Management of Dysuria with Negative Urinalysis
In patients with dysuria and negative urinalysis, clinicians should test for sexually transmitted infections (STIs), particularly Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis, as these are common causes of sterile pyuria and urinary symptoms in sexually active individuals.
Initial Clinical Assessment
The diagnosis of dysuria should prioritize clinical symptoms over laboratory findings, as urinalysis alone has significant limitations 1. When evaluating dysuria with negative UA, focus your history on:
- Sexual history and STI risk factors: Multiple partners, new sexual partner, or history of prior STI significantly increase likelihood of STI-related dysuria 2
- Vaginal symptoms: Presence of vaginal discharge or vulvar irritation substantially decreases the likelihood of UTI and suggests alternative diagnoses including cervicitis or vaginitis 1, 3
- Character of symptoms: Acute-onset dysuria with frequency and urgency without vaginal symptoms has >90% accuracy for UTI in young women, but negative UA requires reconsideration of this diagnosis 1
STI Testing Strategy
All sexually active patients with dysuria and negative UA should undergo comprehensive STI testing 3, 2. The evidence strongly supports this approach:
- In STD clinic populations, 37% of women with confirmed STIs had pyuria, and 74% of those with pyuria had sterile pyuria (negative urine cultures) 4
- Among adolescent females with urinary symptoms, 33% had STIs, and 65% of those with sterile pyuria had documented STI 2
- STIs (particularly Chlamydia, gonorrhea, and Trichomonas) commonly present with dysuria and urinary frequency that mimics UTI 5, 2
Specific testing should include:
- Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae 3, 2
- Testing for Trichomonas vaginalis 2
- If initial STI testing is negative but urethritis or cervicitis persists, test for Mycoplasma genitalium 3
Pelvic Examination Considerations
Perform pelvic examination when 3, 6:
- Vaginal discharge or vulvar symptoms are present
- Initial STI testing is needed
- Diagnosis remains unclear after initial evaluation
The examination should assess for:
- Mucopurulent cervicitis (suggests gonorrhea or chlamydia) 5
- Vaginal discharge characteristics (helps differentiate vaginitis from STI or UTI) 5
- Vulvar lesions or irritation 6
Non-Infectious Causes to Consider
If STI testing is negative and symptoms persist, evaluate for 6:
- Interstitial cystitis/bladder pain syndrome: Consider in patients with chronic symptoms, negative cultures, and sterile UA; pentosan polysulfate sodium is FDA-approved for bladder pain associated with interstitial cystitis 7
- Dermatologic conditions: Lichen sclerosus, lichen planus, or contact dermatitis
- Urethral anatomic abnormalities or local trauma
- Medication-related causes or bladder irritants
Critical Pitfalls to Avoid
- Do not empirically treat for UTI based solely on symptoms when UA is negative 1. This leads to unnecessary antibiotic use and delays appropriate diagnosis
- Do not assume anticoagulation or recent sexual activity explains away symptoms 8. These require the same thorough evaluation
- Avoid relying on pyuria alone to diagnose UTI in sexually active patients, as 74% of pyuria cases with confirmed STIs have sterile pyuria 4
- Do not equate pyuria with infection—inflammation has many causes including STIs 1
Follow-Up Strategy
For persistent symptoms after initial negative evaluation and treatment 3, 6:
- Repeat comprehensive STI testing including Mycoplasma genitalium
- Consider urine culture if not previously obtained
- Reassess for non-infectious causes
- Consider referral to gynecology or urology for specialized evaluation of chronic pain syndromes
The key distinction is that negative UA does not rule out genitourinary pathology—it redirects evaluation toward STIs and non-infectious inflammatory conditions rather than typical bacterial cystitis.