What are the causes of recurrent sterile pyuria in children?

Causes of Recurrent Sterile Pyuria in Children

The most common causes of recurrent sterile pyuria in children include urinary tract infections with atypical pathogens, genitourinary abnormalities, inflammatory conditions, and systemic diseases that affect the urinary tract. 1

Definition and Significance

• Sterile pyuria is defined as the presence of white blood cells in the urine without bacterial growth on standard culture media 2, 1
• It represents a common but often overlooked finding in pediatric patients that requires thorough investigation, especially when recurrent 1

Infectious Causes

Partially Treated Bacterial Infections

• Recent antibiotic therapy may lead to negative urine cultures despite ongoing infection and inflammation 1
• Common uropathogens like E. coli and Klebsiella may be present below detectable thresholds after partial treatment 3

Atypical Pathogens

• Tuberculosis: Mycobacterium tuberculosis infection of the urinary tract can cause persistent sterile pyuria and should be considered in children with recurrent symptoms who don't respond to standard antibiotics 4
• Viral infections: Various viruses can cause urinary tract inflammation without bacterial growth on standard cultures 1
• Fungal and parasitic infections: These organisms require special culture media and may be missed on routine testing 1

Sexually Transmitted Infections

• In adolescents, organisms such as Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis should be considered 1

Non-Infectious Causes

Systemic Inflammatory Conditions

• Kawasaki disease: Sterile pyuria occurs in 30-80% of patients with Kawasaki disease, particularly in children under 1 year of age 5
• The pyuria in Kawasaki disease is characterized by mononuclear cells rather than neutrophils in the urine 5

Genitourinary Abnormalities

• Vesicoureteral reflux (VUR): Children with VUR are at increased risk for recurrent urinary tract inflammation, even in the absence of active infection 6
• Urinary tract obstruction: Any obstruction can lead to inflammation and sterile pyuria 6
• Urolithiasis: Kidney or urinary tract stones can cause persistent inflammation 6

Adjacent Inflammation

• Inflammation of structures adjacent to the genitourinary tract can result in sterile pyuria 1
• This includes conditions like appendicitis or inflammatory bowel disease 1

Renal Diseases

• Glomerulonephritis: Various forms can present with sterile pyuria 1
• Interstitial nephritis: Often medication-induced, can cause persistent sterile pyuria 1

Drug-Related Causes

• Certain medications can cause sterile pyuria as a side effect 1
• Nonsteroidal anti-inflammatory drugs (NSAIDs) are common culprits 1

Diagnostic Approach

• Thorough history and physical examination focusing on systemic symptoms, medication use, and family history 1
• Urinalysis with microscopy to characterize the type of white blood cells present (neutrophils vs. mononuclear cells) 5
• Renal and bladder ultrasonography to detect anatomic abnormalities 6
• Consider specialized tests for tuberculosis (early morning urine samples for acid-fast bacilli) in persistent cases 4
• Voiding cystourethrography (VCUG) is indicated if renal and bladder ultrasonography reveals hydronephrosis, scarring, or other findings suggesting high-grade VUR or obstructive uropathy 6

Management Considerations

• Treatment should target the underlying cause rather than empiric antibiotic therapy 2
• For suspected atypical infections, appropriate cultures and testing should be performed before initiating specific antimicrobial therapy 4
• In cases of anatomical abnormalities, surgical correction may be necessary 6
• For inflammatory conditions like Kawasaki disease, treatment of the underlying condition is essential 5

Prognosis and Complications

• Most cases of sterile pyuria without underlying structural abnormalities have good outcomes 3
• Persistent untreated causes (especially tuberculosis) can lead to renal scarring and potential long-term complications 7, 4
• Children with bilateral renal scarring are at highest risk for developing renal insufficiency 7

Special Considerations

• Sterile pyuria in infants and young children warrants more aggressive evaluation due to higher risk of congenital anomalies 6
• Recurrent episodes should prompt consideration of rare causes and more extensive imaging 6
• The absence of fever does not exclude significant urinary tract pathology 6