What is the differential diagnosis for a patient presenting with bilateral hand and wrist pain involving the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints?

Differential Diagnosis for Bilateral Hand and Wrist Pain Involving MCP and PIP Joints

Bilateral involvement of MCP and PIP joints should immediately raise suspicion for rheumatoid arthritis as the primary diagnosis, as this represents the classic RA pattern with symmetric polyarthritis affecting these specific joint distributions. 1, 2

Primary Differential Diagnoses

Rheumatoid Arthritis (Most Likely)

• RA characteristically targets MCPs, PIPs, and wrists with symmetric involvement, making this the leading diagnosis when both joint groups are affected bilaterally. 1, 2, 3
• Morning stiffness lasting more than 30 minutes (typically at least 1 hour before maximal improvement) strongly supports RA over osteoarthritis. 1, 2
• Soft tissue swelling on palpation indicates inflammatory arthritis rather than bony enlargement seen in OA. 1
• Hand involvement with MCP and PIP synovitis causing tender swelling with severe motion impairment is the typical early manifestation of RA. 2
• Approximately 70% of RA patients develop hand pathologies, especially affecting the MCP joints. 4
• Elevated inflammatory markers (ESR, CRP) and symmetric distribution of lesions in corresponding joint compartments support the diagnosis. 5

Psoriatic Arthritis

• PsA can affect any joint including MCPs and PIPs, though it more commonly presents asymmetrically. 1, 6
• Look for DIP joint involvement, which is characteristic of PsA but distinctly uncommon in RA. 6, 5
• Dactylitis (sausage digits) and enthesitis are additional supporting features. 6
• Skin psoriasis with plaque lesions should be present or have occurred previously. 7
• Proliferative bone changes on radiographs favor PsA over RA. 5

Adult-Onset Still's Disease

• AOSD presents with symmetric polyarthritis affecting knees, wrists, and ankles most frequently, but PIP and MCP joints are also commonly involved (47% and 35% respectively). 8
• The diagnostic triad includes high-spiking quotidian fevers (>39°C, typically late afternoon/evening), salmon-pink evanescent rash, and arthritis/arthralgias. 8
• Markedly elevated inflammatory markers (ESR, CRP) with striking neutrophilia and very high ferritin levels (often >4000 ng/ml, sometimes >30,000 ng/ml) are characteristic. 8
• Sore throat (68-92% of patients), lymphadenopathy, and hepatosplenomegaly may accompany joint symptoms. 8

Seronegative Rheumatoid Arthritis

• Presents similarly to seropositive RA with PIP, MCP, and wrist involvement but lacks rheumatoid factor and anti-CCP antibodies. 5
• Radiographic findings show less aggressive disease with fewer erosions, subluxations, and joint space narrowing compared to seropositive RA. 5
• The ulnar styloid may be more commonly affected than in PsA. 5

Less Common Considerations

Systemic Lupus Erythematosus

• SLE typically causes non-erosive arthritis without joint distortion on radiographs. 6
• Joint involvement is usually symmetric but does not produce the destructive changes seen in RA or PsA. 6

Hemochromatosis

• Primarily targets MCPs and wrists, similar to gout distribution. 1
• Consider in patients with additional systemic features of iron overload.

Immune Checkpoint Inhibitor-Induced Arthritis

• Relevant only in patients receiving cancer immunotherapy (anti-PD-1/PD-L1 or anti-CTLA-4 agents). 8
• Can present with symmetric polyarthritis resembling RA, affecting small and/or large joints. 8
• Markedly elevated inflammatory markers help differentiate from osteoarthritis. 8

Critical Distinguishing Features

Osteoarthritis is UNLIKELY

• Primary hand OA characteristically targets DIP joints, PIP joints, and thumb base (CMC joint), NOT the MCP joints. 1
• MCP involvement should prompt consideration of inflammatory arthritis rather than OA. 1
• Bony enlargement (Heberden's/Bouchard's nodes) rather than soft tissue swelling is characteristic of OA. 1
• Morning stiffness in OA lasts less than 30 minutes, not the prolonged stiffness of inflammatory arthritis. 1

Diagnostic Approach

Clinical Assessment

• Document pattern of joint involvement (symmetric vs asymmetric), duration of morning stiffness, and presence of soft tissue swelling vs bony enlargement. 1, 2
• Examine for extra-articular manifestations: skin rash, psoriatic plaques, fever pattern, lymphadenopathy, or sicca symptoms. 8, 6
• Assess for systemic symptoms including fever, weight loss, malaise, and fatigue. 8, 2

Laboratory Evaluation

• Obtain rheumatoid factor, anti-CCP antibodies, ESR, CRP, and complete blood count. 2, 5
• If AOSD suspected, check ferritin levels (very high levels with low glycosylated fraction <20% are highly suggestive). 8
• Consider ANA, anti-SSA, anti-SSB if features suggest lupus or Sjögren's syndrome. 8

Imaging

• Plain radiographs of bilateral hands (PA and Nørgaard views) are the standard initial imaging. 3, 5
• Look for juxta-articular osteoporosis, marginal erosions, joint space narrowing (RA) vs proliferative changes (PsA). 3, 5
• MRI of bilateral hands including PIPJs demonstrates asymmetric features in early RA and detects synovitis/tenosynovitis with high sensitivity. 9
• Ultrasound can detect synovial thickening and effusions even in early disease. 2, 3

Common Pitfalls

• Do not dismiss inflammatory arthritis based on negative rheumatoid factor—seronegative RA exists and presents similarly to seropositive disease. 5
• Bilateral MCP involvement essentially excludes primary osteoarthritis as the diagnosis. 1
• Asymmetric presentation does not rule out RA, as MRI studies show 21-20% of early RA patients have unilateral severe synovitis. 9
• AOSD can be missed if the classic fever pattern and rash are not specifically queried, as arthritis may be the presenting feature. 8