A pro-active approach is extremely important in the treatment of interstitial cystitis. Self education is a significant part of the treatment program. In addition to the resources below, we encourage our patients and readers to surf the web for other available resources.
Interstitial Cystitis
- Jay D. Burstein, M.D., F.A.C.S.
Background
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 syndrome," is a complex, chronic disorder that has baffled doctors for as long as it has been recognized. Patients with interstitial cystitis may have an inflamed bladder wall that can lead to scarring, decreased bladder capacity, glomerulations (pinpoint bleeding) and, in rare cases, ulceration. In other cases, the bladder wall can appear normal without any evidence of disease process.
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.
An allergic reaction that causes specialized mast cells to release histamin 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 typically have similarities to those of a urinary tract infection:
- Decreased bladder capacity
- Severe urinary frequency, day and night
- Feelings of pressure, pain, and tenderness around the bladder, pelvis and perineum that may increase as the bladder fills and decrease 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.
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, radiation cystitis, kidney stones, endometriosis, neurological disorders, sexually transmitted diseases, and in men, prostatitis. Spasm of the muscular pelvic floor must also be considered.
IC may also be associated with diseases such as vulvodynia (vulvar/vaginal pain), fibromyalgia (musculoskeletal pain) and irritable bowel disease.
Complete evaluation may include 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.
In review, the diagnosis of IC is based on:
- Presence of frequency or pelvic/bladder pain
- Cystoscopic evidence (under anesthesia) of bladder wall inflammation and pinpoint bleeding (glomerulations) or Hunner's ulcers
- Absence of other diseases that may cause the symptoms
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 weeks, months, or years. This is known as IC FLAIR and it is important to understand that the symptoms of IC can recur or "flair" up at any time without cause or reason.
Because we do not know the cause of IC, treatments are aimed at symptomatic relief. One or a combination of treatments, many of which are described below, helps most people for variable periods of time.
Bladder Distension
Bladder distension 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 that provides temporary relief from pain. Improvement in symptoms may last 3 to 6 months and the procedure can be repeated.
Bladder Instillation
Bladder instillation is a treatment procedure that is done in the office. The urethra is anesthetized with topical medication and a soft catheter is placed into the bladder. Medication is then poured into the bladder and the catheter is removed. The patient then empties the bladder about 10 minutes later.
- DMSO (dimethyl sulfoxide, Rimso 50) is the only drug approved by the FDA for bladder instillation. 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. This has been a mainstay for IC treatment, but can it can be very irritating at the beginning of treatment and usually requires long-term maintenance therapy.
- "Rescue Solution" is now becoming first line treatment for initial severe pain and symptoms of flair. This is a mixture of lidocaine, a topical anesthetic and heparin. It is very soothing and quickly reduces pain levels by "breaking the pain cycle". This results in dramatic reduction of anxiety and allows more time for office assessment to determine long term treatment options. Several treatments are usually needed over the course of a week or two to gain durable results.
- Heparin or pentosanpolysulfate (Elmiron) can also be instilled as a single agent and are thought to work by replacing or repairing the "leaky" bladder lining.
- A variety of other drugs have been used experimentally for bladder washes, but have not been shown to be beneficial and in many cases can be extremely irritating. These include silver nitrate, sodium oxychlorosene (Clorpactin WCS-90) and BCG.
Oral Medication
Pentosan polysulfate sodium (Elmiron) and amitriptyine are two medications that have been shown to be effective in randomized, placebo-controlled studies.
- Elmiron is an FDA approved medication which helps restore the damaged 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 is generally well tolerated.. The most common side effect is gastric upset and about four percent have hair loss that is completely reversible when medication is stopped.
- Amitriptyline (Elavil) is an antidepressant that has the ability to block pain and reduce bladder spasms. Studies have now documented statistically significant improvement in pain and urgency when compared to placebo. Most people who respond to this drug show improvement 3 or 4 weeks after starting treatment. Side effects include drowsiness and weight gain.
- Hyoscyamine (Levsin) and oxybutynin (Ditropan, Ditropan-XL) and tolterodine (Detrol, Detrol LA) have excellent properties to reduce bladder spasms and are well tolerated. Dry mouth is the most common side effect of this class of medication.
- Hydroxyzine (Vistaril, Atarax) is an antihistamine that has been reported to be effective in limited studies.
Supplements
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 that 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 beverages, citrus 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 acidity, "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: A different kind of pain.
Most of us are familiar with typical pain of a sprained ankle or a cut finger. This is called "somatic" pain and is easily localized to the area of injury, is easy to describe (sharp, dull or aching) and heals in a short period of time. The pain of IC is called "visceral" pain and is very different because it arises from the bladder, an internal organ located deep in the pelvis. This kind of pain is difficult localize, can be very difficult to describe and occurs on a long-term, chronic basis. One reason why IC is so frustrating is because a patient may have difficulty telling a doctor where the pain is located and be unable to describe its character. A typical patient will point to several areas including the back thighs abdomen and pelvis calling the pain "pressure-like" or "cramping". This is not the typical description of distinct and localized somatic pain that most doctors are familiar with and feel comfortable treating. One of the most important aspects of receiving good care is to choose a physician who is experienced in treating IC and is comfortable assessing and treating visceral pain.
Opioid Narcotics
For some IC patients the most effective control of long-term pain is obtained with the use of opioid narcotics. They are derived from the opium poppy and are excellent at providing pain relief, Vicodin and oxycodone are the most commonly prescribed oral preparations. Side effects include sedation, respiratory depression and constipation. These can be very significant and require careful dose adjustment and monitoring.
Unfortunately, all opioids have the potential for tolerance, physical dependence, and addiction. These characteristics have lead to many misconceptions about narcotic use and prevent many health care providers from considering prescribing them for long-term use.
Tolerance to opioid medication is common. It refers to the progressive decrease in pain control and the need of higher doses to provide the same level of pain relief.
Physical dependence always occurs. with long-term use of opioids. If the medication is abruptly withdrawn or the dose is markedly reduced patients will experience a withdrawal syndrome that includes abdominal cramping, sweating, nausea, diarrhea and irritability. It is strictly a medical condition and should not be taken as a sign of psychological weakness.
Addiction is a behavioral disorder that results in psychological dependence of a substance. It refers to compulsive drug use and continuing drug use despite harm. Unfortunately, addiction is all too often incorrectly equated with physical dependence and withdrawal syndrome. To provide proper chronic pain management it is crucial for physicians to recognize this critical difference.
Objectives of Pain Control
The patient and physician should have realistic expectations regarding the use of opioids.
Obtaining an excellent Quality of Life should be the main goal by adequate control of pain, not the complete elimination of pain. Outcomes should focus on developing a daily routine schedule involving work, participation in social functions, and family needs.
Just like long-term medication controls but does not cure diabetes or high blood pressure, long term medication is required to adequately control chronic pain.
Because of the abuse potential of narcotic pain medication many physicians require patients to agree to an Opioid contract. This is a reasonable approach that creates the obligation of both parties to effectively communicate dose requirements, dose changes, reports of side effects and refill authorization.
Anxiety and IC
Anxiety is a significant component of IC that tends to be misunderstood. Patients coping with chronic pain often restrict activities for fear of increased pain or further injury. Withdrawal from normal activities such as work, family responsibilities and social events can result in a high degree of anxiety, worry, frustration and fear of loss. Research has shown that individuals with a high disposition to become anxious report significantly higher pain levels than those with low levels of anxiety. It is also known that as anxiety increases, the intensity of reported pain increases. This results in a vicious cycle that needs to be treated.
Unfortunately, in many situations the pain-anxiety cycle is not treated because the physician or patient does not recognize or refuses to accept the presence of anxiety. The impact that psychological factors have on the perception of pain does not mean that the pain is "in the persons head" or not real. Those with IC who report pain are really experiencing it, even if a physical cause cannot be identified.
Relief of anxiety can be obtained by two approaches:
- Behavioral changes include relaxation techniques and stress management. There are many options available that can be individualized according to personal preference. These include:
- Progressive muscle relaxation
- Meditation
- Prayer
- Visualization
- Breathing techniques
- Biofeedback
- Medication can relieve symptoms quickly and safely. The most effective and most prescribed class of medication is benzodiazepines (Valium, Xanax, Klonopin). The most common side effect is drowsiness and tolerance (see above) can develop so short-term use is recommended. Because these drugs are often used in combination with antidepressants such as amitriptyline, the lowest possible dose should be prescribed to minimize side effects.
No one should ever be denied treatment for pain. But because of the reluctance of certain physicians to treat chronic pain, there is an alternative to help obtain proper pain management.
Pain Clinics
Pain clinics are now becoming popular for patients who continue to have difficulty obtaining adequate pain control. These are specialized, integrative pain management programs that are available at many community and academic hospitals. Therapies offered typically 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.
Sacral Nerve Stimulation
This can be used to relieve severe frequency when all other options have failed The InterStim device is an implanted stimulation system that sends electrical impulses to the nerve near the tailbone that influences bladder control. Stimulation of this nerve may relieve the symptoms related to urge incontinence.
The effectiveness of the therapy is first tested on an outpatient basis. If the test is successful, the patient may choose to have the device implanted.
The final procedure requires general anesthesia, A small wire is placed near the sacral nerve through an incision and is passed under the skin to a silver dollar sized neurostimulator. The neurostimulator is then placed under the skin in the upper buttock.
Adjustments can be made with a wireless programming device that sends a radio signal through the skin to the neurostimulator. The patient can make further adjustments at the doctor's office or at home.
This treatment is about 50% effective. Complications such as infection are frequent, permanent nerve damage has been reported and migration of the implanted wires can render the system ineffective. However, it is an excellent alternative to any major surgical procedure.
Surgery
This is the option of last resort reserved for those patients refractory to all treatment options whose pain or frequency is debilitating and unrelenting. Augmentation procedures (enlargement of the bladder to increase its capacity) and cystectomy with urinary diversion (removal of the bladder) 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 visit www.ichelp.com which provides access to professional publications, support groups and research funding.
RESOURCES
ICN Patient Handbook. This is an on-line manual available at www.ic-network.com . Very accessible and pertinent information.
The Interstitial Cystitis Survival Guide. Moldwin, New Harbinger, 2000. The most comprehensive review of IC available. Easy to read. Highly recommended.
Overcoming Bladder Disorders. Chalker and Whitmore, HarperPerennial, 1990. An excellent comprehensive manual including self-help strategies. A bit outdated but still extremely useful.
Conquering Bladder and Prostate Problems. Blaivas, Plenum Trade, 1998. Somewhat technical chapters covering all aspects of the urinary system.
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Interstitial Cystitis Updates
In an attempt to further understand this disease and to discover new treatment options and research discoveries, Dr. Burstein will post reviews of recent articles and other significant matters that relate to interstitial cystitis.
Antiproliferative activity is present in bladder but not renal pelvic urine from interstitial cystitis patients.
Keay S, Warren JW, Zhang CO, Tu LM, Gordon DA, Whitmore KE
Department of Medicine' University of Maryland School of Medicine' the
Research Service' Baltimore Veterans Affairs Maryland Health Care System ë21201' USA.; J Urol; 1999 Oct; 162(4):1487-9
PURPOSE: To determine whether an antiproliferative urine factor
that we previously discovered to be specific for urine from interstitial
cystitis (IC) patients originated in the lower urinary tract or a more
proximal site.
MATERIALS AND Methods: Sequential catheterized urine
specimens were collected under sterile conditions from the bladder and renal pelvis of 20 IC patients and one control patient (with stress incontinence). Antiproliferative activity was determined by 3H-thymidine incorporation of primary normal adult bladder epithelial cells cultured with pH- and osmolality-corrected bladder or ureteral urine specimens; significant inhibition was defined as a change in 3H-thymidine incorporation greater than 2 standard deviations from the mean of control cells.
Results: Bladder urine specimens from 19 of 20 IC patients significantly inhibited 3H-thymidine incorporation as compared to cell medium alone (mean change for bladder specimens = -68.7+/-7.5%)' while a renal pelvic specimen from only 1 of 20 IC patients inhibited proliferation significantly (mean change for renal pelvic specimens = 3.2+/-3.4%) (p<.001 by Fisher's exact test). The one inhibitory IC renal pelvic specimen inhibited by 31% while a bladder specimen obtained during the same procedure inhibited by 94%. In comparison neither bladder nor renal pelvic urine from the control patient had inhibitory activity.
Conclusions: The antiproliferative factor previously
found in the urine of IC patients appears to be made and/or activated in the
distal ureter or urinary bladder.
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New Clinical Marker for Interstitial Cysitis
The cause of interstitial cystitis is thought to be a deficiency in the protective mucous layer of the bladder. More specifically, it is thought that potassium diffusion becomes more prominent and potassium acts as an irritant to the superficial and muscle layers of the bladder, producing symptoms of interstitial cystitis.
GP 51 is a urinary glycoprotein that functions as a protective barrier to the bladder wall. A recent study at Thomas Jefferson University evaluated urinary GP 51 levels in patients with and without interstitial cystitis. It was found that these levels are significantly reduced in patients with the disease. Although, it does not explain why levels were lower, it certainly raises the possibility of using GP 51 as a clinical marker for diagnosing interstitial cystitis using a non-invasive urinary test. It may also become an excellent way of monitoring treatment and the ongoing effects of drug therapy.
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Reduce Acid Content in Foods
Many patients with interstitial cystitis have difficulty tolerating acidic foods such as pizza, tomato sauces, coffee and juices. It is thought that the bladder pain is caused by high
levels of potassium that leaks through the bladder wall. A product called Prelief, which reduces acid content in food, is available over the counter as tablets and granules and may be of value in the diets of interstitial cystitis patients who are sensitive to acidic foods. Check out
their website at www.prerelief.com.
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