Approach to a New Case of Polyarthritis: Educational Presentation
Slide 1: Initial Clinical Assessment - The Foundation
Begin by confirming true articular involvement through joint examination to identify definite clinical synovitis that cannot be explained by another disease. 1
Key examination maneuvers:
- Perform squeeze test across metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints bilaterally to detect clinical synovitis 2, 1
- Palpate for warmth, swelling, and tenderness at MCPs, proximal interphalangeal (PIP) joints, wrists, and MTPs 2, 1
- Document morning stiffness duration - stiffness lasting ≥1 hour before maximal improvement strongly suggests inflammatory arthritis 3, 1
- Assess for symmetric versus asymmetric distribution 3
MCQ #1 (Difficult): A 42-year-old woman presents with 8 weeks of bilateral hand pain. On examination, you note swelling of the 2nd and 3rd MCPs bilaterally and the right wrist. Squeeze test is positive. Morning stiffness lasts 90 minutes. Which finding would MOST strongly argue against rheumatoid arthritis?
- A) Normal ESR and CRP
- B) Negative rheumatoid factor
- C) Prominent distal interphalangeal joint involvement
- D) Age under 50 years
Answer: C - Absence of DIP involvement is typical for RA, while prominent DIP involvement suggests osteoarthritis or psoriatic arthritis 2, 3
Slide 2: Inflammatory vs. Non-Inflammatory - The Critical Distinction
Inflammatory arthritis features:
- Warm, swollen joints with palpable synovitis 4, 5
- Prolonged morning stiffness (>1 hour) 3, 4
- Pain improves with activity 4
- Systemic symptoms may be present (fever, weight loss, fatigue) 5
Non-inflammatory arthritis (osteoarthritis) features:
- Variable onset and severity without inflammatory signs 4
- Morning stiffness <1 hour 4
- Pain aggravated by activity, improves with rest 4
- Bony enlargement, crepitus on palpation 5
Critical pitfall: Do not dismiss inflammatory arthritis based on normal ESR/CRP - acute phase reactants can be normal even in active disease 3
Slide 3: Pattern Recognition - Number and Distribution of Joints
Joint count classification for diagnosis:
Distribution patterns that narrow diagnosis:
- Rheumatoid arthritis: Symmetric polyarthritis targeting MCPs, PIPs, wrists, and MTPs; spares DIPs 3, 1
- Psoriatic arthritis: May target DIPs or affect single ray (one finger entirely) 2
- Gout: May superimpose on pre-existing osteoarthritis 2
- Hemochromatosis: Mainly targets MCPs and wrists 2
MCQ #2 (Difficult): A 55-year-old man presents with polyarthritis involving bilateral 2nd and 3rd MCPs, wrists, and 2nd MTPs. RF and anti-CCP are negative. ESR is 45 mm/hr. Which additional finding would MOST strongly suggest an alternative diagnosis to seronegative RA?
- A) Elevated ferritin with transferrin saturation >45%
- B) Presence of subcutaneous nodules
- C) Radiographic periarticular osteopenia
- D) Symptom duration of 12 weeks
Answer: A - Hemochromatosis targets MCPs and wrists, and elevated ferritin with high transferrin saturation suggests iron overload arthropathy 2
Slide 4: Laboratory Workup - Strategic Testing
First-line serologic tests:
- Anti-citrullinated protein antibody (ACPA): 90% specificity, 60% sensitivity 1
- Rheumatoid factor (RF): 70% specificity, 60-80% sensitivity 1
- C-reactive protein (CRP) preferred over ESR - correlates more closely with disease activity and is not age-dependent 1
Essential baseline tests:
- Complete blood count with differential 1
- Comprehensive metabolic panel (renal and hepatic function) 1
- Urinalysis 2
Critical pitfall: Do not delay treatment while waiting for positive serology - seronegative RA occurs in 20-30% of cases and has similar prognosis 3
When to consider additional testing:
- Marked inflammatory symptoms at atypical sites: screen for additional inflammatory arthritides 2
- Consider alternative diagnoses in seronegative disease: psoriatic arthritis, spondyloarthritis, crystal arthropathies, polymyalgia rheumatica, Still's disease 3
Slide 5: Imaging Studies - Establishing Baseline and Detecting Erosions
Baseline radiographic assessment:
- Obtain bilateral hand, wrist, and foot X-rays to detect erosions and establish baseline for monitoring structural damage 1, 7
- Plain radiographs remain the gold standard for morphological assessment 2
- Classical features: joint space narrowing, osteophytes, subchondral sclerosis, subchondral cysts 2
Advanced imaging indications:
- Ultrasound with power Doppler or MRI with IV contrast may detect subclinical synovitis and predict disease progression 1
- These modalities are more sensitive than clinical examination for detecting synovitis 2
MCQ #3 (Difficult): A 38-year-old woman with 10 weeks of symmetric polyarthritis has positive anti-CCP (120 U/mL, normal <20) and RF (85 IU/mL, normal <14). Hand and foot radiographs show only soft tissue swelling without erosions. What is the MOST appropriate next step?
- A) Repeat radiographs in 6 months before starting treatment
- B) Order MRI to confirm diagnosis before treatment
- C) Start methotrexate 15-25 mg weekly immediately with bridging prednisone
- D) Refer to rheumatology and defer treatment decisions
Answer: C - Immediate treatment with methotrexate and bridging glucocorticoids is indicated upon diagnosis; do not delay for imaging confirmation 1, 7
Slide 6: The 2010 ACR/EULAR Classification Criteria for RA
Score-based algorithm requiring ≥6/10 points for definite RA classification: 7
Joint involvement (0-5 points):
- 1 large joint: 0 points 7
- 2-10 large joints: 1 point 7
- 1-3 small joints: 2 points 7
- 4-10 small joints: 3 points 7
10 joints (at least 1 small): 5 points 7
Serology (0-3 points):
- Negative RF and negative ACPA: 0 points 7
- Low-positive RF or low-positive ACPA: 2 points 7
- High-positive RF or high-positive ACPA: 3 points 7
Acute phase reactants (0-1 point):
Duration of symptoms (0-1 point):
Special considerations:
- Patients with erosive disease typical of RA with compatible history should be classified as having RA regardless of score 7
- Patients with long-standing disease who previously fulfilled criteria should be classified as having RA 7
Slide 7: High-Risk Disease Features - Aggressive Therapy Required
High-risk indicators requiring intensive treatment from onset:
- High-positive RF or high-positive ACPA 1
- Presence of erosions on baseline radiographs 1
- High disease activity at presentation 7
Implications of high-risk disease:
- Increased risk of extra-articular manifestations 1
- Shortened life expectancy 1
- Accelerated cardiovascular disease 7
- Potential for pulmonary, cardiac, and ophthalmologic complications 1
MCQ #4 (Difficult): A 50-year-old woman is diagnosed with RA. Anti-CCP is 180 U/mL (normal <20), RF is 120 IU/mL (normal <14). Hand radiographs show early erosions at the 2nd and 3rd MCPs bilaterally. Which statement about her prognosis is MOST accurate?
- A) High-positive serology without erosions indicates better prognosis
- B) She has increased risk of extra-articular manifestations and requires aggressive therapy
- C) Serology levels do not correlate with disease severity
- D) Erosions at presentation indicate treatment failure
Answer: B - High-positive RF/ACPA with erosions indicates high-risk disease requiring aggressive therapy from onset 1
Slide 8: Treatment Initiation - Immediate Action Required
First-line therapy upon diagnosis:
- Start methotrexate 15-25 mg weekly immediately as anchor DMARD 1, 7, 8
- Add prednisone 10-20 mg daily as bridging therapy for rapid symptom control 1
- Treatment should begin immediately after diagnosis to prevent disease progression 7
Alternative first-line agents if methotrexate contraindicated:
Glucocorticoid management:
- Short-term glucocorticoids should be considered when initiating DMARDs 7
- Taper as rapidly as clinically feasible 7
- Optimal duration not well established; guided by patient's clinical condition 2
Critical pitfall: Do not delay treatment waiting for rheumatology consultation or additional testing - early treatment prevents irreversible joint damage 7
Slide 9: Treatment Targets and Monitoring Strategy
Primary treatment target:
- Sustained remission defined as Simplified Disease Activity Index (SDAI) ≤3.3 or Clinical Disease Activity Index (CDAI) ≤2.8 1, 7
- Low disease activity (SDAI ≤11) is acceptable alternative in rare occasions 7
Monitoring frequency:
- Active disease: assess every 1-3 months using composite measures (DAS28, SDAI, CDAI) 7
- If no improvement by 3 months or target not reached by 6 months: adjust therapy 7
Treatment escalation algorithm:
- If inadequate response to methotrexate monotherapy: add or switch to biologic DMARD 7
- For severe disease refractory to non-cyclophosphamide immunosuppressants: switch to cyclophosphamide 2
Critical distinction: ACR/EULAR remission definition is preferred over DAS28<2.6, which is not sufficiently stringent for true clinical remission 7
Slide 10: Differential Diagnosis - Key Distinguishing Features
Erosive hand osteoarthritis:
- Targets DIPs and PIPs with Heberden and Bouchard nodes 2
- Subchondral erosion may progress to marked attrition and ankylosis 2
- Abrupt onset with marked pain, inflammatory symptoms, mildly elevated CRP 2
Psoriatic arthritis:
Adult-onset Still's disease:
- Quotidian fever pattern, evanescent salmon-pink rash 2
- Marked elevation of ferritin 2
- Arthritis may be chronic and destructive 2
Peripheral arthropathy in inflammatory bowel disease:
- Type I: pauciarticular, affects large joints, correlates with UC activity 2
- Type II: polyarticular, affects small joints, independent of UC activity 2
MCQ #5 (Difficult): A 45-year-old man presents with 12 weeks of polyarthritis involving bilateral MCPs, PIPs, and wrists. He also has daily fever spikes to 39.5°C and a transient salmon-pink rash on his trunk. Ferritin is 8,500 ng/mL. RF and anti-CCP are negative. What is the MOST likely diagnosis?
- A) Seronegative rheumatoid arthritis
- B) Adult-onset Still's disease
- C) Systemic lupus erythematosus
- D) Reactive arthritis
Answer: B - Quotidian fever, evanescent rash, markedly elevated ferritin, and seronegative polyarthritis are characteristic of Adult-onset Still's disease 2
Slide 11: Special Populations - Polyarticular Juvenile Rheumatoid Arthritis
Diagnostic considerations:
- Diagnosis requires age of onset <16 years (vs. AOSD requiring onset >18 years) 2
- Shares typical features with adult disease: fever patterns, transient rash, arthritis, neutrophilia 2
Treatment approach:
- Recommended starting dose: 10 mg/m² given once weekly 8
- Doses up to 20-30 mg/m²/week may have better absorption with IM or subcutaneous administration 8
- Limited experience shows increased toxicity risk at doses >20 mg/week in adults 8
Prognostic differences from adult disease:
- Children severely affected are at significant risk of lifelong disability 2
- Up to 50% develop chronic, destructive polyarthritis 5-10 years after diagnosis 2
- May be less responsive to treatment, even with anti-TNF therapy 2
Slide 12: When Polyarthritis is NOT Rheumatoid Arthritis
Acute, self-limited polyarthritis causes:
- Viral infections (rubella, CMV, EBV, parvovirus B19) - symptoms should resolve within 3 months 2, 5
- Crystal-induced arthritis (gout, pseudogout) 5
- Serum sickness reactions 5
Chronic polyarthritis mimics requiring different management:
- Systemic lupus erythematosus 2
- Polymyalgia rheumatica 3
- Spondyloarthropathies 2
- Vasculitides 2
- Hemophagocytic syndrome 2
Red flags for alternative diagnosis:
- Atypical joint distribution (isolated DIP involvement, asymmetric large joint involvement) 2
- Prominent systemic features out of proportion to arthritis 2
- Lack of response to appropriate DMARD therapy 7
Slide 13: Practical Diagnostic Algorithm
Step 1: Confirm true articular involvement
Step 2: Classify as inflammatory vs. non-inflammatory
- Assess for warmth, swelling, prolonged morning stiffness 4, 5
- Non-inflammatory: likely osteoarthritis 4
Step 3: Document pattern of joint involvement
- Count affected joints (monoarthritis, oligoarthritis, polyarthritis) 2
- Note symmetry and specific joints involved 3, 1
Step 4: Obtain strategic laboratory testing
Step 5: Obtain baseline imaging
Step 6: Apply 2010 ACR/EULAR criteria if RA suspected
- Calculate score based on joints, serology, acute phase reactants, duration 7
- Score ≥6/10 confirms RA classification 7
Step 7: Initiate treatment immediately if RA diagnosed
- Methotrexate 15-25 mg weekly + prednisone 10-20 mg daily 1
- Do not delay for additional testing or consultation 7
Slide 14: Common Pitfalls and How to Avoid Them
Pitfall #1: Delaying treatment while waiting for positive serology
- Solution: Seronegative RA occurs in 20-30% of cases; treat based on clinical presentation 3
Pitfall #2: Dismissing inflammatory arthritis due to normal ESR/CRP
- Solution: Acute phase reactants can be normal in active disease; rely on clinical findings 3
Pitfall #3: Waiting for erosions on radiographs before starting treatment
- Solution: Erosions indicate established disease; treat immediately to prevent irreversible damage 1, 7
Pitfall #4: Using DAS28<2.6 as remission target
- Solution: Use ACR/EULAR remission criteria (SDAI ≤3.3 or CDAI ≤2.8) for true remission 7
Pitfall #5: Inadequate monitoring frequency
- Solution: Assess disease activity every 1-3 months in active disease; adjust therapy if no improvement by 3 months 7
Pitfall #6: Failing to consider alternative diagnoses in atypical presentations
- Solution: Prominent DIP involvement, asymmetric distribution, or marked systemic features should prompt consideration of psoriatic arthritis, Still's disease, or other conditions 2, 3
Slide 15: Take-Home Messages
🔑 Confirm true synovitis through joint examination with squeeze test before pursuing extensive workup 2, 1
🔑 Inflammatory arthritis is characterized by warm, swollen joints, prolonged morning stiffness (>1 hour), and improvement with activity 4, 5
🔑 Rheumatoid arthritis typically presents with symmetric polyarthritis targeting MCPs, PIPs, wrists, and MTPs while sparing DIPs 3, 1
🔑 Do not delay treatment waiting for positive serology - seronegative RA occurs in 20-30% of cases and has similar prognosis 3
🔑 Start methotrexate 15-25 mg weekly with bridging prednisone immediately upon RA diagnosis to prevent irreversible joint damage 1, 7
🔑 Target sustained remission (SDAI ≤3.3 or CDAI ≤2.8) with frequent monitoring every 1-3 months and therapy adjustment if target not reached by 6 months 7
🔑 High-positive RF/ACPA indicates high-risk disease requiring aggressive therapy from onset due to increased risk of extra-articular manifestations 1
🔑 Consider alternative diagnoses (psoriatic arthritis, Still's disease, crystal arthropathies) when presentation is atypical or response to therapy is inadequate 2, 3