What is Sterile Pyuria?
Sterile pyuria is a medical condition where there are white blood cells in the urine, but no bacteria is found. These white blood cells can be detected in a urine test if more than 10 of them are found in each cube millimeter (mm³) of urine, or if the urine has more than 3 of these cells per microscopic field of view (WBC/HPF). Another way to detect the presence of white blood cells in the urine is through a test strip that contains chemicals that change color when they come in contact with certain substances in the urine (like leukocyte esterase or nitrites).
Sterile pyuria is confirmed when any of these white blood cell criteria are met, but the urine culture doesn’t show a significant presence of bacteria, which is defined as 105 or more colony-forming units (CFUs), or bacteria colonies, per milliliter of urine.
However, newer testing methods, such as next-generation sequencing, have shown that sterile pyuria doesn’t always mean an absence of bacteria. Researchers like Wolfe and his team have suggested that there might be bacteria present in the urinary tract that are a natural part of the body.
Despite this, sterile pyuria can still be difficult to tell apart from a real urinary tract infection (UTI) in a clinical setting. There are currently no definitive guidelines on how to manage sterile pyuria, leading to a common occurrence of improper treatment for this condition.
What Causes Sterile Pyuria?
“Sterile pyuria” is not actually a medical condition itself, but a term that describes a variety of conditions which all need different treatments. Despite what the name suggests, sterile pyuria is not always germ-free. It can be caused by several types of infectious organisms including some bacteria, viruses, fungi, and protozoa. Some bacteria (like Chlamydia trachomatis and Ureaplasma urealyticum), which don’t grow on commonly used culture media, can also cause it.
Sexual transmitted infections (STIs) including those from the bacteria Chlamydia trachomatis, Neisseria gonorrhoeae, and the parasite Trichomonas vaginalis are particularly important to note in young patients who present with sterile pyuria.
Infections that are not in the urinary tract such as pelvic inflammatory disease, appendicitis, diverticulitis, pneumonia, and sepsis, have also been linked to sterile pyuria. This is possibly due to inflammation in the urinary or genital tract causing white blood cells to move into the urinary tract system.
Non-infectious reasons for sterile pyuria could be inflammatory conditions like Kawasaki disease, systemic lupus erythematosus, and sarcoidosis. Conditions that weaken the immune system like uncontrolled diabetes, chronic steroid use, cancer, AIDS or rejection of a kidney transplant can also cause sterile pyuria. Other reasons could include kidney damage caused by drugs or by things like contrast dyes used in medical imaging, radiation inflammation of the bladder, or long term use of urinary catheters.
Eosinophiluria is a specific type of sterile pyuria. It can be associated with various conditions including allergic interstitial nephritis (kidney inflammation), cystitis (bladder inflammation), urinary tract blockage, immunoglobulin A (IgA) nephropathy (kidney disease), cholesterol emboli (blockage of blood vessels by cholesterol), and kidney failure caused by contrast dyes. Sometimes, the collection of the urine sample can contaminate it causing false positive results for sterile pyuria. This can happen if the urine sample doesn’t show any bacteria or shows growth of multiple types of bacteria.
Risk Factors and Frequency for Sterile Pyuria
Sterile pyuria, a condition where there are white blood cells in the urine but no bacteria, is a fairly common lab result. Based on studies, up to 13.9% of women and 2.6% of men might get this result. People with weaker immune systems or those in the hospital with infections not associated with the urinary tract can have even higher rates of sterile pyuria. It’s also observed that close to 87.5% of patients with acute appendicitis and 72.7% of those with acute diverticulitis showed signs of sterile pyuria.
- Up to 13.9% of women and 2.6% of men can have sterile pyuria.
- Higher rates may be found in people with weak immune systems or those in the hospital for non-urinary tract infections.
- About 87.5% of acute appendicitis patients and 72.7% of acute diverticulitis patients also showed sterile pyuria.
Signs and Symptoms of Sterile Pyuria
When a patient might have sterile pyuria (a condition with white blood cells in the urine but no bacteria), doctors will perform a detailed examination and ask a lot of questions. These questions might be about social life, sexual activity, family history, trips taken, recent infections, use of antibiotics, and any recent medical procedures. Specific urinary symptoms like painful urination or bloody urine could suggest the issue is in the kidneys or urinary system. However, more general symptoms like tiredness, swelling, joint ache, or skin rash might point to a broader body issue.
During the physical check-up, doctors will thoroughly examine the abdomen and pelvic areas to look for signs of inflammation, such as tenderness above the pubic area or around the sides of the back. They also look for signs such as pale skin, enlarged organs, or swollen lymph nodes. If they suspect a sexually transmitted infection, they will take genital cultures for testing.
Testing for Sterile Pyuria
Before further examination, it’s important to ensure the urine sample has been collected correctly to avoid false results. Normal bacteria or white blood cells (also known as leukocytes) from the urethra or vaginal secretions can confuse test results. A second urine test is encouraged to make sure the sample is pure and easy to analyze. Other essential tests include complete blood counts and chemistry panels which can identify early signs of underlying systemic diseases.
The patient’s history and physical examination can help rule out conditions like genitourinary tuberculosis (a form of tuberculosis that affects the urinary system and genitals) or sexually transmitted infections. Tests for specific bacteria like C trachomatis and N gonorrhoeae should also be carried out. If tuberculosis is suspected, a particular urine test should be performed. Additionally, imaging tests of the kidney, bladder and abdomen can help clarify the diagnosis in symptomatic patients.
Recognizing genitourinary tuberculosis can be tricky because regular urine cultures are not suitable for detecting the bacteria that cause this disease. Instead, the gold standard for diagnosing this condition is an AFB urine culture or a tissue biopsy culture. However, since the AFB urine culture’s accuracy rate varies, collecting at least three consecutive first-void morning urine samples is recommended to increase the accuracy. Newer techniques like PCR (Polymerase Chain Reaction) can also be used to identify the bacteria causing tuberculosis more accurately.
Some sexually transmitted infections (STIs) can be linked to sterile pyuria because ordinary culture methods may not detect the disease-causing organisms. Current tests for common STIs are simple, reliable, and affordable. Women are usually tested with a vaginal swab or first-catch urine sample, while men provide a first-catch urine specimen.
Various viral, fungal, and parasitic infections can all cause pyuria or white blood cells in the urine. Detecting these infections typically involves careful microscopic examination of urine samples, urine cultures, and sometimes tissue biopsies. Imaging tests can also be beneficial, particularly when fungal infections cause visible changes like fungal balls in the bladder and kidney masses.
The patient’s surroundings and lifestyle can also influence their risk of infection. People living in areas where certain fungal infections are common or those with a weakened immune system are at a higher risk of having these infections.
In more rare instances, inflammation elsewhere in the body can cause sterile pyuria. Several conditions, including urinary stones, radiation-induced bladder inflammation, and certain kidney diseases, can be linked to pyuria. Therefore, further examination based on the patient’s risk factors may be necessary.
Last but not least, sterile pyuria can sometimes be seen in patients with systemic inflammatory diseases like Kawasaki disease and lupus, and in those with cancers of the bladder, kidney, and prostate. In these cases, pyuria can be used as a potential marker for a recurrence of the tumor or the responsiveness to treatment. But remember, more research is needed in this area. Urinary tract stones can also result in sterile pyuria, which would require imaging tests to confirm.
Treatment Options for Sterile Pyuria
The treatment of sterile pyuria, a condition where there are white blood cells in the urine but no bacteria, largely depends on its root cause.
If sterile pyuria is caused by an infection, doctors usually prescribe antimicrobials, a kind of medication used to kill or stop the growth of microorganisms. The specific type and regimen of antimicrobials prescribed are carefully selected based on the specific infection causing sterile pyuria.
These infections could include:
– Genitourinary tuberculosis: This is a type of tuberculosis that affects the urinary system. A combination of several different drugs is usually used to treat this condition.
– Chlamydia: This is a sexually transmitted infection. It’s treated with medications like doxycycline or azithromycin.
– Gonorrhea: This is another sexually transmitted infection, and it’s typically treated with ceftriaxone and either azithromycin or doxycycline.
– Mycoplasma genitalium: This is a sexually transmitted bacterium. It’s treated with a regimen of doxycycline and azithromycin normally. If the bacterium is resistant to antibiotics, moxifloxacin may be used.
– Genital herpes: This is a viral sexually transmitted infection. Antiviral drugs like acyclovir, valacyclovir, or famciclovir may be prescribed.
– Trichomoniasis: This is a parasitic sexually transmitted infection. Metronidazole is usually the treatment.
For all sexually transmitted infections, it’s essential that sexual partners also receive treatment to prevent reinfection.
If a fungal infection is the cause of sterile pyuria, antifungal drugs like azoles, echinocandins, or amphotericin B might be prescribed. People with weakened immune systems, diabetes, or a history of organ or bone marrow transplants may require multiple antifungals.
In cases where the infection is caused by schistosomiasis, a disease caused by parasitic worms, the patient may be prescribed oral praziquantel, with the dosing adjusted based on the specifics of the patient’s condition.
What else can Sterile Pyuria be?
There are many potential causes for sterile pyuria, which means the presence of white blood cells in the urine without a bacterial infection. These can be divided into two main categories: infectious and noninfectious causes.
Infectious causes may include:
- Recent treatment for urinary tract infections (UTIs)
- Inflammation of the urethra caused by various bacteria like N gonorrhoeae, C trachomatis, or M genitalium
- Genitourinary tuberculosis
- Parasite infections such as trichomoniasis or schistosomiasis
- Infections of the genitourinary tract due to viruses or fungi
- Infections in the genital area
- Balanitis, which is inflammation of the glans penis
- Prostatitis, which is inflammation of the prostate gland
- Appendicitis
Noninfectious causes could be:
- Severe high blood pressure, which can cause blood in urine along with white blood cells
- System-wide inflammatory diseases like Kawasaki disease and sarcoidosis
- Changes in the kidneys due to congenital heart disease
- Pregnancy
- Long-term use of urinary catheters
- Recent urological procedures
- Foreign objects in the urinary tract, such as a leftover stent or surgical mesh in the urethra
- Other conditions related to the urinary tract, such as kidney stones, tumors, abnormal connections like fistulas, and polycystic kidney disease
- Rejection of a kidney transplant
- Blood clot in the renal vein
- Interstitial cystitis or bladder pain syndrome
- Necrosis, or death, of the papillae in the kidneys
- Damage to the kidneys caused by certain medications (e.g., pain relievers or from interstitial nephritis)
What to expect with Sterile Pyuria
Sterile pyuria, a condition where there are white blood cells in the urine but no bacteria, can usually be resolved with the right diagnosis and treatment, particularly if it’s caused by an infection. However, in chronic inflammatory conditions, a weakened immune system, or cancer, the condition might not clear up because these ongoing illnesses cause white blood cells to continually enter the urinary tract.
In many cases, the severity of pyuria often matches with the severity of the disease itself. This is especially true for patients with non-muscle invasive bladder cancer (a type of cancer that hasn’t spread to the muscles of the bladder). It’s been observed that if they have pyuria before surgery, there’s a higher chance of the cancer returning after removal of the tumor through surgery.
Possible Complications When Diagnosed with Sterile Pyuria
Over-interpreting sterile pyuria as a urinary tract infection (UTI) can lead to complications. When misdiagnosed as UTI, unnecessary antibiotics might be prescribed. However, these antibiotics often fail to tackle bacteria causing sexually transmitted infections (STIs) such as Chlamydia trachomatis or Neisseria gonorrhea. Furthermore, this misuse of antibiotics can lead to antibiotic resistance.
Mistaking sterile pyuria for other conditions can also delay the detection and treatment of genitourinary tuberculosis (GU-TB), allowing the illness to worsen. If left untreated, this disease can cause severe narrowing in the urinary tract, leading to blockage. It can result in complications like accumulation of fluid in the ureter (a condition known as hydroureter), a swelling condition of the kidney due to accumulation of urine (known as hydronephrosis) and renal failure.
List of Potential Complications:
- Prescription of unnecessary antibiotics
- Failure to treat bacteria causing STIs
- Antibiotic resistance
- Delay in detecting and treating GU-TB
- Narrowing in the urinary tract due to GU-TB
- Blockage symptoms due to untreated GU-TB
- Hydroureter due to untreated GU-TB
- Hydronephrosis due to untreated GU-TB
- Renal failure due to untreated GU-TB
Preventing Sterile Pyuria
Doctors need to be aware of the different causes and possible conditions related to sterile pyuria. This term refers to the presence of white blood cells, a sign of infection or inflammation, in the urine without any bacteria being present. However, it’s equally crucial for doctors to guide their patients on the importance of check-ups and ongoing tests based on any medical concerns the doctor may have.
Patients should be comforted knowing that having sterile pyuria doesn’t automatically mean they have a serious illness. Often, it can be due to a harmless cause.
