Musculoskeletal · PANCE / PANRE

Reactive Arthritis

Sterile inflammatory arthritis triggered by a preceding gastrointestinal or genitourinary infection.

Also known as: reactive arthritis, ReA, Reiter syndrome (historical), post-infectious arthritis

Overview

A sterile inflammatory arthritis arising 1-4 weeks after an antecedent gastrointestinal or genitourinary infection. Part of the seronegative spondyloarthritis family, sharing HLA-B27 association, asymmetric oligoarthritis, enthesitis, and possible extra-articular features.

Epidemiology

Annual incidence approximately 30-40 per 100,000. Peak ages 20-40. Male predominance for genitourinary-triggered disease; gastrointestinal triggers affect both sexes equally. HLA-B27 positive in 30-50 percent and predicts more severe and chronic disease.

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Risk factors

  • Recent enteric infection — Salmonella, Shigella, Yersinia, Campylobacter, Clostridioides difficile
  • Recent genitourinary infection — Chlamydia trachomatis (most common GU trigger), Mycoplasma genitalium, Ureaplasma
  • HLA-B27 positivity
  • Young adult male sex
  • HIV infection (more severe and chronic reactive arthritis)

Pathophysiology

Molecular mimicry, persistent antigen, and aberrant immune response in genetically predisposed individuals. Bacterial antigens (particularly Chlamydia) may persist in joints despite negative cultures. HLA-B27 contributes through its role in antigen presentation and possible misfolding-related ER stress.

Clinical presentation

Symptoms

  • Asymmetric oligoarthritis of large lower extremity joints (knee, ankle) developing 1-4 weeks after triggering infection
  • Heel pain (Achilles enthesitis or plantar fasciitis)
  • Low back pain and stiffness (sacroiliitis)
  • Dactylitis (sausage digit)
  • Conjunctivitis or acute anterior uveitis
  • Urethritis or cervicitis (may be ongoing or recent)
  • Constitutional symptoms — fever, fatigue, weight loss in active disease

Signs / physical exam

  • Warm, swollen oligoarthritis predominantly of lower extremities
  • Sausage-shaped digits from dactylitis
  • Achilles or plantar fascia tenderness from enthesitis
  • Mucocutaneous: keratoderma blennorrhagicum (hyperkeratotic plaques on palms and soles), circinate balanitis, painless oral ulcers, nail changes
  • Conjunctival injection or anterior chamber inflammation
  • Sacroiliac tenderness with positive provocation tests

Classic findings

Young adult man with the classic triad of asymmetric oligoarthritis, conjunctivitis, and urethritis 2-4 weeks after a sexually acquired Chlamydia infection ('can't see, can't pee, can't climb a tree'); however, the full triad is present in only one-third of cases.

Differential diagnosis

  • Gonococcal arthritis — Migratory polyarthralgia, tenosynovitis, pustular skin lesions, positive urethral/cervical/pharyngeal culture, response to ceftriaxone
  • Septic arthritis (non-gonococcal) — Monoarticular, marked synovial fluid WBC >50,000, positive Gram stain or culture
  • Crystal arthritis (gout, pseudogout) — Monoarticular, crystals on synovial fluid analysis, characteristic distribution
  • Psoriatic arthritis — Psoriasis (may precede arthritis), nail pitting and onycholysis, dactylitis, similar HLA-B27 association in axial disease
  • Inflammatory bowel disease-associated arthritis — Active or recent enteritis/colitis from IBD; oligoarticular peripheral arthritis or axial disease
  • Rheumatic fever — Migratory polyarthritis after streptococcal pharyngitis, carditis, chorea, erythema marginatum, elevated ASO/anti-DNase B

Diagnostic workup

Diagnostic criteria

Clinical diagnosis based on characteristic arthritis temporally associated with documented or strongly suspected GU or GI infection. ASAS criteria for spondyloarthritis can be applied; HLA-B27 supports but is not required.

Labs

  • CBC, ESR, CRP — elevated inflammatory markers
  • Stool culture and Chlamydia/Gonorrhea NAAT (urine, urethral, cervical, or rectal as appropriate) — even if asymptomatic
  • HLA-B27 — supports diagnosis and predicts chronicity
  • ANA, RF, anti-CCP — to exclude alternative diagnoses
  • HIV testing
  • Synovial fluid analysis (inflammatory but sterile, WBC 2,000-50,000, no crystals) to exclude infection and crystal disease

Imaging

  • Plain radiographs of affected joints — typically normal early; later may show enthesophytes, periostitis, asymmetric sacroiliitis
  • MRI or ultrasound to identify enthesitis and early sacroiliitis
  • Echocardiography for new murmur (rare aortic regurgitation)

Diagnostic algorithm

TriggerOrganismsTypical Onset
GenitourinaryChlamydia trachomatis (most common); Mycoplasma genitalium, Ureaplasma1-4 weeks post-exposure
GastrointestinalSalmonella, Shigella, Yersinia, Campylobacter, C. difficile1-4 weeks post-enteritis
Respiratory (less common)Chlamydia pneumoniaeVariable
Common infectious triggers for reactive arthritis.

Treatment

First-line

  • NSAIDs at full anti-inflammatory doses (naproxen, indomethacin, diclofenac) — first-line therapy
  • Intra-articular corticosteroid injection for persistent monoarthritis or oligoarthritis after exclusion of infection
  • Antibiotics for active triggering infection: doxycycline or azithromycin for Chlamydia (treat partners); enteric infections are typically self-limited and antibiotics do not alter arthritis course
  • Physical therapy and joint protection

Second-line / adjunct

  • Sulfasalazine, methotrexate, or other conventional DMARDs for chronic disease (>3-6 months)
  • TNF inhibitors (etanercept, adalimumab, infliximab) for severe, refractory, or chronic disease, particularly with axial involvement
  • Topical glucocorticoids and cycloplegics for anterior uveitis (urgent ophthalmology referral)
  • Long-term doxycycline has been studied for chronic Chlamydia-induced disease but is not standard

Complications

  • Chronic arthritis or recurrence in 15-30 percent
  • Erosive joint disease in chronic HLA-B27 positive cases
  • Anterior uveitis with risk of visual loss if untreated
  • Sacroiliitis evolving into ankylosing spondylitis in some patients
  • Rare cardiac involvement (aortitis, aortic regurgitation, conduction disease)
  • Amyloidosis in chronic uncontrolled disease (rare)

PANCE pearls

  • Reactive arthritis follows infection — synovial fluid is inflammatory but sterile.
  • Chlamydia is the most common genitourinary trigger; partner treatment and STI testing are essential.
  • Acute anterior uveitis associated with reactive arthritis is a vision-threatening emergency — refer urgently to ophthalmology.
  • The term Reiter syndrome has been largely abandoned because of the eponym's Nazi history; reactive arthritis is preferred.
  • HLA-B27 is supportive but not required for diagnosis — its presence predicts more severe and chronic disease.

References

  • ACR — American College of Rheumatology clinical resources on reactive arthritis and spondyloarthritis
  • ASAS — Assessment of SpondyloArthritis International Society classification criteria for axial and peripheral spondyloarthritis (Rudwaleit et al., Ann Rheum Dis 2011)

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