Content:
◉ Introduction
Detection of white blood cells in urine is not uncommon. It occurs as a result of many inflammatory conditions, especially urinary tract infections. White blood cells may be present along with red blood cells, bacteria, altered pH, or urine content.
Sterile pyuria is characterized by the persistence of a high number of white blood cells in the urine without evidence of bacteria using standard laboratory urine culture techniques.
It is a sign that is often accompanied by other clinical signs or symptoms, and further investigations are usually necessary to diagnose the underlying condition.
◉ Definition
The presence of leukocytes in the urine (leukocyturia) is often associated with inflammation of the urinary tract, with or without bacterial infection.
Activation of the immune system leads to the recruitment of leukocytes (primarily neutrophils) into the urine, the intensity of which generally depends on the type and/or severity of the disease.
The search for leukocytes in urine is typically performed as part of urine analysis, where the urine is analyzed through multiple laboratory tests to detect any variations (pH variation, presence of bacteria, presence of nitrites, presence of ketone bodies, presence of hyaline casts, etc.).
In the laboratory, leukocytes are searched for using urine dipstick (Leukocyte Esterase test), microscopy, or automated devices. Positive pyuria is suspected when:
- There are more than 5 leukocytes per high-power field, or
- There are more than 10 leukocytes per µL with the hemocytometer method.
Urine analysis is generally followed by bacterial culture of the urine on culture medium. In the absence of the development of bacterial colonies on the culture media, an incubation period of 24 hours is generally sufficient to conclude that the urine is sterile.
Sterile pyuria is the association of the absence of bacteria in urine (sterile) and a significant amount of leukocytes.
◉ Causes of Sterile Pyuria
Leukocyturia can be caused by various factors other than infections. Here are some additional causes:
◉ Contamination during collection
- Contamination by vaginal secretions.
- Contamination by injury to the vulva or foreskin
- Contamination with an antiseptic.
◉ Infectious causes
These infectious causes require specific laboratory tests and cannot be detected by routine laboratory tests.
- Tuberculosis and other mycobacterial infections.
- Bacteria with specific culture requirements: Neisseria gonorrhoeae, Haemophilus influenzae, Brucella, spirochetes.
- Viral cystitis (herpes, adenovirus, chickenpox-zoster).
- Fungal infections.
- Parasitic infection: Trichomonas or urinary schistosomiasis.
- Urinary infections partially treated (infection decapitated by antibiotics).
- end or start of urinary infections where the number of bacteria is below the detection threshold.
- Infections of structures adjacent to the urinary tract (appendicitis, diverticulitis, prostatitis, perinephric abscess).
- Chlamydial urethritis: Chlamydia trachomatis, a sexually transmitted infection, can lead to leukocyturia.
◉ Non-Infectious Diseases
- Kidney Diseases: Presence of kidney stones, trauma, interstitial nephritis, Glomerulonephritis, Tumors, Hydronephrosis, Nephrocalcinosis, polycystic kidney disease, etc.
- Bladder Diseases: Interstitial cystitis, bladder stones, bladder tumors, etc.
- Sarcoidosis.
- Kawasak disease.
- Systemic lupus erythematosus: often associated with protein and erythrocytes in the urine.
- Sickle Cell Disease.
◉ Other Causes
- Urinary catheterization.
- Pregnancy.
- Obstructive uropathy.
- Foreign body.
- Vaginitis.
- Perimenstrual period (associated hematuria).
- Postoperative: cystectomy, transurethral resection of the prostate, etc.
- Intake of certain medications: For example, Olsalazine, nitrofurantoin, the use of penicillin antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, proton-pump inhibitors, and diuretics.
◉ Diagnosis
Investigating the origin of sterile pyuria typically involves a thorough assessment of the patient's medical history, associated symptoms, and additional diagnostic tests as needed. Here's a breakdown of the process:
◉ History and symptoms
Obtaining a detailed medical history is crucial. Symptoms and signs vary greatly according to the type and severity of the medical condition associated with sterile pyuria. For example
- If the cause was a recently or inadequately treated urinary tract infection resulting from cystitis, symptoms may include burning and/or painful urination, frequent urination, cloudy foul-smelling urine. It may also be associated with weakness and fever. However, if the cause was pyelonephritis, the patient may experience symptoms such as high fever, pain, frequent urination, tachycardia, and vomiting.
- Chlamydia trachomatis should be suspected if a young person who is sexually active and has a history of multiple sexual partners presents with lower urinary tract symptoms such as frequency, urgency, and nocturia.
- If the cause was renal tract tuberculosis, a person is usually immunocompromised and has symptoms of tuberculosis, including unintentional weight loss, night sweats, flank pain, hematuria, dysuria, and frequent urination.
- If the cause was renal or bladder stones, patient symptoms may include severe pain in the side or back, hematuria, burning urination (dysuria), high fever, and foul-smelling cloudy urine.
- If the cause was systemic lupus erythematosus, an autoimmune condition, symptoms may include painful swollen joints and morning stiffness (arthritis), fatigue, excessive tiredness, scaly butterfly rashes, and mouth and nose ulcers.
- If the cause was interstitial cystitis, which is a chronic disorder of unknown cause, symptoms may include chronic pelvic pain and discomfort, increased sensitivity in the bladder area, and a persistent urgent need to urinate.
◉ Laboratory tests
Urinalysis: is a series of tests commonly used to assess the health of the urinary system and detect various abnormalities. Among these tests are:
- Detection of nitrites in the urine
- Detection of crystals in the urine
- Examination for cells
- Identification of bacteria
- Detection of ketones in the urine
- Measurement of urinary density
- Detection of blood in the urine
- Measurement of protein in the urine.
Other tests and analyses can be carried out depending on the specific context, such as:
- Indirect immunofluorescence for antinuclear antibodies (ANA) and Anti-dsDNA antibodies in cases of suspected systemic lupus erythematosus.
- Staining urine with the Ziehl-Neelsen stain if tuberculosis is suspected.
- Using enriched media to culture fastidious organisms.
- PCR to detect Chlamydia trachomatis.
◉ Imaging
Ultrasound is often used as the first imaging modality to evaluate the kidneys and urinary tract. It can detect the presence of kidney or bladder stones, urinary obstructions, kidney cysts, or dilatations of the urinary tract.
Computed tomography (CT) and MRI are less commonly used than ultrasound, but they can be useful in certain cases.
◉ Conclusion
White blood cells can easily be detected through the routine urine analysis test, and it is extremely common. It appears in many inflammatory cases, especially in the urinary tract infections. It can be present alone, in which cases it is called sterile pyuria or it can be detected along with red blood cells, bacteria, altered pH or urine content.
Additional investigations take into account the history, associated symptoms, laboratory tests, and even imaging to help find the exact cause of this situation.