Jay D. Burstein M.D.

Urologist - Board Certified

Interstitial Cystitis
Interstitial cystitis can be a chronic, debilitating disease. Since there is no known cause or cure, our approach has been one of active patient participation and patient education. We welcome the opportunity to assist those in need of attention and understanding as our practice grows with an increasing number of interstitial cystitis patients.

Interstitial cystitis (IC), also known as "painful bladder syndrome" or frequency pain urgency syndrome," is a complex, chronic disorder that has baffled doctors for as long as it has been recognized. Patients with interstitial cystitis have an inflamed bladder wall that can lead to scarring, decreased bladder capacity, glomerulations (pinpoint bleeding) and, in rare cases, ulceration. Estimates of the number of people who have been diagnosed with IC run as high as 700,000. It is likely that millions who suffer this disease have yet to be diagnosed. About 90 percent of IC patients are women. While people of any age can be affected, about two-thirds of the 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 symptoms and severity, many researchers have considered that it may actually be not one, but several diseases. In the past, cases were mainly categorized as ulcerative IC or non-ulcerative IC, based on whether ulcers had formed on the bladder wall. But many 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 or response to treatment as much as other factors do.

Cause
The cause of IC is unknown, but the disorder is believed to be a real, physical phenomenon, not a result, symptom, or sign of an emotional problem. Research has focused on the glycocalyx (mucus) lining of the bladder made up primarily of 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 through the bladder wall mucosa and trigger IC symptoms. The researchers also found that patients with bladder wall ulcers had "leakier" bladders than patients without the ulcers.

Degranulation of mast cells and histamine release is considered another possible cause, however these changes are seen in a minority of biopsy specimens. Infection, drug reactions and autoimmunity are other causes under investigation, however no significant advances have been forthcoming.

Symptoms
The symptoms of IC vary greatly from one person to another but have some similarities to those of a urinary tract infection.

• Decreased bladder capacity
• Urgency
• Frequency, day and night
• Feelings of pressure, pain, and tenderness around the bladder, pelvis and perineum which may increase as the bladder fills and   decreases as it empties.
• Painful sexual intercourse
• In men, discomfort of pain in the penis and scrotum
• In most women, symptoms usually worsen around the menstrual cycle. As with many other illnesses, stress may also intensify   symptoms but does not cause them.

Diagnosis
Because symptoms are similar to those of other disorders of the urinary system, and because there is no definitive test to identify IC, other conditions must be ruled out before considering a diagnosis of IC. Among these disorders is a urinary tract or vaginal infection, bladder cancer, carcinomas in situ, radiation cystitis, kidney stones, endometriosis, neurological disorders, sexually transmitted diseases, and in men, chronic bacterial and nonbacterial prostatitis.

IC may also be associated with diseases such as vulvodynia (vulvar/vaginal pain), fibromyalgia (musculoskeletal pain) and irritable bowel disease.

The diagnosis of IC is based on:

1. Presence of urgency, frequency or pelvic/bladder pain
2. Cystoscopic evidence (under anesthesia) of bladder wall inflammation and pinpoint bleeding (glomerulations) or Hunner's ulcers
3. Absence of other diseases that may cause the symptoms.

Complete evaluation may includes a urinalysis, urine culture, urodynamic (bladder pressure) study, cystoscopy (looking into the bladder using a miniature telescope with anesthesia), biopsy of the bladder wall, and, in men, laboratory examination of prostate secretions.

Because bladder distension is painful in IC patients, cystoscopy must be performed with either regional or general anesthesia. The diagnostic finding is pinpoint hemorrhage, known as "glomerulations" which appear only after the bladder is distended. A small bladder capacity under anesthesia also helps to support the diagnosis of IC.

Treatment
We have not yet found a cure for IC, nor can we 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. Because we do not know the cause of IC, treatments are aimed at symptomatic relief. Most people are helped for variable periods of time by one or a combination of treatments, many of which are described below.

Bladder Distension: this is considered a first line treatment because bladder distention is also used to diagnose IC. During this procedure, the bladder is overfilled with water. It is believed that this produces denervation of the sensory nerves which provides temporary relief from pain. Improvement in symptoms may last 3 to 6 months and the procedure can be repeated.

Bladder Instillation: the only drug approved by the FDA for bladder instillation is dimethyl sulfoxide (DMSO, RIMSO?50). Treatments are given every week 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. The mechanism of action is unknown.

BCG: Bacillus Calmette-Guerin is a promising new therapy which has provided significant relief in 60% of IC patients in a small preliminary study. 89% of the positive responders maintained improvement for 2 years after treatment. Nationwide clinical trials are now underway.

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 triggering an immune response. Heparin and pentosanpolysulfate are thought to work by replacing or repairing the "leaky" bladder lining.

Oral Medication
Elmiron is an FDA approved medication which helps restore the glycocalyx lining of the bladder. Results are evident by the third month of use and there appears to be a 40 % to 50% response rate. It is taken three times a day and has minimal side effects.

There are several other prescription medications which can be used to ameliorate symptoms:

• Amitriptyline (Elavil) has the ability to block pain and reduce bladder spasms. Most people who respond to this drug show   improvement 3 or 4 weeks after starting treatment.
• Hyoscyamine (Levsin) and oxybutynin (Ditropan, Ditropan-XL) have excellent anticholinergic properties to reduce bladder spasms   and are well tolerated.
• Hydroxyzine (Vistaril, Atarax) and nifedipine (Procardia) have been reported to be effective in limited studies.
• Non-prescription supplements are also under investigation and some have been shown to benefit some patients in limited, uncontrolled studies.
• L-Arginine is an amino acid (protein building blocks) that breaks down into nitrous oxide, (a neurotransmitter) that can reduce pain   and frequency in some patients.
• Kava Kava is an herbal preparation that has anti-anxiety effects. Even though this is a plant extract and is not under FDA control, it can produce serious side effects and a physician's supervision is needed if it is taken for more than 3 months.
• Quercitin is one kind of several substances called bioflavonoids that are found in onions, red wine, green tea and other plants. In limited and preliminary clinical reports, a non-standardized preparation seems to have improved symptoms in about half of the patients. Quercitin has strong anti-oxidant and anti-inflammatory properties which may explain its beneficial effects, but further well controlled studies are needed to determine its effectiveness.

Diet
There is no scientific evidence linking diet to IC, however many patients obtain considerable relief by limiting intake of alcohol, tomatoes, spices, chocolate, caffeinated and citrus beverages, and high-acid foods. Some patients also notice a worsening of symptoms after eating or drinking products containing artificial sweeteners. An "elimination diet" can be used to pinpoint specific food irritants and is recommended for all IC patients. For those who are sensitive to food acid, "Prelief" is available locally as tablets or granules that reduce the acidity of food and helps to reduce pain. Their toll-free hotline is 1-800-994-4711.

Pain Control
For those patients for whom pain control becomes a problem, a specialized, integrative pain management clinic is available for referral. Sponsored by the Department of Anesthesiology of Kishwaukee Hospital, the clinic is dedicated to integrating the best of medical science with promising alternative and complimentary therapies for the treatment and control of pain. Therapies offered include conventional pain medications, botanical medicines and herbal remedies, interventional nerve blocks, trigger point injections, acupuncture, neural therapy, massage therapy, physical therapy, deep tissue and spinal manipulation, electro-medicine, dietary recommendations and counseling.

Surgery
This is the option of last resort reserved for those patients refractory to all treatment options whose pain is debilitating and unrelenting. Augmentation procedures and cystectomy with urinary diversion are the two most common procedures to consider. However, regardless of which procedure is performed, outcomes are unpredictable and some patients continue to have urgency, frequency and pain!

Self Help
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. We encourage our patients to visit the superbly designed web site: www.ic-network.com which has a wealth of information regarding all aspects of IC including chat groups. We also suggest our patients join www.ichelp.com which provides access to professional publications, support groups and research funding.

Resources

1. Overcoming Bladder Disorders. Chalker and Whitmore, HarperPerennial, 1990. An excellent comprehensive manual including self-help strategies. A bit outdated but still extremely useful. Highly recommended.
2. ICN Patient Handbook. This is an on-line manual available at www.ic-network.com. Very accessible and pertinent information. Highly recommended.
3. DeKalb Clinic Website www.dekalbclinic.com. Find the Urology section under specialties and scroll for recent updates, abstracts and new information regarding IC and related disorders.
4. Conquering Bladder and Prostate Problems. Blaivas, Plenum Trade, 1998. Somewhat technical, but up-to-date chapters covering all aspects of the urinary system.