Urology

Cystitis --The Bladder On Fire. What Should You Do?

Christopher K. Payne, M.D.

Painful bladder conditions affect a large percentage of women at some point during their lives and yet generate scant research funding and relatively little interest from the medical community. Women and their physicians are often unaware of the variety of possible causes and many effective treatments. Sadly, it is not uncommon for a patient to be incorrectly diagnosed, offered no or inappropriate treatment, and to be denied referral for investigation that may lead to successful therapy. It is equally unacceptable for a woman to be labeled with a general, meaningless diagnosis such as "irritable bladder syndrome" as the endpoint of the evaluation. This article will define the common types of painful bladder conditions, what is known about their causes, review the diagnostic studies that may be required, and outline some of the treatment options. The purpose is to allow a woman to be an active and educated participant in her care.

The two most common painful bladder conditions are bacterial cystitis (urinary tract infection, UTI) and interstitial cystitis (IC). In most cases the correct diagnosis is strongly suggested by the history and examination of the urine and can be confirmed relatively quickly through basic testing. Other cases are very confusing and, despite a real effort on the part of the patient and physician, the diagnosis may be delayed by many months. Such cases require a concerted effort from both the patient and clinician to achieve success.

Urinary tract infections occur when bacteria enter the bladder, multiply and create inflammation and pain. Urine in the bladder is normally sterile (there are no bacteria at all). The symptoms of a UTI typically come on suddenly with frequency, urgency, and burning during urination. Many older women do not experience the burning pain but have only frequency and urinary incontinence (leakage of urine without control). Approximately 20% of women will suffer a UTI during their lifetime and once a woman has had one infection there is about a 25% likelihood of having another in the next five years.

Some women are particularly prone to UTIs and suffer several attacks each year. Research in the 1960s conclusively demonstrated that in almost every case the bacteria were not harbored within the body but entered the bladder from the outside, through the urethra. The infecting bacteria live in the vagina; the female urethra is very short and the bacteria may migrate into the bladder or may be pushed into the bladder during sexual intercourse. Recent research has shown that the major reason some women are susceptible to UTIs is due to the surface of the vagina and urethra. They may have receptors in these tissues to which bacteria can easily attach. This makes it easier for the bacteria to migrate into the bladder and create an infection.

A simple UTI is diagnosed by the typical history of sudden onset of symptoms and by urinalysis (examination of the urine with a chemical test (dipstick) and microscopic evaluation). When everything is in agreement no further tests are needed. The patient is treated with a short course of antibiotics (three days is standard) and marked symptomatic relief is expected in 24-48 hours although milder symptoms may persist for 5-7 days. Urinary analgesics such as Pyridium, Urised and Prosed may relieve the symptoms during the interval before the antibiotic takes effect but do not treat the infection. Within a few days, and certainly within a week, the patient is back to normal bladder function.

The patient with frequent UTIs presents a different problem. Some women seem to get infections every month or so and others report that the symptoms seem to come back as soon as the antibiotics are finished. These cases require more investigation as do women who have kidney infections (high fever, nausea, vomiting and flank pain along with a UTI), women who have infections during pregnancy, and children with UTIs. The first step is to obtain a culture and sensitivity (C & S) each time an infection occurs. This is when some of the urine is sent to a laboratory so that the infecting bacteria can be grown, identified, and tested for susceptibility to different antibiotics. Recurrent infections may be caused by bacteria that have developed resistance to common antibiotics. The pattern of infections will help the physician determine when other tests are necessary and which tests are the most likely to be fruitful. All women with frequent infections should have a careful pelvic exam, a measurement of the residual urine after voiding, and should keep a voiding record. The residual rine is usually measured by passing a catheter, a small plastic tube, through the urethra into the bladder to drain the urine remaining after a void. When carefully performed this produces little discomfort. The residual can also be estimated non-invasively by using ultrasound but this requires specialized equipment not available in most doctor's offices. The catheterization also provides a clean urine specimen for microscopic examination. In the voiding record or diary, the patient notes the time and amount of fluid intake as well as the time and amount of each void for 24 hours. Review of this record often leads to the identification of behavioral issues that predispose to infection or may suggest an underlying bladder abnormality that requires further investigation. Although not routine in adult women, other tests that may be required in certain cases include kidney x-rays (IVP) or ultrasound, cystoscopy (visual examination of the bladder and urethra through a telescope-like instrument), and x-rays taken during urination (voiding cystogram). Some of the abnormalities that predispose women to get infections include urinary incontinence, bladder prolapse (cystocele), urethral diverticulum, and most commonly, low fluid intake and infrequent voiding. The use of spermicides for contraception (with either a diaphragm or condoms) also predisposes to UTI because the spermicide alters the natural balance of organisms living on the surface of the vagina.

In most cases no major abnormality will be uncovered and therapy must focus on prevention of the infections. The most frequent strategy is to use prophylactic (preventative) antibiotics. The patient will take a small dose of antibiotic each night at bedtime (this works best because the antibiotic will concentrate in the urine at night and have the longest exposure to any bacteria in the bladder). If UTIs are associated with sexual activity, another strategy is to take one antibiotic after intercourse only. This is an effective regimen and requires fewer antibiotic doses but some patients find it harder to remember and others have infections unrelated to sex. Studies have demonstrated that >97% of women with recurrent UTIs will respond to such programs. A patient who develops a "breakthrough" infection while on prophylaxis should always have further investigation to look for an underlying anatomic cause for the problem.

After a three to six month period of prophylaxis the antibiotic can be discontinued and about two thirds of women will break out of the cycle of recurrent infections. The odds can be improved if the patient makes an effort to increase fluid intake, voids regularly, and regulates the vaginal bacteria by taking acidophillus preparations. Many of the antibiotics used to treat UTIs also kill the normal vaginal bacteria. This allows the vagina to become colonized with more aggressive bacteria and start the cycle of recurrent infections. It also may lead to overgrowth of yeast in the vagina with symptoms of burning, itching and discharge. The normal bacteria of the intestine and vagina are lactobacillus and are found in the acidophillus preparations, available without a prescription at most health food stores. I recommend that patients take these capsules twice daily for 6-12 weeks and whenever antibiotics are prescribed, in order to prevent changes in the intestine and vagina. Many patients also find that acidophillus improves irritable bowel symptoms. Finally, hormone replacement in the post menopausal female reduces the risk of recurrent infections and should be discussed in the context of the woman's overall health.

In contrast to bacterial cystitis, interstitial cystitis is an inflammation that is not caused by bacteria. Although much less common than UTIs, it is estimated that up to 450,000 Americans are affected. Ninety percent of the patients are female. Although some patients with IC date their symptoms to a UTI from which they never fully recovered and other patients may occasionally have bacterial infections, the definition of IC is that the patient's symptoms must occur consistently and over a substantial period of time in the absence of infection. The cause of IC is unknown. Theories that are being investigated include immune system disorders, disorder of the body's inflammatory response, toxic/irritating substances in the urine, a defect in the protective inner layer of the bladder, inflammation of the bladder nerves, and infection with an as yet undiscovered organism.

The symptoms of IC are similar to UTI but can usually be distinguished by careful questioning. In both conditions frequency, urgency, and pain are present. The IC patient generally has increasing pain on bladder filling that is manifest by pressure, burning, and spasms. The pain typically decreases after voiding only to build up again as the bladder starts to fill. The sensation of a full bladder is very unpleasant but most IC patients feel they can control their bladder and incontinence is uncommon. In contrast, the UTI patient has severe pain during and after voiding and the urge to urinate is sudden, severe, and often results in leakage before the patient reaches the toilet.

Interstitial cystitis has a natural course characterized by spontaneous flares and remissions. Flares may be brought on by certain dietary items, physical or emotional stress, hormonal changes during the menstrual cycle and sexual activity among others. This type of course can seem like bacterial cystitis, especially if the patient is given antibiotics each time a flare occurs and sees gradual improvement. In contrast to the UTI patient the urine culture shows no significant growth and the urinalysis is usually normal. In addition, the IC patient will not have a prompt improvement with the antibiotic, will feel only slight improvement with urinary analgesics, and will not go back to normal bladder function when the flare is over. The IC patient typically has persistently increased voiding frequency and at least some bladder discomfort. Sometimes the patient feels that the bladder is normal between flares, but a voiding diary will usually demonstrate that the capacity is unusually low and careful questioning will bring out pressure and discomfort that is present whenever the patient must delay voiding.

The history is the single most important factor in making the diagnosis of IC and a thorough history will obviate the need for additional testing in many patients. Some cases will not be so clear and additional testing is necessary and appropriate. It is extremely important to exclude other pelvic diseases that may cause bladder irritation such as endometriosis, urethral diverticula, sexually transmitted diseases, as well as bladder and gynecologic cancers. Carcinoma in situ of the bladder can cause very similar symptoms and must always be considered as a possible diagnosis, particularly when the patient is a smoker or blood is present in the urine. When the history, physical exam, and urinalysis do not rule out other conditions imaging studies such as a pelvic ultrasound and IVP (kidney x-ray) may be useful. The most important diagnostic test in the work-up for IC is cystoscopy under anesthesia. In order to properly evaluate a patient for IC the procedure should be done under anesthesia in an operating room so that the bladder can be stretched (distended), a procedure that is too painful without anesthesia. Before distention, the bladder of an IC patient generally looks normal although scarred, ulcerated areas may be visible in some severe cases. After distention, however, small bleeding points will be seen throughout the bladder surface (which represent rupture of the smallest blood vesselsócapillaries) and the lining of the bladder may be observed to crack with linear fissures. These characteristic bleeding points are referred to as glomerulations and are the hallmark of IC. The bladder is usually biopsied to exclude the possibility of cancer as well as to evaluate the degree and nature of the inflammatory response. Alternatively, a bladder wash cytology (essentially a Pap smear of the bladder) may be collected during the cystoscopy to rule out carcinoma in situ without biopsy.

While the day-to-day course of IC is variable as mentioned above, the overall course of the disease is rarely relentlessly progressive. Most patients will reach their maximum symptoms in the first 12-18 months. At this time there is no definite curative treatment. Many effective treatments are available and most patients gain considerable symptomatic relief from either chronic or "as needed" therapy. Our ability to chose the best treatment for a particular patient is limited and there is considerable room for the patient to become involved in the decision making. In general, treatments are chosen to address the most bothersome symptoms and to minimize or take advantage of side effects. The most popular treatments are briefly reviewed.

Although bladder distention is primarily a diagnostic maneuver it is the initial treatment for most IC patients. Approximately 40% of patients will have some therapeutic response. Three quarters of the responders will relapse within one year. Those who have a prolonged response may be managed by repeat distention when a flare occurs and sometimes an office bladder distention under local anesthesia and sedation may be helpful. When the initial distention is not beneficial, DMSO bladder instillations are the most common therapy. DMSO is a liquid that has anti-inflammatory and analgesic properties among others that can be beneficial in IC. It is typically given as a series of six weekly treatments by in and out catheterization. Three oral drugs are commonly used in ICóamitryptiline (Elavil), hydroxyzine (Vistaril/Atarax), and pentosanpolysulfate (Elmiron). Amitryptiline is an antidepressant which is also widely used in chronic pain conditions such as cancer, nerve injury, etc. It is particularly useful for the IC patient with a predominant symptom of pain. The primary side effect is sedation so it is also useful for the patient who is unable to sleep because of the bladder pain and frequency. Its use is limited by the side effects of sedation, constipation, weight gain, and others. Hydroxyzine is a broad acting antihistamine. One of the leading theories about the cause of IC is that it is a disorder of mast cells, the inflammatory cells that mediate our allergic response. It is theorized that these cells are increased and unstable in the bladder, easily releasing inflammatory products in response to stress or irritating substances in the urine. Patients with many allergies do seem to benefit particularly from hydroxyzine therapy and it should be considered when increased mast cells are demonstrated on the bladder biopsy (this requires that the surgeon request a special stain to identify mast cells). The drug is better tolerated than amitriptyline but also has sedative effects. Pentosanpolysulfate is the only oral drug specifically approved for the treatment of IC. It is intended to help repair/augment the bladder's protective lining and prevent absorption of urinary irritants that may create inflammation. It is attractive because it has very few side effects. Probably because of very poor oral absorption the drug must often be used for 3-6 months before a clear response is noted. Thus, it is most appropriate for patients with mild to moderate symptoms. A structurally analogous drug, heparin, is available as a liquid and some patients will instill the drug directly into the bladder by self catheterization. Recently a test has been proposed to identify patients who may be more likely to respond to this form of therapy and to monitor the progress of treatment.

Many other treatments are available for the IC patient who responds inadequately to the above therapies. Narcotic and non-narcotic pain medications, dietary therapy, TENS units and other forms of nerve stimulation, pelvic floor biofeedback, and acupuncture are only a few of the treatments that patients have found to be helpful. Exciting clinical research is also underway. Two large multicenter, international trials are currently recruiting patients and the NIH will be sponsoring a series of trials in five US centers next year. At no time has the outlook for progress in IC research seemed brighter.

Not all patients with urinary frequency or pelvic pain have bacterial cystitis or IC. Patients with very frequent urination and incontinence but no pain may have detrusor instability (bladder spasms). A cystometrogram, a test in which bladder pressure is measured using a small catheter, can differentiate this condition from interstitial cystitis in confusing cases. Detrusor instability and similar conditions with an overactive bladder but no pain respond favorably to bladder relaxant medications which are typically ineffective in IC. There are also conditions in which pelvic pain occurs without a significant change in bladder function. Endometriosis is a gynecologic condition characterized by pelvic pain and infertility. Only rarely is bladder function significantly affected. The urethral syndrome is characterized by pelvic pain during urination in the absence of infection. It is often associated with painful intercourse and pain with defecation. These cases seem to be due to spasm and pain originating in the pelvic floor muscles. Treatment is directed at the muscles through biofeedback, directed massage (myofascial release), and nerve stimulation. In some cases where the involvement is limited to the urethra the cause may be localized infection or a small urethral diverticulum. A voiding cystogram is mandatory in the evaluation of these cases.

The most important message is that most patients with bladder pain and frequency can be effectively treated after only a minimal evaluation, but some patients will not respond favorably. These patients must work with their doctor to establish a clear diagnosis, carefully investigate their own behavior patterns that might be changed to help manage the disease, and patiently work through what is sometimes a frustrating series of treatments to find the solution. Help is available for almost all patients who are willing to participate actively in their care. For the truly refractory patient, current research protocols offer new hope for relief.

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