What is the differential diagnosis for a teenager with intermittent, week‑long episodes of swelling in multiple small joints?

Differential Diagnosis for Teenager with Intermittent Small Joint Swelling

The most likely diagnosis is juvenile idiopathic arthritis (JIA), specifically polyarticular JIA, which requires arthritis affecting five or more joints for at least 6 weeks in patients under 16 years of age. 1

Primary Differential Diagnoses to Consider

Juvenile Idiopathic Arthritis (JIA) - Most Likely

• Polyarticular JIA is defined by arthritis in five or more joints within the first 6 months of disease onset, lasting at least 6 weeks in patients under 16 years. 1
• The intermittent, week-long episodes affecting multiple small joints strongly suggest inflammatory arthritis rather than mechanical causes. 1, 2
• Morning stiffness lasting >30 minutes is a validated predictor of persistent inflammatory arthritis and supports JIA diagnosis. 3
• Small joint involvement (metacarpophalangeal, proximal interphalangeal joints, wrists) is characteristic of polyarticular JIA. 1
• The episodic nature with symptom-free intervals can occur in early JIA before persistent disease develops. 2

Reactive Arthritis/Post-Infectious Arthritis

• Consider if there is a history of preceding infection (gastrointestinal, genitourinary, or upper respiratory). 4
• Typically presents as oligoarthritis (fewer than 5 joints) but can involve multiple joints. 1
• HLA-B27 testing should be considered if symptoms suggest reactive arthritis or seronegative spondyloarthropathy. 4
• Usually self-limiting over weeks to months, which could explain the intermittent pattern. 1

Inflammatory Bowel Disease (IBD)-Associated Arthropathy

• Type I peripheral arthropathy affects large joints acutely and is pauciarticular (less than 5 joints), occurring during IBD flares. 1
• Type II is polyarticular, affecting small joints of the hands independently of IBD activity, seen in 2.5% of UC patients. 1
• Ask specifically about gastrointestinal symptoms (diarrhea, abdominal pain, blood in stool, weight loss). 1

Rheumatoid Factor-Positive Polyarticular JIA

• This subtype resembles adult rheumatoid arthritis and typically affects adolescent females. 1
• Characterized by symmetric polyarthritis of small joints with potential for aggressive, erosive disease. 1
• RF and anti-CCP antibodies are positive and predict severe disease and poor prognosis. 4

Systemic Lupus Erythematosus (SLE)

• Can present with polyarthritis in adolescents, particularly females. 1
• Look for systemic symptoms: fever, rash (malar or discoid), photosensitivity, oral ulcers, serositis. 1
• ANA testing is essential; positive ANA with specific antibodies (anti-dsDNA, anti-Smith) supports SLE. 4

Psoriatic Arthritis

• Can occur in teenagers, sometimes before skin manifestations appear. 1
• Asymmetric oligoarthritis, dactylitis (sausage digits), or nail dystrophy are characteristic. 1, 4
• Family history of psoriasis in first-degree relatives supports diagnosis. 1

Essential Initial Workup

Laboratory Tests - Order Immediately

• Complete blood count (CBC), urinalysis, transaminases, ANA, ESR or CRP, rheumatoid factor (RF), and anti-CCP antibodies constitute the essential initial panel. 4
• CBC, urinalysis, and transaminases exclude non-rheumatologic diseases and assess systemic involvement. 4
• ESR or CRP quantifies inflammation and predicts persistent/erosive disease. 4, 3
• RF should be interpreted as negative (≤ULN), low positive (>ULN but ≤3× ULN), or high positive (>3× ULN). 1, 4
• Anti-CCP antibodies are critical as both RF and anti-CCP positivity predict severe disease. 4

Additional Testing Based on Clinical Suspicion

• HLA-B27 if symptoms suggest reactive arthritis, enthesitis-related arthritis, or axial involvement. 4
• Viral serologies (parvovirus B19, EBV, CMV) if acute onset with systemic symptoms, as infections can cause false positive RF. 4
• Joint aspiration with synovial fluid analysis (cell count, Gram stain, culture, crystal analysis) if septic arthritis is suspected. 4

Imaging Studies

• Plain radiographs of affected joints (hands, wrists, feet) are the initial imaging method of choice. 4, 3
• Radiographs establish baseline for erosions and exclude alternative diagnoses. 3
• Ultrasound with power Doppler or MRI should be considered when clinical examination is equivocal or to detect early synovitis not visible on plain films. 4, 3
• MRI can identify bone marrow edema (osteitis), the best predictor of future disease progression in early inflammatory arthritis. 5

Critical Clinical Features to Document

History Elements

• Duration of each episode and symptom-free intervals between episodes. 1, 2
• Morning stiffness duration (>30 minutes strongly suggests inflammatory arthritis). 3, 5
• Specific joints involved and whether involvement is symmetric or asymmetric. 1, 4
• Preceding infections, trauma, or systemic symptoms (fever, rash, weight loss). 1
• Family history of autoimmune diseases, psoriasis, or inflammatory bowel disease. 1

Physical Examination Findings

• Palpable synovitis (warm, swollen joints with boggy consistency) indicates true inflammation. 4
• Positive "squeeze test" (pain with compression of MCP or MTP joints) indicates inflammatory arthritis. 4
• Assess all peripheral joints for tenderness, swelling, warmth, and range of motion. 4
• Examine for extra-articular manifestations: rash, nail changes, dactylitis, enthesitis, uveitis. 1

Urgent Rheumatology Referral Criteria

Refer to pediatric rheumatology within 6 weeks of symptom onset if arthritis involves more than one joint with swelling not caused by trauma or bony enlargement. 4, 3

• Earlier treatment initiation improves outcomes and prevents joint damage in JIA. 3
• There is a critical "window of opportunity" for DMARD therapy to arrest progressive disease. 3
• Patients at risk of persistent or erosive arthritis should start DMARDs as early as possible, even if not yet fulfilling classification criteria. 3

Common Pitfalls to Avoid

• Do not dismiss intermittent symptoms as "growing pains" - JIA can present with episodic symptoms before becoming persistent. 2
• Infections (mononucleosis, CMV, parvovirus) can cause false positive RF; interpret RF with anti-CCP and clinical findings. 4
• Normal radiographs do not exclude JIA - early inflammatory arthritis may show no radiographic changes. 5
• Do not delay referral waiting for positive serology - seronegative JIA is common and diagnosis is primarily clinical. 1, 2
• Avoid starting DMARDs before rheumatology consultation, as these require specific monitoring protocols. 4

Initial Symptomatic Management Pending Rheumatology Evaluation

• Consider NSAIDs (such as naproxen) after evaluating gastrointestinal, renal, and cardiovascular status. 4
• NSAIDs provide symptomatic relief but do not alter disease progression. 1
• Document response to NSAIDs, as good response supports inflammatory arthritis diagnosis. 1
• Physical and occupational therapy can help maintain joint function and range of motion. 1