What is the likely diagnosis and management for a 12-year-old female patient with joint pains, fever, and moderate mitral regurgitation, who has a positive Antinuclear Antibody (ANA) test?

Likely Diagnosis: Acute Rheumatic Fever

This 12-year-old girl with joint pains, fever, moderate mitral regurgitation on echocardiography, and positive ANA most likely has acute rheumatic fever (ARF), though the positive ANA requires careful interpretation and does not exclude this diagnosis.

Diagnostic Approach

Primary Consideration: Acute Rheumatic Fever

Apply the Revised Jones Criteria for diagnosis, which requires evidence of preceding group A streptococcal (GAS) infection plus either 2 major manifestations OR 1 major plus 2 minor manifestations 1.

Major criteria in this patient:

• Carditis (present): The moderate mitral regurgitation on 2D echo qualifies as carditis, which can be either clinical and/or subclinical (echocardiographic valvulitis) 1
• Arthritis: Joint pains—determine if this represents polyarthritis (in low-risk populations) or monoarthritis/polyarthritis/polyarthralgia (in moderate-to-high-risk populations) 1

Critical diagnostic steps:

• Document preceding GAS infection through throat culture, rapid streptococcal antigen test, or elevated/rising streptococcal antibody titers (ASO, anti-DNase B) 1
• Assess inflammatory markers: ESR ≥60 mm/h and/or CRP ≥3.0 mg/dL (low-risk) or ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL (moderate/high-risk) as minor criteria 1
• Evaluate for other major criteria: fever ≥38.5°C (low-risk) or ≥38°C (moderate/high-risk), erythema marginatum, subcutaneous nodules, chorea 1

Echocardiographic Confirmation of Carditis

The moderate mitral regurgitation must meet pathological criteria to distinguish it from physiological regurgitation 1. Key features include:

• Jet characteristics: holosystolic signals with peak velocity ≥3.0 m/s are more likely pathological 1
• Leaflet morphology: ARF typically shows anterior mitral valve leaflet tip prolapse without billowing of the medial portion or body 1
• Jet direction: typically posterolaterally directed in rheumatic valvulitis 1

Measure blood pressure during echocardiography as circulatory loading conditions affect regurgitation severity 1.

Addressing the Positive ANA

The positive ANA does NOT exclude acute rheumatic fever and requires contextualization:

• ANA can be positive in acute and chronic infections, including the inflammatory state of ARF 2
• Low pretest probability for SLE: While SLE can cause arthritis, fever, and valvular disease, the positive predictive value of ANA for lupus in patients with nonspecific symptoms is only 2.1% 3
• ANA testing has limited value when performed for nonspecific symptoms like joint pain and fever without other lupus-specific features 4
• Key distinguishing features for SLE that are ABSENT in typical ARF: photosensitive rash, cytopenias, nephritis, serositis, and specific autoantibodies (anti-dsDNA, anti-Sm) 4

If ANA titer is <1:160, no ANA-associated rheumatic disease is likely 3.

Differential Diagnoses to Exclude

Adult-Onset Still's Disease (AOSD)/Systemic JIA

While uncommon at age 12, consider if:

• Quotidian fever pattern (daily spiking >39°C) 1
• Evanescent salmon-pink rash 1
• Markedly elevated ferritin (>1000 ng/mL with glycosylated ferritin ≤20%) 1
• Leukocytosis >10,000 with >80% granulocytes 1
• Negative RF and ANA (though ANA can be positive in 7-10% of cases) 1

Systemic Lupus Erythematosus

Consider only if additional features present:

• Malar or discoid rash, photosensitivity 4
• Nephritis (proteinuria, cellular casts) 4
• Cytopenias (hemolytic anemia, leukopenia, thrombocytopenia) 4
• Specific autoantibodies: anti-dsDNA, anti-Sm, antiphospholipid antibodies 4

Isolated positive ANA with joint pain and fever is insufficient for SLE diagnosis 4, 3.

Infective Endocarditis

Must be excluded urgently given valvular involvement:

• Blood cultures (before antibiotics) 5
• Assess for vegetation on echocardiography 5
• Look for peripheral stigmata (splinter hemorrhages, Osler nodes, Janeway lesions) 5

Management Algorithm

If Acute Rheumatic Fever is Confirmed:

Immediate treatment:

• Eradicate GAS infection: Benzathine penicillin G 1.2 million units IM single dose (or penicillin V 250 mg PO QID for 10 days if penicillin allergy, use erythromycin) 1
• Anti-inflammatory therapy:
  • Aspirin 80-100 mg/kg/day divided QID for arthritis and carditis without cardiomegaly 1
  • Prednisone 1-2 mg/kg/day (max 60-80 mg/day) for severe carditis with cardiomegaly or heart failure 1
• Supportive care: Bed rest during acute phase, manage heart failure if present 1

Secondary prophylaxis (critical to prevent recurrence):

• Benzathine penicillin G 1.2 million units IM every 3-4 weeks 1
• Duration depends on cardiac involvement:
  • With carditis and residual heart disease: until age 40 or lifelong 1
  • With carditis but no residual disease: 10 years or until age 25 1
  • Without carditis: 5 years or until age 21 1

If Diagnosis Remains Uncertain:

Obtain additional testing:

• Complete autoantibody panel: anti-dsDNA, anti-Sm, complement levels (C3, C4), antiphospholipid antibodies 4
• Ferritin with glycosylated ferritin percentage 1
• Complete blood count with differential 1
• Comprehensive metabolic panel, urinalysis 4
• Blood cultures if any suspicion of endocarditis 5

Serial echocardiography to assess progression of valvular disease and ventricular function 1.

Critical Pitfalls to Avoid

• Do not dismiss ARF based solely on positive ANA—infections and inflammatory states commonly cause positive ANA 2
• Do not delay treatment while awaiting streptococcal serology—if clinical suspicion is high, begin therapy 1
• Do not confuse physiological mitral regurgitation with pathological—use strict Doppler criteria and assess leaflet morphology 1
• Do not order ANA reflexively for nonspecific symptoms—the positive predictive value is extremely low without specific clinical features 3
• Do not miss concomitant endocarditis—always obtain blood cultures in febrile patients with new valvular disease 5