What are the possible causes of dysuria (burning on urination) and the recommended work‑up and treatment?

Differential Diagnosis and Work-Up of Dysuria (Burning with Urination)

Primary Diagnostic Approach

The most common cause of dysuria is bacterial cystitis, but you must systematically rule out infectious, inflammatory, and non-infectious etiologies through targeted history, examination, and urinalysis before initiating treatment. 1, 2

Immediate Triage Questions

• Is the patient male or female? Men with dysuria require more extensive evaluation because all UTIs in males are considered complicated and sexually transmitted infections are more common in younger men. 3, 4
• Are there systemic signs? Fever >38.3°C, rigors, flank pain, nausea/vomiting, or hypotension suggest pyelonephritis or urosepsis requiring urgent culture and extended therapy (7–14 days). 3
• Is the patient pregnant? Pregnancy mandates urine culture before treatment and converts any bacteriuria to a treatment indication. 3
• Are there complicating factors? Diabetes, immunosuppression, indwelling catheter, recent urologic procedure, or anatomic abnormalities classify the infection as complicated. 3

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Differential Diagnosis by Category

Infectious Causes (Most Common)

Bacterial Cystitis

• Presentation: Acute dysuria, frequency, urgency, suprapubic pain; typically no fever. 1, 2
• Pathogens: E. coli (80–90%), Klebsiella, Proteus, Enterococcus. 1
• Diagnosis: Pyuria (≥10 WBC/HPF or positive leukocyte esterase) plus acute urinary symptoms. 3
• Pitfall: Do not treat asymptomatic bacteriuria (15–50% prevalence in elderly); it requires no antibiotics except in pregnancy or before urologic procedures with mucosal bleeding. 3

Urethritis (Gonococcal and Non-Gonococcal)

• Presentation: Dysuria with urethral discharge (mucopurulent or purulent), often without frequency or urgency. 3
• Pathogens: Neisseria gonorrhoeae (GU), Chlamydia trachomatis (23–55% of NGU), Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis. 3
• Diagnosis: Urethral swab for nucleic acid amplification testing (NAAT); leukocyte esterase on first-void urine can screen for urethritis. 3
• Key distinction: Urethritis causes dysuria throughout voiding; cystitis causes terminal dysuria. 2

Pyelonephritis

• Presentation: Dysuria plus fever >38.3°C, costovertebral angle tenderness, nausea/vomiting, or flank pain. 3
• Diagnosis: Urine culture mandatory; blood cultures if urosepsis suspected. 3
• Treatment: 7–14 days of fluoroquinolone or IV cephalosporin; imaging (ultrasound or CT) if symptoms persist >72 hours. 3

Vaginitis

• Presentation: Dysuria (external burning) with vaginal discharge, pruritus, or odor; no frequency or urgency. 2
• Pathogens: Candida (yeast), Trichomonas vaginalis, bacterial vaginosis. 2
• Diagnosis: Pelvic examination with vaginal pH, wet mount, and KOH prep. 2

Prostatitis (Men)

• Presentation: Dysuria, perineal/suprapubic pain, obstructive voiding symptoms, fever (acute bacterial prostatitis). 4, 5
• Diagnosis: Tender prostate on digital rectal exam; urine culture; avoid vigorous prostatic massage in acute cases (risk of bacteremia). 4, 5
• Treatment: Acute bacterial prostatitis requires 30 days of fluoroquinolone or trimethoprim-sulfamethoxazole; chronic bacterial prostatitis may need 6–12 months. 5

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Non-Infectious Inflammatory Causes

Interstitial Cystitis/Bladder Pain Syndrome

• Presentation: Chronic dysuria (>6 weeks), frequency, urgency, suprapubic pain relieved by voiding; sterile pyuria (negative cultures). 2
• Diagnosis: Diagnosis of exclusion after ruling out infection, stones, malignancy; cystoscopy may show Hunner lesions or glomerulations. 2

Urolithiasis

• Presentation: Dysuria with colicky flank pain, hematuria; symptoms may mimic UTI. 1, 2
• Diagnosis: Non-contrast CT or renal ultrasound. 2

Urethral Foreign Body or Trauma

• Presentation: Dysuria after catheterization, instrumentation, or sexual activity. 2
• Diagnosis: History of recent procedure or trauma; cystoscopy if foreign body suspected. 2

Dermatologic Conditions

• Presentation: Dysuria with visible vulvar or penile lesions (erythema, ulcers, plaques). 2
• Causes: Lichen sclerosus, lichen planus, contact dermatitis, herpes simplex virus. 2
• Diagnosis: Dermatologic examination; HSV PCR if vesicles present. 2

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Non-Inflammatory Causes

Medication-Induced

• Agents: Cyclophosphamide (hemorrhagic cystitis), intravesical BCG, chemotherapy. 2
• Diagnosis: Temporal relationship between drug initiation and symptom onset. 2

Atrophic Vaginitis (Postmenopausal Women)

• Presentation: Dysuria, vaginal dryness, dyspareunia; no discharge or fever. 2
• Diagnosis: Pale, thin vaginal mucosa on examination; elevated vaginal pH >5. 2
• Treatment: Vaginal estrogen therapy reduces recurrent UTI risk in postmenopausal women. 3

Urethral Anatomic Abnormalities

• Causes: Urethral stricture, diverticulum, caruncle. 2
• Diagnosis: Cystoscopy or urethrography. 2

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Recommended Work-Up Algorithm

Step 1: Targeted History

• Symptom characterization: Onset (acute vs. chronic), timing (throughout vs. terminal voiding), associated symptoms (discharge, hematuria, fever, flank pain). 2
• Sexual history: New partner, unprotected intercourse, symptoms in partner (suggests STI). 3, 2
• Complicating factors: Male sex, pregnancy, diabetes, immunosuppression, catheter, recent procedure, recurrent UTI (≥2 in 6 months or ≥3 in 12 months). 3
• Medication review: Recent antibiotics, cyclophosphamide, intravesical therapy. 2

Step 2: Physical Examination

• Vital signs: Fever, tachycardia, hypotension (urosepsis). 3
• Abdominal exam: Suprapubic tenderness (cystitis), costovertebral angle tenderness (pyelonephritis). 2
• Genital exam: Urethral discharge, vulvovaginal erythema/discharge, penile lesions. 2
• Men: Digital rectal exam for prostatic tenderness (prostatitis). 4, 5

Step 3: Urinalysis (Dipstick + Microscopy)

• Leukocyte esterase + nitrite: Combined sensitivity 93%, specificity 72% for culture-positive UTI. 3, 6
• Negative leukocyte esterase + negative nitrite: Effectively rules out bacterial UTI (negative predictive value 90.5%). 3, 6
• Pyuria (≥10 WBC/HPF) + bacteria: Proceed to culture if symptoms present. 3, 6
• Hematuria: Gross hematuria in adults ≥35 years or with malignancy risk factors warrants urologic referral after infection treatment. 3, 6

Step 4: Urine Culture (When Indicated)

• Mandatory indications: Men, pregnant women, recurrent UTI, treatment failure, atypical symptoms, suspected pyelonephritis, complicating factors. 3, 6
• Not needed: Healthy, non-pregnant women <60 years with classic uncomplicated cystitis symptoms. 3, 6
• Collection technique: Midstream clean-catch (men); in-and-out catheterization (women with contaminated specimens). 3, 6

Step 5: Additional Testing (Selected Cases)

• Urethral/vaginal swab for NAAT: Dysuria with discharge or sexual risk factors (test for C. trachomatis, N. gonorrhoeae, M. genitalium). 3
• Vaginal wet mount/KOH prep: Dysuria with vaginal symptoms (vaginitis). 2
• Imaging (ultrasound or CT): Suspected pyelonephritis not improving after 72 hours, recurrent UTI in men, hematuria persisting >6 weeks, suspected stone or obstruction. 3, 2
• Cystoscopy: Chronic dysuria with sterile pyuria (interstitial cystitis), suspected foreign body, persistent hematuria. 2

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Treatment Principles

Uncomplicated Cystitis (Women)

• First-line: Nitrofurantoin 100 mg PO BID × 5–7 days (resistance <5%). 3
• Alternatives: Fosfomycin 3 g PO × 1 dose; trimethoprim-sulfamethoxazole 160/800 mg PO BID × 3 days (only if local resistance <20%). 3
• Avoid fluoroquinolones as first-line due to resistance, adverse effects, and microbiome disruption. 3

Complicated UTI or Pyelonephritis

• Duration: 7–14 days. 3
• Empiric options: Fluoroquinolone (ciprofloxacin 500 mg PO BID or levofloxacin 750 mg PO daily) if local resistance <10%; IV ceftriaxone 1–2 g daily for severe cases. 3

Urethritis

• Gonococcal: Ceftriaxone 500 mg IM × 1 dose plus azithromycin 1 g PO × 1 dose (dual therapy). 3
• Non-gonococcal: Azithromycin 1 g PO × 1 dose or doxycycline 100 mg PO BID × 7 days. 3

Prostatitis

• Acute bacterial: Fluoroquinolone or trimethoprim-sulfamethoxazole × 30 days. 5
• Chronic bacterial: Low-dose therapy × 6–12 months. 5

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Common Pitfalls to Avoid

• Never treat asymptomatic bacteriuria (except in pregnancy or before urologic procedures with mucosal bleeding); it increases resistance and provides no benefit. 3, 6
• Do not assume dysuria = UTI in elderly patients; non-specific symptoms (confusion, falls) without acute urinary symptoms do not justify treatment. 3, 6
• Do not treat based on pyuria alone; both pyuria and symptoms are required. 3, 6
• Do not miss STIs in sexually active patients; urethritis requires different treatment than cystitis. 3
• Do not delay imaging in pyelonephritis with persistent fever >72 hours; obstruction or abscess must be ruled out. 3