Interstitial Cystitis

Interstitial Cystitis

What Is Interstitial Cystitis?

Interstitial cystitis (IC), one of the chronic pelvic pain disorders, is a condition resulting in recurring discomfort or pain in the bladder and the surrounding pelvic region. The symptoms of IC vary from case to case and even in the same individual. People may experience mild discomfort, pressure, tenderness, or intense pain in the bladder and surrounding pelvic area. Symptoms may include an urgent need to urinate (urgency), frequent need to urinate (frequency), or a combination of these symptoms. Pain may change in intensity as the bladder fills with urine or as it empties. Women's symptoms often get worse during menstruation.

In IC, the bladder wall may be irritated and become scarred or stiff. Glomerulations (pinpoint bleeding caused by recurrent irritation) may appear on the bladder wall. Some people with IC find that their bladders cannot hold much urine, which increases the frequency of urination. Frequency, however, is not always specifically related to bladder size; many people with severe frequency have normal bladder capacity. People with severe cases of IC may urinate as many as 60 times a day.

Also, people with IC often experience pain during sexual intercourse. IC is far more common in women than in men. Of the more than 700,000 Americans estimated to have IC, 90 percent are women.

What Causes IC?

Some of the symptoms of IC resemble those of bacterial infection, but medical tests reveal no organisms in the urine of patients with IC. Furthermore, patients with IC do not respond to antibiotic therapy. Researchers are working to understand the causes of IC and to find effective treatments.

One theory being studied is that IC is an autoimmune response following a bladder infection. Another theory is that a bacterium may be present in bladder cells but not detectable through routine urine tests. Some scientists have suggested that certain substances in urine may be irritating to people with IC, but no substance unique to people with IC has as yet been isolated. Researchers are beginning to explore the possibility that heredity may play a part in some forms of IC. In a few cases, IC has affected a mother and a daughter or two sisters, but it does not commonly run in families. No gene has yet been implicated as a cause.

Are There Different Types of IC?

Because IC varies so much in symptoms and severity, most researchers believe that it is not one, but several, diseases. In the past, cases were mainly categorized as ulcerative IC or nonulcerative IC, based on whether ulcers had formed on the bladder wall. But many researchers and clinicians have questioned the usefulness of this classification, since the vast majority of cases do not involve ulcers, and their presence or absence does not influence treatment options as much as other factors do.

Factors that influence treatment options include whether bladder capacity under anesthesia is great or small, and whether mast cells are present in the tissue of the bladder wall, which may be a sign of an allergic or autoimmune reaction. In some cases, the success or failure of a treatment helps characterize the type of IC. For example, some cases respond to changes in diet while others do not.

How Is IC Diagnosed?

Because symptoms 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 pelvic area, eosinophilic and tuberculous cystitis, kidney stones, endometriosis, neurological disorders, sexually transmitted diseases, low-count bacteria in the urine, and, in men, chronic bacterial and nonbacterial prostatitis.

The diagnosis of IC in the general population is based on

Pinpoint bleeding on the bladder wall.

presence of urgency, frequency, or pelvic/bladder pain
cystoscopic evidence (under anesthesia) of bladder wall inflammation, including Hunner's ulcers or glomerulations (present in 90 percent of patients with IC)
absence of other diseases that could cause the symptoms

Diagnostic tests that help identify other conditions include urinalysis, urine culture, cystoscopy, biopsy of the bladder wall, distention of the bladder under anesthesia, urine cytology, and, in men, laboratory examination of prostate secretions.

Urinalysis and Urine Culture
These tests can detect and identify the most common organisms that infect the urine and that may cause symptoms similar to IC. There are, however, organisms such as Chlamydia that cannot 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, the doctor may consider a diagnosis of IC.

Culture of Prostate Secretions
In men, the doctor might obtain prostatic fluid and examine it for signs of an infection, which can then be treated with antibiotics.

Cystoscopy Under Anesthesia with Bladder Distention
During cystoscopy, 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 distention is painful in patients with IC, they must be given some form of anesthesia for the procedure. These tests can detect bladder wall inflammation; a thick, stiff bladder wall; and Hunner's ulcers. Glomerulations are usually seen only after the bladder has been stretched to capacity.

The doctor may also test the patient's maximum bladder capacity--the maximum amount of liquid or gas the bladder can hold. This must be done under anesthesia since the bladder capacity is limited by either pain or a severe urge to urinate. A small bladder capacity under anesthesia helps support the diagnosis of IC.

Biopsy
A biopsy is a tissue sample that is then examined under a microscope. Samples of the bladder and urethra may be removed during a cystoscopy and later examined with a microscope. A biopsy helps rule out bladder cancer.

Future Diagnostic Tools

As researchers learn more about the causes of IC, more accurate and less invasive diagnostic procedures are likely to emerge. For example, some researchers are studying the possibility that urine samples from people with IC contain substances not found in normal urine. If an IC marker in the urine can be found, patients may not have to undergo a cystoscopic examination or biopsy to receive a diagnosis.

What Are the Treatments for IC?

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, they may return after days, weeks, months, or years. Scientists do not know why.

Because the causes of IC are unknown, current treatments are aimed at relieving symptoms. Most people are helped for variable periods by one or a combination of treatments. As researchers learn more about IC, the list of potential treatments will change, so patients should discuss their options with a doctor.

Bladder Distention
Because many patients have noted an improvement in symptoms after a bladder distention done to diagnose IC, the procedure is often thought of as one of the first treatment attempts.

Researchers are not sure why distention helps, but some believe that it may increase capacity and interfere with pain signals transmitted by nerves in the bladder. Symptoms may temporarily worsen 24 to 48 hours after distention, but should return to predistention levels or improve after 2 to 4 weeks.

Bladder Instillation
During a bladder instillation, also called a bladder wash or bath, the bladder is filled with a solution that is held for varying periods of time, averaging 10 to 15 minutes, before being emptied.

The only drug approved by the U.S. Food and Drug Administration (FDA) for bladder instillation is dimethyl sulfoxide (DMSO, RIMSO-50). DMSO treatment involves guiding a narrow tube called a catheter 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 who respond to DMSO notice improvement 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 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, it may reach tissue more effectively to reduce inflammation and block pain. It may also prevent muscle contractions that cause pain, frequency, and urgency.

A bothersome but relatively insignificant side effect of DMSO treatments is a garlic-like taste and odor on the breath and skin that may last up to 72 hours after treatment. Long-term treatment has 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.

Oral Drugs
Pentosan polysulfate sodium (Elmiron), the first oral drug developed for IC, was approved by the FDA in 1996. In clinical trials, Elmiron improved symptoms in 38 percent of patients treated. Doctors do not know exactly how it works, but one theory is that it may repair defects that might have developed in the lining of the bladder.

The FDA-recommended dosage of Elmiron is 100 mg, three times a day. Patients may not feel relief from IC pain for the first 2 to 4 months. A decrease in urinary frequency may take up to 6 months. Patients are urged to continue with therapy for at least 6 months to give it an adequate chance to relieve symptoms.

Elmiron's side effects are limited primarily to minor gastrointestinal discomfort. A small minority of patients experienced some hair loss, but hair grew back when they stopped taking the drug. Researchers have found no negative interactions between Elmiron and other medications.

Elmiron may affect liver function, which should therefore be monitored by the doctor.

Because Elmiron has not been tested in pregnant women, the manufacturer recommends that it not be used during pregnancy, except in the most severe cases.

Other Oral Medications
Aspirin and ibuprofen are easy to obtain and may be a first line of defense against mild discomfort. Doctors may recommend other drugs to relieve pain.

Some patients have experienced improvement in their urinary symptoms by taking antidepressants or antihistamines. Antidepressants help reduce pain and may also help patients deal with the psychological stress that accompanies living with chronic pain. In patients with severe pain, narcotic analgesics such as Tylenol with codeine or longer acting narcotics may be necessary.

All drugs--even those sold over the counter--have side effects. Patients should always consult a doctor before using any drug for an extended time.

Transcutaneous Electrical Nerve Stimulation
With transcutaneous electrical nerve stimulation (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 just above the pubic area, 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 do not know exactly how TENS works, it has been suggested that the electric pulses may increase blood flow to the bladder, strengthen pelvic muscles that help control the bladder, or trigger the release of substances 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. It has been most helpful in relieving pain and decreasing frequency in patients with Hunner's ulcers. Smokers do not respond as well as nonsmokers. If TENS is going to help, improvement is usually apparent in 3 to 4 months.

Diet
There is no scientific evidence linking diet to IC, but many doctors and patients find that alcohol, tomatoes, spices, chocolate, caffeinated and citrus beverages, and high-acid foods may contribute to bladder irritation and inflammation. Some patients also note that their symptoms worsen after eating or drinking products containing artificial sweeteners. Patients may try eliminating various products from their diet and reintroducing them one at a time to determine which, if any, affect symptoms. It is important, however, to maintain a varied, well-balanced diet.

Smoking
Many patients feel that smoking makes their symptoms worse. Because smoking is the major known cause of bladder cancer, one of the best things smokers can do for their bladder is to quit.

Exercise
Many patients feel that gentle stretching exercises help relieve IC symptoms.

Bladder Training
People who have found adequate relief from pain may be able to reduce frequency by using bladder training techniques. Methods vary, but basically patients decide to void (that is, empty their bladder) at designated times and use relaxation techniques and distractions to keep to the schedule. Gradually, patients try to lengthen the time between scheduled voids. A diary that records voiding times is usually helpful in keeping track of progress.

Surgery
Many approaches and techniques are used, each of which has its own advantages and complications that should be discussed with a surgeon. Surgery should be considered only if all available treatments have failed and the pain is disabling. Most doctors are reluctant to operate because the outcome is unpredictable--some people still have symptoms after surgery.

Those considering surgery should discuss the potential risks and benefits, side effects, and long- and short-term complications with a surgeon and with their family, as well as with people who have already 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.

Two procedures--fulguration and resection of ulcers--can be done with instruments inserted through the urethra. Fulguration involves burning Hunner's ulcers with 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 are done under anesthesia and use special instruments inserted into the bladder through a cystoscope. Laser surgery in the urinary tract should be reserved for patients with Hunner's ulcers and should be done only by doctors who have had special training and have the expertise needed to perform the procedure.

Another surgical treatment is augmentation, which makes the bladder larger. In most procedures, scarred, ulcerated, and inflamed sections of the patient's bladder are removed, leaving only the base of the bladder and healthy tissue. A piece of the patient's bowel (large intestine) is then removed, reshaped, and attached to what remains of the bladder. After the incisions heal, the patient may void less frequently. The effect on pain varies greatly; IC can sometimes recur on the segment of bowel used to enlarge the bladder.

Even in carefully selected patients--those with small, contracted bladders--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 the bladder.

Bladder removal, called a cystectomy, is another surgical option. Once the bladder has been removed, different methods can be used to reroute urine. In most cases, ureters are attached to a piece of bowel that opens onto the skin of the abdomen; this procedure is called a urostomy, and the opening is called a stoma. Urine empties through the stoma into a bag outside the body. Some urologists are using a second 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 be very careful to keep the area in and around the stoma clean to prevent infection. Serious potential complications may include kidney infection and small bowel obstruction.

A third method to reroute urine involves making a new bladder from a piece of the patient's bowel and attaching it to the urethra. After healing, the patient may be able to empty the newly formed bladder by voiding at scheduled times or by inserting 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 IC symptoms in the form of phantom pain. Therefore, the decision to undergo a cystectomy should be undertaken only after testing all alternative methods and after seriously considering the potential outcome.

A surgical variation of TENS, called saccral nerve root stimulation, involves permanent implantation of electrodes and a unit emitting continuous electrical pulses. Studies of this experimental procedure are now under way.

Are There Any Special Concerns?

Cancer

There is no evidence that IC increases the risk of bladder cancer.

Pregnancy
Researchers have little information on pregnancy and IC but believe that the disorder does not affect fertility or the health of the fetus. Some women find that their IC goes into remission during pregnancy, while others experience a worsening of their symptoms.

Coping
The emotional support of family, friends, and other people with IC is very important in helping patients cope. Studies have found that patients who learn about the disorder and become involved in their own care do better than patients who do not. See "IC Patient Support" for an association that can refer you to the nearest support group.

Is Any Research Being Done?

Although answers may seem slow in coming, researchers are working hard to solve the painful riddle of IC. Some scientists receive funds from the Federal Government to help support their research, while others receive support from their employing institution, drug companies, or patient support associations.

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 NIDDK result from 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 particular 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 NIDDK's National Advisory Council. This council is made up of non-Government scientists, health professionals, and people who represent voluntary groups interested in the Institute's research. Approved applications are eligible for funding based on a rating of scientific merit, or priority score, assigned by the initial reviewers. Applications are usually funded in order of priority score; the best applications are funded first.

Largely because of special solicitations, NIDDK's investment in scientifically meritorious IC research across the country has grown considerably since 1987. The Institute now supports research that is looking at various aspects of IC, such as how the components of urine may injure the bladder and what possible role organisms identified by 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.

Database
An important part of NIDDK's IC research program has been the National IC Database Study, the first systematic, long-term look at a large number of people with IC. Baseline data have been analyzed to provide a foundation for subsequent studies in the IC Clinical Trials Group.

Clinical Trials Group
In 1998, NIDDK initiated the IC Clinical Trials Group, a project designed to develop and test new treatment strategies for patients with IC. The first trial will test two oral drugs. One group will be treated with Elmiron, a second with Atarax, a third with both drugs, and a fourth with placebo.

The second trial will test whether the bacterium Bacillus Calmette-Guérin (BCG) will relieve the pelvic pain and frequent urination that are hallmarks of IC. Participants will be randomly assigned to have either a BCG or saline solution temporarily placed in the bladder during each of six clinic visits. Neither doctors nor patients will know who received the BCG until the study ends. Patients whose symptoms are not relieved by the initial series will be openly offered BCG.

Other Resources

American Foundation for Urologic Disease
The Bladder Health Council
1128 North Charles Street
Baltimore, MD 21201
Phone: 1-800-242-2383 or (410) 468-1800
Email: admin@afud.org
Internet: www.afud.org

American Pain Society
4700 West Lake Avenue
Glenview, IL 60025
Phone: (847) 375-4715
Email: info@ampainsoc.org
Internet: www.ampainsoc.org

American Urogynecologic Society
2025 M Street NW., Suite 800
Washington, DC 20036
Phone: (202) 367-1167
Fax: (202) 367-2167
Email: augs@dc.sba.com
Internet: www.augs.org

Interstitial Cystitis Association
51 Monroe Street, Suite 1402
Rockville, MD 20850
Phone: 1-800-HELP-ICA or (301) 610-5300
Email: icamail@ichelp.org
Internet: www.ichelp.org

International Association for the Study of Pain
909 Northeast 43rd Street, Suite 306
Seattle, WA 98105-6020
Phone: (206) 547-6409
Email: IASP@locke.hs.washington.edu
Internet: www.iasp-pain.org

National Chronic Pain Outreach Association
7979 Old Georgetown Road, Suite 100
Bethesda, MD 20814-2429
Phone: (301) 652-4948

National Kidney Foundation
30 East 33rd Street, Suite 1100
New York, NY 10016
Phone: 1-800-622-9010 or (212) 889-2210
Email: info@kidney.org
Internet: www.kidney.org

National Organization of Social Security Claimants' Representatives
6 Prospect Street
Midland Park, NJ 07432-1691
Phone: 1-800-431-2804 or (201) 444-1415
Email: nosscr@worldnet.att.net
Internet: www.nosscr.org

Social Security Administration
Write or call your local office: look in the telephone book under
U.S. Government, Department of Health and Human Services
or call 1-800-772-1213,
visit www.ssa.gov on the internet,
or write the Office of Public Inquiries at
Social Security Administration
Office of Public Inquiries
6401 Security Boulevard, Room 4-C-5 Annex
Baltimore, MD 21235-6401

United Ostomy Association
19772 MacArthur Boulevard, Suite 200
Irvine, CA 92612-2405
Phone: 1-800-826-0826
Email: info@uoa.org
Internet: www.uoa.org

The U.S. Government does not endorse or favor any specific commercial product or company. Trade, proprietary, or company names appearing in this document are used only because they are considered necessary in the context of the information provided. If a product is not mentioned, this does not mean or imply that the product is unsatisfactory.

National Kidney and Urologic Diseases Information Clearinghouse

3 Information Way
Bethesda, MD 20892-3580
Email: nkudic@info.niddk.nih.gov

The National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health under the U.S. Department of Health and Human Services. Established in 1987, the clearinghouse provides information about diseases of the kidneys and urologic system to people with kidney and urologic disorders and to their families, health care professionals, and the public. NKUDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about kidney and urologic diseases.

Publications produced by the clearinghouse are carefully reviewed by both NIDDK scientists and outside experts.

This e-text is not copyrighted. The clearinghouse encourages users of this e-pub to duplicate and distribute as many copies as desired.

NIH Publication No. 02-3220
March 2002

IC Interstitial Cystitis Chronic bladder pain