Reactive Arthritis

Overview

Reactive arthritis is a seronegative spondyloarthropathy that occurs after a genitourinary or gastrointestinal infection, typically presenting as an asymmetric oligoarthritis, often with associated conjunctivitis and urethritis (formerly Reiter’s syndrome). It most commonly affects young adults aged 20–40 and shows a strong association with HLA-B27. Incidence is estimated at 30–40 per 100,000, with higher rates in HLA-B27–positive individuals following infection.

Anatomy and Physiology

Aetiology and Risk Factors

• Infectious triggers (precede arthritis by ~1–4 weeks):
  • GU: Chlamydia trachomatis
  • GI: Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile
• HLA-B27 positivity (increases risk and severity)
• Young age (20–40 years)
• Male sex (especially with genitourinary infections)
• Immunogenetic susceptibility

Pathophysiology

• Initial GI or GU infection triggers immune activation
• Bacterial antigens persist in synovium or gut mucosa (molecular mimicry)
• Dysregulated immune response involving CD8+ T cells, cytokines (IL-17, TNF-α)
• Results in sterile synovitis, enthesitis, and extra-articular inflammation

Clinical Manifestations

• Arthritis
  • Asymmetric oligoarthritis (knees, ankles, MTPs)
  • Dactylitis (“sausage digit”)
  • Heel pain (enthesitis)
  • Lower back pain (sacroilitis)
• Ocular Conjunctivitis (mild), anterior uveitis (painful)
• Urogenital: Urethritis, cervicitis, prostatitis
• Mucocutaneous:
  • Oral ulcers
  • Circinate balanitis
  • Keratoderma blennorrhagicum (psoriasiform rash)
• Systemic symptoms: Fever, malaise, weight loss

Diagnosis

No dedicated ReA classification criteria. Often diagnosed clinically based on:
– Acute oligoarthritis
– Preceding GI/GU infection
– Absence of live pathogen in joint fluid

Investigations

• Stool or urine PCR/culture: to identify trigger organism
• HLA-B27 testing: positive in ~50–80% of cases
• CRP/ESR: often elevated
• Joint aspiration: to rule out septic arthritis (crystals, WBCs, culture)
• X-ray/MRI: May show periostitis, enthesitis, sacroiliitis in chronic cases

Differential Diagnoses:

Condition	Differentiating Features
Septic arthritis	Fever, single joint, positive culture
Gonococcal arthritis	Young sexually active adults, migratory arthritis, tenosynovitis, skin pustules. Positive culture.
Viral Arthralgia	Joint pain without swelling following viral illness
Gout	Crystals in joint aspirate, often 1st MTP
Psoriatic arthritis	Skin/nail psoriasis, symmetric or axial involvement
IBD-related arthritis	History of Crohn’s/UC, gut symptoms

Treatment

Acute management

• NSAIDs: first-line for arthritis and enthesitis
• Intra-articular corticosteroids: for persistent monoarthritis
• Short course oral corticosteroids: if polyarthritis or systemic symptoms
• Antibiotics: only if infection is still active (e.g. Chlamydia)

Chronic/refractory disease

• DMARDs: sulfasalazine or methotrexate for persistent arthritis
• Anti-TNF agents: for chronic or axial disease unresponsive to DMARDs

Supportive: Physiotherapy, sexual health counselling, patient education

Complications and Prognosis

• Most cases resolve within 3–6 months
• ~30% may have chronic arthritis or relapsing flares
• Chronic ReA more likely with HLA-B27, severe initial disease, or poor treatment response
• Extra-articular complications (e.g. uveitis, enthesitis, sacroiliitis) may persist
• Rare: aortic valve involvement, amyloidosis

Poor Prognostic Factors

• HLA-B27 positivity
• Chronic sacroiliitis
• High inflammatory markers
• Recurrent infection

References

1. Hannu T. Reactive arthritis. Best Pract Res Clin Rheumatol. 2011;25(3):347–357.
2. Colmegna I, Cuchacovich R, Espinoza LR. HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations. Clin Microbiol Rev. 2004;17(2):348–369.
3. Braun J, Kingsley G, van der Heijde D, Sieper J. On the difficulties of establishing a consensus definition of reactive arthritis. J Rheumatol. 2000;27(10):2185–2187.
4. Carter JD, Hudson AP. Reactive arthritis: clinical aspects and medical management. Rheum Dis Clin North Am. 2009;35(1):21–44.