What is reactive arthritis?

Reactive Arthritis: Definition, Diagnosis, and Management

Reactive arthritis (ReA) is a sterile inflammatory arthritis that develops following an extra-articular infection, typically affecting the urogenital, gastrointestinal, or respiratory tract, characterized by inflammation in joints without the presence of live bacteria in the synovial fluid. 1

Epidemiology and Pathogenesis

• The prevalence of reactive arthritis is estimated at approximately 40/100,000 with an incidence of 5/100,000 in the general population 1
• In the United States, the frequency is estimated at 3.5 to 5 patients per 100,000 2
• ReA represents a classic interplay between host genetic factors and environmental triggers (infectious agents) 3
• There is a strong association with HLA-B27, present in approximately 50% of patients with reactive arthritis 1

Triggering Infections

• Common bacterial triggers include:
  • Gastrointestinal infections: Salmonella, Shigella, Campylobacter, and Yersinia 4
  • Urogenital infections: Chlamydia trachomatis (most common) 1
  • Respiratory infections: Chlamydia pneumoniae 1
• The infection may be asymptomatic in approximately 25% of cases 4
• Pathogen components (antigens or DNA) can be detected in affected joints despite negative cultures, suggesting persistent intra-articular interaction between host and pathogen components 1

Clinical Manifestations

• Arthritis typically develops within 2-4 weeks following the triggering infection 4
• The classic clinical presentation includes:
  1. Asymmetric oligoarticular arthritis (primarily affecting larger joints)
  2. Urethritis
  3. Conjunctivitis 2
• However, most patients do not present with the complete classic triad of symptoms 3
• Additional clinical features may include:
  • Dactylitis (sausage digits)
  • Enthesitis (inflammation at tendon/ligament insertion sites)
  • Axial involvement (less common) 1
  • Mucocutaneous lesions 3

Diagnosis

Diagnosis is primarily clinical, based on:

• Typical clinical presentation of acute oligoarticular arthritis developing within 2-4 weeks after a preceding infection 4
• Evidence of a triggering infection through:
  • Cultures (stool cultures for enteric pathogens)
  • Nucleic acid amplification tests (for Chlamydia trachomatis)
  • Serological tests demonstrating evidence of previous infection 4
• Exclusion of other causes of arthritis 1

Differential Diagnosis

• Septic arthritis (requires joint aspiration to rule out)
• Other spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis)
• Rheumatoid arthritis
• Crystal-induced arthropathies (gout, pseudogout)
• Post-streptococcal reactive arthritis (PSRA) 5

Post-Streptococcal Reactive Arthritis vs. Rheumatic Fever

Important distinctions between PSRA and acute rheumatic fever (ARF) include:

• PSRA occurs approximately 10 days after group A streptococcal pharyngitis, while ARF arthritis occurs 14-21 days after infection 5
• PSRA arthritis is cumulative and persistent, involving large joints, small joints, or axial skeleton, while ARF arthritis is migratory, transient, and usually involves only large joints 5
• PSRA does not respond readily to salicylates, unlike ARF arthritis 5
• PSRA may occasionally progress to valvular heart disease, requiring careful cardiac monitoring 5

Treatment

1. Non-pharmacological approaches:

   • Physical therapy and exercise to maintain joint function 1

2. Pharmacological management:

   • First-line: Nonsteroidal anti-inflammatory drugs (NSAIDs) for symptomatic relief 1
   • Second-line: Glucocorticoids (local injections or systemic) for persistent symptoms 1
   • For persistent arthritis: Disease-modifying antirheumatic drugs (DMARDs)
     • Sulfasalazine
     • Methotrexate 1
   • For refractory cases: Biologics or Janus kinase inhibitors may be considered in individual cases 1

3. Antibiotics:

   • Treatment of Chlamydia infection is important when identified 4
   • However, antibiotic treatment of established reactive arthritis generally does not shorten disease duration 1

Prognosis and Outcomes

• Most cases are self-limiting, resolving within 3-12 months 1
• Approximately 25-50% of patients may experience recurrent episodes of acute arthritis, particularly with new triggering infections 4
• About 25% of patients progress to chronic spondyloarthritis of varying activity 4
• Recent data suggests that modern cases of ReA may more frequently progress to spondyloarthritis compared to historical cohorts 6
• Without proper management, ReA can progress to chronic destructive arthritis 2

Key Considerations for Clinical Practice

• Prompt recognition and early intervention are essential for better outcomes and fewer complications 2
• Monitor for cardiac involvement, particularly in post-streptococcal reactive arthritis 5
• Consider secondary prophylaxis for up to 1 year in PSRA, though its effectiveness is not well established 5
• If valvular disease develops in PSRA, reclassify as ARF and continue secondary prophylaxis 5