Diagnosing and treating interstitial cystitis

If only it were as simple as a urinary tract infection.

Interstitial cystitis is a chronic inflammation of the bladder that sends many women on urgent trips to the bathroom to urinate — sometimes painfully — as often as 40, 50, or 60 times a day, around the clock. The discomfort can be so excruciating and difficult to manage that only about half of women with the disorder work full time. Their quality of life, research suggests, resembles that of a person on kidney dialysis or suffering from chronic cancer pain. Not surprisingly, the condition is officially recognized as a disability.

Of the more than 700,000 Americans who have interstitial cystitis, as many as 90% are women. The average age at onset is 40. Several other disorders are associated with the condition, including allergies, inflammatory bowel syndrome, fibromyalgia (a condition causing muscle pain), and vulvitis (pain in the soft folds of tissue outside the vagina).

There’s no cure for interstitial cystitis, but many treatments offer some relief, either singly or in combination. Fortunately, increasing awareness is helping to speed diagnosis of this frustrating condition and encourage research into how it develops. Surgery is rarely needed.

Difficult to pin down

Interstitial cystitis can vary greatly from woman to woman and even in a given individual. Symptoms may change from day to day or week to week, or they may remain constant for months or years and then resolve spontaneously, with or without therapy. Bladder pain ranges from dull and achy to acute and stabbing. Discomfort while urinating also varies, from mild stinging to burning. Sexual intercourse may ignite pain that lasts for several days.

In premenopausal women, symptoms often worsen with menstruation. Data suggest that some pregnant patients experience complete relief during the second and third trimesters.

Women who have interstitial cystitis don’t have any special risk factors except for childhood bladder problems, such as day and night wetting, which are 10–12 times more likely in women with the disorder than in those without it. Most are initially treated for urinary tract infections, that is, with antibiotics. When symptoms persist and urine cultures are negative, a woman may seek further evaluation. But the condition is so variable that it may take two or more years before she receives a proper diagnosis and referral to a urologist.

Diagnosis by deciding what it’s not

Unlike a urinary tract infection, interstitial cystitis cannot be diagnosed with a simple urinalysis or urine culture. Rather, it’s a diagnosis of exclusion, which means that a clinician — usually a urologist or gynecologist — will first take a thorough history and then perform tests designed to rule out other conditions. These include infection, bladder stones, bladder cancer, kidney disease, multiple sclerosis, endometriosis, and sexually transmitted diseases.

The next step is a procedure called cystoscopy with hydrodistension, which is performed under general anesthesia. The clinician inserts a fiber-optic tube through the urethra and into the bladder. The bladder is then filled beyond its usual capacity with liquid or gas to stretch it and allow a closer view of the bladder lining.

The most common sign of interstitial cystitis is red pinpoint spots of blood (glomerulations) covering much of the bladder wall surface (see below). Sometimes there are scars or lesions called Hunner’s ulcers, accompanied by low bladder capacity due to tissue stiffening (fibrosis).

During cystoscopy, the clinician may take a biopsy (tissue sample) of the bladder to rule out bladder cancer and look for evidence of the mast cells that indicate an allergic reaction or autoimmune response. Interestingly, distending the bladder can itself be therapeutic. About half of patients get some relief for about three months after the procedure.

Treating interstitial cystitis

Treatment (see chart) is aimed at relieving pain and reducing inflammation. The two main approaches are oral medications and bladder instillations — drugs that are introduced into the bladder by catheter and held for 15 minutes. The procedure usually takes place in a physician’s office, but in some cases these drugs can be self-administered at home.

No single treatment alleviates all symptoms, and some may stop working over time, so finding what works is often a matter of trial and error. The good news is that in 50% of cases, the disease will disappear on its own.

Because interstitial cystitis can be both physically and psychologically disabling, people who have it often need help coping with its many effects. One option is individual psychotherapy, especially if depression or anxiety is a problem. Another is a support group, which gives people a chance to talk with others who are in a similar situation. Also, learning as much as possible about interstitial cystitis may help a woman attain some sense of control over her condition.

More options

In a procedure called transcutaneous electrical nerve stimulation (TENS), pain pathways are modified by a device worn on the body. The device produces electrical impulses, which pass through electrodes that are attached to the body with small adherent pads. Patients can adjust the level of electrical stimulation themselves. Good results have been reported in about one-quarter of those using TENS.

An implantable device called InterStim directly stimulates the sacral nerve in the lower back. Already approved for treating bladder control problems, it’s now under study as a potential treatment for interstitial cystitis pain.

Some people report that stress reduction, exercise, biofeedback, or warm tub baths improve their symptoms, but no research has evaluated the effectiveness of these strategies. Bladder training — that is, learning to urinate only at specific times (despite the urge to go) — can help reduce urinary frequency. There’s no scientific evidence linking diet to interstitial cystitis, but many people believe that their symptoms are made worse by tomatoes, chocolate, caffeine, alcohol, and beverages that acidify the urine, such as cranberry juice.

Surgery is usually a last resort and undertaken only when the pain is crippling. The surgical procedure typically involves removal of the bladder and the creation of a new one (a neobladder) using intestinal tissue. Most people need to catheterize the neobladder themselves in order to empty it.

Many possible causes

No one knows the exact cause of interstitial cystitis. One theory is that it’s caused by infection with an undiscovered agent, such as a virus. Another is that it’s an autoimmune disorder set in motion by a bladder infection; cells that normally fight infection attack the bladder lining instead, causing pain, redness, and swelling (inflammation). Yet another theory is that mast cells normally involved in allergic responses release histamine into the bladder.

Some research has focused on defects in the layer of protective mucus that lines the bladder, which causes so-called leaky bladder syndrome. A leaky bladder allows harmful substances in the urine to leak through the mucous layer and inflame or ulcerate tissue below.

Another idea is that sensory nerves within the bladder “turn on” and spur the release of inflammatory substances. Because interstitial cystitis is mainly a woman’s disease, researchers think that hormones possibly contribute.

What’s new?

Although interstitial cystitis is still poorly understood, researchers and clinicians know a lot more about it than they did just a few years ago. That’s led to several developments.

Scientists seeking a diagnostic test have begun to identify substances unique to the urine of interstitial cystitis patients. They’ve also found that certain factors required for healthy cell growth appear to be missing from the urine, a discovery that could lead to a new therapy.

Researchers just completed a nationwide trial of resiniferatoxin (RTX) as a bladder instillation to treat interstitial cystitis. RTX is similar to capsaicin, the extract of chili peppers that has proven useful in treating arthritis pain. It is thought to block the sensory nerves in the bladder that contribute to pain and urinary urgency and frequency. (For more information about the trial, visit www.clinicaltrials.gov/ct/gui/show/NCT00056251.)

The National Institutes of Health has earmarked $5 million to fund new research into the causes and development of interstitial cystitis. It has also awarded nearly $4 million for a center at the University of California at Los Angeles that will study interstitial cystitis and other disorders that affect mainly women.

An international symposium of experts who investigate and treat interstitial cystitis met in October 2003 to discuss their latest findings. (For more information about the event, visit www.niddk.nih.gov/fund/other/ic.)