How do you differentiate and treat reactive arthritis vs rheumatoid arthritis?

Differentiating Reactive Arthritis from Rheumatoid Arthritis

Reactive arthritis presents as acute asymmetric oligoarthritis of large joints following a gastrointestinal or urogenital infection by 1-6 weeks, while rheumatoid arthritis manifests as chronic symmetric polyarthritis predominantly affecting small joints of the hands and feet with morning stiffness lasting over 1 hour. 1, 2

Key Clinical Distinctions

Joint Involvement Pattern

Reactive Arthritis:

• Asymmetric mono- or oligoarthritis affecting primarily large joints (knees, ankles, wrists) 3, 1
• Develops acutely within 2-4 weeks following remote infection 4
• Lower extremity joints most commonly affected 1

Rheumatoid Arthritis:

• Symmetric polyarthritis involving small joints: metacarpophalangeal (MCP), proximal interphalangeal (PIP), wrists, and metatarsophalangeal (MTP) joints 5, 2
• Distal interphalangeal joints, first carpometacarpal joints, and first MTP joints are typically spared 5
• Carpal and pericapitate abnormalities develop progressively, with ankylosis occurring after 1.5-3 years 2
• Large joints (shoulders, elbows, hips, knees, ankles) may also be affected but in symmetric distribution 5

Temporal Presentation

Reactive Arthritis:

• Acute onset following documented or suspected gastrointestinal (Salmonella, Shigella, Yersinia, Campylobacter) or urogenital (Chlamydia trachomatis) infection 1, 4
• Infection precedes arthritis by minimum 1 week to maximum 3-6 weeks 1
• Usually self-remittent within 6 months 3

Rheumatoid Arthritis:

• Insidious onset with gradual progression 2
• Morning stiffness lasting ≥1 hour is characteristic 2
• Chronic progressive course without treatment 2

Serological Markers

Reactive Arthritis:

• Seronegative: negative rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) 1
• HLA-B27 positive in many cases but should not be used as diagnostic tool for acute reactive arthritis 4
• Elevated acute phase reactants (ESR, CRP) during active disease 1
• Serum antibodies to triggering organism may be detected 1

Rheumatoid Arthritis:

• RF positive in approximately 70-80% of cases (specificity 70%, sensitivity 60-80%) 5, 6
• ACPA positive in 60% of cases (specificity 90%, sensitivity 60%) 2, 5
• Seronegative RA accounts for 20-30% of cases 5
• Elevated ESR and CRP, though can be normal even in active disease 5

Extra-Articular Manifestations

Reactive Arthritis:

• Classic triad: arthritis, urethritis, and conjunctivitis (Reiter's syndrome) 1
• Ocular involvement: conjunctivitis, anterior uveitis 1
• Mucocutaneous lesions: keratoderma blennorrhagicum, circinate balanitis 1
• Enthesitis (Achilles tendon, plantar fascia) 1

Rheumatoid Arthritis:

• Subcutaneous rheumatoid nodules 2
• Interstitial lung disease 2
• Vasculitis 2
• Inflammatory eye disease (scleritis, episcleritis) 2
• Pericarditis 2

Diagnostic Approach

For Suspected Reactive Arthritis:

1. Document preceding infection within 1-6 weeks: obtain history of diarrheal illness or urogenital symptoms 1, 4
2. Confirm seronegative status: RF and ACPA should be negative 1
3. Assess joint pattern: look for asymmetric oligoarthritis of large joints 3, 1
4. Exclude septic arthritis: synovial fluid cultures should be negative (unlike septic arthritis which presents with fever, systemic infection signs, and positive cultures) 1
5. Check for extra-articular features: urethritis, conjunctivitis, skin lesions 1

For Suspected Rheumatoid Arthritis:

1. Apply 2010 ACR/EULAR Classification Criteria requiring ≥6/10 points: 5, 7

   • Joint involvement (0-5 points): 1-3 small joints = 2 points, 4-10 small joints = 3 points, >10 joints = 5 points 5
   • Serology (0-3 points): low positive RF or ACPA = 2 points, high positive RF or ACPA = 3 points 5
   • Acute phase reactants (0-1 point): abnormal CRP or ESR = 1 point 5
   • Duration ≥6 weeks = 1 point 5

2. Perform squeeze test of MCPs and MTPs to assess for clinical synovitis 5

3. Obtain baseline imaging: bilateral hand, wrist, and foot X-rays to detect erosions and monitor progression 5

4. Consider ultrasound or MRI if clinical examination is equivocal, as these detect subclinical synovitis and predict disease progression 5, 2

Treatment Strategies

Reactive Arthritis Management:

First-line therapy:

• NSAIDs are the initial treatment regardless of prognostic factors 8

Second-line therapy:

• Glucocorticoids (oral or intra-articular) for inadequate NSAID response 8

Third-line therapy:

• DMARDs (sulfasalazine) for chronic cases lasting >6 months 8, 3
• Prolonged antibiotic therapy (tetracyclines) may benefit Chlamydia-induced reactive arthritis, both acute and chronic cases 4, 3
• No confirmed benefit of antibiotics for other forms of reactive arthritis 4

Refractory cases with poor prognostic factors:

• TNF inhibitors (adalimumab) for non-responders with multiple poor prognostic factors (HLA-B27 positivity, recurrent infections) 8, 3

Rheumatoid Arthritis Management:

Immediate initiation upon diagnosis:

• Methotrexate 15-30 mg/week is the anchor drug and first-line therapy 5, 7, 6
• Short-term low-dose glucocorticoids (10-20 mg prednisone daily) as bridge therapy, tapered rapidly 5, 7

Treatment target:

• Sustained remission (SDAI ≤3.3, CDAI ≤2.8, or DAS28 <2.6) or low disease activity (SDAI ≤11) 5, 7

Monitoring and escalation:

• Assess disease activity 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
• Add biologic agents (TNF inhibitors) or triple DMARD therapy for inadequate methotrexate response 5

Pre-treatment screening:

• Test for hepatitis B, hepatitis C, and tuberculosis before starting biologic agents 5, 6

Critical Pitfalls to Avoid

For Reactive Arthritis:

• Do not confuse with septic arthritis: reactive arthritis has negative synovial fluid cultures and lacks systemic infection signs 1
• Do not use HLA-B27 as a diagnostic tool for acute reactive arthritis 4
• In 25% of cases, the triggering organism remains unidentified—do not exclude diagnosis based on lack of documented infection 3
• Consider subclinical infections and inflammatory bowel disease as potential triggers 3

For Rheumatoid Arthritis:

• Do not delay treatment waiting for positive serology—seronegative RA is common (20-30%) and has similar prognosis 5
• Do not dismiss diagnosis based on normal ESR/CRP—acute phase reactants can be normal even in active disease 5
• Do not misdiagnose as reactive arthritis when considering difficult-to-treat RA—reactive arthritis can mimic ongoing RA disease activity 2
• Consider alternative diagnoses in seronegative disease: psoriatic arthritis, spondyloarthritis, crystal arthropathies, polymyalgia rheumatica, Still's disease 2