What is the diagnosis and treatment for a patient with bilateral upper joint pain and swelling, limited range of motion, and elevated inflammatory markers, including C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR), with lab results showing hyperuricemia, elevated Antistreptolysin O (ASO) antibodies, and positive Rheumatoid Factor (RF)?

Diagnosis: Undifferentiated Peripheral Inflammatory Arthritis with Elevated Inflammatory Markers

This patient presents with acute-onset bilateral polyarthritis affecting upper and lower extremities with markedly elevated inflammatory markers (CRP 78-98.5, ESR 29), but negative or low-titer autoantibodies, most consistent with undifferentiated peripheral inflammatory arthritis (UPIA) requiring urgent evaluation to exclude infectious causes and establish a specific diagnosis. 1

What These Lab Results Tell Us

Inflammatory Markers - Highly Significant

• CRP 78 mg/L and cardiac CRP 98.5 mg/L are markedly elevated, confirming active systemic inflammation and ruling out non-inflammatory causes like osteoarthritis 1, 2
• ESR 29 mm/h is elevated, though less dramatically than CRP, which is expected as CRP is more reliable and not age-dependent 2
• These elevated inflammatory markers are consistent with inflammatory arthritis and help differentiate from degenerative joint disease 1

Autoantibody Profile - Seronegative Pattern

• Rheumatoid Factor 14.1 is essentially negative (typically positive >40-60 depending on lab), making classic seropositive RA less likely but not excluded 2
• Anti-CCP IgG 8 is negative, further reducing likelihood of RA but seronegative RA accounts for 20-30% of cases 2
• ANA negative makes systemic lupus erythematosus and other connective tissue diseases less likely 1, 2
• Negative serology does NOT exclude RA or other inflammatory arthritis - seronegative disease has similar prognosis and requires the same aggressive treatment 2

Other Results

• Uric acid 4.6 mg/dL is normal, effectively excluding gout as the primary diagnosis 1
• ASO titer 142 is mildly elevated (normal <200), raising concern for post-streptococcal reactive arthritis given the acute 2-day onset 1

Critical Next Steps - Immediate Workup Required

Rule Out Infectious Causes FIRST

Given the acute onset (2 days), severe pain (10/10), and elevated ASO, you must exclude septic arthritis and post-streptococcal reactive arthritis before assuming autoimmune disease 1:

• Arthrocentesis of at least one swollen joint for cell count, Gram stain, culture, and crystal analysis 1
• Blood cultures if febrile 1
• Throat culture or rapid strep test given elevated ASO 1
• Complete blood count with differential to assess for leukocytosis suggesting infection 1, 2

Additional Baseline Testing

• Comprehensive metabolic panel including liver and renal function 2, 3
• Hepatitis B, Hepatitis C, and tuberculosis screening before any immunosuppressive therapy 2, 4
• Plain X-rays of hands, wrists, feet, and any other affected joints to establish baseline and look for erosions 1, 2
• Consider HLA-B27 testing if reactive arthritis pattern emerges (oligoarthritis, back pain, conjunctivitis, urethritis) 1

Advanced Imaging if Diagnosis Unclear

• Ultrasound or MRI of affected joints if arthrocentesis is negative and diagnosis remains uncertain, as these can detect subclinical synovitis 1, 2

Differential Diagnosis Priority List

1. Post-streptococcal reactive arthritis - Most likely given acute 2-day onset, elevated ASO, and migratory polyarthritis pattern 1
2. Seronegative rheumatoid arthritis - Possible given symmetric small joint involvement, but acute onset is atypical 2, 4
3. Viral arthritis - Consider given acute onset and polyarticular pattern 1
4. Early undifferentiated connective tissue disease - Remains on differential with negative ANA 1
5. RS3PE syndrome - Consider if bilateral hand/foot edema present 5

Immediate Treatment Approach

For Severe Pain (10/10) - Grade 3-4 Inflammatory Arthritis

Hold any potential immunosuppressive therapy until infection is excluded 1:

• Prednisone 0.5-1 mg/kg/day (approximately 40-60 mg daily for average adult) for severe inflammatory arthritis 1, 6
• NSAIDs at therapeutic doses (e.g., naproxen 500 mg twice daily or ibuprofen 800 mg three times daily) for additional pain control 1
• Avoid opioids as inflammatory pain responds poorly to them and improvement with NSAIDs/corticosteroids confirms inflammatory etiology 1

If Infection Excluded and RA Suspected

• Start methotrexate 15 mg weekly as first-line DMARD, escalating to 20-25 mg weekly based on response 2, 4, 7
• Continue prednisone 10-20 mg daily as bridge therapy while awaiting DMARD effect, then taper over 4-6 weeks 1, 2
• Folic acid 1 mg daily to reduce methotrexate toxicity 3, 4

Critical Pitfalls to Avoid

1. Do NOT delay treatment waiting for positive serology - seronegative inflammatory arthritis requires the same aggressive treatment as seropositive disease 2
2. Do NOT dismiss the diagnosis based on normal-ish ESR - acute phase reactants can be normal even in active disease, and CRP is markedly elevated here 2
3. Do NOT start DMARDs before excluding infection - the acute 2-day onset and elevated ASO mandate infection workup first 1
4. Do NOT use daily low-dose prednisone long-term without DMARD - this leads to steroid dependence and does not prevent joint damage 2, 6

Rheumatology Referral - URGENT

Refer immediately to rheumatology given:

• Definite synovitis with severe functional impairment (unable to move hands) 1
• Grade 3-4 disease severity requiring aggressive immunosuppression 1
• Diagnostic uncertainty between reactive arthritis and early RA 1, 8

Monitor with serial rheumatologic examinations and inflammatory markers every 4-6 weeks once treatment is initiated 1, 8