Reactive Arthritis (Reiter Syndrome)

Reactive arthritis is an acute, sterile, inflammatory arthritis that develops following a distant infection, typically genitourinary or gastrointestinal. Previously known as Reiter syndrome (now deprecated due to historical associations), it is classified as a seronegative spondyloarthropathy.

Understanding the pathophysiology of reactive arthritis is essential for both diagnosis and management. The condition involves an aberrant immune response to microbial antigens in genetically susceptible individuals.

Triggering Infections

Immunopathogenesis

Chronicity Factors

• HLA-B27 positivity
• Enteric rather than GU trigger (Yersinia especially)
• Persistent infection (untreated Chlamydia)
• Early sacroiliac joint involvement

The Classic Triad

Mucocutaneous Features

Physical Examination

Laboratory Studies

Synovial Fluid Analysis

Gold standard to exclude septic arthritis:

• WBC: 10,000-50,000/microL (inflammatory)
• Predominantly neutrophils
• Gram stain and culture NEGATIVE
• Crystal analysis NEGATIVE

Imaging

The viva explicitly asks "what if cultures grow Neisseria gonorrhoeae?", and the topic repeatedly stresses excluding a septic joint - but the single most important specific mimic is never developed. In a young, sexually active patient who presents with arthritis after a genitourinary infection, the two diagnoses on the table are reactive arthritis (sterile, post-infectious) and disseminated gonococcal infection (DGI - a true, treatable infection). Getting this wrong is dangerous: DGI is a septic process that needs urgent antibiotics, not NSAIDs.

DGI has two overlapping presentations:

• The arthritis-dermatitis (bacteraemic) syndrome: migratory polyarthralgia, tenosynovitis (classically of the wrist/hand/ankle - a distinguishing feature), and a sparse vesiculopustular/haemorrhagic rash.
• A purulent (septic) monoarthritis or oligoarthritis, usually of a large joint.

Practically: any acutely inflamed joint is aspirated and cultured first; in the sexually active patient add mucosal nucleic-acid amplification tests (urethral/cervical/pharyngeal/rectal) and blood cultures, because gonococcus is fastidious and the joint fluid culture is often negative even in true DGI. If gonococcus is found anywhere, treat as DGI (ceftriaxone) - it is not reactive arthritis, even though both can follow the same sexual exposure.

The topic names conjunctivitis as part of the triad and warns that progression to anterior uveitis is "more serious," "sight-threatening," and needs ophthalmology - but never develops the distinction, which is exactly what an examiner probes. The two are very different problems and must not be conflated.

The decisive features are pain and photophobia with a unilateral red eye - these flag uveitis, not conjunctivitis. Acute anterior uveitis is the shared eye lesion of the whole HLA-B27 spondyloarthritis family (also seen in ankylosing spondylitis), it is recurrent, and untreated it scars the eye (posterior synechiae, secondary glaucoma, cataract) and can cause permanent visual loss - hence the same-day ophthalmology referral. Conjunctivitis, by contrast, is benign and needs only reassurance.

Indications for Surgery

Surgical intervention is rarely required in reactive arthritis. Indications include:

1. Joint destruction: Rare, but end-stage arthropathy may require arthroplasty
2. Tendon rupture: Achilles tendon rupture from chronic enthesitis
3. Persistent effusion: Arthroscopic synovectomy in refractory cases

Disease Complications

• Chronic arthritis: 30-50% develop chronic or recurrent disease
• Ankylosing spondylitis: May evolve to AS in HLA-B27+ patients
• Vision loss: From untreated uveitis
• Cardiovascular: Aortitis and conduction defects (rare)
• Amyloidosis: Secondary amyloidosis in chronic disease

Prognosis

• Self-limiting: 50% recover fully within 6 months
• Recurrent: 15-30% have recurrent episodes
• Chronic: 15-30% develop chronic disease
• HLA-B27: Associated with worse prognosis

Reactive arthritis is a worldwide diagnosis with no single authoritative guideline; management is extrapolated from the broader peripheral spondyloarthritis literature (ASAS/EULAR, ACR).

Global epidemiology:

• Population-based annual incidence 0.6 to 27 per 100,000 (the wide range reflects inconsistent case definitions, not true variation alone)
• Post-enteric ReA dominates where Campylobacter, Salmonella, Shigella and Yersinia are common; post-chlamydial ReA tracks the local burden of Chlamydia trachomatis
• HLA-B27 background prevalence varies markedly by population (high in Northern Europe and some Indigenous groups, very low in equatorial Africa and parts of East Asia), influencing both incidence and chronicity
• Up to 1 to 4% of patients develop reactive joint symptoms after a documented enteric outbreak

Side-by-side guidance (no ReA-specific society guideline exists):

• Role of prolonged antibiotics: Only PCR-proven chronic Chlamydia-induced ReA has RCT support for 6-month combination therapy (Carter 2010). For enteric-triggered and acute disease, antibiotics do not alter the natural history (Laasila 2003), yet the practice is sometimes applied too broadly.
• Diagnostic criteria: There are no universally agreed criteria. The very term "reactive arthritis" is applied inconsistently, which inflates the reported incidence range (0.6 to 27 per 100,000) and undermines cross-study comparison (Townes 2010).
• HLA-B27 as a test: HLA-B27 is prognostic, not diagnostic. A negative result does not exclude ReA and a positive result in an unselected patient has poor specificity; it should not be used to make the diagnosis (Hannu 2011).
• Triad reliance: The full triad (arthritis, urethritis, conjunctivitis) is present in a minority. Waiting for the complete triad delays diagnosis; most patients present with arthritis plus a recent trigger only.
• Terminology: "Reiter syndrome" is being abandoned for both ethical and descriptive reasons, but lingers in older literature and some exam material.
• Biologic timing and persistence concern: TNF inhibitors help refractory disease, but the theoretical risk of reactivating a persistent intra-articular organism remains debated; available data (Flagg 2005) showed no clinical flare despite synovial bacterial DNA.