What is the most likely diagnosis for a diabetic patient with a 6-month history of bilateral pain in the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints, dry eyes, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and negative anti-SSA antibodies?

Rheumatoid Arthritis

The most likely diagnosis is Rheumatoid Arthritis (Answer A). This diabetic patient presents with the classic triad of symmetric small joint polyarthritis (PIP and MCP involvement), elevated inflammatory markers (ESR and CRP), and sicca symptoms (dry eyes), which collectively point strongly toward RA despite negative anti-SSA antibodies.

Clinical Reasoning for Rheumatoid Arthritis

The bilateral involvement of MCP and PIP joints over 6 months with elevated inflammatory markers is pathognomonic for RA. 1 The symmetric distribution affecting small joints of the hands—specifically metacarpophalangeal and proximal interphalangeal joints—represents the characteristic presentation pattern that distinguishes RA from other arthropathies. 2

Key Diagnostic Features Present:

• Joint pattern: Bilateral MCP and PIP involvement is the hallmark of RA, with these joints being the primary targets in early disease 1, 2
• Duration: 6-month history meets the ≥6 weeks criterion (worth 1 point in ACR/EULAR classification) 1
• Inflammatory markers: Elevated ESR and CRP indicate active systemic inflammation (worth 1 point in classification criteria) and predict aggressive disease with high risk of erosive progression 1
• Sicca symptoms: Dry eyes can occur as part of secondary Sjögren's syndrome in RA patients, which develops in approximately 15-30% of RA cases 3

Scoring Using ACR/EULAR 2010 Criteria:

The patient likely scores ≥6/10 points needed for definite RA classification 1:

• Joint involvement: 4-10 small joints = 3 points 1
• Duration: ≥6 weeks = 1 point 1
• Acute phase reactants: Abnormal CRP or ESR = 1 point 1
• Serology: Unknown RF/ACPA status, but even if negative (0 points), the score reaches 5 points

Critical point: Seronegative RA accounts for 20-30% of cases, and negative RF does not exclude RA diagnosis. 1 The clinical presentation with definite synovitis in multiple small joints takes precedence over serologic findings. 1

Why Not the Other Options?

B - Sjögren Syndrome (Excluded):

• Negative anti-SSA antibodies strongly argue against primary Sjögren's syndrome, as anti-SSA (anti-Ro) is positive in 40-60% of primary Sjögren's cases
• Primary Sjögren's typically presents with sicca symptoms (dry eyes/mouth) as the dominant feature, with arthralgia being common but true inflammatory polyarthritis being less prominent
• The prominent inflammatory polyarthritis with markedly elevated CRP/ESR is more consistent with RA with secondary sicca features 3

C - Diabetic Cheiroarthropathy (Excluded):

• Diabetic cheiroarthropathy presents with painless limitation of joint mobility and skin thickening, not painful inflammatory arthritis
• It does not cause elevated inflammatory markers (ESR/CRP remain normal)
• The "prayer sign" (inability to press palms together) is characteristic, not tender swollen joints
• This is a non-inflammatory condition affecting joint capsules and periarticular tissues

D - Osteoarthritis (Excluded):

• OA characteristically involves DIP joints (Heberden's nodes) and spares MCP joints, which is the opposite pattern seen here 4
• OA causes bony enlargement, not soft tissue swelling from synovitis 4
• Inflammatory markers (ESR/CRP) remain normal or only mildly elevated in OA 4
• Morning stiffness in OA is brief (<30 minutes), whereas RA causes prolonged stiffness (>1 hour) 2
• The 6-month history of bilateral symmetric small joint pain with elevated inflammatory markers is incompatible with OA 4

Essential Next Steps

Immediate Laboratory Workup:

• RF and anti-CCP (ACPA) antibodies: High specificity (90%) for RA diagnosis, though negative results don't exclude it 1
• Complete blood count: Assess for cytopenias before starting treatment 1
• Comprehensive metabolic panel: Baseline liver and renal function for DMARD monitoring 1
• Hepatitis B, C, and tuberculosis screening: Required before initiating biologic therapy 1

Baseline Imaging:

• Bilateral hand, wrist, and foot X-rays: Assess for erosions, which predict RA diagnosis and disease persistence 1
• If X-rays are negative but clinical suspicion remains high, ultrasound with Power Doppler can detect subclinical synovitis that predicts disease progression 1

Treatment Initiation:

Do not delay treatment waiting for complete serologic workup. 1 Early treatment prevents irreversible joint damage.

• Start methotrexate 15 mg weekly as first-line DMARD immediately, escalating to 20-25 mg weekly as tolerated 1
• Add short-term low-dose prednisone (10-20 mg daily) as bridge therapy while awaiting DMARD effect 1
• Target remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 1
• Reassess disease activity every 4-6 weeks using composite measures (SDAI or CDAI) 1

Critical Pitfalls to Avoid

• Never dismiss RA diagnosis based on negative serology alone—seronegative RA has similar prognosis and requires equally aggressive treatment 1
• Never delay treatment waiting for positive antibodies—early DMARD therapy within 6 weeks of symptom onset prevents irreversible joint damage 1
• Never dismiss diagnosis based on normal ESR/CRP in future visits—acute phase reactants can be normal even in active disease 1
• Always refer to rheumatology within 6 weeks of symptom onset for any patient with polyarticular joint swelling 1