Interstitial Cystitis: Overview
May 2001; Volume 3; 36-39
By Lucretia Perilli and Vicki Ratner, MD
Interstitial cystitis (ic), a chronic inflammatory condition of the bladder, is characterized by pelvic/ perineal pain, urinary urgency, and frequency in the absence of bacterial infection or other identifiable causes. The etiology of IC is unknown, and there is no cure. For many years IC was dismissed as a "hysterical female condition" as late as 1985, Campbell’s Urology described IC as "a disease that ... may represent the end stage of a bladder that has been made irritable by emotional disturbance.... A pathway for the discharge of unconscious hatreds."1 The text finally has been revised, and attitudes are changing slowly.
Epidemiology
There are an estimated 700,000 cases of IC in the United States, with projections running as high as several million; 90% of IC patients are female. IC can occur at any age, including childhood and adolescence (25% of patients are < 30). The prevalence of IC in the United States is three-fold greater than that reported in Europe.2 Recently, the National Institutes of Health allocated $7.5 million to be used for epidemiologic studies of IC.
Symptoms and Causes
Pain, urinary frequency, and urgency are the paramount symptoms of IC. Dyspareunia can be so severe that many women abstain from all sexual activity. Bladder and suprapubic pain and pressure can range from mild to severe and may be accompanied by urinary frequency (as often as 60 times a day). Patients also may report urethral, vaginal, or rectal pain, and lower back and thigh pain. These symptoms can disrupt every aspect of patients’ personal and professional lives, resulting in sleep deprivation, depression, and in some cases, suicide. Many patients are unable to work full-time, thus limiting their access to affordable health insurance. Others may be unable to work at all. Some have pain so severe it prevents them from riding in a car or even leaving their homes. The quality of life of IC patients has been documented to be worse than that of women undergoing dialysis for end-stage renal disease.3 IC can be associated with other chronic conditions such as fibromyalgia, vulvodynia, migraines, allergic reactions, and gastrointestinal problems.4
The etiology of IC remains unknown but a number of theories are being investigated including: a defect in the bladder lining allowing substances in the urine to damage the bladder wall; an immunologic/autoimmune response; an allergic reaction; an unidentified bacterium, fungus, or virus; and a neurogenic inflammatory response.5 A familial or genetic component also is being investigated.
Diagnosis
No IC-specific urinary marker has yet been identified but two factors are under investigation: a glycoprotein (GP51) and an anti-proliferative factor.6,7 Also, a rhamnose/lactulose blood assay to test for bladder permeability (thought to be correlated with IC) is being studied.8
Cystoscopy with hydrodistension performed under general or regional anesthesia is considered the "gold standard" for confirmation of diagnosis and is therapeutic as well in some patients. Office cystoscopy may be too painful for IC patients and may not distend the bladder sufficiently to reveal the signs of IC: pinpoint hemorrhages or glomerulations (present in 90% of patients) and Hunner’s ulcers (present in 5-10% of patients). Up to 10% of IC patients may show no signs of glomerulations or Hunner’s ulcers with cystoscopy under general anesthesia.9 A potassium chloride sensitivity test has been proposed as a possible diagnostic tool for IC. The test consists of instilling a solution of potassium chloride into the bladder via urinary catheter and measuring pain response. A positive pain response may indicate a defect in the GAG lining, which may be diagnostic of IC. However, this painful test compounds an already painful condition. A recent study reports only 60% accuracy with this test.10
Conventional Treatments
A recent report from the Interstitial Cystitis Database, established in 1993, reported that of 581 women in the database, 105 (18%) were receiving no treatment.11 An astounding 183 different treatments for urinary symptoms were prescribed by physicians. The most common physician-prescribed treatments for women at baseline were cystoscopy/hydrodistension (32.9%), amitriptyline (16.9%), phenazopyridine (14.3%), special diet (9.3%), intravesical heparin (9.1%), hyoscamine (7.1%), oxybutynin (5.9%), oral pentosan polysulfate sodium (5.5%), propoxyphene plus acetaminophen (4.8%), and urinary antiseptic combinations (4.5%). The authors point out that current pentosan polysulfate sodium is probably much higher; the drug was approved by the FDA in 1996, after most women had entered the database Although this report was recently published, data in this paper date from 1990-1995; the IC Database has been concluded for several years.
The researchers note that there is a paucity of good, placebo-controlled, randomized clinical trials of therapies, and clearly there is no consensus on treatment.
Oral medications. The only oral medication approved specifically for IC, pentosan polysulfate sodium, is a glycosaminoglycan-like material thought to help restore the bladder surface.12 In double-blind, placebo-controlled trials, 38% of the patients treated with pentosan polysulfate sodium for three months reported improvement of their IC symptoms. In open-label trials, 61% of the patients reported improvement.12 Low-dose tricyclic antidepressants (10-75 mg qhs) have been used both for their analgesic and anticholinergic effects that can help decrease urinary frequency.13 Selective serotonin reuptake inhibitors (SSRIs) also are used, but no research has been conducted on SSRIs. The most widely used antihistamine to treat IC is hydroxyzine, which inhibits mast cell degranulation, thought to play a part in some IC symptoms. It also has sedative and anxiolytic effects.14 Pain medications include anticonvulsants such as gabapentin or carbamazepine, and short- or long-acting narcotics. Other oral medications used in the treatment of IC include: antispasmodics (methenamine), anticholinergics (tolterodine tartrate, oxybutynin, hyoscyamine), H2 blockers (cimetidine, ranitidine), urinary alkalinizing agents (sodium citrate, potassium citrate), and adrenergic blockers (doxazosin, terazosin). None of these has been approved by the FDA specifically for IC.
Intravesical medications. Although oral medications are used more frequently to treat IC, medications instilled directly into the bladder still are considered a mainstay of treatment. DMSO (dimethylsulfoxide)—approved for use in IC in 1978—commonly is used as part of a "cocktail" instillation combined with heparin, steroids, and/or anesthetics. BCG (bacillus Calmette-Guerin) is an experimental treatment currently in phase III clinical trials; hyaluronic acid also is undergoing clinical trials.
Transcutaneous electrical nerve stimulation. Some IC patients have reported temporary relief of symptoms with the use of transcutaneous electrical nerve stimulation (TENS). A small study comparing TENS (using the posterior tibial nerve) with acupuncture found little benefit for either;15 other studies have found TENS to be a useful tool in treating the pain of IC.16-18 Transvaginal biofeedback and electrical stimulation have also been used to treat pelvic pain caused by IC; no trials were identified on this treatment in IC patients.
Surgery. Laser surgery is used specifically to treat Hunner’s ulcers. While not a cure, laser therapy can help to alleviate the symptoms of Hunner’s ulcers for extended periods of time.19 Other types of surgery for IC, such as augmentation cystoplasty or urinary diversion, rarely are recommended because of potentially serious complications and its failure to relieve IC pain in many cases.
Sacral nerve stimulation implants. Sacral nerve stimulation implants, recently approved by the FDA for urge incontinence, urinary frequency, and urgency, currently are undergoing preclinical trials testing for use in the treatment of IC and pain. A case series tested percutaneous sacral nerve root neuromodulation (via test stimulation, not permanent implant) in 15 women with refractory IC.20 Mean voided volume during treatment increased from 90 to 143 ml (P < 0.001). Mean daytime urinary frequency significantly decreased (from 20 to 11) and nocturia decreased (from six to two times) (P = 0.01 for both). Mean bladder pain decreased from 8.9 to 2.4 points on a 10-point scale (P < 0.001). Several quality-of-life parameters significantly improved; 73% of participants requested to proceed to complete sacral nerve root implantation. Another case series in six women found significant improvement in voiding frequency, pelvic pain, and urinary urgency (all P < 0.05) after five days of continuous sacral nerve root stimulation.21 Controlled trials of this therapy should be done.
Self-Help Techniques
There are no treatments that work for all IC patients. Patients with mild cases of IC may find significant symptom relief by implementing self-help strategies. Patients with more severe IC symptoms also may benefit by adding these strategies as adjuncts to their treatment regimen. None of the following treatments have been subjected to controlled clinical trials, but have been reported helpful by patients.
Diet. (See Table 1.) Avoiding caffeine, artificial sweeteners, alcohol, and tobacco can help to reduce IC symptoms. A diet low in acidic foods and beverages may help symptoms; some patients add Prelief® (a dietary supplement containing calcium glycerophosphate) to foods and beverages to reduce acidity. Diets low in the amino acids tyramine, tyrosine, and tryptophan are used by some patients. Some IC patients follow salt- and/or sugar-restricted diets; others avoid foods containing yeast.22 The consumption of vitamin C or some stimulant supplements, such as ephedra, may aggravate IC symptoms.
| Table 1: The IC Diet | |
| Restricted Foods, Beverages and Other Ingredients | |
| Milk/Dairy Products: | aged cheeses, sour cream, yogurt, and chocolate |
| Vegetables: | fava beans, lima beans, onions, tofu, soybeans, and tomatoes |
| Fruits: | apples, apricots, avocados, bananas, cantaloupes, citrus fruits, cranberries, grapes, nectarines, peaches, pineapples, plums, pomegranates, rhubarb, strawberries, and juices made from these fruits |
| Carbohydrates and Grains: | rye and sourdough bread |
| Meats and Fish: | aged, canned, cured, processed or smoked meats and fish, anchovies, caviar, chicken livers, corned beef, and meats that contain nitrates or nitrites |
| Nuts: | most nuts, with the exception of almonds, cashews, and pine nuts |
| Beverages: | alcoholic beverages, beer, carbonated drinks such as sodas, coffee, tea, cranberry juice, and wine |
| Seasonings: | mayonnaise, miso, spicy foods (especially such ethnic foods as Chinese, Indian, Mexican, and Thai), soy sauce, salad dressing, and vinegar |
| Preservatives and Additives: | benzol alcohol, citric acid, monosodium glutamate (MSG), aspartame (Nutrasweet®), saccharin, and foods containing preservatives, artificial ingredients, and colors |
| Miscellaneous: | tobacco, caffeine, diet pills, junk foods, recreational drugs, cold and allergy medications containing ephedrine or pseudoephedrine, and certain vitamins |
| Adapted from: Interstitial Cystitis Association's IC & Diet brochure. | |
Stress-reduction techniques. Strategies used by IC patients include meditation, visualization, biofeedback, self-hypnosis, massage therapy, and psychotherapy tailored toward the needs of the chronically ill.
Exercise. Exercise plans may include gentle stretching exercises that avoid tightening or jarring the pelvic region, pelvic floor relaxation exercises, yoga, low-impact aerobics, Tai Chi, and swimming. However, chlorinated swimming pool water may cause IC symptoms to flare.
Bladder retraining. The bladder retraining program is a self-help process by which patients learn to control their urge to urinate. It is essential that pain be under control before this program is attempted. When patients experience bladder pain or urgency, the normal impulse is to urinate to stop the symptom. A pattern of frequent voiding can be difficult to reverse. The goal of the bladder retraining program is to use a series of simple steps to achieve longer and longer periods between urinations. Working with a health care practitioner, a program is established for each patient beginning with a four-week period of holding the urine for a specific number of minutes or hours (based on the individual’s current average voiding schedule). The patient is encouraged to wait a specified period after the first urge is felt before urinating (15 minutes, for example). If severe pain is felt before the period has elapsed, voiding is encouraged. If after waiting, the patient finds that the need to urinate has diminished, then she/he should wait until the next urge to void is felt. At the end of one month, the time interval is increased, and at the end of the second month, the interval is increased again. It is acceptable if intervals are occasionally longer or shorter, as long as the minimum interval occurs most of the time.
Pain relief. Self-help sources of IC pain relief include cold packs and/or hot packs placed on the pelvic floor region, sitz baths, and, for those not on salt-restricted diets, drinking a solution of water and a teaspoon of baking soda during flare-ups. There are no established guidelines for this practice, and patients should be cautioned about repeatedly consuming several teaspoons of baking soda because of potential health risks.
Other self-help techniques. Learning new sexual techniques that do not place as much stress and pressure on the bladder is helpful. Female IC patients have found that positions other than the missionary position put less stress on the bladder. Water-based lubricants can be helpful. Also, "outercourse" (i.e., oral sex, sensual massage, mutual masturbation) can be a helpful sexual strategy for IC patients. Wearing loose-fitting clothing and using unbleached and unscented toilet paper can also help to alleviate IC symptoms.
References
1. Harrison JH, et al. eds. Campbell’s Urology. Philadelphia: WB Saunders; 1979; 1906-1907.
2. Curhan GC, et al. Epidemiology of interstitial cystitis: A population based study. J Urol 1999;161:549-552.
3. Ratner V. Pain in interstitial cystitis: Changing attitudes, changing treatments. Pain Forum 1999;8: 154-157.
4. Alagiri M, et al. Interstitial cystitis: Unexplained associations with other chronic diseases and pain syndromes. Urology 1997;49(5A suppl):52-57.
5. Erickson DR. Interstitial cystitis: Update on etiologies and therapeutic options. J Womens Health Gend Based Med 1999;8:745-758.
6. Byrne DS, et al. The urinary glycoprotein GP51 as a clinical marker for interstitial cystitis. J Urol 1999;161:1786-1790.
7. Keay S, et al. A diagnostic in vitro urine assay for interstitial cystitis. Urology 1998;52:974-978.
8. Erickson DR, et al. A new direct test of bladder permeability. J Urol 2000;164:419-422.
9. Sant GR. Interstitial cystitis. Curr Opin Obstet Gynecol 1997;9:332-336.
10. Teichman JMH, Nielsen-Omeis BJ. Potassium leak test predicts outcome in interstitial cystitis. J Urol 1999;161:1791-1796.
11. Rovner E. Treatments used in women with interstitial cystitis: The interstitial cystitis data base (ICDB) study experience. Urology 2000;56:940-945.
12. Hanno PM. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology 1997;49(5A suppl):93-99.
13. Hanno PM. Amitriptyline in the treatment of interstitial cystitis. Urol Clin North Am 1994;21:89-91.
14. Theoharides TC. Hydroxyzine in the treatment of interstitial cystitis. Urol Clin North Am 1994;21: 113-119.
15. Geirsson G, et al. Traditional acupuncture and electrical stimulation of the posterior tibial nerve. A trial in chronic interstitial cystitis. Scand J Urol Nephrol 1993;27:67-70.
16. Bristow SE, et al. TENS: A treatment option for bladder dysfunction. Int Urogynecol J Pelvic Floor Dysfunct 1996;7:185-190.
17. Pontari MA, et al. Logical and systematic approach to the evaluation and management of patients suspected of having interstitial cystitis. Urology 1997; 49(5A Suppl):114-120.
18. Fall M, Lindstrom S. Transcutaneous electrical nerve stimulation in classic and nonulcer interstitial cystitis. Urol Clin North Am 1994;21:131-139.
19. Shanberg AM, Malloy T. Use of lasers in interstitial cystitis. In: Sant GR, ed. Interstitial Cystitis. New York: Lippincott-Raven; 1997:215-217.
20. Maher CF, et al. Percutaneous sacral nerve root neuromodulation for intractable interstitial cystitis. J Urol 2001;165:884-886.
21. Chai TC, et al. Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis. Urology 2000;55: 643-646.
22. Laumann B. A Taste of the Good Life: A Cookbook for an Interstitial Cystitis Diet. Tustin, CA: Freeman Family Trust Publications; 1998.
May 2001; Volume 3; 36-39
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