How should undiagnosed genital or urethral symptoms be managed?

Management of Undiagnosed Genital or Urethral Symptoms (TUGS)

Undiagnosed genital or urethral symptoms should be evaluated with diagnostic testing for common sexually transmitted infections (STIs), particularly gonorrhea and chlamydia, followed by appropriate antimicrobial therapy based on test results or empiric treatment if testing is unavailable. 1

Initial Evaluation

Diagnostic Testing

• Test for both gonorrhea and chlamydia (strongly recommended)
  • Specific diagnosis improves treatment compliance and partner notification
  • Both infections are reportable to health departments

Clinical Assessment

• Check for objective signs of urethritis:
  • Mucoid or purulent urethral discharge
  • ≥5 polymorphonuclear leukocytes per oil immersion field on intraurethral swab
  • Leukocyte esterase test (LET) can screen urine, but confirm with Gram stain

Common Etiologies

• Nongonococcal urethritis (NGU):

  • Chlamydia trachomatis (23-55% of cases)
  • Ureaplasma urealyticum (20-40%)
  • Trichomonas vaginalis (2-5%)
  • HSV (occasionally)
  • Mycoplasma genitalium (emerging cause) 1

• Other causes to consider:

  • Neisseria gonorrhoeae
  • Lichen sclerosus (especially with meatal involvement) 1
  • Condylomata acuminata (genital warts) 2

Treatment Algorithm

1. If diagnostic testing available:

A. For confirmed chlamydial infection:

• First-line: Azithromycin 1g orally in a single dose 1
• Alternative: Doxycycline 100mg orally twice daily for 7 days 1

B. For confirmed gonococcal infection:

• Follow current CDC guidelines for gonorrhea treatment

C. For nongonococcal, nonchlamydial urethritis:

• First-line: Azithromycin 1g orally in a single dose 1
• Alternative: Doxycycline 100mg orally twice daily for 7 days 1

2. If diagnostic testing unavailable:

Empiric treatment for both gonorrhea and chlamydia:

• Treat according to current CDC guidelines for both infections 1

3. For persistent or recurrent urethritis:

If patient was compliant with initial regimen and re-exposure excluded:

• Metronidazole 2g orally in a single dose PLUS
• Azithromycin 1g orally in a single dose (if not used for initial episode) 1

Alternative regimen:

• Moxifloxacin 400mg orally once daily for 7 days (effective against M. genitalium) 1

Follow-Up Recommendations

• Instruct patients to return if symptoms persist or recur
• Symptoms alone without objective signs of urethritis are not sufficient for retreatment
• Abstain from sexual intercourse for 7 days after single-dose therapy or until completion of multi-day regimen
• Repeat testing 3-6 months after treatment for patients with documented chlamydia or gonorrhea due to high reinfection rates 1

Partner Management

• Refer all sexual partners within preceding 60 days for evaluation and treatment
• Partner management recommended even if specific etiology not identified
• Expedited partner treatment is an alternative approach 1

Special Considerations

For persistent symptoms without objective signs:

• Consider chronic prostatitis/chronic pelvic pain syndrome in males with:
  • Persistent pain (perineal, penile, or pelvic)
  • Discomfort
  • Irritative voiding symptoms
  • Pain during/after ejaculation
  • New-onset premature ejaculation lasting >3 months 1

For urethral stricture or anatomical concerns:

• Consider urologic evaluation with uroflowmetry, retrograde urethrogram, and/or cystoscopy 1
• Meatal disease may progress to urethral involvement if untreated 1

For transgender patients post-genital reconstruction:

• Evaluate for potential urethrocutaneous fistula or urethral stricture
• Assessment may require specialized imaging including retrograde urethrography, voiding cysto-urethrogram, and MRI 3

Common Pitfalls to Avoid

1. Treating without objective evidence of urethritis
2. Failing to test for both gonorrhea and chlamydia
3. Not addressing partner treatment
4. Missing non-infectious causes like lichen sclerosus
5. Overlooking the possibility of sexual abuse in pediatric cases with genital symptoms 1
6. Failing to consider M. genitalium in treatment failures

By following this structured approach to undiagnosed genital and urethral symptoms, clinicians can effectively diagnose and treat these conditions while preventing complications and further transmission.