The differential diagnosis for acute rheumatic fever (ARF) is extensive due to its diverse range of clinical presentations. When evaluating a patient for ARF, it’s crucial to consider and rule out various autoimmune conditions, inflammatory diseases, malignancies, and other illnesses that may mimic its symptoms 1.
Differential Diagnoses to Consider
To effectively diagnose acute rheumatic fever, clinicians must consider a broad spectrum of conditions in their differential diagnosis. These include:
Autoimmune Diseases
Several autoimmune diseases share overlapping symptoms with ARF, necessitating careful differentiation:
- Juvenile Idiopathic Arthritis (JIA): JIA, particularly systemic JIA, can present with fever, arthritis, and rash, similar to ARF. However, JIA often involves more persistent and chronic joint inflammation.
- Rheumatoid Arthritis (RA): While less common in children, RA can present with polyarthritis. Distinguishing features of RA include symmetrical joint involvement and the presence of rheumatoid factor and anti-CCP antibodies (though these can be negative in early disease and JIA).
- Systemic Lupus Erythematosus (SLE): SLE is another autoimmune disease that can mimic ARF with symptoms like fever, arthritis, and carditis. Key differentiating features of SLE include a malar rash, photosensitivity, renal involvement, and characteristic autoantibodies (ANA, anti-dsDNA, anti-Smith).
Cancers
Certain malignancies can present with systemic symptoms that may initially be confused with ARF:
- Leukemia: Leukemias, especially acute lymphoblastic leukemia, can present with bone pain, fever, and fatigue, which might overlap with ARF symptoms. A complete blood count with differential is crucial to rule out leukemia.
- Hodgkin’s Disease (Hodgkin Lymphoma): While less likely to mimic ARF directly, Hodgkin’s disease can present with fever and systemic symptoms, requiring consideration in the differential diagnosis, particularly in cases with unexplained fever and lymphadenopathy.
Inflammatory Diseases
A variety of inflammatory conditions should be considered in the differential diagnosis:
- Gout: While typically affecting adults, gout can present with acute, painful monoarthritis or oligoarthritis. Uric acid levels and joint fluid analysis can help differentiate gout from ARF arthritis.
- Henoch-Schonlein Purpura (HSP): HSP, or IgA vasculitis, is characterized by palpable purpura, abdominal pain, arthritis, and renal involvement. The distinctive rash of HSP is a key differentiating feature.
- Infective Endocarditis: Infective endocarditis can present with fever, heart murmur, and systemic symptoms, including arthritis. Blood cultures and echocardiography are essential to diagnose infective endocarditis and differentiate it from ARF carditis.
- Sarcoidosis: Sarcoidosis is a systemic inflammatory disease that can affect multiple organs, including the heart and joints. While less common in children, it should be considered in cases with unexplained systemic inflammation and potential cardiac involvement.
- Septic Arthritis: Septic arthritis presents with acute, painful, and swollen joint(s), usually monoarticular. Joint aspiration and culture are crucial to diagnose septic arthritis, which requires urgent antibiotic treatment.
- Viral Myocarditis: Viral myocarditis can cause chest pain, shortness of breath, and fatigue, mimicking ARF carditis. Viral studies and cardiac biomarkers can help differentiate viral myocarditis.
Other Conditions
Additional conditions to consider include:
- Lyme Disease: Lyme disease, transmitted by tick bites, can present with fever, arthritis (often oligoarticular and migratory), and, in some cases, carditis. Lyme serology and a history of potential tick exposure are important for diagnosis.
- Serum Sickness: Serum sickness is a type III hypersensitivity reaction that can occur after exposure to certain medications. Symptoms include fever, rash, arthralgia, and lymphadenopathy, which can overlap with ARF. A history of recent medication exposure is key to considering serum sickness.
Jones Criteria: Guiding the Diagnosis
There is no single definitive laboratory test for acute rheumatic fever. Diagnosis relies on the revised Jones Criteria, a set of clinical guidelines that help establish the probability of ARF.
Defining Risk Populations According to Revised Jones Criteria
The Jones Criteria are applied differently based on the population’s risk for rheumatic fever:
Low-Risk Population
- Defined as a population with:
- Acute rheumatic fever incidence of ≤2 per 100,000 school-aged children per year.
- All-age rheumatic heart disease prevalence of ≤1 per 1000 population per year.
Moderate- and High-Risk Populations
- Populations not meeting the low-risk criteria are classified as moderate or high risk based on their specific epidemiological data.
Manifestation Classification by Population
The criteria for major and minor manifestations differ slightly between low-risk and moderate- to high-risk populations:
Low-Risk Populations
Major Manifestations:
- Carditis (clinical or subclinical)
- Arthritis (polyarthritis only)
- Chorea (Sydenham chorea)
- Erythema marginatum
- Subcutaneous nodules
Minor Manifestations:
- Polyarthralgia
- Fever (≥38.5°C or ≥101.3°F)
- Elevated acute phase reactants (ESR ≥60 mm/hr or CRP ≥3.0 mg/dL)
- Prolonged PR interval on electrocardiogram (ECG), adjusted for age variability (unless carditis is present as a major criterion)
Moderate- and High-Risk Populations
Major Manifestations:
- Carditis (clinical or subclinical)
- Arthritis (monoarthritis or polyarthritis, or polyarthralgia if other causes are ruled out)
- Chorea (Sydenham chorea)
- Erythema marginatum
- Subcutaneous nodules
Minor Manifestations:
- Monoarthralgia
- Fever (≥38.5°C or ≥101.3°F)
- Elevated acute phase reactants (ESR ≥30 mm/hr or CRP >3.0 mg/dL)
- Prolonged PR interval on electrocardiogram (ECG), adjusted for age variability (unless carditis is present as a major criterion)
Abbreviations:
- ESR = Erythrocyte Sedimentation Rate
- CRP = C-Reactive Protein
- mm = Millimeters
- mg/dL = Milligrams per Deciliter
Diagnosing Initial Acute Rheumatic Fever Illness
Criteria for Initial ARF
A high probability of initial acute rheumatic fever is indicated by the presence of:
- Two major manifestations
OR - One major and two minor manifestations
Important Considerations:
- Joint Manifestations: If more than one joint manifestation is present (e.g., arthritis and arthralgia), they are counted as either one major or one minor criterion, not both. Arthritis (major) takes precedence over arthralgia (minor).
- Cardiac Manifestations: Similarly, if multiple cardiac manifestations are present (e.g., carditis and prolonged PR interval), they are counted as either one major or one minor criterion, not both. Carditis (major) takes precedence over prolonged PR interval (minor).
Evidence of Preceding Streptococcal Infection
In most cases, a preceding Group A Streptococcal (GAS) infection should be documented to support the diagnosis of ARF. Evidence includes:
- Positive throat culture or rapid streptococcal antigen test.
- Elevated or rising streptococcal antibody titers (e.g., Anti-Streptolysin O (ASO) or Anti-DNase B).
Presumptive Diagnosis
In certain situations, a presumptive diagnosis of ARF may be necessary even if the full Jones Criteria are not met. Clinical judgment is crucial, especially in high-incidence areas where clinical evidence may be lacking 2.
ARF should be considered in cases of chorea and indolent, chronic carditis, even without complete fulfillment of the Jones Criteria or laboratory confirmation of a preceding GAS infection 2.
Diagnosing Recurrent Rheumatic Fever
Risk of Recurrence
Individuals with a history of rheumatic heart disease or a prior episode of ARF are at significantly increased risk for recurrent ARF episodes upon re-exposure to GAS.
Criteria for Recurrent ARF
A presumptive diagnosis of recurrent acute rheumatic fever can be made with:
- Two major manifestations
OR - One major and two minor manifestations
OR - Three minor manifestations
Important Note: When relying on three minor manifestations for diagnosing recurrent ARF, it is critical to exclude other more likely diagnoses thoroughly.
Documentation of Preceding Infection
Evidence of a preceding Group A Streptococcal infection should be documented in cases of recurrent ARF.
Recommended Supplemental Tests
Routine echocardiography/Doppler is now recommended for all confirmed or suspected cases of acute rheumatic fever 2.
This recommendation applies regardless of whether a murmur is auscultated on physical examination, as echocardiography can detect subclinical carditis.
Resources for Diagnosis Guidelines
Diagnostic Resources
- 2015 Revision of the Jones Criteria for the Diagnosis of Acute Rheumatic Fever in the Era of Doppler Echocardiography: American Heart Association
- Criteria for Echocardiographic Diagnosis of Rheumatic Heart Disease—An Evidence-Based Guideline: World Heart Federation
These resources provide comprehensive guidelines and updates on the diagnosis of acute rheumatic fever and rheumatic heart disease.
References
[1] Centers for Disease Control and Prevention. (n.d.). Rheumatic Fever. https://www.cdc.gov/rheumaticfever/index.html
[2] Gewitz, M. H., Baltimore, R. S., Tani, L. Y., Sable, C. A., Shulman, S. T., Carapetis, J., … & Taubert, K. A. (2015). Revision of the 2003 Jones Criteria for the diagnosis of acute rheumatic fever. Circulation, 131(19), 1806-1818.
