What is the differential diagnosis (Ddx) for pyuria?

Differential Diagnosis for Pyuria

Pyuria has exceedingly low positive predictive value for infection and indicates genitourinary inflammation from numerous infectious and noninfectious causes—never diagnose or treat based on pyuria alone without accompanying clinical symptoms. 1

Infectious Causes

Urinary Tract Infections

• Cystitis: Bladder inflammation with dysuria, urgency, and suprapubic pain, typically without fever 1
• Pyelonephritis: Kidney infection presenting with fever (≥38°C), flank pain, costovertebral angle tenderness, with or without lower urinary symptoms 1, 2, 3
• Complicated UTI: Infections involving catheters, foreign bodies, structural anomalies, immunosuppression, or systemic symptoms 1
• Asymptomatic bacteriuria: Positive urine culture (>10⁵ CFU/mL) with pyuria but no symptoms—prevalence 15-50% in elderly institutionalized patients 4
• Catheter-associated infections: Pyuria weakly correlates with infection in catheterized patients, especially for gram-positive cocci and yeasts 5

Other Infectious Etiologies

• Renal tuberculosis: Presents with fever, frequency, urgency, dysuria, and hematuria with sterile pyuria (culture-negative pyuria) 6
• Fungal infections (Candidiasis): Particularly in immunosuppressed patients or those on long-term antibiotics, produces minimal pyuria 6, 5
• Sexually transmitted infections: Urethritis from Chlamydia or Neisseria gonorrhoeae can cause pyuria 4
• Prostatitis: In males with dysuria, frequency, and pelvic/perineal pain 7

Noninfectious Causes

Inflammatory Conditions

• Interstitial cystitis: Chronic bladder inflammation with sterile pyuria and urinary symptoms without infection 1
• Chemical irritation: From medications, soaps, or other irritants causing genitourinary inflammation 1
• Urolithiasis: Kidney or bladder stones causing mechanical irritation and inflammation 3

Structural and Anatomic Abnormalities

• Vesicoureteral reflux: Anatomic abnormality causing chronic inflammation 2
• Urinary tract obstruction: From stones, strictures, or masses 2, 3
• Foreign bodies: Including indwelling catheters, stents, or other devices 1

Systemic and Metabolic Conditions

• Glomerulonephritis: Renal parenchymal inflammation with pyuria and hematuria 1
• Renal transplant rejection: Can present with pyuria in transplant recipients 1
• Diabetes mellitus: Associated with noninfectious pyuria and increased infection risk 1, 2

Contamination and Collection Issues

• Vaginal contamination: High epithelial cells with pyuria suggests poor specimen collection 4
• Perineal flora contamination: From inadequate cleansing during midstream collection 1

Diagnostic Algorithm

Step 1: Assess Clinical Context

• Presence of specific urinary symptoms: Dysuria, frequency, urgency, fever, gross hematuria, or flank pain 1, 4
• Absence of symptoms: Do not order urinalysis or culture in asymptomatic patients 4

Step 2: Evaluate Specimen Quality

• High epithelial cells (>5/hpf): Suggests contamination; obtain catheterized specimen if clinical suspicion remains high 4
• Proper collection method: Catheterization or suprapubic aspiration in infants/children; midstream clean-catch in cooperative adults 4

Step 3: Interpret Urinalysis Results

• Negative leukocyte esterase AND negative nitrite: Effectively rules out UTI (negative predictive value 82-91%) 4
• Positive leukocyte esterase OR nitrite WITH symptoms: Proceed to culture in complicated cases, pyelonephritis, or recurrent UTI 1, 4
• Pyuria alone without symptoms: Consider asymptomatic bacteriuria, contamination, or noninfectious causes—do not treat 4

Step 4: Culture Indications

• Always culture: Suspected pyelonephritis, complicated UTI, recurrent UTI, immunosuppressed patients, pregnant patients 1, 4
• Culture not needed: Simple uncomplicated cystitis in healthy nonpregnant patients with typical symptoms 1
• Sterile pyuria (culture-negative): Consider tuberculosis, fungal infection, stones, interstitial cystitis, or recent antibiotic use 6

Critical Pitfalls to Avoid

• Never treat pyuria alone: Pyuria without symptoms represents asymptomatic bacteriuria or noninfectious inflammation in most cases 1, 4
• Do not diagnose UTI in elderly with delirium/confusion alone: Nonspecific symptoms without dysuria, frequency, urgency, or fever do not warrant UTI treatment 4
• Avoid overinterpretation in catheterized patients: Pyuria has only 37% sensitivity for catheter-associated UTI and should not trigger cultures without symptoms 5
• Recognize low specificity: Pyuria >10 WBC/hpf has only 61.8% specificity for bacteriuria; positive predictive value is 35.5% in some populations 8, 9
• Consider optimal cutoff: Pyuria >25 WBC/hpf provides better diagnostic accuracy (53.8% bacteriuria rate) compared to lower thresholds 8