Acute rheumatic fever (ARF) is an autoimmune reactive systemic disease secondary to group A streptococcal infection. Although it can involve many parts of the body, almost all clinical manifestations may disappear completely. The important exception is damaged heart valves (rheumatic heart disease (RHD)), which can persist after other symptoms have resolved.
I. Epidemiology
ARF occurs mainly in children aged 5-14 years, rarely in adolescents, and rarely in adults older than 30 years. In contrast, ARF relapses are relatively common in adolescents, unlike RHD, which is common in patients aged 25-40 years. ARF has no gender predilection, but RHD is more common in females and can occur twice as often as in males.
II. Clinical manifestations
There is an incubation period of about 3 weeks (1-5 weeks) after group A streptococcal infection until clinical signs of ARF appear. The exceptions are chorea and anaphylaxis, where the incubation period can be up to 6 months. Although some patients can give a history of preexisting sore throat, most preexisting group A streptococcal infections are subclinical and can be confirmed only by streptococcal antibody testing. The most common clinical signs are polyarthritis (occurring in 60-75% of patients) and cardiac inflammation (50-60%). the incidence of chorea in patients with ARF is highly variable across populations, fluctuating from 2-30%. Circumscribed erythema and subcutaneous nodules have recently been rare, occurring in less than 5% of reports.
III. Cardiac involvement
Up to 60% of patients with ARF may progress to RHD, and the endocardium, pericardium, or myocardium may be involved. Valve damage is the hallmark of rheumatic heart disease. The mitral valve is almost always involved, sometimes in combination with the aortic valve, and aortic valve involvement alone is rare. Damage to the pulmonary and tricuspid valves is often secondary to pulmonary hypertension due to left-sided valvular disease. Early valve damage leads to regurgitation. In the following years, recurrent valve leaflet thickening, scar formation, and calcification, mostly due to recurrence, can lead to valve stenosis. Thus, the characteristic manifestation of cardiac inflammation in new cases is mitral regurgitation, sometimes accompanied by aortic regurgitation. Inflammation of the myocardium can affect the electrical conduction pathways of the heart, leading to prolonged PR intervals (degree I AV block or rare higher block) and diminished first heart sounds.
Patients with RHD are often asymptomatic for several years before their valvular lesions progress to heart failure. In addition, especially in resource-poor areas, it is often difficult to make the diagnosis of ARF, so children, adolescents, and young adults may have RHD but not be aware of it. These cases can be diagnosed by echocardiography, and auscultation lacks sensitivity and specificity for asymptomatic RHD patients. In populations with a high prevalence of RHD, screening echocardiography in school-aged children has become increasingly common, thanks to technological developments in portable echocardiography and the harmonization of UCG-based guidelines for the diagnosis of RHD. Although secondary prevention therapy should be initiated after making a diagnosis of RHD based on echocardiography, the clinical significance of this critical RHD has not been clarified.
IV. Joint involvement
The most common form of joint involvement in ARF is arthritis, i.e., objective evidence of inflammation manifested by erythema and pain in a joint, often larger than one joint involved (i.e., polyarthritis). ARF almost always involves large joints, most commonly the knee, ankle, hip and elbow, and is often asymmetric. Pain is severe and often leads to functional impairment, which may improve with anti-inflammatory medications.
Mild joint involvement is also relatively common and is considered the most common underlying symptom in high-risk groups in the Australian diagnostic guidelines, but at the time of writing this was not yet included in the Jones classification criteria. Arthralgia without objective evidence of arthritis often involves large joints, as does wandering polyarthritis. In some populations, aseptic monoarthritis may also be seen, which may be related to early anti-inflammatory drug involvement before the onset of migratory polyarthritis.
The joint symptoms of ARF respond well to salicylates and other NSAIDs. In fact, joint involvement with symptoms that persist for 1-2 days after the addition of salicylates is likely not due to ARF.
V. Chorea
Chorea minor often occurs in the absence of other clinical symptoms, has a long incubation period after group A streptococcal infection, and is most often seen in women. Chorea-like movements often involve the head (resulting in characteristic tongue carving-like activity) and upper extremities (Chapter 448). These symptoms may be generalized or confined to one limb (lateralized chorea). In mild cases, only a detailed examination can reveal them, however, in most severe cases, the affected patient has difficulty taking care of himself/herself. They are often accompanied by emotional instability and obsessive-compulsive traits, and these can last longer than chorea-like movements (often 6 weeks to recover, but can also last up to 6 months).
VI. Skin manifestations
The typical rash of ARF is erythema annulare (Chapter 24), which begins as a pinkish red patch with a normal central area and a creeping outwardly expanding rim. The rash is easily dissipated and appears on and off in front of the examiner. It occurs mostly on the trunk, partly on the extremities, but almost never on the face.
Subcutaneous nodules are small painless, well-mobile subcutaneous masses (0.5-50 px) located on the surface of bony prominences, especially in the hands, feet, elbows, occiput and occasionally in the vertebrae. They are mostly late onset symptoms, appearing 2-3 weeks after the onset of the disease, lasting several days to 3 weeks, and are mostly associated with cardiac inflammation.
VII. Other manifestations
Fever occurs in most patients with ARF, but is rare in simple chorea. Although high fever (>39°C) is characteristic, hypothermia is not uncommon. Acute chronotropic reactive protein is also elevated in most patients.
VIII. Determining the diagnosis.
Given the absence of a definitive confirmatory test, the diagnosis of ARF relies on a typical set of clinical manifestations and evidence of antecedent group A streptococcal infection, while other diagnoses need to be excluded. This uncertainty led Dr. T. Duckett Jones to propose a series of classification criteria in 1944 (subsequently referred to as the Jones classification). The existing diagnostic guidelines are the WHO revised Jones criteria of 1992, but it is important to note that other guidelines, including the Australian and New Zealand criteria, have a higher diagnostic sensitivity in people at high risk for ARF.