What are the symptoms and treatment options for a patient with suspected Rheumatoid Arthritis (RA)?

Rheumatoid Arthritis: Symptoms and Treatment

Clinical Symptoms

Rheumatoid arthritis typically presents with symmetric polyarthritis affecting small joints of the hands and feet, accompanied by morning stiffness lasting at least 1 hour or longer. 1

Key Presenting Features

• Joint involvement: Symmetric swelling and tenderness, particularly affecting metacarpophalangeal joints, proximal interphalangeal joints, wrists, and metatarsophalangeal joints 1
• Morning stiffness: Duration of 1 hour or more before maximal improvement, correlating with disease activity 1, 2
• Joint swelling: Soft tissue swelling is the most critical sign of inflammation, with joints being tender and warm but typically not hot or red 2, 3
• Constitutional symptoms: Fatigue, malaise, weight loss, and low-grade fever may accompany joint symptoms 1, 2

Extra-Articular Manifestations (Markers of Severe Disease)

• Subcutaneous rheumatoid nodules 1
• Interstitial lung disease 1
• Vasculitis 1
• Inflammatory eye disease 1

Pattern Recognition

The most common presentation is insidious onset with symmetric small joint involvement, though approximately 25% present acutely or subacutely. 2 Distal interphalangeal joints, sacroiliac joints, and lumbar spine are characteristically spared. 2

Diagnostic Approach

Urgent Referral Criteria

Refer urgently to a rheumatologist for anyone with suspected persistent synovitis, even if rheumatoid factor is negative or acute-phase reactants are normal, particularly when: 1, 4

• Small joints of hands or feet are affected 1
• More than one joint is involved 1
• Delay of 3 months or longer between symptom onset and seeking medical advice 1

Early referral within 1-2 weeks is critical, as timely intervention reduces disease burden and improves long-term outcomes. 1

Laboratory Testing

• Rheumatoid factor (RF): Test in all patients with suspected RA and synovitis; present in approximately 75% of patients but 30-40% may be RF-negative 1, 4, 3
• Anti-citrullinated protein antibody (ACPA): High specificity (90%) and moderate sensitivity (60%); particularly valuable in RF-negative patients when considering combination therapy 1, 4
• C-reactive protein (CRP): Preferred over ESR as it is more reliable, not age-dependent, and correlates with clinical assessment and radiographic changes 1, 2

Classification Criteria

Definite RA requires a score of 6 or higher using the ACR/EULAR criteria, incorporating: 1

• Joint involvement (0-5 points): Number and size of affected joints 1
• Serology (0-3 points): RF and/or ACPA levels 1
• Acute-phase reactants (0-1 point): Elevated CRP or ESR 1
• Symptom duration (0-1 point): ≥6 weeks scores 1 point 1

A patient with early-morning stiffness, swollen wrist joint, and strongly positive ACPA for 6 weeks (or less with abnormal CRP) fulfills criteria and should begin disease-modifying therapy immediately. 1

Treatment Strategy

Primary Treatment Goal

The primary target of therapy is clinical remission, defined as absence of signs or symptoms of inflammatory disease activity, which is achievable particularly with early diagnosis and treat-to-target strategies. 1

Remission is defined by ACR/EULAR as: tender joints ≤1, swollen joints ≤1 (28-joint count), CRP ≤1 mg/dL, and patient global assessment ≤1 on 10-cm scale, or alternatively SDAI ≤3.3. 1

First-Line Therapy

Methotrexate should be initiated immediately upon diagnosis confirmation. 5, 6, 7

• Methotrexate is the typical first-line disease-modifying antirheumatic drug (DMARD) 8, 7
• Can be used alone or in combination with other agents 1, 6
• Glucocorticoids, NSAIDs, salicylates, or analgesics may be continued during treatment 6, 8

Adjunctive Therapy

Short-term low to moderate dose glucocorticoids added to DMARD therapy provide rapid symptomatic improvement while awaiting DMARD effect. 5

• NSAIDs and glucocorticoids control pain, inflammation, and stiffness but do not slow radiographic progression 8
• Glucocorticoids should be used as bridging therapy, not long-term monotherapy 5

Treatment Escalation

If methotrexate monotherapy is insufficient, add or switch to other DMARDs or biologic agents. 5, 7

Biologic options include: 6, 8

• TNF-alpha inhibitors (etanercept, infliximab, adalimumab) 6, 8
• IL-1 inhibitors (anakinra) 8
• Costimulation blockers (abatacept) 8
• Anti-CD20 antibodies (rituximab) 8

Treat-to-Target Approach

Use tight-control treatment strategy with goal of DAS28 <2.6, which leads to faster and more frequent remission than usual care. 1

• Monitor disease activity using composite measures (DAS28, SDAI, or CDAI) 1
• Adjust treatment aggressively based on quantitative disease activity assessment 1
• Achievement of remission by week 14 predicts radiographic nonprogression at 1 year 1

Non-Pharmacological Management

• Regular aerobic and resistance exercise programs improve muscle strength and reduce stiffness 5
• Hand therapy exercises maintain strength and function 5
• Joint protection techniques reduce stress on affected joints 5

Critical Pitfalls to Avoid

Do not delay referral or treatment based on negative RF or normal inflammatory markers—these are present in only 60-75% of RA patients. 1, 4

Do not wait for radiographic changes before initiating DMARDs—80% of erosions occur within the first 2 years, and early aggressive treatment prevents irreversible joint damage. 1

Screen for tuberculosis, hepatitis B/C before initiating biologic therapy, as these agents significantly increase infection risk. 6, 7

Prognostic Considerations

• More than one-third of patients experience work disability; 80% are working at 2 years, 68% at 5 years 1
• Life expectancy is shortened by 3-5 years, especially with extra-articular disease 1
• High-positive RF or ACPA and dual positivity predict higher risk of persistent and erosive disease 4
• Early aggressive therapy with DMARDs and biologics has demonstrated improved long-term outcomes in clinical trials 1, 8