What is the best initial therapy for a young man with knee pain, conjunctivitis, and dysuria 3 weeks after diarrhea, who is HLA-B27 (Human Leukocyte Antigen B27) positive?

Reactive Arthritis: Best Initial Therapy

The best initial therapy for this young man with reactive arthritis is high-dose NSAIDs (such as naproxen or indomethacin) as first-line treatment, combined with doxycycline 100 mg twice daily for 3 months if Chlamydia infection is suspected or confirmed. 1, 2

Clinical Diagnosis

This patient presents with the classic triad of reactive arthritis (formerly Reiter's syndrome):

• Asymmetric oligoarthritis (knee pain) 1, 2
• Conjunctivitis 1, 3
• Urethritis (dysuria) 1, 3
• Post-infectious trigger (diarrhea 3 weeks prior) 1, 2
• HLA-B27 positivity (present in over two-thirds of reactive arthritis patients) 1, 2

Reactive arthritis is the most common inflammatory polyarthritis in young men and typically follows genitourinary infection with Chlamydia trachomatis or enteric infections with Salmonella or Shigella. 1, 2

First-Line Pharmacologic Treatment

NSAIDs (Strongly Recommended)

• Initiate high-dose potent NSAIDs immediately as the cornerstone of initial therapy 4, 1
• NSAIDs should be used at the lowest effective dose, but "high doses" are appropriate for acute reactive arthritis 4, 1
• If the first NSAID is ineffective after 2-4 weeks, switch to another NSAID 4
• 75% of patients with spondyloarthritis show good response to NSAIDs within 48 hours 4
• Common choices include naproxen, indomethacin, or diclofenac 5, 1

Important caveat: NSAIDs carry risks of gastrointestinal ulceration and bleeding, cardiovascular events, and should be used at the lowest effective dose for the shortest duration necessary. 5

Antibiotic Therapy (Conditionally Recommended)

• Doxycycline or its analogs can shorten the course or abort the onset of arthritis when Chlamydia is the triggering organism 1
• Treatment with doxycycline is appropriate given the urethritis and should be initiated empirically while awaiting Chlamydia testing 1, 6, 3
• Antibiotics are NOT effective for post-enteric reactive arthritis (Salmonella/Shigella), so if stool cultures confirm enteric pathogens, antibiotics should be discontinued 1

Adjunctive Therapies

Intra-articular Corticosteroid Injection

• Patients with large-joint involvement (like this patient's knee) may benefit from intra-articular corticosteroid injection 1
• This provides rapid symptomatic relief for monoarticular or oligoarticular disease 1

Sulfasalazine (Second-Line)

• If symptoms persist despite NSAIDs and antibiotics, sulfasalazine can be added 7, 6
• Typical dosing: Start 1-2 g daily divided doses, increase to 3-4 g daily as tolerated 7
• Sulfasalazine has demonstrated efficacy in persistent peripheral arthritis associated with spondyloarthropathies 8, 6

Critical warning: Sulfasalazine requires monitoring with complete blood counts and urinalysis due to risks of blood dyscrasias, hepatotoxicity, and serious infections. 7

Systemic Corticosteroids: NOT Recommended

• Systemic corticosteroids are NOT recommended for ankylosing spondylitis or reactive arthritis 4
• While oral prednisolone was used in some case reports, guideline-level evidence does not support systemic steroids as initial therapy 4, 6

Physical Therapy and Exercise

• All patients should be referred for structured exercise programs 4
• Home exercises are effective and should be recommended 4
• Physical therapy helps maintain joint mobility and prevent long-term disability 4

Rheumatology Referral

• Early referral to rheumatology is indicated given this patient meets criteria: back pain (if present), age <45, inflammatory symptoms, HLA-B27 positivity, and arthritis 4
• Rheumatology consultation is particularly important if symptoms persist beyond 4 weeks or if there is evidence of sacroiliitis 8, 4

Monitoring and Prognosis

• The majority of patients have a self-limiting course, but some develop chronic spondyloarthropathy requiring immunomodulatory therapy 2
• HLA-B27 positivity serves as a prognostic indicator for chronicity and axial involvement 1, 2
• Monitor for development of chronic symptoms, which may require escalation to anti-TNF therapy 4

Critical Pitfalls to Avoid

• Do not delay NSAID therapy while awaiting confirmatory testing 4, 1
• Do not use systemic corticosteroids as initial therapy 4
• Do not withhold antibiotics if Chlamydia is suspected—treatment can modify disease course 1
• Do not assume antibiotics will help if the trigger was enteric infection rather than Chlamydia 1
• Screen for HIV as reactive arthritis may be the first manifestation of HIV infection 1