What is the recommended treatment plan for reactive arthritis, including first‑line NSAIDs, corticosteroids, antibiotics for Chlamydia, disease‑modifying antirheumatic drugs, and biologic therapy?

Reactive Arthritis Treatment Plan

Start with NSAIDs as first-line therapy for symptomatic control, add sulfasalazine if symptoms persist beyond 6 months, and treat Chlamydia-induced cases with antibiotics while avoiding antibiotics for enteric-triggered reactive arthritis. 1

First-Line Symptomatic Management

NSAIDs and Local Measures

• Initiate NSAIDs immediately for pain and inflammation control in all patients with acute reactive arthritis. 1, 2
• Combine NSAIDs with local measures including arthrocentesis (joint aspiration), cold pads, and rest of the affected joint. 1
• NSAIDs remain the most commonly used drugs for reactive arthritis treatment alongside sulfasalazine. 2

Glucocorticoids for Refractory Cases

• Administer glucocorticoids when inflammatory symptoms are resistant to NSAIDs. 2
• Use intra-articular corticosteroid injections for persistent monoarticular involvement that fails NSAID therapy. 1

Antibiotic Therapy: Critical Distinction by Trigger

Chlamydia-Induced Urogenital Reactive Arthritis

• Treat with antibiotics if the triggering Chlamydia bacterium can be isolated from the urogenital tract. 1
• Prescribe doxycycline 100 mg twice daily for 10-14 days, OR erythromycin 500 mg four times daily for 10-14 days, OR azithromycin 1 g as a single dose. 1
• Treat the sexual partner concurrently to prevent reinfection. 1
• For Chlamydia-induced reactive arthritis without positive cultures, consider a 3-month antibiotic course, though evidence is limited and further studies are needed before routine recommendation. 1

Enteric-Triggered Reactive Arthritis (Yersinia, Shigella, Salmonella, Campylobacter)

• Do not use antibiotics for enteric forms of reactive arthritis—they show no benefit over placebo even with prolonged treatment. 1
• This applies despite evidence that bacterial remnants and even bacterial RNA can be demonstrated in the joint. 1

Disease-Modifying Therapy for Chronic Cases

Sulfasalazine as Second-Line Agent

• Add sulfasalazine 2 g/day for reactive arthritis lasting longer than 6 months while continuing NSAIDs. 1, 2
• Sulfasalazine was moderately superior to placebo and well tolerated in several placebo-controlled studies. 1

Other DMARDs for Refractory Disease

• Consider other disease-modifying antirheumatic drugs (methotrexate, azathioprine, cyclosporin) in individual patients who do not respond to sulfasalazine. 1, 2
• Carefully discuss the risk-benefit ratio with the patient before initiating these agents, as no controlled studies are available for DMARDs other than sulfasalazine in reactive arthritis. 1

Biologic Therapy for Severe or Progressive Cases

TNF-Alpha Blockers

• Consider TNF-alpha blockers in more aggressive cases or when reactive arthritis evolves toward ankylosing spondylitis. 2
• This represents an effective choice for patients with severe disease unresponsive to conventional therapy. 2

Treatment Timeline and Monitoring

Expected Disease Course

• Typical reactive arthritis affects one knee or ankle for weeks to several months. 1
• Up to 20% of patients experience a chronic course lasting more than 1 year. 1

Monitoring Strategy

• Reassess at 6 months to determine if disease has become chronic and requires escalation to sulfasalazine. 1
• Monitor for extra-articular manifestations including enthesitis, tenosynovitis, bursitis, and dactylitis. 2
• Watch for axial involvement, which may indicate evolution toward spondyloarthropathy requiring biologic therapy. 2

Common Pitfalls to Avoid

• Do not prescribe prolonged antibiotics for enteric-triggered reactive arthritis—this wastes resources and exposes patients to unnecessary antibiotic risks without benefit. 1
• Do not use DMARDs earlier than 6 months unless disease is particularly severe, as most cases resolve with NSAIDs alone. 1
• Do not forget to treat the sexual partner in Chlamydia-induced cases, as reinfection will perpetuate the arthritis. 1
• Do not delay biologic therapy in patients with severe disease or those evolving toward ankylosing spondylitis. 2