Initial Treatment of Synovitis with Suspected Rheumatoid Arthritis
Start methotrexate 15 mg weekly immediately with folic acid 1 mg daily, combined with short-term low-dose prednisone (10-20 mg daily) as bridge therapy, and refer to rheumatology within 6 weeks of symptom onset. 1, 2, 3
Immediate Clinical Assessment
Perform a focused 28-joint examination assessing proximal interphalangeal joints (PIPs), metacarpophalangeal joints (MCPs), wrists, elbows, shoulders, and knees for tenderness and swelling 4. The presence of joint swelling not caused by trauma or bony swelling, preferably involving at least two joints, confirms synovitis 2. A positive "squeeze test" of MCPs and metatarsophalangeal joints (MTPs) helps identify inflammatory joint involvement 4, 2.
Morning stiffness lasting ≥30 minutes (or ≥1 hour in rheumatoid arthritis) is characteristic of inflammatory synovitis and should be specifically documented 2, 5. Calculate disease activity using the Simplified Disease Activity Index (SDAI), which includes tender joint count (0-28), swollen joint count (0-28), patient global assessment (0-10 cm), evaluator global assessment (0-10 cm), and CRP in mg/dL 4.
Essential Laboratory Workup
Order the following tests immediately 4:
- Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA/anti-CCP) - ACPA has 90% specificity with 60% sensitivity; RF has 70% specificity with similar sensitivity 4
- CRP (preferred over ESR) - more reliable, not age-dependent, and essential for SDAI calculation 4, 2
- Complete blood count with differential - assess for cytopenias before starting treatment 4
- Comprehensive metabolic panel - including liver function tests, renal function, glucose, and urate levels 4
- Hepatitis B, Hepatitis C, and tuberculosis screening - required before any biologic therapy 4, 6
- Urinalysis - part of standard initial workup 4
Obtain baseline bilateral hand, wrist, and foot X-rays to assess for erosions, which predict RA diagnosis and disease persistence 4. If clinical examination shows no definite synovitis but suspicion remains high, order ultrasound with Power Doppler or MRI, as these detect subclinical synovitis that predicts disease progression 4, 2.
First-Line Treatment Protocol
Methotrexate is the anchor drug and must be started immediately 1, 2, 3. Begin at 15 mg weekly orally with folic acid 1 mg daily 1. Plan to escalate to 20-25 mg weekly or switch to subcutaneous administration if inadequate response 1. Lower doses are required in elderly patients and those with chronic kidney disease 1.
Add short-term low-dose prednisone (10-20 mg daily) as bridge therapy while awaiting DMARD effect 4. Systemic glucocorticoids reduce pain and swelling and should be considered as adjunctive temporary treatment 2. Use intra-articular glucocorticoid injections for localized joint inflammation 4.
Critical pitfall to avoid: Do not delay treatment waiting for positive serology - seronegative RA accounts for 20-30% of cases and has similar prognosis 4. Do not dismiss the diagnosis based on normal ESR/CRP, as acute phase reactants can be normal even in active disease 4.
Treatment Target and Monitoring Schedule
The primary target is remission, defined as SDAI ≤3.3, or low disease activity (SDAI ≤11) 1, 4, 2. Reassess disease activity using SDAI every 4-6 weeks 4. Repeat CRP at each visit to monitor disease activity 4. Obtain repeat hand, wrist, and foot X-rays at 6 months and 12 months to monitor radiographic progression 4.
Treatment Escalation at 3 Months
If high disease activity (SDAI >26 or CDAI >22) persists at 3 months despite optimized methotrexate and prednisone, the probability of attaining remission at 1 year is low without escalation 1. Add either triple-DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) or a TNF inhibitor (infliximab, etanercept, adalimumab), or T-cell costimulation blockade (abatacept) 1.
TNF inhibitors and abatacept are approved and recommended biologic response modifiers for step-up treatment at this stage 1. Anakinra (interleukin-1 receptor antagonist) is generally less effective than these agents and cannot be recommended at this disease stage 1.
Treatment Escalation at 6-12 Months
If low disease activity (SDAI ≤11 or CDAI ≤10) is not achieved at 6-12 months, escalate treatment 1. For patients on methotrexate monotherapy, add sulfasalazine and hydroxychloroquine for triple-DMARD therapy, or add TNF inhibition or abatacept 1. For patients already receiving combined methotrexate plus biologic therapy, switch to an alternative biologic response modifier 1.
Abatacept is more effective than placebo in patients with inadequate response to TNF inhibitors and has a good safety record 1. Anti-interleukin-6 receptor monoclonal antibody (tocilizumab) and anti-CD20 (rituximab) are indicated after inadequate response to at least one TNF inhibitor 1.
Adjunctive Non-Pharmacologic Interventions
Refer to occupational therapy for joint protection education, assistive devices, and splinting 4. Prescribe dynamic exercise programs incorporating aerobic exercise and progressive resistance training, which improve fitness and strength with salutary benefits on lean body mass 1, 2. Advise adequate rest during periods of poorly controlled inflammation 1, 4. Provide tobacco cessation counseling, as smoking is a modifiable predictor of adverse outcomes 4.