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It contains information on the causes, diagnosis, and treatment of interstitial cystitis as well as information on current research studies that aim to understand and treat the disorder.
Basic and clinical research is advancing our knowledge of interstitial cystitis, but the disorder still poses many questions that scientists cannot answer. Only further research and the efforts of patients and doctors working together will shed light on improved treatments and, ultimately, a cure for this debilitating disorder.
The urinary system consists of the kidneys, ureters, bladder, and urethra. The kidneys, a pair of purplish-brown organs, are located below the ribs toward the middle of the back. The kidneys remove liquid waste from the blood in the form of urine, keep a stable balance of salts and other substances in the blood, and produce erythropoietin, a hormone that aids the formation of red blood cells. Narrow tubes called ureters carry urine from the kidneys to the bladder, a triangle-shaped chamber in the lower abdomen. Like a balloon, the bladder's elastic walls relax and expand to store urine and contract and flatten when urine is emptied through the urethra. The typical adult bladder can store about 1 1/2 cups of urine.
Adults pass about a quart and a half of urine each day. The amount of urine varies, depending on the fluids and foods a person consumes. The volume formed at night is about half that formed in the daytime.
Normal urine is sterile. It contains fluids, salts and waste products, but it is free of bacteria, viruses and fungi. The tissues of the bladder are isolated from urine and toxic substances by a coating that discourages bacteria from attaching and growing on the bladder wall.
People with interstitial cystitis (IC) have an inflamed, or irritated, bladder wall. This inflammation can lead to scarring and stiffening of the bladder, decreased bladder capacity, glomerulations (pinpoint bleeding) and, in rare cases, ulcers in the bladder lining.
IC, also known as painful bladder syndrome and frequency-urgency-dysuria syndrome, is a complex, chronic disorder that has baffled doctors for as long as it has been recognized.
Estimates of the number of people who have IC run as high as 500,000, but no one knows for sure how many people have it. About 90 percent of IC patients are women. While people of any age can be affected, about two-thirds of patients are in their twenties, thirties, or forties. IC is rare in children. In a few cases, IC has afflicted both mother and daughter, but there is no evidence that the disorder is hereditary, or genetically passed from parent to child.
Because IC varies so much in its symptoms and severity, most researchers believe that it is not one but several diseases. Two types of IC are usually described; they are mainly distinguished by whether ulcers have formed on the bladder wall. Most researchers believe that IC does not generally progress from the nonulcerative to the ulcerative form.
This disorder is the most common type of IC. It usually affects young to middle-age women who have a normal, near normal, or increased bladder capacity when measured under general anesthesia. Glomerulations can be seen in the bladder wall.
This type of IC tends to be found in middle-age to older women. Bladder capacity is low (less than 1 1/2 cups) when measured under general anesthesia. The decrease is thought to result in part from fibrosis, the formation of threadlike
tissue that makes the bladder stiff and small. Cracks, scars, and Hunner's ulcers (star-shaped sores) in the bladder wall may bleed when the bladder is filled to capacity during a cystoscopy.
No one knows what causes IC, but doctors studying the disorder believe it is a real, physical problem-not a result, symptom, or sign of an emotional problem.
One area of research on the cause of IC has focused on the lining of the bladder called the glycocalyx, made up primarily of substances called mucins and glycosaminoglycans (GAGs). This layer normally protects the bladder wall from toxic effects of urine and its contents. Researchers at the University of California, San Diego, found that this protective layer of the bladder was "leaky" in about 70 percent of IC patients they examined and may allow substances in urine to pass into the bladder wall and trigger IC symptoms. The researchers also found that patients with Hunner's ulcers had "leakier" bladders than patients without the ulcers.
Some people are diagnosed with IC after taking antibiotics for a presumed urinary tract infection. Therefore, it has been suggested that antibiotics may damage the bladder wall and make it "leaky." This idea has been studied carefully, but antibiotics have never been found to harm the bladder wall. Thus, other ideas are more likely to explain why some IC patients are diagnosed after a urinary tract infection. It is possible that the infection started an autoimmune response against the bladder, the patient's original symptoms were from IC all along, or an infecting organism is in bladder cells but is not detectable through routine tests.
The symptoms of IC vary greatly from one person to another but have some similarities to those of a urinary tract infection:
Because the symptoms of IC are similar to those of other disorders of the urinary system, and because there is no definitive test to identify IC, doctors must rule out other conditions before considering a diagnosis of IC. Among these disorders are urinary tract or vaginal infections, bladder cancer, bladder inflammation or infection caused by radiation to the abdomen, eosinophilic and tuberculous cystitis, kidney stones, endometriosis, neurological disorders, sexually transmitted diseases, low-count bacteriuria, and, in men, chronic bacterial and abacterial prostatitis.
The diagnosis of IC in the general population is based on
Medical tests that help identify other conditions include a urinalysis, urine culture, cystoscopy, biopsy of the bladder wall and, in men, laboratory examination of prostate secretions.
These tests can detect and identify the most common organisms in the urine that may be causing symptoms. There are, however, organisms such as the bacteria chlamydia that can't be detected with these tests, so a negative culture does not rule out all types of infection. A urine sample is obtained either by catheterization or by the "clean catch" method. For a "clean catch," the patient washes the genital area before collecting urine "midstream" in a sterile container. White and red blood cells and bacteria in the urine may indicate an infection of the urinary tract, which can be treated with an antibiotic. If urine is sterile for weeks or months while symptoms persist, a doctor may consider a diagnosis of IC.
In men, the doctor will obtain prostatic fluid from the patient. This fluid will be examined for signs of an infection, which can be treated with antibiotics.
During cystoscopy to diagnose IC, the doctor uses a cystoscope-an instrument made of a hollow tube about the diameter of a drinking straw with several lenses and a light-to see inside the bladder and urethra. The doctor will also distend or stretch the bladder to its capacity by filling it with a liquid or gas. Because bladder distension is painful in IC patients, before the doctor inserts the cystoscope through the urethra into the bladder, the patient must be given either regional or general anesthesia. These tests can detect inflammation; a thick, stiff bladder wall; Hunner's ulcers; and glomerulations (pinpoint bleeding) that may be seen only after the bladder is stretched.
The doctor may also test the patient's maximum bladder capacity, the amount of liquid or gas the bladder can hold under anesthesia. Without anesthesia, capacity is limited by either pain or a severe urge to urinate. Many people with IC have normal or large maximum bladder capacities under anesthesia. However, a small bladder capacity under anesthesia helps to support the diagnosis of IC.
A biopsy is a microscopic examination of tissue. Samples of the bladder and urethra may be removed during a cystoscopy and examined with a microscope later. A biopsy helps rule out bladder cancer and confirm bladder wall inflammation.
Scientists have not yet found a cure for IC, nor can they predict who will respond best to which treatment. Symptoms may disappear without explanation or coincide with an event such as a change in diet or treatment. Even when symptoms disappear, however, they may return after days, weeks, months, or years. Scientists do not know why.
Because doctors do not know what causes IC, treatments are aimed at relieving symptoms. Most people are helped for variable periods of time by one or a combination of treatments, many of which are described briefly in this booklet. However, as researchers learn more about IC, the list of potential treatments may change. Patients should discuss treatment options with a doctor.
Because some patients have noted an improvement in symptoms after a bladder distension done to diagnose IC, the procedure is often thought of as one of the first treatment attempts.
Researchers are not sure why distension helps, but some believe that the procedure may increase bladder capacity and interfere with pain signals transmitted by nerves in the bladder. Symptoms may temporarily worsen 24 to 48 hours after distension, but should then return to predistension levels or improve after 2 to 4 weeks.
This procedure may also be called a bladder wash or bath. During a bladder instillation, the bladder is filled with a solution that is held for varying periods of time, from a few seconds to 15 minutes, before being drained through a narrow tube called a catheter.
The only drug approved by the U.S. Food and Drug Administration (FDA) for bladder instillation is dimethyl sulfoxide (DMSO, RIMSO-50). With DMSO treatments a narrow tube (catheter) is guided up the urethra into the bladder. A measured amount of DMSO is passed through the catheter into the bladder, where it is retained for about 15 minutes before being expelled. Treatments are given every week or two for 6 to 8 weeks, and repeated as needed. Most people with IC who respond to DMSO notice improvement of symptoms 3 or 4 weeks after the first 6- to 8-week cycle of treatments. Highly motivated patients who are willing to catheterize themselves may, after consultation with their doctor, be able to have DMSO treatments at home. Self-administration of DMSO is less expensive and more convenient than going to the doctor's office.
Doctors think DMSO works in several ways. Because it passes into the bladder wall, DMSO may more effectively reach tissue to reduce inflammation and block pain. It may also prevent muscle contractions that may cause pain, frequency, and urgency.
A bothersome but relatively insignificant side effect of DMSO treatments is a garlic-like taste and odor from the breath and skin. This may last up to 72 hours after a treatment. Long-term DMSO treatments have caused cataracts in animal studies, but this side effect has not appeared in humans. Blood tests, including a complete blood count and kidney and liver function tests, should be done about every 6 months.
A variety of other drugs have been used experimentally for bladder washes, including silver nitrate, sodium oxychlorosene (Clorpactin WCS-90), heparin, and pentosanpolysulfate (Elmiron).
Silver nitrate and oxychlorosene sodium are thought to work by first attacking the bladder lining. This triggers the body's immune system to step in and start the healing process. Some patients have been successfully treated with these drugs, but the frequent, painful treatments usually must be done under general anesthesia. Neither drug can be used in people who have urinary reflux, a condition in which urine flows backward up the ureters into the kidneys.
Heparin and pentosanpolysulfate are thought to work by replacing or repairing the "leaky" bladder lining.
There are no oral drugs approved by the FDA specifically for the treatment of IC, but a variety of drugs such as aspirin, ibuprofen, antihistamines, and the urinary tract pain reliever phenazopyridine (available by prescription as Pyridium and over-the-counter as Azo-Standard) may help lessen symptoms.
A blend of atropine, hyoscyamine, methenamine, methylene blue, phenyl salicylate and benzoic acid (Urised) may inhibit the growth of organisms in the urine and reduce bladder spasms that cause frequency, urgency, and nighttime trips to the bathroom. Drugs such as oxybutynin chloride (Ditropan) also may reduce bladder spasms. In separate studies of only a few patients each, hydroxyzine (Vistaril and Atarax), an antihistamine, and nifedipine (Procardia), a heart disease and high blood pressure treatment, have been reported to reduce symptoms in some IC patients. But, as stated by the authors of these reports, further studies are needed to determine the drugs' true value in IC patients. All of these drugs must be prescribed by a physician.
Amitriptyline (Elavil) is an FDA-approved tricyclic antidepressant, but its ability to block pain and reduce bladder spasms makes it helpful in treating IC. Amitriptyline may cause drowsiness but can be taken at night to reduce this effect. Most people who respond to this drug show improvement 3 or 4 weeks after starting treatment. The dose may need adjustment for the best possible results.
The experimental drug sodium pentosanpolysulfate (Elmiron) is thought to repair the layer lining the bladder. In several studies, 19 percent to 65 percent of patients reported at least partial symptom relief. Most people who respond to pentosanpolysulfate see improvement within 6 to 8 weeks after starting treatment. There are few side effects, but the most common is skin rash. Clinical trials have been completed, and the drug's manufacturer has requested FDA approval to market pentosanpolysulfate as a treatment for IC. Until approved by FDA, doctors can prescribe the drug only by first obtaining approval for compassionate use in individual patients, or by having patients participate in an FDA-approved clinical trial.
Another experimental drug, nalmefene hydrochloride (Incystene), blocks the body's receptors to pain, thus inhibiting the sensation of pain. Nalmefene is currently being evaluated in the treatment of IC in an FDA-approved clinical study sponsored by the drug's manufacturer.
Because drugs have side effects, patients should always consult a doctor before using any drug for an extended time.
With TENS, mild electric pulses enter the body for minutes to hours two or more times a day either through wires placed on the lower back or the suprapubic region, between the navel and the pubic hair, or through special devices inserted into the vagina in women or into the rectum in men. Although scientists don't know exactly how it works, it has been suggested that the electric pulses may increase blood flow to the bladder, strengthen pelvic muscles that help control the bladder, and trigger the release of hormones that block pain.
TENS is relatively inexpensive and allows the patient to take an active part in treatment. Within some guidelines, the patient decides when, how long, and at what intensity TENS will be used. TENS has been most helpful in relieving pain and decreasing frequency in IC patients who have Hunner's ulcers. Smokers do not respond as well as nonsmokers. If TENS is going to help, change usually occurs in 3 to 4 months.
There is no scientific evidence linking diet to IC, but some doctors and patients believe that alcohol, tomatoes, spices, chocolate, caffeinated and citrus beverages, and high-acid foods may contribute to bladder irritation and inflammation. Some patients also notice a worsening of symptoms after eating or drinking products containing artificial sweeteners. Patients may try eliminating such products from their diet and reintroduce them one at a time to determine which, if any, affect symptoms. It is important, however, to maintain a well-balanced and varied diet.
Many IC patients feel that smoking worsens their symptoms. (Because smoking is the major known cause of bladder cancer, one of the best things a smoker can do for the bladder is to quit smoking.)
Many IC patients feel that regular exercise helps relieve symptoms and, in some cases, hastens remission.
People who have found some relief from pain may be able to reduce frequency using bladder training techniques. Methods vary, but basically the patient decides to void at designated times and use relaxation techniques and distractions to help keep to the schedule. Gradually, the patient tries to lengthen the time between the scheduled voids. A diary of voids is usually helpful in keeping track of progress.
This option is considered only if an IC patient has failed all available treatments and the pain is severe. Most doctors are reluctant to operate because the outcome is unpredictable in individual patients-some people have surgery and still have symptoms.
Anyone considering surgery should discuss the potential risks and benefits, side effects, and long- and short-term complications with a surgeon and family, as well as with people who already have had the procedure. Surgery requires anesthesia, hospitalization, and weeks or months of recovery, and as the complexity of the procedure increases, so do the chances for complications and failure.
To locate a surgeon experienced in performing specific procedures, check with your doctor.
Transurethral fulguration and resection of ulcers. Fulguration involves burning Hunner's ulcers using electricity or a laser. When the area heals, the dead tissue and the ulcer fall off, leaving new, healthy tissue behind. Resection involves cutting around and removing the ulcers. Both treatments, done under anesthesia, use special instruments inserted into the bladder through a cystoscope. Laser surgery in the urinary tract should only be done by doctors who have the special training and expertise needed to perform the procedure.
Denervation is a complicated procedure done by surgeons who have special training and expertise. Rarely used in the treatment of IC, it involves cutting some of the nerves to the bladder, interfering with pain signals. Many approaches and techniques are used, each of which has its own advantages and complications that should be discussed with the surgeon.
Augmentation makes the bladder larger, most often by adding a section of the patient's small intestine, a tube-like structure that absorbs and transports nutrients from food for use by the body. With this treatment, scarred, ulcerated and inflamed sections of the patient's bladder are removed, leaving only healthy tissue and the base of the bladder. A piece of the patient's small intestine is removed, reshaped, and attached to what remains of the bladder. After the incisions heal, the patient may be able to void normally.
Even in carefully selected patients-those with small, contracted bladders-the pain, frequency, and urgency may remain or return after surgery and the patient may have additional problems with infections in the new bladder and difficulty absorbing nutrients from the shortened intestine. Some patients are incontinent while others cannot void at all and must insert a catheter into the urethra to empty urine from the bladder.
Bladder Removal (Cystectomy). Different methods can be used to reroute urine once the bladder has been removed. In most cases, the ureters are attached to a piece of bowel that opens onto the skin of the abdomen, called a stoma. Urine empties through the stoma into a bag outside the body. This procedure is called a urostomy. Some urologists are using a technique that also requires a stoma but allows urine to be stored in a pouch inside the abdomen. At intervals throughout the day, the patient puts a catheter into the stoma and empties the pouch. Patients with either type of urostomy must use very clean, or sterile, steps to prevent infections in and around the stoma.
With a third method, a new bladder is made from a piece of the patient's bowel (large intestine) and attached to the urethra in place of the removed bladder. After a time of healing, the patient may be able to empty the bladder by voiding at scheduled times or may insert a catheter into the urethra. Few surgeons have the special training and expertise needed to perform this procedure.
Even after total bladder removal, some patients still experience variable symptoms of IC. Therefore, the decision to undergo a cystectomy should only be undertaken after serious deliberation on the potential outcome.
Electrical Nerve Stimulation. This surgical treatment is a variation of TENS, described previously, but involves permanent implantation of electrodes and a unit that emits continuous electrical pulses. This relatively new procedure has variable short-term results, unknown long-term effects and, therefore, is not widely used.
There is no evidence that IC increases the risk of bladder cancer. However, the long-term effects of IC require further observation and research.
Researchers have little information about pregnancy and IC, but believe that the disorder does not affect fertility or the health of the fetus. Some women have a remission from IC during pregnancy, while others have more pain and pressure during the third trimester, possibly due to the weight of the fetus on the bladder.
Symptom flare-ups that result in frequent absences from work may make it difficult to get or keep a job. The Social Security Administration provides information on Social Security Disability benefits. The National Organization of Social Security Claimants' Representatives can refer you to a lawyer experienced with Social Security claims. (See "Other Resources.")
The emotional support of family, friends, and other people with IC is very important in helping patients cope with the disorder. Studies have found that IC patients who learn about the disorder and become involved in their own care do better than patients who do not. The Interstitial Cystitis Association can provide the address and phone number of the nearest support group. (See "Other Resources.")
Although answers may seem slow in coming, researchers are working every day to solve the painful riddle of IC. Some scientists receive funds from the Federal Government to help support their research, and some receive support from other sources such as their employing institution, drug companies, and the Interstitial Cystitis Association. Researchers and doctors around the country, regardless of who funds their work, may competently diagnose and treat IC.
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a part of the National Institutes of Health (NIH), leads the Federal Government's research efforts on IC. Most studies funded by the NIDDK are a result of unsolicited grant applications sent to NIH by scientists at universities and medical centers throughout the United States. Other NIDDK-funded studies result from solicitations issued to encourage increased research on a certain topic.
By law, all applications sent to NIH are first reviewed by non-Government experts in the field of the proposed research for scientific merit and feasibility before being reviewed by the NIDDK's National Advisory Council. The council is made up of non-Government scientists, health professionals, and individuals who represent voluntary groups with an interest in the research of the institute. Approved applications are eligible for funding based on a scientific merit rating, or priority score, assigned by the initial reviewers. Applications are usually funded in priority score order, with the best applications funded first.
The NIDDK's investment in scientifically meritorious IC research has grown considerably since 1987, largely due to special solicitations. We now support research across the country that is looking at various aspects of IC, such as how urine contents may injure the bladder and what possible role organisms identified using nonstandard methods may have in causing IC. In addition to funding research, NIDDK sponsors scientific workshops where investigators share the results of their studies and discuss future areas for investigation.
An important part of the NIDDK IC research program is the National IC Database Study, which will provide the first systematic, long-term look at a large number of people with IC. The database is expected to provide clues about how IC develops, how to diagnose and categorize patients, and how to treat the disorder more effectively.
Nine clinical centers and a data coordinating center have joined forces in this national project to collect and analyze dietary, diagnostic, symptom, treatment, and other information from more than 1,300 people with mild, moderate, or severe symptoms of IC. Patients may enroll at any listed center, regardless of where they live, but must be willing to travel to that center for evaluation and followup. Patients will be enrolled and monitored through April 1997.
California
University of California, San Diego Medical Center
Mail Code 8897
200 West Arbor
San Diego, CA 92103-8897
Research Coordinator:
Diana LeBow, 619/543-5611
Henry Ford Hospital
2799 West Grand Boulevard
Detroit, MI 48202
Research Coordinator:
Michelle Fedon, R.N., 313/556-8265
Oklahoma
University of Oklahoma
Health Sciences Center
920 Stanton L. Young Boulevard
Fifth Floor, Room 330
Oklahoma City, OK 73104
Research Coordinator:
Linda Walker, R.N.,
405/271-1693 or 6900
The Graduate Hospital
1800 Lombard Street, Suite 606
Pepper Pavilion
Philadelphia, PA 19146
Research Coordinator:
Marilou Foy, R.N., 215/349-5874
Temple University Hospital
Department of Urology
3401 North Broad Street
Parkinson Pavilion, Suite 350
Philadelphia, PA 19140
Research Coordinator:
Marilou Foy, R.N., 215/349-5874
Wisconsin
University of Wisconsin Hospital and Clinics
G5/348 CSC
600 Highland Avenue
Madison, WI 53792
Research Coordinator:
Diane Pauk, B.S., 608/263-9721 or 1363
Data Coordinating Center
(not accepting patients)
Center for Biostatistics and Epidemiology
Hershey Medical Center
Pennsylvania State University College of Medicine
500 University Drive
Hershey, PA 17033
Patients enrolled in NIDDK-supported research studies must fit strict diagnostic criteria so that researchers can reliably compare patients and study results. When too many variables are involved in research studies it is difficult, if not impossible, to clearly evaluate disease processes and potential treatments.
The diagnostic criteria for research studies were established in 1987 and refined in 1988 as a result of NIDDK-sponsored workshops that brought together basic and clinical researchers and patient groups. As our knowledge about IC develops, these criteria likely will be revised.
Diagnostic Criteria for NIDDK-Supported Research
Patients must have:
The materials listed below may be found in medical libraries, many college and university libraries, through interlibrary loan in most public libraries, and at bookstores. Items are listed for information only; inclusion does not imply endorsement by the NIH.
Budish, AD. Avoiding the Medicaid Trap: How To Beat the Catastrophic Costs of Nursing Home Care. New York, Holt, 1989.
Schrotenboer, K, Berkman, S. The Woman Doctor's Guide To Overcoming Cystitis. New York, Nal Penguin, Inc., 1987.
American Foundation for Urologic Disease
The Bladder Health Council
300 West Pratt Street, Suite 401
Baltimore, MD 21201
410/727-2908 or 1-800-242-2383
This epub is not copyrighted.
Readers are encouraged to duplicate and distribute as many copies as needed. Single printed copies may be obtained from the National Kidney and Urologic Diseases Information Clearinghouse, 3 Information Way, Bethesda, MD 20892-3580.
NIH Publication No. 94-3220
August 1994