1. Overview and Description of Symptoms

From the outside, Rebecca Johnson appears to be perfectly healthy. But inside, she quietly suffers from chronic, unremitting pain. Six years ago, she was diagnosed with a urinary tract infection (UTI). After taking the prescribed course of antibiotics, she felt better--but after a few days, her symptoms came back. She felt intense burning whenever she urinated, the need to urinate even when her bladder was nearly empty, and pelvic pain. When she returned to her doctor, however, he told her that she no longer had a UTI. During the next three years, she went to five urologists and three gynecologists, none of whom were able to give a diagnosis. She repeatedly tested negative for UTIs and for sexually transmitted diseases whose symptoms of similar to the ones Johnson experiences. Two of the doctors recommended that she see a psychiatrist, assuring her that the problem was all in her head.

"It totally disrupted my life," Johnson explains. "I'm in constant pain. Sex is usually painful--imagine having sex when you're in the middle of what feels like a urinary tract infection. My husband didn't believe me--he thought I was being a hypochondriac and was crazy to keep going to doctor after doctor." After three years and nine doctors, Johnson was finally diagnosed with interstitial cystitis (IC).

IC is a complex, enigmatic urinary tract disease about which little is known. It primarily strikes women--about ninety percent of IC patients are female. Though it is not fatal, IC is a sometimes debilitating disease that is often more painful than many life-threatening diseases (Ratner 3). IC symptoms are similar to those one experiences with a urinary tract infection, but people with IC, though they may get UTIs occasionally, have the symptoms while testing negative for infection. People with IC tend to have a urinary frequency of at least twice during the night and from eight to fifty times during the day. They experience feelings of urgency even when their bladders are empty or only partially full. (Keller et al, 67-68)

Dr. Vicki Ratner, who has IC, wrote in an article published in the Journal of Urology, "Imagine feeling like you have a lit match in your urethra--like your pelvis is on fire. Imagine having to void 60 to 80 times a day and 10 to 30 times a night--never getting a decent night's sleep. Think what it would feel like to have your doctor tell you that there is nothing wrong with you, that your problem is just stress, and that you should try to relax" (Ratner 2).

Much to the misfortune of those who have suffered from it for years, IC is just now beginning to gain credibility in the medical community. For years, many doctors dismissed IC as a psychosomatic, hysterical women's disease and directed complaining patients towards psychiatric rather than physical treatments. The 1985 edition of Campbell's urology described IC as "a disease that is taunting in its evasion of being understood 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" (Ratner et al, p. 2).

Since the mid-1980s, this attitude has decreased somewhat. More and more doctors are aware of IC. This is due largely to efforts by the Interstitial Cystitis Association (ICA), which Vicki Ratner founded in 1984. Ratner developed IC while she was in medical school. Like many other women, Ratner was told that there was nothing she could do to ameliorate her pain and discomfort. But unlike most other IC sufferers, Ratner was armed with two valuable tools: medical knowledge and credibility due to her status as a soon-to-be doctor. Through researching in medical journals, Ratner diagnosed herself. She then reached out to other women with the disease and built a network of support. Through her networking in both the lay and medical communities, Ratner raised awareness about IC. The ICA has been modestly successful in lobbying Congress and the National Institutes of Health (NIH) to direct research funds towards the study of IC: one-third of the NIH's Urology budget is devoted to IC research (ICA newsletter).The ICA is often pointed out as a model for political action committees that are seeking to raise funds for research on health-related issues.

Though much progress has been made in the past decade, IC continues to be one of the biggest puzzles in the medical community today. It is predicted that as many as 450,000 American women have IC (ICA web page). Doctors and researchers offer many diverse speculations, but no known, definite cause exists. Most experts believe that there are many different types of IC; indeed, some assert that "IC" is an umbrella term for several different diseases that are categorized together due to their common symptoms. As such, treatments vary widely. There is no cure for IC. This article is divided into five subjects: Overview and Description of Symptoms; Causes and Subsets of IC; Diagnosis; Treatments; and the Role of the ICA.

2. What causes IC symptoms?

There is no known, definite cause for IC. Scientists suspect that there may be several different causes, leading to several different diseases that all share a common symptomology. Researchers have suggested a variety of possible explanations, such as that IC patients have a damaged bladder lining, an autoimmune disorder, or an undetectable infection, or a combination of the four.

One popular theory is that the mucus lining of the bladder wall is damaged in IC patients. If the gycosaminoglycan (GAG) layer is damaged, this would allow for increased permeability of aggravating urine solutes into the bladder epithelium (Warren, p. 33). The question is, how and why would the lining get damaged in the first place? Possible answers include antibiotics, infection, and an autoimmune disorder.

Indeed, an autoimmune disorder may cause IC in at least a subset of patients. An autoimmune disorder can occur when mast cells, which send a signal to the body to release histamines in order to fight off possibly harmful substances, perceive that benign substances are harmful irritants. In order to protect the body, the mast cells release histamines. Increased mast cell activation causes allergic reactions like hay fever, asthma, and, perhaps, IC. One esteemed study indicates that at least some IC patients have higher mast cell activation than normal. The average number of mast cells in a group of 26 IC patients was four times higher than the average of the control group, which consisted of people with incontinence and chronic bacterial cystitis (Theorides et al, 629-36). Epidemiological studies offer further evidence that IC may be an autoimmune disorder, for autoimmune disorders are more prevalent in the IC than in the general population. According to one study, more than 50 percent of IC patients have allergies, 30 percent have irritable bowel syndrome, and 20 percent suffer from migraine headaches on a regular basis. There are also higher degrees of irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and other autoimmune disorders among people with IC (Koziol et al, p. 10). The fact that the vast majority of IC patients are women could also serve as evidence that IC may be an autoimmune disorder, as women are much more likely to have such disorders. Though scientists have few definitive answers about autoimmune disorders, women who have them tend to experience of fluctuation of symptoms with their menstrual cycle (Theoharides, p. 630). IC patients often report a worsening of symptoms at ovulation or premenstrually (Whitmore, p. 123), as do many women with autoimmune disorders.

Another possibility is that IC patients suffer from a bacterial infection that cannot be detected by lab tests nor cured by typical antibiotics. Three main reasons suggest this could be the case. Women are much more likely than men to have UTIs because of the connection between vaginal and bacterial colonization and the short female urethra, which makes it much easier for bacteria to enter the bladder. Secondly, almost all IC patients have a history of UTIs. And, most importantly perhaps, IC seems to lack an inheritable trait; rather, it seems to be an acquired disease with an acute onset, which is typical of an infection (Warren, p. 33). Some doctors propose that IC patients may have infectious agents bound so securely to the bladder wall that passing urine cannot dislodge them. The infection theory may be compatible with other theories on the pathology of IC. For example, an infection could lead to the disruption of the GAG layer that lines the bladder wall. In another scenario, infection could lead to bladder injury and the exposure of the lining of the bladder to sequestered urine antigen, which could lead to an autoimmune problem (Warren, pp. 32-5).

Doctors and researchers are currently compiling a database of the symptoms and histories of IC patients across the country, hoping to discern certain patterns and categories. Dr. Alan Wein, Chairman of Urology and Professor at the University of Pennsylvania, suggests the following characteristics of IC could be used to classify different subsets of the disease: bladder capacity; whether or not there is increased concentration of mast cells in the bladder wall; whether certain factors such as diet, stress, and infection exacerbate symptoms; the severity of symptoms; and how patients respond to various treatments. (ICA Online Info Center) This database should shed light on the issue of why IC occurs in the first place.

3. How is IC diagnosed?

As mentioned earlier, the medical community scorned the idea of IC for years, and many doctors are still skeptical of its existence. It can take many years and many different doctors to finally get a diagnosis of IC.

One woman wrote to the ICA, "I am a nurse and I have interstitial cystitis. It took over 15 doctors and over two and a half years to even get a diagnosis. Needless to say, 14 doctors didn't believe me and recommended psychiatric care. I knew something was wrong and persisted. I wish it were possible to put some doctors in my body so they could feel what it is like to have this pain" (Ratner et al, p. 2).

The diagnostic standards vary widely from doctor to doctor. The process is usually one of excluding other diseases with similar symptoms, such as UTI, vaginitis, ovarian cysts, bladder cancer, kidney disease, bladder tumors, cancer, and herpes. A cystoscopy, in which a thin metal microscope is inserted up the urethra in order to examine the bladder walls, is required for diagnosis. During cystoscopy, doctors can determine if there are ulcers, hemorrhages, or other damages to the bladder lining (Johansson et al, p. 55). However, IC can be present even if these are not observed on the bladder wall. In addition, "although light microscopy can differentiate ulcerative (classic) from nonulcerative forms of the disorder, the finding are far from characteristic enough to enable de novo diagnosis of IC based on tissue in the absence of clinical history" (Hanno, p. 65).

4. Treatments

There is no cure for IC and no single treatment strategy. Rather, a plethora of treatments exist that are highly experimental. Self-care strategies such as diet and exercise are often just as or more important in controlling IC's symptoms.

The first line of treatment is often oral medications. Antihistamines are often tried, based on the theory that IC is caused by higher than normal mast cell activation. Ditropan, Urised, and Pyridium are often used to reduce bladder spasms. Whereas antihistamines may be treating the underlying cause of IC, ditropan, urised, and pyridium treat, or attempt to treat, the symptoms.

The next line of treatments used on IC is bladder distension, in which the bladder is distended with liquids beyond normal capacity in order to increase bladder capacity and interfere with pain signals. Though symptoms worsen for a few days, many patients experience temporary relief, ranging from weeks to months. Another popular treatment is bladder instillation of dimethyl sulfoxide (DMSO). DMSO, an anti-inflammatory drug, is inserted into the bladder by traveling through a tube in the urethra. The process must be repeated periodically, and often the procedure alleviates symptoms the first few times, then slowly stops working (Parsons, pp. 504-7).

The most exciting treatment for IC is a new drug called Elmiron. Elmiron is similar to the lining of the bladder, the GAG layer. Many believe that IC symptoms result from a damaged bladder lining. Elmiron works by coating the bladder wall like Pepto Bismol coats the stomach lining. Relief often does not come until the patients have been on the pill for three to six months. Some patients do not experience any alleviation of symptoms upon taking Elmiron, and the drug has some side effects, including skin rash and hair loss (ICA news release). Self-care strategies are crucial in treating IC. An important factor is diet control. Many IC patients and doctors have found that certain foods aggravate IC symptoms. The most commonly irritating foods are alcohol, citrus juices and fruits, highly acidic foods like tomatoes, spices, caffeine, artificial sweeteners, and carbonated beverages. However, many other foods may be irritants as well, such as yogurt, brewer's yeast, vinegar, hydrogenated fats, cheese, mayonnaise, tap water, foods with molds, sugar, smoked, or barbecued foods, fried foods, synthetic vitamins, beans, and more (Whitmore, p. 125). Doctors stress that IC patients should maintain a healthy, balanced diet, then hand them a list of foods to avoid--a list so long that at least one of the items is in practically every meal. Though it is difficult, the effort of diet manipulation often pays off. Approximately 60 percent of IC patients can identify foods and fluids that aggravate symptoms (Whitmore, p. 125). Like everything connected to IC, no one is quite sure why diet influences symptoms. One theory is that, since the bladder wall of IC patients is inflammed or damaged, the bladder is more sensitive to such foods. Acidic foods irritate the damaged lining. Another theory, which does not necessarily exclude the former, is that the foods cause an allergic reaction within the bladder, which ties into the theory that some IC patients may have an autoimmune disorder.

Exercise is often cited as a way to reduce IC symptoms. Exercise improves circulation, reduces stress, and improves energy levels. Many exercises, such as bicycling and running, exacerbate IC symptoms by putting pressure on the bladder and pelvic floor. Swimming is sometimes a good exercise, but chemicals in the pool can cause irritation. Possible exercises are low impact aerobics, weight training, and yoga.

5. The Role of the Interstitial Cystitis Association

The Interstitial Cystitis Association was founded in 1984 by then-medical school student Vicki Ratner. Upon developing IC, Ratner had a frustrating experience with the medical community that is typical for IC patients. She was told that her symptoms were nothing and that she should just try to ignore them. Refusing to give in, Ratner researched in medical journals and discovered several articles that discussed the phenomenon of IC. Ratner founded the ICA to reach out to educate the medical community and the general public about the disease. The ICA serves as a source of information and support for patients. Its media outreach has resulted in getting articles on IC published in women's magazines and major newspapers such as "The New York Times," and garnering appearances on shows like the "Today Show." Often after these media events, many women whose complaints have been brushed aside by their doctors contact the ICA and receive information on the disease and names of doctors in their area who can help.

In addition, the ICA raises funds for research. This is done through soliciting funds from IC patients and their supporters, and, more importantly, through lobbying Congress to allocate funds to IC within the budget for the National Institute of Health. In the past five years, the ICA has persuaded Congress to allocate 11 million dollars towards IC research.

Currently, the ICA is leading a lobbying effort for 2.5 million in additional funds be provided for 1998's budget. They are asking all supporters to write letters to their representatives, senators, and the chairs of the committees that control research funds. The letter should include a summary of the disease, how further research could improve the quality of life for those with IC, and the following:

"I urge you to help us achieve the following: 1) That at least $2.5 million in additional funds be provided to the Urology Program of the NIDDK in Fiscal Year 1998 specifically to support further IC research and to continue and expand the next phase of the National IC database; 2) That the NIDDK issue an RFA specifically for IC in FY 1998 and designate funds for that purpose; 3) That the RFA focus on clinical studies which would address the areas of IC diagnosis, prevention, treatment, and epidemiology and that the next phase of the Database include multi-centered clinical trials."

A copy of each letter should be sent to: the chairs of the committees that control research spending--1) Sen. Arlen Specter/ Chairman, Senate Labor-Health and Human Services/ Education Sub-committee, SR/ Washington, DC 20510; 2) Representative John Porter/ Chairman, House Labor- Health and Human Services Committee/ Education sub-committee, RHOB/ Washington, DC 20515; and your own representatives and senators, whose names and addresses you can find out by calling Project Vote Smart at 1-800-622-SMART. Personal letters can make a big impact on Congress. Representative and Senators feel obligated to respond to every letter, and thus your letter will force them to look into the issue in order to write a response.

IC is a deeply puzzling disease. Doctors are unsure of its causes and can offer no cure-all treatments. But in the past ten years, the medical community has taken a big step towards helping people with the disease simply by beginning to acknowledge that it exists. Though it is a challenge to live with IC, people with IC can hang onto one hopeful thought: the medical knowledge about the disease is constantly increasing. If urologists and researchists continue to put effort into piecing this puzzle together, some new and promising treatments may arise on the horizon within the next decade.

Bibliography

1. Gillespie, Larrian.You Don't Have to Live With Cystitis. New York: Avon Books, 1986 and 1996.

2. Hanno, et al: Diagnosis of IC. Urol-Clin-North-Am 21 (1): 63-6, 1994.

3. Interstitial Cystitis Web Site: www.ichelp

4. Johansson, et al: Pathology of IC. Urol-Clin-North-Am 21 (1): 55-62, 1994.

5. Keller, et al: Measurement of Symptoms of IC. Urol-Clin-North-Am 21 (1): 67-71, 1994.

6. Koziol, et al. Epidemiology of IC. Urol-CLin-North-Am 21 (1): 7-20, 1994.

7. National Institute of Diabetes and Digestive and Kidney Diseases Information Booklet. NIH Publication No. 94-3220. August 1994.

8. Parsons, et al. Treatment of IC. Br-J-Urol 73 (5): 504-7, 1994.

9. Ratliff, et al. The Etiology of IC. Urol-Clin-North-Am 21 (1): 21-30, 1994.

10. Ratner, et al. IC: A Patient's Perspective. Urol-Clin-North