Reactive arthritis

Definition

Triggers

• Gastrointestinal: Salmonella, Yersinia enterocolitica, Shigella flexneri, Campylobacter jejuni.
• Genitourinary: Chlamydia trachomatis is the most common trigger. Neisseria gonorrhoeae, Mycoplasma genitalium and Ureaplasma are also implicated.
• Post-streptococcal arthritis and Giardia are generally excluded from ReA. They lack the other spondyloarthritis features and the HLA-B27 link.

Epidemiology and pathobiology

• Peak onset is at age 20 to 40. Gut-triggered ReA affects both sexes equally, and Chlamydia-triggered ReA is more common in men.
• In Salmonella or Yersinia outbreaks, 2 to 7% of infected people develop ReA. The figure is up to 20% in HLA-B27-positive people.
• HLA-B27 raises the risk of arthritis, axial involvement and chronicity. Toll-like receptor 2 (TLR-2) variants point to a role for innate immunity.
• PCR on synovium is most consistently positive after Chlamydia. This suggests viable organisms persist in the joint in an altered metabolic state.

Clinical features

• The classic pattern is an asymmetric oligoarthritis of the lower limbs.
• Enthesitis (Achilles tendinitis, plantar fasciitis) and dactylitis ("sausage digit") are common.
• Sacroiliitis can occur.

• Urethritis or cervicitis: cervicitis is often asymptomatic, so ReA is underdiagnosed in women.
• Circinate balanitis: the most common mucocutaneous lesion, seen in about 50% of men. It looks like painless, serpiginous erosive or crusted plaques on the glans.
• Keratoderma blennorrhagicum: hyperkeratotic papules and plaques on the palms and soles, seen in about 10% of patients. They appear 1 to 2 months after onset and look like psoriasis.
• Mouth: painless oral ulcers and migratory glossitis.
• Nails: thickening, ridging or subungual keratosis. Pitting is not typical.
• Eyes: conjunctivitis is bilateral and often painful. Acute anterior uveitis is usually unilateral and less painful.
• Erythema nodosum: uncommon, and linked to Yersinia.

Diagnosis

• Major criteria: asymmetric mono- or oligoarthritis of the lower limb, plus a preceding symptomatic enteritis or urethritis 3 days to 6 weeks before arthritis onset.
• Minor criteria: evidence of the triggering infection, such as a positive Chlamydia swab or PCR, or stool culture.

• Synovial fluid: culture it first, because Yersinia and Salmonella can cause septic arthritis, which is the key differential (Goldman-Cecil).
• Infection testing: Chlamydia NAAT, stool culture, and HIV and other STI screening.
• HLA-B27: supportive but not diagnostic.
• Inflammatory markers: ESR and CRP are raised.

• Peripheral joints show soft-tissue swelling and juxta-articular osteopenia, with periostitis in later disease.
• Sacroiliitis is asymmetric, unlike the symmetric sacroiliitis of ankylosing spondylitis.
• Chronic syndesmophytes are bulky, non-marginal and asymmetric, unlike the thin marginal syndesmophytes of ankylosing spondylitis.

Management

1. Treat the trigger. Treat active urethritis or cervicitis, and treat the partner. A single 1 g dose of azithromycin is as effective as doxycycline 100 mg twice daily for 7 days. Antibiotics are generally not indicated for post-dysenteric ReA.
2. NSAIDs (indomethacin, naproxen) are first line for symptoms. They do not shorten the disease course.
3. Intra-articular or intralesional corticosteroids help for oligoarthritis, enthesitis and dactylitis. Prolonged systemic steroids are discouraged.
4. DMARDs are used if there is no response after about 1 month, or in chronic disease. Sulfasalazine (1 g two to three times daily) is often effective if started within 3 months. Methotrexate is an alternative.
5. Prolonged antibiotics for Chlamydia-induced ReA. Cecil describes 6 months of rifampicin 300 mg/day plus doxycycline 100 mg twice daily or azithromycin. In that study 65% responded, versus about 20% on placebo, and 20% had complete remission, versus 0% on placebo. This was for patients PCR-positive for C. trachomatis or C. pneumoniae. Other trials of antibiotics have been mixed, so this is not routine.
6. Biologics (anti-TNF) are sometimes used in chronic HLA-B27-positive disease or axial disease. Efficacy is unproven.

Prognosis

Recent evidence check