What is the best course of treatment for an elderly female patient with increasing leg stiffness and mobility issues, who has a positive Antinuclear Antibody (ANA) titer of 1:320, but a negative Rheumatoid Arthritis (RA) workup?

Diagnostic and Treatment Approach for Elderly Female with Leg Stiffness and ANA 1:320

This patient requires urgent evaluation for polymyalgia rheumatica (PMR) or inflammatory arthritis, not a neurological stiff-person syndrome, given the clinical presentation of bilateral leg stiffness in an elderly female with elevated ANA. 1

Immediate Clinical Assessment

Perform a focused joint examination to identify clinical synovitis as the essential first step before pursuing further workup. 2 Specifically examine:

• Bilateral shoulders, hips, and proximal limb girdle muscles for tenderness and range of motion limitation, as these are characteristic sites for PMR 3
• Metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, wrists, and metatarsophalangeal (MTP) joints bilaterally for symmetric swelling and tenderness to assess for rheumatoid arthritis 1, 2
• Perform squeeze test across MCPs and MTPs to assess for clinical synovitis 2
• Document morning stiffness duration - stiffness lasting ≥1 hour before maximal improvement strongly suggests inflammatory arthritis, while PMR typically presents with severe morning stiffness lasting >45 minutes 1, 2
• Assess for temporal artery tenderness, jaw claudication, or visual disturbances to exclude giant cell arteritis, which can cause permanent vision loss within days 3

Essential Laboratory Workup

Order the following tests immediately:

• ESR and CRP - ESR is specifically preferred for PMR diagnosis and monitoring, with high ESR (>40 mm/1st hour) being an independent risk factor for relapse 4. Both should be measured as part of the basic laboratory dataset 4
• Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACCP) - ACCP has 90% specificity and 60% sensitivity for RA, while RF has 70% specificity 1, 2
• Complete blood count with differential to assess for cytopenias 1
• Comprehensive metabolic panel including liver and renal function 1
• Creatine kinase (CK) to evaluate for myositis, which can present with limb-girdle myalgia and weakness mimicking PMR 3

Critical interpretation points:

• ANA 1:320 is commonly seen in RA patients - 54% of RA patients are ANA-positive, with titers ranging from 1:80 to 1:3200, and only 35 patients with ANA >1:160 in reported series 3
• Normal ESR/CRP does not exclude inflammatory arthritis - acute phase reactants can be normal in some patients with PMR-like presentations and are poor predictors of disease 3, 1
• Seronegative RA accounts for 20-30% of cases - negative RF does not exclude RA diagnosis 1

Imaging Studies

Obtain bilateral hand, wrist, and foot X-rays at baseline to assess for erosions and establish baseline for monitoring structural damage progression. 1, 2 Radiographic findings include periarticular osteopenia, uniform joint space narrowing, and osseous erosions, which predict RA diagnosis and disease persistence. 1, 2

Consider ultrasound with power Doppler or MRI with IV contrast if clinical examination does not reveal definite synovitis but suspicion remains high, as these modalities can detect subclinical synovitis and predict disease progression. 1, 2

Differential Diagnosis Priority

1. Polymyalgia Rheumatica (Most Likely)

• Elderly female demographic fits classic presentation 3
• Bilateral proximal limb girdle stiffness and pain 3
• "Legs not wanting to work" suggests severe functional limitation 3
• ANA positivity at 1:320 can occur in PMR-like presentations 3

2. Seronegative Rheumatoid Arthritis

• Negative RF workup but ANA-positive (seen in 54% of RA patients) 3, 5
• Bilateral leg involvement could represent lower extremity polyarthritis 1
• ANA-positive RA patients have higher rates of secondary Sjögren's syndrome (19.5% vs 4.1%) and higher IgG/IgM levels 5

3. Myositis (Must Exclude)

• Can present with limb-girdle myalgia and weakness mimicking PMR 3
• Potentially life-threatening complication requiring urgent recognition 3
• CK elevation would be diagnostic 3

Treatment Algorithm

If PMR is confirmed (proximal girdle pain/stiffness, elevated ESR/CRP, no clinical synovitis):

• Grade 1 (Mild stiffness/pain): Continue monitoring, initiate acetaminophen and/or NSAIDs if no contraindications 3
• Grade 2 (Moderate stiffness/pain limiting instrumental ADL): Initiate prednisone 20 mg/day, taper after 3-4 weeks if symptoms improve, escalate to Grade 3 if no improvement after 4 weeks 3
• Grade 3-4 (Severe stiffness/pain limiting self-care ADL): Initiate prednisone 40 mg/day, refer to rheumatology, consider IL-6 antagonists as steroid-sparing agents if prolonged high-dose steroids needed 3

If inflammatory arthritis is confirmed (clinical synovitis in ≥1 joint):

• Start methotrexate 15-25 mg weekly immediately as first-line DMARD 1, 2
• Add prednisone 10-20 mg daily as bridging therapy for rapid symptom control 1, 2
• Target remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) with reassessment every 4-6 weeks 1
• If inadequate response after 3 months: Consider triple DMARD therapy or adding biologic agent 1

If myositis is confirmed (elevated CK, proximal weakness):

• Urgent referral to rheumatologist and/or neurologist 3
• Initiate prednisone 1 mg/kg/day or methylprednisolone IV 1-2 mg/kg for severe compromise 3
• Consider plasmapheresis or IVIG for acute/severe disease 3

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive RF/ACCP - seronegative inflammatory arthritis is common and has similar prognosis 1
• Do not dismiss diagnosis based on normal ESR/CRP - inflammatory markers can be normal even in active disease 3, 1
• Do not attribute symptoms to osteoarthritis or aging without excluding inflammatory conditions - the bilateral nature and functional limitation demand systematic evaluation 1
• Do not miss giant cell arteritis - urgent ophthalmology referral if temporal arteritis symptoms present, as permanent vision loss can occur within days 3
• Do not overlook myositis - check CK in all patients with proximal weakness, as this is potentially life-threatening 3

Monitoring and Follow-up

Reassess disease activity every 4-6 weeks using composite measures (SDAI or CDAI) if inflammatory arthritis is diagnosed. 1 For PMR, monitor ESR at each visit as it is associated with relapse rates and need for prolonged therapy. 4 Repeat hand, wrist, and foot X-rays at 6 and 12 months to monitor radiographic progression if RA is diagnosed. 1