Reactive arthritis

Reactive arthritis (formerly known as Reiter syndrome) is a postinfectious autoimmune condition that is most commonly preceded by bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondyloarthropathy and is associated with HLA-B27. Reactive arthritis often affects young adults and manifests with musculoskeletal and/or extraarticular symptoms. The classic triad of arthritis, conjunctivitis, and urethritis is only seen in about one-third of patients. The diagnosis is based on clinical features such as patient history and physical examination and may be supported by laboratory or imaging findings, although there are no specific confirmatory tests for reactive arthritis. Reactive arthritis usually resolves spontaneously within 6–12 months; treatment during this acute phase is primarily supportive (e.g., NSAIDs for arthritis). Underlying infections should be identified and treated. A small proportion of patients develop severe or chronic arthritis; for these individuals, systemic corticosteroids or disease-modifying antirheumatic drugs (DMARDs) may be required.

• Genetic predisposition and association with HLA-B27 (see “Seronegative spondyloarthritis”)
• Commonly affects young men ^[1]
• HIV infection is associated with an increased risk of reactive arthritis. ^[2][3]

Epidemiological data refers to the US, unless otherwise specified.

Postinfectious autoimmune disorder ^[4]

• Posturethritis: after infection with Chlamydia (common) or Ureaplasma urealyticum
• Postenteritis: after infection with Shigella, Yersinia, Salmonella, or Campylobacter ^[1]
• In rare cases: after infection with Bartonella henselae ^[5]

She Cherishes Cooking Yummy Salmon: Shigella, Chlamydia, Campylobacter, Yersinia, and Salmonella are the most common causes for reactive arthritis.

• Latency period: 1–4 weeks
• Musculoskeletal symptoms
  • Oligoarthritis (sometimes polyarthritis)
    • Acute onset
    • Often asymmetrical with a migratory character
    • Occurs predominantly in the lower extremities
  • Sacroiliitis
  • Enthesitis
  • Dactylitis
• Extra‑articular symptoms
  • Conjunctivitis, iritis, episcleritis, or keratitis
  • Dermatologic manifestations ; ^[2]
    • Balanitis circinata: skin lesions of the glans resembling psoriasis
    • Keratoderma blenorrhagicum: hyperkeratinization of the palms and soles
  • Urethritis
  • Oral ulcers
  • Cardiac manifestations ^[1]
    • Aortic regurgitation ^[7]
    • Atrioventricular blocks
    • Pericarditis
• Symptoms from preceding infection
  • Diarrhea
  • Urogenital tract symptoms (dysuria, pelvic pain, prostatitis)

Classic triad of reactive arthritis (seen in approximately one-third of affected individuals): “can't see (conjunctivitis), can't pee (urethritis), can't climb a tree (arthritis)”. ^[8]

Overview

• Reactive arthritis is primarily a clinical diagnosis. ^[6]
• Laboratory studies and imaging typically show nonspecific signs of inflammation.
• Further studies may be necessary to:
  • Identify underlying infections (e.g., via stool culture, urethral swabs)
  • Exclude differential diagnoses of reactive arthritis (e.g., rheumatoid factor, arthrocentesis and synovial fluid analysis)

Laboratory studies ^[1][6]

• Blood tests: Consider in all patients although findings are often nonspecific.
  • CBC: ↑ WBC, ↑ platelets ^[6]
  • Inflammatory markers: ↑ ESR, ↑ CRP ^[1]
  • Rheumatoid factor or anti-CCP antibodies: negative ^[9]
• Arthrocentesis with synovial fluid analysis: indicated if the diagnosis is unclear or if there is a concern for septic arthritis ^[6]
  • ↑ WBC count: 5000–50,000/mm³; neutrophil predominant
  • Gram stain and cultures: typically negative ^[1]
  • Crystals: absent
• Stool culture: Perform only in ongoing diarrhea; send culture for Shigella, Yersinia, Salmonella, and Campylobacter.
• STI testing: indicated for patients with risk factors for STIs
  • Perform NAAT on urine or urogenital samples for genitourinary chlamydia.
  • Consider diagnostic studies for gonorrhea if there is concern for disseminated gonococcal infection.
  • Consider HIV testing if:
    • The presentation is atypical (e.g., widespread dermatologic manifestations) ^[2]
    • The patient has risk factors for bloodborne viruses

As with other seronegative arthropathies, there is an association between reactive arthritis and HLA-B27 (approximately 50–80% of HLA-B27 tests are positive in patients with reactive arthritis); however, HLA-B27 testing is not required to diagnose reactive arthritis and does not change the management of the condition. ^[1][6]

Genitourinary chlamydia infection is frequently asymptomatic; have a low threshold for testing for chlamydia in patients with reactive arthritis. ^[1]

Imaging ^[1][10]

• Suspected arthritis
  • Recommended modality: x-ray of affected region(s)
  • Findings: may show erosions and bone proliferation
• Suspected synovitis or enthesitis
  • Recommended modalities: MRI with IV gadolinium or ultrasound
  • Findings: may include synovial hypertrophy, hypervascularization of soft tissue, tendon thickening

Additional studies

• Suspected cardiac manifestations
  • ECG to screen for atrioventricular blocks and pericarditis
  • Echocardiogram for aortic regurgitation
• Suspected ocular manifestations: slit lamp examination for keratitis and anterior uveitis

Aortic regurgitation can be fatal if missed; request an echocardiogram if there are any concerning clinical features. ^[7]

Overview

• Acute reactive arthritis
  • Management is primarily supportive as reactive arthritis is typically self-limiting. ^[11]
  • Identify and treat underlying infections, e.g., genitourinary chlamydia.
  • Refer patients to rheumatology and physiotherapy; consider additional referrals (e.g., ophthalmology, cardiology) as needed.
• Chronic reactive arthritis (i.e., persistence of symptoms > 6 months) or severe disease: DMARDs (e.g., sulfasalazine) may be required.

Supportive therapy

Arthritis

• NSAIDs: first-line treatment for all symptomatic patients ^[1][11]
  • Choose medication based on patient characteristics; start with a high dose and titrate to the lowest effective dose. ^[12]
    • No NSAID has shown greater efficacy over another in trials; long-acting agents e.g., naproxen may improve adherence.^[12]
    • In patients with risk factors for peptic ulcer disease, consider selective COX-2 inhibitors or coadministration of NSAIDs and a PPI. ^[13]
  • See “Oral analgesics” for further information, including dosages.
• Glucocorticoids: indicated in patients with inadequate response or contraindications to NSAIDs
  • Monoarthritis or oligoarthritis: intraarticular glucocorticoids ^[1]
  • Polyarthritis or severe extraarticular disease: systemic glucocorticoids, e.g., prednisone ^[6][12]
• DMARDs: indicated in patients with chronic (> 6 months) or severe disease ^[12]
  • Options include either conventional DMARDs (e.g., sulfasalazine or methotrexate) or biopharmaceuticals. ^[1][6]
  • There is limited research about the effect of DMARDs on patients with reactive arthritis; sulfasalazine currently has the largest evidence base. ^[12]
• Antibiotics
  • Long courses of antibiotics (up to 6 months) are used by some specialists to manage reactive arthritis.
  • Evidence to support this approach is mixed. ^[11][14][15]

Extraarticular manifestations ^[6][15]

Treatment should be overseen by the relevant specialist.

• Ocular ^[16]
  • Management of anterior uveitis, keratitis, and episcleritis follows standard best practice for these conditions.
  • Treatment usually involves symptomatic relief and topical or systemic glucocorticoids.
• Dermatologic: Treatment typically involves topical steroids and keratolytics.^[17]
• Cardiac
  • Pericarditis: high dose glucocorticoids or DMARDs ^[18]
  • Depending on severity, AV block may require a pacemaker and aortic regurgitation valve replacement. ^[7]

Management of underlying infections ^[6][11]

• Treat active infections.
  • Treat all patients with genitourinary chlamydia (even if asymptomatic).
  • Consider treatment for patients with severe bacterial gastroenteritis, especially if immunocompromised. ^[6]
• For sexually transmitted infections:
  • Perform contact tracing for sexual partners and offer testing.
  • Gonorrhea/chlamydia infection ^[19]
    • Treat all sexual partners from the last 60 days.
    • OR treat the most recent partner if no partners in the last 60 days.
  • Counsel on safer sex practices.
• Report notifiable diseases to the relevant state and/or national authorities.

Infection-associated arthritis ^[20]

Non-infectious arthritis ^[20]

• Rheumatoid arthritis
• Other seronegative spondyloarthritis
• Crystal-induced arthritis (i.e., gout, pseudogout)
• Systemic lupus erythematosus

The differential diagnoses listed here are not exhaustive.

• Resolves spontaneously within a year
• High rate of recurrence