagnosis The diagnosis of ARF is established on clinical grounds. The probability of ARF is high in the setting of GAS infection followed by two major criteria or one major and two minor criteria. The criteria are modified slightly for patients in moderate- to high-risk populations (table 1). (See 'Diagnosis' above.)

Late sequelae – The most common sequela of ARF is rheumatic heart disease (RHD). RHD usually occurs 10 to 20 years after the original illness and is the most common cause of acquired valvular disease in the world. (See 'Rheumatic heart disease' above and "Clinical manifestations and diagnosis of rheumatic heart disease".)

Differential diagnosis – The differential diagnosis of polyarticular joint pain in children (table 5) and adults (table 6) is broad and includes other causes such as infection, postinfection immune reactions, autoimmune or autoinflammatory disease, malignancy, and other systemic illnesses. Some cases of arthritis occurring after a streptococcal infection are not accompanied by sufficient additional Jones Criteria to meet diagnostic requirements for ARF. This disorder has been called poststreptococcal reactive arthritis (PSRA). (See 'Differential diagnosis' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges John B Zabriskie, MD (deceased), who contributed to earlier versions of this topic review.

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Topic 3177 Version 32.0

References

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