A man presents with severe bilateral pain in his hands, ankles, knees, and elbows, recovering from a sore throat with recent fevers, and a history of recent unprotected receptive oral intercourse. He has an erythematous pharynx, tender cervical lymphadenopathy, and elevated inflammatory markers. What is the most likely diagnosis?

Reactive Arthritis (Reiter's Syndrome)

This patient most likely has reactive arthritis triggered by recent urogenital infection with Chlamydia trachomatis or Neisseria gonorrhoeae, given the classic triad of asymmetric polyarthritis, pharyngitis with exudates, and recent unprotected oral sexual contact. 1, 2

Clinical Reasoning

The diagnosis is based on the following key features:

• Asymmetric oligoarthritis affecting large and small joints (PIPs, MCPs, wrists, ankles, MTPs) developing within 2-4 weeks of urogenital exposure 1, 2, 3
• Pharyngitis with pustular exudates and cervical lymphadenopathy, consistent with either streptococcal pharyngitis or gonococcal pharyngitis from oral sexual contact 4
• Recent unprotected receptive oral intercourse establishing urogenital pathogen exposure 4
• Elevated inflammatory markers (ESR and CRP) supporting active inflammatory arthritis 1, 3
• Sterile joint inflammation (no mention of septic arthritis features like single hot joint requiring aspiration) 1, 2

Distinguishing Features from Disseminated Gonococcal Infection (DGI)

While DGI can present with polyarthritis and pharyngitis, this case favors reactive arthritis because:

• Symmetric bilateral involvement of multiple small and large joints is more consistent with reactive arthritis than the typical migratory tenosynovitis or monoarticular septic arthritis of DGI 5
• Patient is afebrile on examination, whereas DGI typically presents with fever 4
• No rash described, while DGI classically presents with painless pustular or vesiculopustular skin lesions 4
• Boggy, warm joints with passive and active tenderness suggests inflammatory synovitis rather than septic arthritis 1, 3

Pathophysiology

Reactive arthritis develops as sterile inflammatory arthritis following remote infection, most commonly urogenital (Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae) or enteric pathogens 1, 2, 3. Chlamydial elementary bodies and antigenic material have been demonstrated in synovial tissue despite negative joint cultures, suggesting direct pathogenic interaction 6. The pharyngitis likely represents either concurrent gonococcal pharyngeal infection from oral contact or post-streptococcal reactive features 4.

Diagnostic Workup Required

Immediate testing should include:

• Urogenital testing for N. gonorrhoeae and C. trachomatis using nucleic acid amplification tests (NAATs) on urine or urethral swab 4
• Pharyngeal culture or NAAT for N. gonorrhoeae given oral sexual exposure 4
• Throat culture for Group A Streptococcus to evaluate pharyngitis 4
• Serologic testing for chlamydial antibodies if cultures/NAATs are negative but clinical suspicion remains high 1, 2
• Joint aspiration if monoarticular involvement or concern for septic arthritis to exclude bacterial infection 4

HLA-B27 testing is NOT recommended for diagnosis of acute reactive arthritis, though it confers 30-50 times increased risk 2, 5

Treatment Approach

For confirmed or suspected urogenital infection:

• Ceftriaxone 125 mg IM single dose PLUS Azithromycin 1 g PO single dose to cover both gonorrhea and chlamydia 4
• Alternative: Cefixime 400 mg PO single dose PLUS Doxycycline 100 mg PO twice daily for 7 days 4

For pharyngeal gonococcal infection (if confirmed):

• Same regimen as above, as pharyngeal gonorrhea is more difficult to eradicate 4

For reactive arthritis symptoms:

• NSAIDs for initial management of joint inflammation 1, 2
• Intra-articular corticosteroid injections if only one or two joints severely affected 4
• Systemic corticosteroids may be needed if NSAIDs insufficient 4, 1

Prolonged antibiotic therapy (3-6 months) for Chlamydia-induced reactive arthritis may benefit chronic cases, though evidence for acute reactive arthritis is limited 2

Critical Pitfalls to Avoid

• Do not delay treatment waiting for culture results in sexually active patients with compatible exposure history 4
• Do not miss pharyngeal gonorrhea, which requires specific testing as it is often asymptomatic and more difficult to treat 4
• Do not assume joint cultures will be positive in reactive arthritis—they are characteristically sterile 1, 2, 6
• Do not use HLA-B27 as a diagnostic criterion for acute reactive arthritis 2
• Treat sex partners within 60 days of exposure regardless of symptoms 4

Prognosis

• Most patients (50-75%) recover completely within 3-6 months 1, 2
• 25-50% develop recurrent acute arthritis, especially with reinfection 1, 2
• 25% progress to chronic spondyloarthritis of varying activity 1
• Long-term outcome is generally favorable for enteric reactive arthritis; data for chlamydial reactive arthritis are limited 2