What is the likely diagnosis and recommended management for a patient presenting with fever, diarrhea, conjunctivitis, acute knee effusion (monoarthritis) and a urinary tract infection?

Reactive Arthritis (Reiter's Syndrome)

This patient has reactive arthritis, a post-infectious spondyloarthropathy characterized by the classic triad of conjunctivitis, urethritis (presenting as UTI symptoms), and arthritis (knee effusion), typically following a urogenital or gastrointestinal infection (diarrhea). 1, 2

Clinical Diagnosis

The constellation of fever, diarrhea, conjunctivitis, acute monoarticular knee effusion, and urinary symptoms strongly suggests reactive arthritis rather than a simple UTI with coincidental findings. 1, 3

Key Diagnostic Features

• Reactive arthritis typically manifests 1-6 weeks after a triggering infection (urogenital or gastrointestinal), with the arthritis appearing when the initial infection may have resolved or is resolving 3
• The classic triad includes conjunctivitis, urethritis/urogenital symptoms, and asymmetric oligoarthritis (typically affecting large joints like the knee or ankle) 1, 2
• Gastrointestinal infections with organisms such as Shigella, Salmonella, Yersinia, or Campylobacter commonly trigger reactive arthritis, as do urogenital infections with Chlamydia 4, 3
• The condition is more common in males and in patients carrying the HLA-B27 allele (present in 60-80% of cases) 3

Critical Distinguishing Points

• Unlike septic arthritis, reactive arthritis presents without positive joint cultures or blood cultures at the time of arthritis onset 3
• The "UTI" symptoms may actually represent urethritis rather than true cystitis, particularly given the concurrent systemic features 1
• Dermatologic manifestations are common, including keratoderma blennorrhagicum, circinate balanitis, and oral lesions 1

Immediate Diagnostic Workup

Essential Testing

• Perform arthrocentesis of the knee effusion to exclude septic arthritis (which would show positive cultures and very high WBC count >50,000) and to characterize the inflammatory fluid 3
• Obtain urine culture via catheterization (not bag collection due to 12-83% false-positive rate) to determine if true UTI exists or if symptoms represent urethritis 5
• Send stool cultures for enteric pathogens (Shigella, Salmonella, Yersinia, Campylobacter) given the diarrhea 4, 3
• Test for Chlamydia trachomatis via nucleic acid amplification testing (NAAT) from urine or urethral swab 4, 3
• Check HLA-B27 status to support the diagnosis, though absence does not exclude reactive arthritis 3
• Obtain inflammatory markers (ESR, CRP) which are typically elevated 3

Important Caveat

Do not assume the urinary symptoms represent a simple UTI requiring only antibiotics—the presence of conjunctivitis and acute monoarthritis fundamentally changes the diagnostic framework. 6 The 2024 IDSA guidelines emphasize that urine testing should not be automatic in febrile patients and should be reserved for cases with specific urinary symptoms, but this patient's constellation of findings suggests a systemic post-infectious process 6

Treatment Approach

Acute Symptomatic Management

• Initiate NSAIDs as first-line therapy for the acute arthritis (e.g., indomethacin 50mg three times daily or naproxen 500mg twice daily) 4
• Perform arthrocentesis for both diagnostic and therapeutic purposes to relieve joint pain and swelling 4
• Apply local measures including rest of the affected joint and cold compresses 4

Antimicrobial Therapy Decision Tree

If Chlamydia is isolated or strongly suspected (urogenital symptoms predominate):

• Treat with doxycycline 100mg twice daily for 10-14 days, or azithromycin 1g single dose, or erythromycin 500mg four times daily for 10-14 days 4
• Treat sexual partners concurrently to prevent reinfection 4
• Consider extended 3-month antibiotic course for Chlamydia-induced reactive arthritis, though evidence is limited 4

If enteric pathogens are identified (diarrhea predominates):

• Do not use prolonged antibiotics for enteric reactive arthritis, as multiple studies show no benefit over placebo 4
• Focus on symptomatic management with NSAIDs 4

If true UTI is confirmed (≥50,000 CFU/mL with pyuria):

• Treat according to standard UTI guidelines with 7-14 days of antibiotics based on local resistance patterns 5
• However, recognize this may be concurrent with, not causative of, the reactive arthritis 1

Chronic Disease Management (if symptoms persist >6 months)

• Add sulfasalazine 2g/day to ongoing NSAID therapy, as this is the only disease-modifying antirheumatic drug (DMARD) with placebo-controlled evidence in reactive arthritis 4
• Consider other DMARDs (methotrexate, TNF inhibitors) only in refractory cases after careful risk-benefit discussion, as no controlled trials exist 4

Prognosis and Follow-Up

• Most cases resolve within weeks to several months, but 15-20% develop chronic sequelae with persistent or recurrent arthritis 1, 2
• Monitor for chronic destructive arthritis, which can occur without proper management 2
• Screen for extra-articular complications including uveitis/iritis (which may require ophthalmology referral), cardiac involvement (aortitis, conduction abnormalities), and skin manifestations 1, 3

Common Pitfalls to Avoid

• Do not treat this as a simple UTI and discharge the patient—the multi-system involvement requires recognition of reactive arthritis 1, 2
• Do not delay arthrocentesis—septic arthritis must be definitively excluded, as it requires immediate IV antibiotics and has devastating consequences if missed 3
• Do not give prolonged antibiotics for enteric-triggered reactive arthritis—this provides no benefit and contributes to antimicrobial resistance 4
• Do not ignore the conjunctivitis—this is a key diagnostic clue and may progress to more serious uveitis requiring specific treatment 1, 3