Sjögren Syndrome (Option B)
The most likely diagnosis is Sjögren syndrome (Option B), despite the negative Anti-SSA antibody, because this patient presents with the classic triad of dry eyes, systemic inflammation (elevated ESR and CRP), and an underlying autoimmune condition (diabetes mellitus, which frequently coexists with other autoimmune diseases). 1, 2
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 diagnosis can still be made with a total score of ≥4 points using other objective criteria including Schirmer test (≤5 mm/5 minutes scores 1 point), abnormal ocular staining score (scores 1 point), and unstimulated salivary flow rate (≤0.1 ml/minute scores 1 point). 2
Approximately 10% of patients with clinically significant aqueous deficient dry eye have underlying primary Sjögren syndrome, making this a common presentation that ophthalmologists and primary care physicians should actively screen for. 1, 2
The elevated ESR and CRP indicate systemic inflammation consistent with an autoimmune process, though notably, primary Sjögren syndrome is characterized by a relatively low CRP response compared to other inflammatory disorders - so even modest CRP elevation can be significant in this context. 3
Why the Other Options Are Less Likely
Rheumatoid Arthritis (Option A)
- While RA can cause dry eyes as part of secondary Sjögren syndrome, the question stem does not mention joint symptoms, morning stiffness, or joint deformities that would be expected with RA. 2
- RA typically presents with symmetric polyarthritis affecting small joints of hands and feet, which is not described here. 4
Diabetic Cheiroarthropathy (Option C)
- This condition causes limited joint mobility and waxy skin thickening of the hands but does not cause dry eyes or elevated inflammatory markers (ESR/CRP). 5
- While diabetic patients do have higher rates of dry eye syndrome (52.8% vs 9.3% in controls), this is typically due to neuropathy and metabolic dysfunction, not systemic inflammation with elevated ESR/CRP. 5
Osteoarthritis (Option D)
- OA is a degenerative joint disease that does not cause dry eyes or elevated inflammatory markers. 2
- OA is not an autoimmune or inflammatory condition and would not explain the clinical presentation. 2
Critical Diagnostic Approach for This Patient
Proceed with additional objective testing even with negative Anti-SSA, including:
- Schirmer test without anesthesia (≤5 mm/5 minutes is abnormal) 2
- Ocular surface staining with lissamine green or fluorescein (ocular staining score ≥5 is abnormal) 2
- Unstimulated whole salivary flow rate (≤0.1 ml/minute is abnormal) 2
- Consider minor salivary gland biopsy if clinical suspicion remains high (focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² scores 3 points) 2
Screen for systemic manifestations including:
Mandatory rheumatology referral is essential because:
- Approximately 5% of Sjögren syndrome patients develop lymphoid malignancy, representing a 320 cases per 100,000 patient-years increased incidence 1
- Decreased C4 levels at diagnosis are associated with higher lymphoma risk 4, 2
- Co-management is required due to potential systemic complications affecting multiple organ systems 1, 2
Key Clinical Pitfalls to Avoid
Do not dismiss Sjögren syndrome based solely on negative Anti-SSA - seronegative Sjögren syndrome exists and can be diagnosed using the weighted scoring system with other objective criteria. 2
Do not attribute dry eyes in diabetic patients solely to diabetes - when accompanied by elevated inflammatory markers (ESR/CRP), this suggests an additional autoimmune process requiring investigation. 5
Maintain high index of suspicion when dry eye occurs with systemic symptoms like fatigue or elevated inflammatory markers, as ophthalmologists should have a low threshold for serological work-up in patients with clinically significant dry eye. 1