How do I diagnose and treat a 30‑year‑old patient who developed asymmetric oligoarthritis of the knees and ankles, urethritis, and conjunctivitis 2 weeks after an enteric or genitourinary infection (suspected reactive arthritis)?

Diagnosis and Management of Reactive Arthritis

In a 30-year-old patient presenting with asymmetric oligoarthritis of the knees and ankles, urethritis, and conjunctivitis 2 weeks after an enteric or genitourinary infection, you should diagnose reactive arthritis clinically and initiate treatment with NSAIDs for joint symptoms, test for and treat any active Chlamydia infection with doxycycline 100mg twice daily for 10-14 days, and reserve sulfasalazine for cases persisting beyond 6 months. 1, 2

Clinical Diagnosis

The diagnosis of reactive arthritis is primarily clinical and does not require validated diagnostic criteria. 1 The classic presentation includes:

• Acute oligoarticular arthritis affecting larger joints (knees, ankles) developing within 2-4 weeks of a preceding infection 1
• Asymmetric joint involvement distinguishing it from rheumatoid arthritis 3
• Extra-articular manifestations including conjunctivitis, urethritis, and occasionally enthesopathy or keratoderma blenorrhagicum 4

Important caveat: In approximately 25% of patients, the triggering infection may be asymptomatic, so absence of recalled diarrhea or urethritis does not exclude the diagnosis. 1

Diagnostic Workup

Identify the Triggering Infection

Urogenital tract testing:

• Obtain urethral swab or first-void urine for Chlamydia trachomatis testing using nucleic acid amplification (ligase chain reaction) 1
• If Chlamydia is isolated, this confirms the diagnosis and mandates specific antibiotic treatment 2

Enteric pathogen testing:

• Stool cultures for Salmonella, Shigella, Yersinia, and Campylobacter 1
• Consider Clostridium difficile testing if recent antibiotic exposure or healthcare contact 4
• Critical limitation: By the time arthritis develops, stool cultures are often negative, requiring reliance on serological testing 1, 5

Laboratory Assessment

• Acute phase reactants: ESR and CRP are obligatory for diagnosis and prognosis 3
• HLA-B27 testing: Consider if symptoms suggest spondyloarthropathy (spinal involvement, sacroiliitis) 6, 5
• Serological testing: For enteric pathogens when cultures are negative, though these tests are not standardized 1
• Autoimmune panel: RF and anti-CCP should be negative; positive results suggest alternative diagnosis 3

Imaging

• Plain radiographs of affected joints to exclude metastases, evaluate for joint damage, and establish baseline 6
• Ultrasound or MRI if persistent arthritis unresponsive to treatment or suspicion for septic arthritis 6

Critical pitfall: You must exclude septic arthritis through joint aspiration if infection is suspected, as this is a medical emergency requiring immediate treatment. 7

Treatment Algorithm

Acute Phase Management (First 6 Months)

For all patients:

• NSAIDs as first-line therapy for joint symptoms 2
• Local measures: Arthrocentesis for large effusions, cold pads, and rest of affected joints 2
• Short-term prednisone 10-20mg daily can be used as bridge therapy for severe symptoms 6

If Chlamydia trachomatis is isolated:

• Doxycycline 100mg twice daily for 10-14 days (preferred) 2
• Alternative: Erythromycin 500mg four times daily for 10-14 days 2
• Alternative: Single-dose azithromycin 1g 2
• Treat sexual partners concurrently to prevent reinfection 2

For enteric-triggered reactive arthritis:

• Do not use antibiotics for established arthritis from enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter), as controlled studies show no benefit over placebo even with prolonged courses 2

Chronic Phase Management (Beyond 6 Months)

If arthritis persists beyond 6 months:

• Sulfasalazine 2g daily in addition to continued NSAIDs 2
• Sulfasalazine is moderately superior to placebo in placebo-controlled studies and well-tolerated 2

If inadequate response to sulfasalazine:

• Consider other DMARDs on an individual basis, though no controlled studies exist for agents other than sulfasalazine 2
• Discuss risk-benefit ratio carefully with the patient given lack of evidence 2

Prognosis and Monitoring

• Long-term outcome is usually good, with most cases resolving within weeks to several months 1, 2
• 25-50% of patients develop recurrent acute arthritis, depending on triggering infection and possible new infections 1
• Up to 25% progress to chronic spondyloarthritis of varying activity 1
• 20% experience chronic course lasting more than 1 year 2

Monitor patients with serial rheumatologic examinations and inflammatory markers every 4-6 weeks after treatment initiation. 6

Common Pitfalls to Avoid

• Do not delay NSAID treatment while awaiting culture results, as symptomatic relief is important and diagnosis is clinical 1, 2
• Do not prescribe prolonged antibiotics for enteric reactive arthritis, as this provides no benefit and exposes patients to unnecessary adverse effects 2
• Do not miss Chlamydia infection, as this is the one scenario where antibiotic treatment of the triggering infection is both indicated and effective 2
• Do not forget to treat sexual partners in Chlamydia-induced cases to prevent reinfection 2
• Consider Clostridium difficile as an under-recognized cause, particularly in patients with recent antibiotic exposure 4