What is the most likely diagnosis for a diabetic patient with dry eyes, elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP), and a negative Anti-SSA (Anti-Sjögren's Syndrome A) test?

Sjögren Syndrome is the Most Likely Diagnosis

Despite the negative Anti-SSA antibody, Sjögren syndrome remains the most likely diagnosis in this diabetic patient with dry eyes and elevated inflammatory markers (ESR and CRP), as approximately 30-40% of Sjögren patients can be seronegative for Anti-SSA/Ro antibodies, and the diagnosis can still be confirmed through other objective criteria including Schirmer test, ocular surface staining, salivary flow rate, or minor salivary gland biopsy. 1

Why Sjögren Syndrome Despite Negative Anti-SSA

• Anti-SSA negativity does not exclude Sjögren syndrome - while Anti-SSA/Ro antibody positivity scores 3 points in the diagnostic criteria, the total diagnostic threshold is ≥4 points, which can be achieved through other objective measures 1

• The American College of Rheumatology classification criteria allow diagnosis through alternative pathways: focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² (3 points), abnormal ocular staining score (1 point), Schirmer test ≤5 mm/5 minutes (1 point), or unstimulated salivary flow rate ≤0.1 ml/minute (1 point) 1

• Research demonstrates that among patients with primary Sjögren syndrome diagnosed at dry eye centers, only 66.6% tested positive for SSA/SSB antibodies, with one-third requiring minor salivary gland biopsy for definitive diagnosis despite negative serology 2

Why Not the Other Options

Rheumatoid Arthritis (Option A) - Less Likely

• While RA can cause dry eyes, 90% of RA patients with dry eye do NOT meet criteria for secondary Sjögren syndrome 3
• RA typically presents with joint deformities, morning stiffness, and positive rheumatoid factor or anti-CCP antibodies - none of which are mentioned in this case 4
• The severity of dry eye in RA patients is independent of RA disease activity and does not correlate with inflammatory markers 5, 3
• If this were RA-associated dry eye, you would expect prominent joint symptoms as the primary complaint, not isolated dry eyes 5

Diabetic Cheiroarthropathy (Option C) - Not Consistent

• This condition presents with limited joint mobility and waxy skin thickening of the hands, not dry eyes or elevated inflammatory markers
• Diabetes does increase dry eye prevalence to 17.5%, but this is typically non-inflammatory and would not explain elevated ESR/CRP 1

Osteoarthritis (Option D) - Not Consistent

• OA is a degenerative, non-inflammatory condition that would not cause elevated ESR/CRP 1
• OA does not cause dry eyes or systemic autoimmune manifestations 1

Critical Next Steps for Diagnostic Confirmation

Immediate objective testing required to reach diagnostic threshold:

• Schirmer test without anesthesia - positive if ≤5 mm/5 minutes (scores 1 point) 1
• Ocular surface staining with lissamine green or fluorescein - positive if ocular staining score ≥5 or van Bijsterveld score ≥4 (scores 1 point) 1
• Unstimulated whole salivary flow rate - positive if ≤0.1 ml/minute (scores 1 point) 1
• Minor salivary gland biopsy - if clinical suspicion remains high and other tests are inconclusive, looking for focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² (scores 3 points) 1, 2

Expand serological workup:

• Rheumatoid factor (RF) - often positive in Sjögren syndrome 1
• Antinuclear antibody (ANA) - may be positive even when Anti-SSA is negative 2
• Consider point-of-care testing for salivary protein 1 (SP1), carbonic anhydrase 6 (CA6), and parotid secretory protein (PSP) for early detection 1

Essential Management Considerations

• Mandatory rheumatology referral - approximately 5% of Sjögren patients develop lymphoma, with decreased C4 levels at diagnosis indicating higher risk 1, 6
• The female-to-male ratio is 20:1, but the disease can occur in all demographics including diabetic patients 1, 6
• Approximately 10% of patients with clinically significant aqueous deficient dry eye have underlying primary Sjögren syndrome 1, 6

Common Diagnostic Pitfall to Avoid

Do not dismiss Sjögren syndrome based solely on negative Anti-SSA antibodies - research shows that a significant proportion of confirmed Sjögren patients are seronegative and require tissue diagnosis through minor salivary gland biopsy 2. The elevated inflammatory markers (ESR and CRP) in this case strongly support an autoimmune etiology rather than diabetes-related dry eye alone 1.