Clinical Evaluation and Diagnosis of Acute Rheumatic Fever

Joint symptoms (arthritis and arthralgia)

Joint involvement is typically the presenting symptom of ARF. It is also the most common major manifestation, occurring in upwards of 75% of patients overall, affecting almost all young adults, most teenagers (82%), and children (66%). Joint involvement may qualify as a major manifestation or minor manifestation (see Diagnosis section).

Rheumatic joint involvement is notoriously variable, ranging from the classic migratory polyarthritis of large joints, to monoarthritis, polyarthralgia, and monoarthralgia. In the context of ARF, involvement of two or more joints is defined as polyarthritis. When joint symptoms are the sole major manifestation, the diagnosis of ARF may be problematic. Nevertheless, in patients from medium- to high-risk populations, ARF should always be included in the differential diagnosis of children and young adults presenting with arthritis and/or arthralgia.

The key to diagnosis is a detailed history and examination. It may take some time for the joint involvement to fully manifest (e.g., a monoarthritis on presentation may evolve into a polyarthritis several days later). Joint pain in ARF is usually asymmetrical, with a predilection for large joints including the knees, ankles, hips, elbows, and wrists (the leg joints are usually affected first). The small joints of the hands, feet, and spine are occasionally involved in ARF.

Rheumatic arthritis is usually extremely painful, often limiting movement and is often out of proportion to objective local signs of inflammation such as joint swelling, erythema, and increased temperature. Any child who refuses to put any weight on the affected limb is however a “red flag” for serious illness, such as infection (e.g., septic arthritis) or malignancy (e.g., leukemia)—see Differential Diagnosis. A history of inability to walk due to hip pain is regarded by some guidelines as arthritis, even if the signs of arthritis have resolved. The joint inflammation is characteristically transient, quickly disappearing from each joint often over a period of hours or just a few days and then appearing in another joint. Classically, multiple joints are often affected in quick succession, termed migratory arthritis. If subsequent joints are involved while preceding ones are still inflamed this can be termed “additive” polyarthritis, although this pattern is less specific to ARF than migratory polyarthritis. Joint involvement may number 6–16 in untreated patients.

Polyarthralgia, although very common and highly nonspecific in low-risk populations, is considered a major manifestation in high-risk populations where it is more specific for ARF. The same applies to monoarthritis and monoarthralgia, which are both common manifestations of ARF in these populations. For example, aseptic monoarthritis was a major manifestation in 19% of high-risk children in Australia. It is important however to first exclude septic arthritis in those who present with monoarthritis before diagnosing ARF. Close liaison with orthopedic colleagues may be necessary. The synovial fluid white cell count in joints affected by ARF contains 10,000–100,000 white blood cells/mm ³ (mostly neutrophils), while a count of >100,000 cells/mm ³ significantly increases the likelihood of the diagnosis of septic arthritis. Other findings on synovial fluid analysis in rheumatic arthritis include a protein concentration of approximately 4 g/dL, normal glucose levels, and presence of a mucin clot.

Aspirin, naproxen, ibuprofen and other NSAIDs, and corticosteroids often produce a dramatic improvement in joint symptoms. The arthritis of ARF is so responsive to NSAIDs that rapid resolution is strongly supportive of the diagnosis of ARF. Conversely, if there is no improvement within 72 h of starting antiinflammatories, an alternative diagnosis should be considered. In patients who present with monoarthritis or monoarthralgia, it is important to withhold NSAIDs, instead using paracetamol or codeine for pain relief, to prevent masking any evolution of joint symptoms. NSAIDs can be commenced once a second joint is involved, and the diagnosis is clear. Monoarthritis is now accepted as a major manifestation of ARF whether or not NSAIDs have been prescribed. The indiscriminate use of NSAIDs in some low- and middle-income countries (LMICs) may in part be responsible for the apparent fall in incidence of ARF in these populations.

There is no evidence that temporarily withholding antiinflammatory therapy leads to worse outcomes. The only long-term sequela of rheumatic arthritis is Jaccoud arthropathy, although this is very rare. Originally thought to be associated only with ARF, Jaccoud arthropathy has since been shown to also occur with systemic lupus erythematosus (SLE), Sjögren syndrome, scleroderma, dermatomyositis, psoriatic arthritis, vasculitis, and ankylosing spondylitis.

An episode of ARF lasts for approximately 3 months on average when unaltered by antiinflammatory medication. In most treated patients, the polyarthritis is severe for less than 1 week in two-thirds of cases and continues for another 1–2 weeks in the remainder before resolving completely. Symptoms persisting beyond 4 weeks should trigger a search for alternative pathologies, including juvenile idiopathic arthritis or SLE. Chronic ARF occurs in fewer than 5% of cases and is defined as the presence of active symptoms for more than 6 months.

Carditis

Rheumatic carditis is the most important prognostic factor in ARF because carditis can evolve to chronic RHD. Depending on whether the diagnosis is made based on clinical assessment alone, or combined with echocardiography, the incidence of carditis during an initial attack of ARF ranges from 40% to 91%. In the 1951 Bland and Duckett review of 1000 patients with ARF, 65% were diagnosed with carditis and in the 1987 outbreak of ARF in Utah in the United States, 91% had carditis when clinical examination was combined with echocardiographic evaluation. More recent studies that report both clinical and subclinical carditis show similar rates of carditis: for example, 85% of 66 children with definite or probable ARF had carditis. In general, the younger the patient the higher the incidence of carditis during an episode of ARF.

Carditis can be found at presentation along with fever and arthritis although it often appears within 2–4 weeks of the acute illness, highlighting the importance of repeatedly examining the patient after initial presentation. The clinical findings of rheumatic carditis can be variable, ranging in severity from mild subclinical involvement (up to 53%) to severe carditis (20%), leading to acute heart failure. Death is also a rare but well-described complication of the acute illness. In most of those who present with ARF for the first time, however, carditis tends not to be severe: a New Zealand study of true first episodes of ARF found that severe carditis occurred in <10% of such patients. In those with recurrent ARF, carditis almost invariably recurs if the initial episode involved the heart, and with each episode the cumulative heart valve damage can worsen. Internationally, acute carditis on chronic RHD may be as common as a true first episode of ARF. However, this chapter focuses on first episodes of ARF not chronic RHD.

Rheumatic carditis may involve all layers of the heart, including the pericardium (pericarditis), myocardium (myocarditis), and endocardium (endocarditis), hence some descriptions of rheumatic carditis use the term “pancarditis.” It is worth emphasizing that the endocarditis part of rheumatic carditis is inflammatory and not infective in origin and is characterized by inflammation of the left-sided heart valves, leading to acute or subacute valvular regurgitation (valvulitis). Given that the term endocarditis is potentially confusing in this context, it should be avoided and valvulitis used instead.

Pericarditis and myocarditis rarely, if ever, occur without concomitant valvulitis. Therefore, a diagnosis of rheumatic carditis should be reevaluated if clinical features of pericarditis or myocarditis occur in the absence of valvulitis.

Infrequently, carditis can also develop more subtly over several months after the GAS infection (known as indolent (insidious onset) carditis), and may be the only presenting feature of ARF. Indolent carditis is characterized by a subacute illness of several weeks or months with severe cardiac involvement and little or no joint symptoms. The presentation is with subacute heart failure in many cases. Younger children may have cardiac cachexia with weight loss. In those patients with severe heart failure, heart valve surgery may be contraindicated due to severely impaired left ventricular function, with heart transplantation the only surgical option.

Rheumatic Valvulitis. Valvulitis is the sine qua non of rheumatic carditis. It manifests as mitral regurgitation (MR) or aortic regurgitation (AR), or both, either clinically by detection of a corresponding murmur ( Box 3.2 ) or subclinically by echocardiography (see next section). The mitral valve is almost always affected in rheumatic valvulitis, with the aortic valve also involved in up to one-third of cases. Isolated aortic valvulitis only occurs in 2% of patients and right-sided valvulitis only occurs in combination with the left : therefore, carditis cannot be diagnosed on the basis of right-sided regurgitation alone. It is also important to rule out volume and pressure overload from left-sided lesions before attributing even moderate tricuspid regurgitation to valvulitis. Stenotic valvular lesions do not occur as part of the acute illness but occur after the transition from rheumatic carditis to the chronic valvular changes that define RHD, which evolve over months to years following one or more episodes of ARF.

In addition to acute/subacute valvular regurgitation, cardiomegaly and heart failure make up the three most common clinical manifestations of valvulitis. Each of these features can be used to assess the severity of rheumatic carditis ( Table 3.1 ), which helps guide appropriate medical and surgical management and determine the duration of secondary prophylaxis in the long term. In patients with both right- and left-sided lesions, diagnostic severity is determined by the left-sided lesion.

Valvulitis may not always be evident at presentation. Those who do subsequently go on to develop valvulitis usually do so within 2 weeks or, at the latest, within 4 weeks. Therefore, if the initial echocardiogram is negative or equivocal, a second echocardiogram should be performed within 2–4 weeks of presentation to confidently exclude rheumatic valvulitis.

Subclinical carditis. Echocardiographic-based studies over the last 20 years have also revealed that a considerable number of patients with rheumatic valvulitis (up to 53%) do not have a murmur. This has given rise to the term subclinical carditis , which refers exclusively to the circumstance where a patient is found to have pathological MR and/or AR on echocardiography but where classic auscultatory findings are not present or are not recognized by the examining clinician.

The clinical course of subclinical carditis is similar to mild carditis detected by a murmur. A 2007 meta-analysis that included 23 studies from around the world showed that echocardiographic findings persisted or progressed in 44.7% of patients diagnosed with subclinical carditis. Therefore, although a murmur remains an important manifestation of valvulitis, it is no longer the only means of diagnosing carditis: both clinical and subclinical carditis are now considered a major criterion of ARF by the American Heart Association in both low- and moderate-to-high-risk settings (see Diagnosis of Acute Rheumatic Fever).

Pericarditis. Acute pericarditis often appears 7–10 days after the initial fever and arthritis and occurs in approximately 15% of patients. Pericarditis should be suspected if the patient complains of chest pain or is found to have a friction rub or muffled heart sounds. The friction rub can mask cardiac murmurs. The early ECG changes that often characterize pericarditis (i.e., diffuse concave upward ST elevation with upright T waves and PR segment depression) are usually absent in rheumatic pericarditis.

The chest pain is usually precordial or retrosternal and may radiate to involve the trapezius ridge (bottom portion of the scapula), neck, left shoulder, or left arm. The chest pain is typically exacerbated on lying down or during inspiration and relieved by sitting up and bending forward. Rheumatic pericarditis may result in a pericardial effusion, which is usually small to moderate in size and only very rarely leads to cardiac tamponade (see Chapter 16 ). Constrictive pericarditis is also a very rare complication of ARF.

Myocarditis. Rheumatic myocarditis is often asymptomatic. Different from many other forms of myocarditis, rheumatic myocarditis does not lead to impaired ventricular function in the absence of valvulitis and does not produce elevated serum cardiac troponins. Instead, the left ventricular enlargement and systolic dysfunction associated with severe carditis is secondary to volume overload from acute valve dysfunction. If troponins are elevated, this should raise suspicion of an alternative diagnosis such as viral myocarditis (see Differential Diagnosis (later) and Chapter 16 ).

Chorea

Rheumatic chorea, also known as Sydenham chorea or St Vitus' dance, is characterized by purposeless, involuntary movements of the trunk or extremities. Chorea is a neuropsychiatric disorder that occurs in 10%–30% of patients who have had ARF. It is the most common form of acquired chorea in childhood (accounting for up to 96% of cases), most commonly occurring in those aged between 5 and 13 years and is rare after the age of 20 years. Females are more frequently affected than males by a ratio of 2:1.

Sydenham chorea has the longest latency period of all ARF manifestations, presenting 1–8 months after the initial GAS infection. As a consequence, it only features as part of the acute illness in 5%–10% of patients, where it may be associated with other disease manifestations, although joint symptoms and chorea seldom occur simultaneously due to disparities in their respective latency periods. In other patients, it may be the only manifestation of ARF, developing several weeks to months after the acute illness when other features of the disease have typically disappeared. For this reason, chorea is considered a stand-alone criterion for establishing the diagnosis of ARF, but only when other differential diagnoses have been excluded. Sydenham chorea is also commonly associated with carditis (28%–63% of cases), regardless of the presence of cardiac murmurs. As with all patients suspected of having ARF, echocardiography should therefore be performed and the finding of subclinical carditis by echocardiography will support the diagnosis of chorea as a manifestation of ARF.

Sydenham chorea is characterized by chorea (involuntary, brief, jerky, uncoordinated movements of the limbs and face), hypotonia (which may be diffuse), emotional liability, and psychiatric manifestations. The caudate nucleus in the basal ganglia is involved and so there is no pyramidal tract or sensory involvement. Symptoms are often bilateral, although are frequently more marked on one side and are unilateral (hemichorea) in 20%–30% of cases. Movements are accentuated by purposeful movement, excitement, and emotional stress, and disappear during sleep. Sometimes the movements are subtle and intermittent and might only be observed after a short period of observation. In severe cases, the chorea may impair the ability to eat and increase the risk of injury, requiring medication (see Chapter 4 , Management of Acute Rheumatic Fever).

Speech can be explosive and dysarthric and the individual often has trouble counting rapidly. The tongue is sometimes said to resemble a “bag of worms” on inspection and some patients may demonstrate motor impersistence, involuntarily withdrawing the tongue when asked to protrude it for 30 s (known as a “darting tongue”). Facial involvement often leads to erratic movements that resemble grimaces, grins, and frowns. The handwriting can be clumsy and is a good objective means of monitoring the course of the disease. When examining the hands, there are three specific signs to look for:

• 1.

  Milkmaid's grip: when asked to grip the physician's fingers, the patient is unable to maintain grip, resulting in rhythmic squeezing and is another manifestation of motor impersistence

• 2.

  Spooning sign: flexion of the wrists and extension of the fingers when the hands are extended

• 3.

  Pronator sign: the arms and palms turn outwards (pronate) when the arm is held above the head

Psychiatric and cognitive disorders, such as attention deficit hyperactivity disorder and anxiety, are also commonly associated with Sydenham chorea and early recognition of these symptoms may aid in the management of the disorder. Mental status however is usually normal and a confusional state suggests an alternative diagnosis, such as encephalitis.

Restlessness and abnormal behavior, such as easy crying and irritability and inappropriate laughing are also observed. In rare cases, patients may develop a transient psychosis, which can present many years after the initial onset of chorea symptoms. Not unsurprisingly, there is often a high burden of distress for the patient and their family, with missed school days and poor school performance, or self-isolation due to embarrassment, causing a significant reduction in functionality. However, no cases of permanent serious neurological deficits have been observed.

The manifestations of chorea may also wax and wane over its course, often during times of intercurrent illness and stress. It usually resolves gradually and the median duration of symptoms is 12–15 weeks, although rarely symptoms may last 2–3 years. Of all the ARF manifestations, chorea is one most likely to recur, doing so in 15%–30% of cases and usually within 2–3 years. In most patients, recurrence is usually due to a repeat GAS infection. Some recurrences may occur despite faithful adherence to penicillin prophylaxis, while other episodes may be seen with pregnancy (chorea gravidarum) or the oral contraceptive pill, suggesting a relation to hormonal factors.

Erythema Marginatum

Erythema marginatum is usually an evanescent, pink rash seen with pale centers and rounded or serpiginous margins. This is a rare and difficult to detect manifestation, particularly in dark-skinned patients, hence careful inspection is required. Although estimates vary, it is usually observed in <6% of patients with ARF. When present, it usually occurs early in the course of the illness but may also occur during recovery. It may also persist or recur after all other manifestations have resolved. It rarely occurs in isolation and is usually associated with carditis. Therefore, ARF should almost never be diagnosed on the basis of erythema marginatum alone without the presence of other major criteria.

It is a distinctive rash and is neither painful nor pruritic. It appears as bright pink, slightly raised macules or papules that blanch under pressure. They are seen initially on the trunk and proximal ends of the extremities and never on the face. The lesions begin as a macule and expand centrifugally with central clearing ( Fig. 3.1 ). Rapid migration (up to 2–10 mm in 12 h) is a characteristic feature of this rash and this movement can be documented with the use of ink markers on the skin ( Fig. 3.2 ). The macules may be oval, ring, or crescentic shaped and the outer edge of the lesions is usually sharp whereas the inner edge is diffuse. The macules can fuse and coalesce to form a serpiginous pattern, and when circular, the rash is known as erythema annulare. It should not be confused with the circinate (circular) rash of Lyme disease, erythema chronicum migrans.

The rash may be characteristically evanescent, disappearing over a matter of hours and reappearing intermittently over the course of weeks, months, or even years; some lesions may appear and then disappear before the examiner's eyes, appearing like “smoke rings” beneath the skin. It may be more apparent or reappear after a warm shower or bath and it is not affected by antiinflammatory medication.

Subcutaneous Nodules

Similar to erythema marginatum, these are also rare, occurring in less than 2% of patients with ARF. When present, they are highly specific for ARF but, similar to erythema marginatum, they rarely appear as a sole manifestation of the illness and should be accompanied by additional major criteria to establish a diagnosis of ARF. They are strongly associated with severe carditis and usually appear 1–2 weeks after the illness starts, lasting usually 1–2 weeks but rarely longer than a month.

The nodules are firm, round, painless, and freely mobile, usually 0.5–2.0 cm in diameter and are typically located over extensor surfaces (near bony prominences or tendons) of the elbows, wrists, knees, ankles, Achilles tendon, occiput, and the spinous processes of the thoracic and lumbar vertebrae ( Fig. 3.3 ). The overlying skin is not inflamed. They are usually symmetrical and occur in crops of up to 12, but the average number is 3–4. The nodules of ARF may resemble those seen in rheumatoid arthritis, although the former are smaller and shorter lived. Although nodules most commonly occur on the elbow in both conditions, ARF nodules occur more commonly on the olecranon whereas rheumatoid nodules tend to be found 3–4 cm distally.