History
Acute rheumatic fever (ARF) is associated with 2 distinct patterns of presentation. The first pattern is sudden onset, which typically begins as polyarthritis 2-6 weeks after streptococcal pharyngitis and is usually characterized by fever and toxicity. The second pattern is insidious or subclinical onset, which may occur if the initial abnormality is mild carditis.
Age at onset influences the order of complications. Younger children tend to develop carditis first, whereas older patients tend to develop arthritis first. [31]
Physical Examination
According to the revised Jones Criteria, the requirements for the diagnosis of initial ARF are the presence of two major manifestations or one major and two minor manifestations. For recurrent ARF, the criteria are as follows:
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Two major manifestations or
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One major and two minor manifestations or
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Three minor manifestations
Major manifestations of ARF are the same across all populations, regardless of risk. Minor manifestations vary between low-risk populations and moderate- and high-risk populations. A low-risk population is defined as having an ARF incidence of < 2 per 100,000 school-aged children or all-age rheumatic heart disease prevalence of ≤1 per 1000 population per year. Patients who are not from a low-risk population are defined as being at moderate or high risk depending on their reference population. [20, 1]
Major manifestations comprise the following:
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Carditis, clinical and/or subclinical (i.\e., detected by echocardiography)
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Arthritis*
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Chorea
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Erythema marginatum
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Subcutaneous nodules
*In patients from low-risk populations, arthritis must be polyarthritis. For patients from moderate- and high-risk populations, either monoarthritis or polyarthritis qualifies; polyarthralgia may qualify if other causes for the joint pain have been excluded.
Minor manifestations in low-risk populations comprise the following:
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Polyarthralgia
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Fever ≥38.5°C
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Acute phase reactions: Erythrocyte sedimentation rate (ESR) ≥60 mm in the first hour and/or C-reactive protein (CRP) level ≥3.0 mg/L
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Prolonged PR interval, after accounting for age variability (unless carditis is a major criterion)
Minor manifestations in moderate- and high-risk populations comprise the following:
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Monoarthralgia
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Fever ≥38°C
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ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL
Carditis
Carditis usually presents as chest discomfort, shortness of breath, fatigue, and possibly palpitations; yet not all patients with carditis will have clinical symptoms. The realization that subclinical carditis could be identified with Doppler echocardiography prompted the revision of the historic Jones criteria to ensure that this major manifestitation and its associated morbidity and mortality do not go unrecognized. [20]
Polyarthritis
Polyarthritis occurs early in the disease course and is a common complaint for patients with rheumatic fever. Joint involvement ranges from arthralgia without objective findings to overt arthritis with warmth, swelling, redness, and exquisite tenderness. The larger joints such as the knees, ankles, elbows, and wrists are involved most frequently. Symptoms may be migratory. The arthritis is transient and self-limited, with no long-term sequelae. [1, 30]
Sydenham chorea
Sydenham chorea is characterized by neuropsychiatric changes that may present suddenly or gradually. Specific symptoms include dyspraxia or coordination problems, ataxia, dysarthria, weakness, involuntary muscle movements, emotional lability, anxiety, depression, problems with concentration, and even obsessive-compulsive behaviors.
Sydenham chorea can occur as an isolated entity (separate from ARF) up to 6 months after the intial group A streptococcal (GAS) infection. Regardless of time of onset, symptoms usually resolve within 3 to 6 weeks; however, some children may experience symptoms lasting months. In addition, some children may experience a recurrence within the next 1.5-2.5 years. [25, 33]
Erythema marginatum
Erythema marginatum is an annular erythematous lesion that occurs in about 10% of pediatric ARF cases and may be difficult to identify in darker-skinned individuals. If present, it is usually found on the trunk and proximal extremities. It spares the face, hands, and feet. The rash begins as a red or pink macule or papule that spreads outward. The center clears, and the edges become raised and erythematous. The rash is neither painful nor pruritic. The lesions may fade and reappear, and they can last for months. [34]
Subcutaneous nodules
Subcutaneous nodules appear about 4-6 weeks after the initial GAS infection. The painless lesions affect extensor surfaces, elbows, knees, dorsal surfaces of the hands and feet, scalp, and vertebral prominences. They are uncommon, occurring in less than 2% of cases, but they are invariably associated with carditis. The nodules usually resolve within one month, but may persist for longer. [35, 34]
Complications
Patients with carditis as part of the initial episode are at greater risk of developing recurrent ARF and of sustaining further cardiac injury. Those without carditis during the initial episode have a relatively low risk of developing carditis during recurrences. Approximately 10% of patients with ARF will develop heart failure, and recurrent rheumatic fever can trigger heart failure even in the absence of valvular disease. Isolated heart failure, without valvular dysfunction, is reversible with proper treatment. [36, 30]
Cardiac involvement is the major cause of long-term morbidity. ARF causes inflammation of valvular endocardium. One or more valves (most commonly the mitral valve) may be permanently deformed by the cycle of inflammation and fibrosis. Those valves then become stenotic and dysfunctional, which may lead to left ventricular dilation and congestive heart failure, sometimes decades later. Oftentimes women are unaware of their RHD until they become pregnant and the cardiovascular changes of pregnancy lead to accelerated RHD and cardiac dysfunction. RHD is a leading cause of infant and maternal morbidity and mortality in high burden regions. [23]
Vegetations may develop on damaged valves and become infected, leading to infective endocarditis. A retrospective study at a single center in Auckland, New Zealand from 2016-2018 concluded that "patients with RHD experienced infective endocarditis at a younger age, had a higher incidence of prosthetic valve endocarditis and a prior history of infective endocarditis." Mortality in the RHD patients was almost exclusively as a result of infective endocarditis. [37]
Although cardiac complications are very well described, the understanding of neurologic involvement and persistent morbidity is still evolving. Literature began to appear in 1998 suggesting that ARF might be associated with PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). [38] Sydenham chorea is a result of antineuronal autoantibodies attacking the dopamine receptors in the basal ganglia; symptoms of Sydenham chorea usually resolve without long-term sequelae. [6]
In PANDAS, the autoimmune response is also triggered by molecular mimicry, but the clinical entity presents differently. The antibodies responsible for PANDAS bind to a different subtype of dopamine receptors and/or lysoganglioside antigens, and result in persistence of clinical neuropsychaitric symptoms. Research is ongoing, but as Cunningham and Cox note, "Sydenham chorea may be a prototype for other group A streptococcal or infection-related movement and neuropsychiatric conditions." [39]
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Medication
- Medication Summary
- Antimicrobials
- Penicillins, Natural
- Penicillins, Amino
- Antibiotics, Lincosamide
- Macrolides
- Cephalosporins, 1st Generation
- Glucocorticoids
- Anti-inflammatory agents
- Anticonvulsants, Other
- Diuretics
- Diuretics, Loop
- Diuretics, Potassium-Sparing
- Nitrates
- Nitrates, Angina
- Immunosuppressants
- Antipsychotics, 2nd Generation
- SV2A Ligands
- Show All
- References
