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Causes of The UTI That Isn't

Many women may be familiar with the problems of recurrent/frequent urinary tract infections (UTIs) , or even apparent UTI symptoms for which no bacterial infection can be found. This later condition, which one urologist likes to call “The UTI That Isn’t” can be especially frustrating. Let’s talk about the possible causes of “The UTI That Isn’t”.

Urethral Syndrome
While the symptoms of frequency/urgency/pain are present in almost all true UTIs, 30-50% of patients with these symptoms do not have significant bacteria in their urine (Najar, 2009). However, many of those without bacteria may have white blood cells (sign of infection or inflammation) in their urine. This likely reflects the presence of other infections which may not be bacterial. The presence of white blood cells, no bacteria, and UTI symptoms is the one common description of “urethral syndrome.”

Many of the organisms thought to be causes of urethal syndrome are also causes of vaginal infections. Included in this category are chlamydia, Ureaplasma urealyticum, gonorrhea and trichomoniasis. In a study of 63 women with urethral syndrome (Mutlu, 2001), evidence for chlamydia was found in 38% of the group. The organism Ureaplasma urealyticum was identified in 192 women with urethral syndrome (Skerk, 2001). Gonorrhea can infect the urethra in both men and women. Trichomoniads (“trich”) can find their way into the female urethra from vaginal secretions (or infected male ejaculate). Less commonly, a genital herpes lesion within the urethra can prompt urinary symptoms. Even a vaginal yeast infection, while it does not infect the urethra, can be associated with pain as the urine stream touches irritated skin on the vulva. Fortunately, both trich and yeast can be seen on a microscope slide of vaginal secretions. This is one reason why continued UTI symptoms need to be seen in the clinic rather than using repeated, telephoned prescriptions.

Once an organism is identified appropriate medications can be given. In a treatment study for chlamydia of the urethra (Skerk, 2001), researchers determined that women may require longer duration of antibiotic dosing than used for vaginal/cervical chlamydia . If urethral symptoms had been present for three weeks or longer, better cure rates were achieved with six days of azythromycin 500mg/day or fourteen days of doxycycline  100mg/twice a day. For those with Ureaplasma, the best dose (Skerk, 2001) was also an extended duration of azithromycin 500mg/day for six days.

Overactive Bladder Syndrome
Overactive Bladder (OAB) can be distinguished from a UTI, or urethral syndrome, by the absence of any type of infection. Moreover, OAB does not cause pain with voiding. The hallmark of OAB is pronounced urgency and frequency. Many women have episodes of incontinence where large amounts of urine are suddenly released — often as they run for the toilet. Most GYNs are adept at diagnosing OAB; it can be confirmed by urodynamic studies. OAB is thought to be caused by the inappropriate firing of nerves in the bladder wall. These impulses tell the brain that the bladder is full and needs to be emptied, even if there are only small amounts present. Treatments include Kegel exercises, bladder training, lifestyle changes, and medications to decrease the inappropriate urge to void.

Anatomic Abnormalities

Less commonly, pain coupled with urgency and frequency may indicate an anatomic problem. Fletcher and Zimmern (2009) list urethral diverticulum, a cyst of the Skene’s gland, and strictures/narrowing of the urethra as conditions to be ruled out. A urethral diverticulum is a small “pouch” in the urethral canal where urine can collect. Skene’s glands are located on either side of the urethra. These glands can develop a cyst, or an abscess, which would narrow the diameter of the urethra. A stricture of the urethra would also narrow the outlet through which urine needs to pass.

Interstitial Cystitis/ Painful Bladder Syndrome (IC/PBS)
IC/PBS is a characterized by urinary frequency, urgency, and lower abdominal pain where no identifiable pathology can be found (Butrick, 2003). It can be misdiagnosed as chronic UTI, OAB, or even chronic pelvic pain. Unlike a UTI, pain tends to improve with urination; unlike OAB there is an element of pain. Unlike chronic pelvic pain, one study (Warren 2008), found that pain above the pubic bone and pain in the urethra were more common than genital pain among 226 women with IC/PBS.

The cause(s) of IC/PBS are hotly debated. Each presumed cause has a distinctly different treatment modality. Let’s summarize the three of the most currently researched causes of IC/PBS.

1.  A defect in the layer of mucus that protects the bladder wall from direct contact with urine. A defect in the mucus (also known a GAG layer) layer has been caused from a severe UTI, damage from childbirth, or some other trauma. Consequently, irritants in the urine create inflammation, tissue changes, and increased pain signals to the brain. Treatments include avoidance of caffeine, alcohol, artificial sweeteners, carbonation, and spicy and acidic foods. There are two FDA approved prescriptive treatments. One is a pill (Elmiron®) that is taken three times/day. The other is DMSO that is instilled in the bladder by a urologist.

2.  A neurological disorder in pain processing pathways of the central nervous system. The limbic system in the brain has an increased sensitivity to pain signals from the pelvic organs, which then triggers muscle contractions in the involved area (Birder, 2010).  Treatments not submitted to the FDA for approval but often used include: amitriptyline or noretriptyline pills, or local anesthetics instilled in the bladder by a urologist.

3.  The presence of tissue than is transforming one cell type into a more mature cell type (“metaplasia”) in the bladder neck region. Women not receiving relief from medications were treated with a laser to remove metaplasia. Three months after treatment biopsies of the area showed no metaplasia in the 68% of patients that improved, but metaplasia was still present in the 32% who did not improve (Constantini, 2006).

Overall, IC/PBS is perceived to be a complex condition with no one clearly identified cause. As such, many treatment approaches may be combined. The addition of biofeedback, physical therapy, education, and support may enhance response to treatment.  The following are some sites which offer more detailed information/support for persons with IC/PBS:

What’s the bottom line?

In summary, if you are having symptoms of a UTI you should get checked out with at least a urine dipstick. Treat promptly with antibiotics if indicated and expect that symptoms may take three to four days to improve. If symptoms return, go back for follow up.

If you are a woman with persisting urinary symptoms, and cultures negative for bacteria, one of the important things you can do is to educate yourself about some of the possible causes of such symptoms. A GYN may be relieved if you raise the issue that it might not be bacteria in the urine that is causing your symptoms.

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