What is the appropriate initial workup and treatment approach for a patient presenting with polyarthritis?

Polyarthritis Differential Diagnosis and Initial Management

Initial Diagnostic Workup

The initial evaluation of polyarthritis (≥5 joints involved) should focus on distinguishing inflammatory from non-inflammatory causes through targeted history, examination, and laboratory testing to guide appropriate treatment. 1

Key Historical Features to Elicit

• Pattern of joint involvement: Symmetric small joint involvement (MCPs, PIPs, wrists) suggests rheumatoid arthritis, while asymmetric large joint involvement may indicate psoriatic or reactive arthritis 2, 1
• Morning stiffness duration: Stiffness lasting ≥1 hour before maximal improvement is characteristic of inflammatory arthritis, particularly RA 2
• Presence of redness, warmth, or swelling: These findings indicate synovitis and inflammatory disease 1
• Systemic symptoms: Fever, weight loss, malaise, or fatigue suggest systemic inflammatory disease 2
• Skin manifestations: Psoriatic plaques or nail changes point toward psoriatic arthritis 3
• Exposure history: Recent infections may indicate reactive or viral arthritis 1

Physical Examination Priorities

• Joint count and pattern: Document number and distribution of swollen and tender joints 3, 1
• Evidence of synovitis: Assess for joint swelling, warmth, and tenderness to palpation 2
• Extra-articular manifestations: Examine for rheumatoid nodules, psoriatic skin lesions, enthesitis, dactylitis, or nail involvement 3, 2

Essential Laboratory Testing

Order the following tests for all patients with suspected inflammatory polyarthritis:

• Inflammatory markers: ESR and CRP to assess acute phase response 3, 4, 5
• Autoantibodies: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies when RA is suspected 3, 4, 5
• Antinuclear antibodies (ANA): To evaluate for connective tissue diseases 3
• Complete blood count with differential: To assess for anemia, thrombocytosis, or leukopenia 4
• Hepatic and renal function: Baseline assessment before initiating DMARDs 4

The presence of RF or anti-CCP antibodies, along with elevated CRP or ESR, strongly supports a diagnosis of rheumatoid arthritis in patients with inflammatory arthritis. 4, 5

Imaging Studies

• Plain radiographs: Standard initial imaging for suspected RA to assess for erosive changes, though early disease may show only soft tissue swelling and juxtaarticular osteoporosis 2, 1
• Musculoskeletal ultrasound: Highly useful for detecting synovial thickening, effusions, and erosions in early disease when radiographs are normal 2, 1
• Joint aspiration with synovial fluid analysis: Perform when monoarthritis or oligoarthritis is present to exclude infection or crystal arthropathy 3

Treatment Approach Based on Diagnosis

For Rheumatoid Arthritis

Initiate disease-modifying antirheumatic drug (DMARD) therapy rapidly upon diagnosis, with methotrexate as the preferred first-line agent, to prevent irreversible joint damage. 4, 5

Initial Therapy

• Methotrexate monotherapy: First-line DMARD for RA 4, 5
• NSAIDs: May be used for symptomatic relief but should not be used as monotherapy 3
• Bridging glucocorticoids: Low-dose prednisone (10-20 mg/day) for <3 months may be considered during DMARD initiation if high disease activity is present 3

Treatment Escalation

• Add biologic DMARD: If inadequate response to methotrexate after 3 months, add a TNF inhibitor, IL-6 inhibitor (tocilizumab), or T-cell costimulation inhibitor (abatacept) 3, 6, 5
• JAK inhibitors: Consider if inadequate response to at least one csDMARD and one bDMARD 3

For Psoriatic Arthritis

In patients with polyarticular psoriatic arthritis, initiate a csDMARD rapidly, with methotrexate preferred when significant skin involvement is present. 3

Treatment Algorithm

• Methotrexate: First-line for polyarticular disease with skin involvement 3
• Biologic therapy: If inadequate response to csDMARD, initiate IL-17 inhibitor or IL-12/23 inhibitor (preferred with skin involvement) or TNF inhibitor 3
• Local glucocorticoid injections: Appropriate for adjunctive therapy; systemic glucocorticoids should be used cautiously at lowest effective dose 3

For Juvenile Idiopathic Arthritis (Polyarticular)

For children with polyarticular JIA, DMARD therapy is strongly recommended over NSAID monotherapy, with methotrexate as the preferred initial agent. 3, 7, 8

Initial Treatment

• Methotrexate: Strongly recommended as first-line DMARD, with subcutaneous route preferred over oral 7, 8
• Biologic therapy: May be considered initially for patients with risk factors (positive RF or anti-CCP, joint damage) and high-risk joint involvement (cervical spine, wrist, hip) or high disease activity 7, 8

Subsequent Therapy

• Add biologic: If moderate/high disease activity persists despite methotrexate, add TNF inhibitor, abatacept, or tocilizumab 7
• Switch to non-TNF biologic: If inadequate response to first TNF inhibitor, switch to tocilizumab or abatacept rather than second TNF inhibitor 7

Critical Pitfalls to Avoid

• Do not delay DMARD initiation: Earlier treatment with DMARDs is associated with better outcomes and prevention of irreversible joint damage 4, 5
• Do not use chronic systemic glucocorticoids as monotherapy: Glucocorticoids should only be used for short-term bridging (<3 months) during DMARD initiation 3, 9
• Do not combine multiple biologic agents or JAK inhibitors: Concomitant use of potent immunosuppressants increases infection risk without proven additional benefit 6
• Do not miss infectious causes: Always consider and exclude septic arthritis, particularly in monoarticular or oligoarticular presentations 3
• Do not overlook screening before biologics: Test for hepatitis B, hepatitis C, and tuberculosis before initiating biologic therapy 4, 5

Treatment Goals

The primary goal is to achieve remission or low disease activity through regular assessment and appropriate therapy adjustment, thereby maximizing quality of life, preventing structural damage, and maintaining function. 3, 5