What are the typical symptoms and treatment options for a patient with rheumatoid arthritis?

Rheumatoid Arthritis: Clinical Presentation and Management

Typical Symptoms

Rheumatoid arthritis characteristically presents with symmetric joint swelling (synovitis) affecting small joints, particularly the metacarpophalangeal joints, proximal interphalangeal joints, wrists, and metatarsophalangeal joints, accompanied by morning stiffness lasting 1 hour or longer. 1, 2

Cardinal Clinical Features

• Joint involvement: Definite clinical synovitis (soft tissue swelling around joints, not bony enlargement) in at least one joint not better explained by another disease is the cornerstone finding 3, 2
• Morning stiffness: Duration of ≥1 hour before maximal improvement is a typical sign, with duration correlating to disease activity 1, 2
• Pattern of involvement: Symmetric distribution affecting multiple small joints bilaterally, though large joints (shoulders, elbows, hips, knees, ankles) may also be affected 1, 3
• Joints typically spared: Distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints are characteristically not involved 1, 3, 2

Associated Manifestations

• Systemic symptoms: Fatigue, malaise, weight loss, and low-grade fever commonly accompany active disease 1, 2
• Extra-articular features: Subcutaneous rheumatoid nodules, interstitial lung disease, vasculitis, and inflammatory eye disease indicate severe disease 1, 4
• Functional impact: Progressive disability with work disability beginning early—80% working at 2 years, declining to 68% at 5 years 1

Treatment Options

The primary treatment goal is achieving remission (defined as absence of signs or symptoms of inflammatory disease activity) through early aggressive therapy with disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate as first-line therapy. 1, 3, 5

First-Line Treatment Strategy

• Methotrexate monotherapy: Start 15 mg weekly (oral or subcutaneous) with folic acid supplementation as the anchor drug for initial treatment 3, 5, 6
• Bridging therapy: Add short-term low-dose glucocorticoids (prednisone 10-20 mg daily) or intra-articular injections while awaiting DMARD effect 1, 3
• Dose escalation: Plan to increase methotrexate to 20-25 mg weekly if needed for disease control 3

Treatment Targets and Monitoring

• Target disease activity: Aim for remission (SDAI ≤3.3 or CDAI ≤2.8) or low disease activity (SDAI ≤11) 1, 3
• Monitoring frequency: Reassess disease activity using composite measures (SDAI, CDAI, or DAS28) every 4-6 weeks initially 1, 3
• Treatment adjustment: If inadequate response after 3 months of methotrexate monotherapy, add triple DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) or a biologic agent 3, 5

Second-Line and Biologic Therapies

• TNF inhibitors: Adalimumab 40 mg subcutaneously every other week (can be used alone or with methotrexate) for patients with inadequate response to conventional DMARDs 7, 8
• Other biologics: Rituximab (anti-CD20), abatacept (costimulation blocker), or anakinra (IL-1 inhibitor) as alternatives 8
• Combination therapy: Methotrexate combined with biologic agents often produces superior outcomes compared to monotherapy 1, 7

Critical Pre-Treatment Screening

• Mandatory testing before biologics: Screen for hepatitis B, hepatitis C, and tuberculosis (including latent TB) before initiating any biologic therapy 3, 7, 6
• Contraindications: Methotrexate should be used with caution in patients with hematologic abnormalities, hepatic dysfunction, or active infections 3

Treat-to-Target Approach

• Tight control strategy: Use validated composite disease activity measures to guide aggressive treatment modification, achieving DAS28 <2.6 leads to faster and more frequent remission than usual care 1
• Remission criteria: ACR/EULAR define remission as tender joints ≤1, swollen joints ≤1, CRP ≤1 mg/dL, and patient global assessment ≤1 (on 0-10 scale), or alternatively SDAI ≤3.3 1
• Early intervention benefit: Remission achieved by week 14 predicts radiographic nonprogression at 1 year regardless of therapy type 1

Non-Pharmacologic Interventions

• Occupational therapy: Joint protection education, assistive devices, and splinting 3
• Exercise program: Dynamic aerobic exercise and progressive resistance training, with adequate rest during active inflammation 3
• Lifestyle modifications: Tobacco cessation (smoking predicts worse outcomes), weight management, and regular dental care 3, 9

Common Pitfalls to Avoid

• Do not delay treatment waiting for positive serology: Seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease 3
• Do not dismiss diagnosis based on normal inflammatory markers: ESR and CRP can be normal even in active disease; prioritize clinical synovitis over laboratory values 1, 3
• Do not use composite measures uncritically: Patients with fibromyalgia can have falsely elevated disease activity scores due to high tender joint counts without swollen joints or elevated acute phase reactants 1
• Avoid corticosteroid monotherapy beyond 1-2 years: Long-term use increases risks of cataracts, osteoporosis, fractures, and potentially cardiovascular disease 1
• Recognize central pain amplification: When joint tenderness and subjective symptoms are disproportionate to objective findings, investigate noninflammatory causes (osteoarthritis, regional pain syndromes) rather than escalating immunosuppression 1

Prognostic Implications of Untreated Disease

• Life expectancy: Shortened by 3-5 years, especially with extra-articular manifestations 1
• Cardiovascular risk: 50% increase in cardiovascular morbidity and mortality compared to general population, with risk equivalent to being 10 years older 10
• Joint destruction: Irreversible damage occurs early without treatment, emphasizing the critical importance of early aggressive intervention 10