What is the most likely diagnosis for a patient with bilateral arthritis, arthralgia, severe dry eyes, and elevated Erythrocyte Sedimentation Rate (ESR), with a negative anti-SSA (Anti-Sjögren's Syndrome A) test?

Diagnosis: Sjögren's Syndrome (B)

Despite the negative anti-SSA antibody, this patient most likely has Sjögren's syndrome based on the combination of bilateral polyarthritis affecting PIPs and MCPs, severe dry eyes, elevated ESR, and the clinical presentation lasting months. 1

Diagnostic Reasoning

Why Sjögren's Syndrome is Most Likely

The current diagnostic criteria for Sjögren's syndrome use a weighted scoring system where a total of ≥4 points establishes the diagnosis: 1

• Anti-SSA/Ro antibody: 3 points (negative in this case = 0 points)
• Focal lymphocytic sialadenitis (focus score ≥1 foci/4 mm²): 3 points (not yet assessed)
• Abnormal ocular staining score ≥5: 1 point (likely positive given "severe dry eyes")
• Schirmer test ≤5 mm/5 minutes: 1 point (should be performed)
• Unstimulated salivary flow rate ≤0.1 ml/minute: 1 point (should be assessed)

Critical point: Anti-SSA negativity does NOT exclude Sjögren's syndrome. Only about 60-70% of Sjögren's patients are anti-SSA positive, meaning 30-40% are seronegative. 1

Clinical Features Supporting Sjögren's

• Severe dry eyes (keratoconjunctivitis sicca): This is a cardinal feature of Sjögren's syndrome 1, 2
• Bilateral polyarthritis (PIPs and MCPs): Arthralgias and arthritis are common systemic manifestations in Sjögren's, occurring in approximately half of patients 2, 3
• Elevated ESR: Reflects the chronic inflammatory nature of the disease 4
• Chronic duration (months): Consistent with the chronic autoimmune process 5

Why NOT Rheumatoid Arthritis Alone

While RA can cause dry eyes, the presentation here is more consistent with Sjögren's: 4

• Dry eye in RA is typically mild to moderate, not "severe" as described 4
• Dry eye severity in RA correlates with disease duration, not activity 4
• Secondary Sjögren's syndrome occurs in 10-30% of RA patients, making this potentially secondary Sjögren's if RA is confirmed 3, 5
• The question states "most likely differential diagnosis: Psoriatic Arthritis" was considered, suggesting RA serology may not be strongly positive

Essential Next Steps for Confirmation

Immediate Objective Testing Required

1. Schirmer test without anesthesia (abnormal if ≤5 mm/5 minutes) 1
2. Ocular surface staining with lissamine green or fluorescein (abnormal if OSS ≥5 or van Bijsterveld score ≥4) 1
3. Unstimulated salivary flow rate (abnormal if ≤0.1 ml/minute) 1

Additional Serological Testing

• Anti-SSB/La antibody: Can be positive even when anti-SSA is negative 6, 5
• Rheumatoid factor (RF): Often positive in Sjögren's syndrome 6, 5
• Antinuclear antibody (ANA): Frequently positive 6, 5
• Complement C4 level: Low C4 indicates higher risk of lymphoma (5% lifetime risk in Sjögren's) 2, 7, 8

Definitive Diagnostic Test if Score <4

Minor salivary gland biopsy showing focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² (scores 3 points and can establish diagnosis even with negative serology) 1, 4

Critical Management Implications

Immediate Actions

• Co-management with rheumatologist is mandatory due to systemic complications and 5% lymphoma risk 1, 2, 7
• Ophthalmology referral for comprehensive dry eye evaluation and management 1

Monitoring Requirements

• Screen for lymphoma development, especially if C4 is low at diagnosis 2, 7, 8
• Assess for extraglandular manifestations: pulmonary involvement, renal disease, peripheral neuropathy, vasculitis 2, 3, 5

Common Pitfalls to Avoid

• Do not exclude Sjögren's based solely on negative anti-SSA: 30-40% of patients are seronegative 1
• Do not attribute all symptoms to RA if present: Secondary Sjögren's requires specific evaluation and management 3, 5
• Do not overlook the need for objective dry eye testing: Patient-reported symptoms alone are insufficient 1
• Do not delay rheumatology referral: The 5% lymphoma risk and potential for serious systemic complications require specialist oversight 2, 7