Disease: Interstitial Cystitis (IC)/Painful Bladder Syndrome (PBS)

    Interstitial cystitis facts

    • PBS/IC is an inflammatory disease of the bladder that can cause ulceration and bleeding of the bladder's lining and can lead to scarring and stiffening of the bladder.
    • The symptoms of PBS/IC are
      • pelvic pain,
      • frequent urination,
      • urinary urgency.
    • PBS/IC has a variable clinical course, meaning that symptoms can appear and disappear over time. Moreover, the intensity of symptoms varies among individuals and even within the same individual over time.
    • The cause of PBS/IC is unknown, but abnormalities in the leakiness or structure of the lining of the bladder are believed to play a role in the development of PBS/IC.
    • The diagnosis of PBS/IC is based on the symptoms, an abnormal potassium sensitivity test (PST), and elimination of other conditions that may be responsible for the symptoms.
    • Treatment for PBS/IC most commonly utilizes heparinoid drugs to help restore integrity of the bladder lining along with other oral medications. Bladder distension and intravesical drug therapy are other treatments that may provide relief in PBS/IC.

    Overview of urinary function

    The urinary system consists of the kidneys, ureters, bladder, and urethra. The kidneys, a pair of purplish-brown organs, are located below the ribs toward the middle of the back. The kidneys remove water and waste from the blood in the form of urine, keeping a stable balance of salts and other substances in the blood. The kidneys also produce erythropoietin, a hormone that stimulates the formation of red blood cells. Narrow tubes called ureters carry urine from the kidneys to the bladder, a triangle-shaped, muscular chamber in the lower abdomen. Like a balloon, the bladder's muscular, elastic walls relax and expand to store urine and contract and flatten when urine is emptied through the urethra. The typical adult bladder can store about 1 ½ cups of urine.

    Adults urinate about 1 ½ quarts of urine each day. The amount of urine varies depending on the fluids and foods a person consumes. The volume formed at night is about half that formed during the day.

    Normal urine contains fluids, salts and waste products, but it is free of bacteria, viruses, and fungi. The tissues of the bladder are isolated from urine and toxic substances by a coating on the inside of the bladder that discourages bacteria from attaching and growing on the bladder wall.

    Picture of the urinary system

    What is interstitial cystitis (IC)?

    Interstitial cystitis (IC) is a term that has been used to refer to a clinical syndrome characterized by chronic urinary urgency (feeling the need to urinate immediately) and frequency (frequent urination), usually with suprapubic discomfort or pressure and usually relieved by urinating. The symptoms of this condition vary among individuals and may even vary with time in the same individual. The term cystitis refers to any inflammation of the bladder. In contrast to bacterial cystitis that results from an infection in the bladder, a type of urinary tract infection (UTI), no infectious organism has been identified in people with interstitial cystitis.

    There has been controversy in the medical literature regarding the definition of interstitial cystitis and use of the term. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the U.S. National Institutes of Health (NIH) established a set of diagnostic criteria for inclusion in research studies relating to interstitial cystitis and its causes that were used for research purposes until 2002. However, the NIDDK criteria were felt to be overly restrictive for diagnostic use, and in 2002, new criteria were proposed for the diagnosis of painful bladder disorders, including the condition referred to as painful bladder syndrome (PBS) by the International Continence Society (ICS). These criteria felt that the term PBS was preferable and that the term IC should be restricted to use in those patients having typical findings observed upon cystoscopy and biopsy of the bladder tissues.

    The ICS criteria state the following:

    • Painful bladder syndrome is the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology...The ICS believes this to be a preferable term to "interstitial cystitis." Interstitial cystitis is a specific diagnosis and requires confirmation by typical clinical cystoscopic and possibly histological features.

    In 2006, another set of diagnostic criteria were proposed by the European Society for the Study of IC/BPS, suggesting the use of the term bladder pain syndrome (BPS):

    • A diagnosis of bladder pain syndrome (BPS) is made of the basis of the symptom of chronic pain related to the urinary bladder accompanied by at least one other urinary symptom such as daytime and nighttime frequency, and exclusion of confusable diseases as the cause of the symptoms, and cystoscopy with hydrodistension and biopsy if indicated (to document the type of BPS/IC).

    Until agreement is reached about terminology and definition of the condition, it will be difficult to determine the true prevalence of PBS/IC. Estimates of the number of affected people vary widely and are dependent upon the criteria used for diagnosis. Many experts believe that about 3.3 million women in the U.S. (over age 18) may be affected as well as 1.6 million men.

    Despite the lack of agreement about the diagnosis of PBS/IC, studies agree that the majority of those affected are women. While individuals of any age can be affected, including children, the average age of onset is around 40. PBS/IC has not been considered to be a hereditary disorder, but multiple cases have occurred among some families, prompting ongoing investigation of the possible role of hereditary factors in the development of PBS/IC.

    Some associations with other medical conditions are seen with PBS/IC. Women with PBS/IC are more likely to have had frequent urinary tract infections (UTIs) and to have had previous gynecologic surgery than women without PBS/IC. Certain chronic illnesses have been described as occurring more frequently in people with PBS/IC than in the general population. Examples of these associated conditions are inflammatory bowel disease, systemic lupus erythematosus, irritable bowel syndrome (IBS), vulvodynia (chronic discomfort in the vulvar area), allergies, endometriosis, and fibromyalgia. While each of these conditions has been described in at least some studies to be more common in people with PBS/IC than in the general population, there is no evidence that any of these conditions is the cause of PBS/IC.

    Observations from cystoscopy (visual examination of the inside of the bladder via a probe) studies have found that two patterns exist for IC, ulcerative and nonulcerative, depending upon the presence or absence of ulcerations in the bladder lining. Star-shaped ulcerations in the bladder wall are known as Hunner's ulcers. These are found in less than 10% of cases of PBS/IC in the U.S.

    Over time, interstitial cystitis can cause physical damage to the bladder wall. Scarring and stiffening of the bladder wall may occur as a result of the chronic inflammation, leading to a decrease in bladder capacity. Glomerulations (areas of pinpoint bleeding) and petechial hemorrhage may be seen on the bladder wall.

    What is the cause of interstitial cystitis?

    No one knows what causes PBS/IC, but doctors believe that it is a real physical problem and not a result, symptom, or sign of an emotional problem. Because the symptoms of PBS/IC are varied, most researchers believe that it represents a spectrum of disorders rather than one single disease.

    One area of research on the cause of PBS/IC has focused on the layer that coats the lining of the bladder called the glycocalyx, made up primarily of substances called mucins and glycosaminoglycans (GAGs). This layer normally protects the bladder wall from toxic effects of urine and its contents. Researchers have found that this protective layer of the bladder is "leaky" in about 70% of PBS/IC patients and have hypothesized that this may allow substances in urine to pass into the bladder wall where they might trigger PBS/IC, making these patients susceptible to chemicals in the urine, including those from foods or beverages.

    Along with altered permeability of the bladder wall, researchers are also examining the possibility that PBS/IC results from decreased levels of protective substances in the bladder wall. Reduced levels of GAGs (discussed previously) or other protective proteins might also be responsible for the damage to the bladder wall seen in PBS/IC.

    No matter what the mechanism for disruption of the bladder lining, potassium is one substance that may be involved in damage to the bladder wall. Potassium is present in high concentrations in urine and is normally not toxic to the bladder lining. However, if the tissues lining the inside of the bladder (urothelium) are disrupted or are abnormally leaky, potassium could then penetrate the lining tissues and enter the muscle layers of the bladder where it can cause damage and promote inflammation.

    Researchers have isolated a substance known as antiproliferative factor (APF) that appears to block the normal growth of cells that make up the lining of the bladder. APF has been identified almost exclusively in the urine of people suffering with PBS/IC. Research is under way to clarify the potential role of APF in the development of PBS/IC.

    Increased activation of sensory nerves (neurologic hypersensitivity) in the bladder wall is also thought to contribute to the symptoms of PBS/IC. Cells known as mast cells, which play a role in the body's inflammatory response to injury, release chemicals that are believed to be capable of contributing to the symptoms of PBS/IC.

    Other theories about the cause of PBS/IC are that it is a form of autoimmune disorder or that infection with an unidentified organism may be producing the damage to the bladder and the accompanying symptoms.

    What are interstitial cystitis symptoms and signs?

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

    • decreased bladder capacity;
    • an urgent need to urinate frequently day and night (urinating frequently is referred to as urinary frequency; having a strong urge to urinate is referred to as urinary urgency);
    • feelings of pressure, pain, and tenderness around the bladder, pelvis, and perineum (the area between the anus and vagina or anus and scrotum) which may increase as the bladder fills and decrease as it empties;
    • painful sexual intercourse (dyspareunia);
    • discomfort or pain in the penis and scrotum.

    Most people suffering from PBS/IC have both urinary frequency/urgency and pelvic pain, although these symptoms may also occur singly or in any combination. In most women, symptoms usually worsen around the time of their periods. As with many other illnesses, stress also may intensify the symptoms, but it does not cause them. The symptoms usually have a slow onset, and urinary frequency is the most common early symptom. As PBS/IC progresses over a few years, cycles of pain (flares) and remissions occur. Pain may be mild or so severe as to be debilitating. Symptoms can vary from day to day.

    How is interstitial cystitis diagnosed?

    Because the symptoms of PBS/IC are similar to those of other disorders of the urinary system and because there is no definitive test to identify PBS/IC, doctors must exclude other conditions before making a diagnosis of PBS/IC. Among the disorders to be excluded are urinary tract or vaginal infections, bladder cancer, bladder inflammation or infection caused by radiation to the abdomen, eosinophilic and tuberculous cystitis, kidney stones, endometriosis, neurological disorders, sexually transmitted diseases, urinary tract infection with small numbers of bacteria, and, in men, chronic bacterial and nonbacterial prostatitis.

    Medical tests that help identify other conditions include a urinalysis, urine culture, cystoscopy, biopsy of the bladder wall and, in men, laboratory examination of prostatic secretions.

    Physical examination

    Physical examination of an individual with PBS/IC may reveal tenderness of the bladder either when pushing on the abdomen over the bladder (just above the pubic bone) or during the pelvic examination in women. No specific physical findings are associated with PBS/IC.

    Laboratory tests

    Urinalysis and urine culture. These tests can detect and identify the most common bacteria in the urine that may be causing PBS/IC-like symptoms. 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 a sample of urine "midstream" in a sterile container. White and red blood cells and bacteria in the urine suggest an infection of the urinary tract that can be treated with antibiotics. If urine is sterile for weeks or months while symptoms persist, a doctor may consider a diagnosis of PBS/IC.

    Culture of prostatic secretions. In men, the doctor can obtain a sample of prostatic fluid. This fluid is examined under the microscope for signs of an infection such as red and white blood cells and also can be cultured for bacteria. Prostatic infections can be treated with antibiotics.

    Potassium sensitivity test. A test known as the intravesical potassium sensitivity test (PST) has been developed to evaluate the leakiness of the protective lining of the bladder. Some experts recommend its use in the evaluation of PBS/IC, but it is not used routinely for this purpose because the results are not specific for PBS/IC; abnormal results can also be due to other conditions. The test also can be painful. Many people with PBS/IC have an abnormal PST suggesting an overly leaky urothelium (bladder lining). In the PST test, two different solutions (sterile water and a solution of potassium) are instilled separately into the bladder. The patient rates the severity of pain and/or urgency that occur when each solution is instilled. Using a scale of 0 to 5, the test is considered abnormal (positive) if the potassium solution induces at least a pain level of "2" and causes more pain than the sterile water.

    Lidocaine instillation. Filling the bladder with a solution containing the local anesthetic drug lidocaine has been described as an "anesthetic bladder challenge." Improvement of symptoms after lidocaine has been instilled into the bladder suggests PBS/IC. However, like the potassium sensitivity test, this test is not specific for PBS/IC and is not routinely performed.

    Cystoscopy under anesthesia with bladder distension. 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 source of light - to look 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 distension is painful in PBS/IC patients, before the doctor inserts the cystoscope through the urethra into the bladder, the patient must be given either regional or general anesthesia. Cystoscopy with distension of the bladder with fluid can detect inflammation, a thick and stiff bladder wall, and Hunner's ulcers. After the fluid has been drained from the bladder, small red spots, called glomerulations, that represent enlarged blood vessels and pinpoint areas of bleeding can be seen in the bladder's lining.

    The doctor may also determine a patient's bladder capacity -- the maximum amount of liquid or gas the bladder can hold under anesthesia. (Without anesthesia, capacity is limited by either pain or a severe urge to urinate.) Most people without PBS/IC have normal or large maximum bladder capacities under anesthesia. A small bladder capacity (due to scarring) under anesthesia helps to support the diagnosis of PBS/IC.

    Before the relatively recent development of the PST, cystoscopy was the best diagnostic test available for PBS/IC. However, cystoscopy has its limitations. Ulcers are generally not observed in mild or early cases of PBS/IC, and glomerulations have been observed in normal individuals without symptoms of PBS/IC. Due to these limitations, cystoscopy is recommended only to exclude other possible causes of symptoms and not as the definitive diagnostic measure in PBS/IC.

    One important note is that the distension often performed with cystoscopy may lead to relief of symptoms in some patients with PBS/IC, which generally lasts from several weeks to months following the procedure.

    Biopsy. A biopsy is a microscopic examination of a small sample of tissue. Samples of the bladder and urethra may be removed during cystoscopy and examined with a microscope later. A biopsy helps to exclude bladder cancer. It also may confirm the presence of mast cells or inflammation of the bladder wall that are consistent with a diagnosis of PBS/IC. Nevertheless, there is nothing on the biopsy that can make an absolute diagnosis of PBS/IC.

    What is the treatment for interstitial cystitis?

    Diet

    (Please see the later discussion of diet, "Are lifestyle modifications of value in managing interstitial cystitis?")

    Oral medications

    Oral medications that may be used to treat PBS/IC include antidepressants of the tricyclic group such as amitryptiline (Elavil). This is not due to a belief that PBS/IC is a psychological condition; rather, tricyclic antidepressants can help reduce the hyperactivation of nerves within the bladder wall. The antiseizure medication gabapentin (Neurontin, Gabarone) also has been used to treat nerve-related pain and has sometimes been used to treat the pain of IC/PBS. Oral antihistamines also may be prescribed to help reduce allergyic symptoms that may be worsening the patient's PBS/IC.

    For patients who may not respond well to amitryptiline, another type of oral medication that can be used is the heparinoid (heparin-like) drug pentosan polysulfate sodium (PPS; brand name Elmiron). PPS is chemically similar to the substance that lines the bladder, and it is believed that PPS assists in the repair or restoration of the lining tissues in the bladder. Even after therapy with PPS has begun, patients may still experience symptoms for some time because the sensory nerves in the bladder have been hyperactive, and it takes time for the nerves to return to their normal state of activation. Therefore, doctors recommend giving up to one year of PPS treatment in mild PBS/IC (and two years in severe PBS/IC) before deciding if the drug is effective or not. Between one-third and two-thirds of patients will improve after three months of treatment.

    For those individuals who are unable to sleep well because of the discomfort of PBS/IC, antihistamines such as hydroxyzine can be given to facilitate sleep.

    Aspirin (Bayer) and ibuprofen (Advil) are sometimes used as a first line of defense against mild discomfort. However, they may make symptoms worse in some patients. Over-the-counter forms of phenazopyridine hydrochloride (Azo-Standard, Prodium, and Uristat) may provide some relief from urinary pain, urgency, frequency, and burning. Higher doses of the drug are available by prescription as Prodium and phenazopyridine (Pyridium).

    Bladder distension

    As mentioned previously, because some patients have noted an improvement in symptoms after bladder distension done to diagnose PBS/IC, bladder distension (termed hydrodistension) sometimes is used for therapy of PBS/IC. Bladder distension helps reduce symptoms in many patients with interstitial cystitis. (Studies have shown an improvement in 40-80% of patients.) When it is effective, the relief of symptoms persists for several weeks to months after the procedure. It is usually performed under anesthesia or heavy sedation, and some patients have a temporary worsening of symptoms following the procedure.

    Bladder instillation (intravesical therapy)

    This procedure may also be called a bladder wash or bath. During a bladder instillation, the bladder is filled with a solution that is held for varying periods of time, from a few seconds to 15 minutes, before being drained through a narrow tube called a catheter.

    In severe cases of PBS/IC, intravesical solutions may be administered along with oral PPS to provide relief until the oral medication has had time to take effect.

    Drugs that have been used for bladder instillations include dimethyl sulfoxide (DMSO, RIMSO-50), heparin, sodium bicarbonate, PPS, and hydrocortisone (a steroid).

    Other surgical therapies for interstitial cystitis

    In severe cases of PBS/IC that do not respond well to oral medications or to bladder distension or instillation, more invasive surgical procedures may be attempted. A procedure known as sacral neuromodulation has been shown to be effective in controlling symptoms in some people with PBS/IC. The term "neuromodulation" refers to an alteration of the nervous system. In sacral neuromodulation, a device is implanted that allows for electrical impulses to stimulate the nerves in the sacral (lower back) area. Sacral neuromodulation is believed to work by inhibiting the hyperactive signals from the sensory nerves within the bladder wall. For sacral neuromodulation, a wire from an electrical impulse generator is implanted in the sacral region of the spinal column. If there is relief of symptoms, the impulse generator can be implanted beneath the skin in the region of the buttocks. A remote control programmer allows the patient to adjust the impulse frequency and power to provide optimal relief of symptoms.

    Therapies that also have been used include transcutaneous electrical nerve stimulation (TENS), a form of neuromodulation that does not involve surgical placement of wires or an impulse generator. With TENS, mild electric pulses enter the body for minutes to hours two or more times a day either through wires placed on the surface of the lower back or the suprapubic region, between the navel and the pubic hair, or through special devices inserted into the vagina in women or into the rectum in men. It is believed that the electric pulses may increase blood flow to the bladder, strengthen pelvic muscles that help control the bladder, and trigger the release of hormones that block pain. TENS is generally more effective in reducing pain than in reducing urinary frequency.

    Other surgical procedures that may rarely be performed to treat severe PBS/IC include peripheral denervation (disrupting the nerves to the bladder wall), bladder augmentation to increase bladder capacity, and cystectomy (bladder removal) with diversion, or re-routing, of urine flow.

    Are lifestyle modifications of value in the management of interstitial cystitis?

    Diet

    There is no scientific evidence linking diet to PBS/IC, but doctors and patients believe that certain foods, including alcohol, spices, chocolate, and caffeinated and citrus beverages, may contribute to bladder irritation and inflammation. Foods containing acid, for example, carbonated beverages, tomatoes, vitamin C, citrus fruits and beverages, vinegar, cranberries, strawberries, grapes, guava, mango, and pineapple also are believed to aggravate PBS/IC. Other foods that may increase symptoms because they contain the natural chemical tyramine include wine, beer, cheese, nuts, yogurt, bananas, soy sauce, chicken livers, raisins, sour cream, avocados, canned figs, corned beef, fava beans, brewers' yeast, and chocolate.

    Some patients with PBS/IC also have noticed a worsening of symptoms after eating or drinking products containing artificial sweeteners. Patients may try eliminating such products from their diet and, if there is a reduction of symptoms, they can reintroduce them one at a time to determine which product seems to be aggravating their symptoms.

    Smoking

    Many PBS/IC patients feel that smoking worsens their symptoms. (Because smoking is the major known cause of bladder cancer, one of the best things a smoker can do for the bladder is to quit smoking.)

    Exercise

    Many PBS/IC patients feel that regular exercise helps relieve symptoms and, in some cases, hastens remission.

    Bladder training

    People who have found some relief from pain may then be able to reduce frequency using bladder training techniques. Methods vary but basically the patient decides to urinate at designated times and uses relaxation techniques and distractions to help keep to the schedule. Gradually, the patient lengthens the time between urinations. A diary usually is helpful in keeping track of progress.

    What is interstitial cystitis (IC)?

    Interstitial cystitis (IC) is a term that has been used to refer to a clinical syndrome characterized by chronic urinary urgency (feeling the need to urinate immediately) and frequency (frequent urination), usually with suprapubic discomfort or pressure and usually relieved by urinating. The symptoms of this condition vary among individuals and may even vary with time in the same individual. The term cystitis refers to any inflammation of the bladder. In contrast to bacterial cystitis that results from an infection in the bladder, a type of urinary tract infection (UTI), no infectious organism has been identified in people with interstitial cystitis.

    There has been controversy in the medical literature regarding the definition of interstitial cystitis and use of the term. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the U.S. National Institutes of Health (NIH) established a set of diagnostic criteria for inclusion in research studies relating to interstitial cystitis and its causes that were used for research purposes until 2002. However, the NIDDK criteria were felt to be overly restrictive for diagnostic use, and in 2002, new criteria were proposed for the diagnosis of painful bladder disorders, including the condition referred to as painful bladder syndrome (PBS) by the International Continence Society (ICS). These criteria felt that the term PBS was preferable and that the term IC should be restricted to use in those patients having typical findings observed upon cystoscopy and biopsy of the bladder tissues.

    The ICS criteria state the following:

    • Painful bladder syndrome is the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology...The ICS believes this to be a preferable term to "interstitial cystitis." Interstitial cystitis is a specific diagnosis and requires confirmation by typical clinical cystoscopic and possibly histological features.

    In 2006, another set of diagnostic criteria were proposed by the European Society for the Study of IC/BPS, suggesting the use of the term bladder pain syndrome (BPS):

    • A diagnosis of bladder pain syndrome (BPS) is made of the basis of the symptom of chronic pain related to the urinary bladder accompanied by at least one other urinary symptom such as daytime and nighttime frequency, and exclusion of confusable diseases as the cause of the symptoms, and cystoscopy with hydrodistension and biopsy if indicated (to document the type of BPS/IC).

    Until agreement is reached about terminology and definition of the condition, it will be difficult to determine the true prevalence of PBS/IC. Estimates of the number of affected people vary widely and are dependent upon the criteria used for diagnosis. Many experts believe that about 3.3 million women in the U.S. (over age 18) may be affected as well as 1.6 million men.

    Despite the lack of agreement about the diagnosis of PBS/IC, studies agree that the majority of those affected are women. While individuals of any age can be affected, including children, the average age of onset is around 40. PBS/IC has not been considered to be a hereditary disorder, but multiple cases have occurred among some families, prompting ongoing investigation of the possible role of hereditary factors in the development of PBS/IC.

    Some associations with other medical conditions are seen with PBS/IC. Women with PBS/IC are more likely to have had frequent urinary tract infections (UTIs) and to have had previous gynecologic surgery than women without PBS/IC. Certain chronic illnesses have been described as occurring more frequently in people with PBS/IC than in the general population. Examples of these associated conditions are inflammatory bowel disease, systemic lupus erythematosus, irritable bowel syndrome (IBS), vulvodynia (chronic discomfort in the vulvar area), allergies, endometriosis, and fibromyalgia. While each of these conditions has been described in at least some studies to be more common in people with PBS/IC than in the general population, there is no evidence that any of these conditions is the cause of PBS/IC.

    Observations from cystoscopy (visual examination of the inside of the bladder via a probe) studies have found that two patterns exist for IC, ulcerative and nonulcerative, depending upon the presence or absence of ulcerations in the bladder lining. Star-shaped ulcerations in the bladder wall are known as Hunner's ulcers. These are found in less than 10% of cases of PBS/IC in the U.S.

    Over time, interstitial cystitis can cause physical damage to the bladder wall. Scarring and stiffening of the bladder wall may occur as a result of the chronic inflammation, leading to a decrease in bladder capacity. Glomerulations (areas of pinpoint bleeding) and petechial hemorrhage may be seen on the bladder wall.

    What is the cause of interstitial cystitis?

    No one knows what causes PBS/IC, but doctors believe that it is a real physical problem and not a result, symptom, or sign of an emotional problem. Because the symptoms of PBS/IC are varied, most researchers believe that it represents a spectrum of disorders rather than one single disease.

    One area of research on the cause of PBS/IC has focused on the layer that coats the lining of the bladder called the glycocalyx, made up primarily of substances called mucins and glycosaminoglycans (GAGs). This layer normally protects the bladder wall from toxic effects of urine and its contents. Researchers have found that this protective layer of the bladder is "leaky" in about 70% of PBS/IC patients and have hypothesized that this may allow substances in urine to pass into the bladder wall where they might trigger PBS/IC, making these patients susceptible to chemicals in the urine, including those from foods or beverages.

    Along with altered permeability of the bladder wall, researchers are also examining the possibility that PBS/IC results from decreased levels of protective substances in the bladder wall. Reduced levels of GAGs (discussed previously) or other protective proteins might also be responsible for the damage to the bladder wall seen in PBS/IC.

    No matter what the mechanism for disruption of the bladder lining, potassium is one substance that may be involved in damage to the bladder wall. Potassium is present in high concentrations in urine and is normally not toxic to the bladder lining. However, if the tissues lining the inside of the bladder (urothelium) are disrupted or are abnormally leaky, potassium could then penetrate the lining tissues and enter the muscle layers of the bladder where it can cause damage and promote inflammation.

    Researchers have isolated a substance known as antiproliferative factor (APF) that appears to block the normal growth of cells that make up the lining of the bladder. APF has been identified almost exclusively in the urine of people suffering with PBS/IC. Research is under way to clarify the potential role of APF in the development of PBS/IC.

    Increased activation of sensory nerves (neurologic hypersensitivity) in the bladder wall is also thought to contribute to the symptoms of PBS/IC. Cells known as mast cells, which play a role in the body's inflammatory response to injury, release chemicals that are believed to be capable of contributing to the symptoms of PBS/IC.

    Other theories about the cause of PBS/IC are that it is a form of autoimmune disorder or that infection with an unidentified organism may be producing the damage to the bladder and the accompanying symptoms.

    What are interstitial cystitis symptoms and signs?

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

    • decreased bladder capacity;
    • an urgent need to urinate frequently day and night (urinating frequently is referred to as urinary frequency; having a strong urge to urinate is referred to as urinary urgency);
    • feelings of pressure, pain, and tenderness around the bladder, pelvis, and perineum (the area between the anus and vagina or anus and scrotum) which may increase as the bladder fills and decrease as it empties;
    • painful sexual intercourse (dyspareunia);
    • discomfort or pain in the penis and scrotum.

    Most people suffering from PBS/IC have both urinary frequency/urgency and pelvic pain, although these symptoms may also occur singly or in any combination. In most women, symptoms usually worsen around the time of their periods. As with many other illnesses, stress also may intensify the symptoms, but it does not cause them. The symptoms usually have a slow onset, and urinary frequency is the most common early symptom. As PBS/IC progresses over a few years, cycles of pain (flares) and remissions occur. Pain may be mild or so severe as to be debilitating. Symptoms can vary from day to day.

    How is interstitial cystitis diagnosed?

    Because the symptoms of PBS/IC are similar to those of other disorders of the urinary system and because there is no definitive test to identify PBS/IC, doctors must exclude other conditions before making a diagnosis of PBS/IC. Among the disorders to be excluded are urinary tract or vaginal infections, bladder cancer, bladder inflammation or infection caused by radiation to the abdomen, eosinophilic and tuberculous cystitis, kidney stones, endometriosis, neurological disorders, sexually transmitted diseases, urinary tract infection with small numbers of bacteria, and, in men, chronic bacterial and nonbacterial prostatitis.

    Medical tests that help identify other conditions include a urinalysis, urine culture, cystoscopy, biopsy of the bladder wall and, in men, laboratory examination of prostatic secretions.

    Physical examination

    Physical examination of an individual with PBS/IC may reveal tenderness of the bladder either when pushing on the abdomen over the bladder (just above the pubic bone) or during the pelvic examination in women. No specific physical findings are associated with PBS/IC.

    Laboratory tests

    Urinalysis and urine culture. These tests can detect and identify the most common bacteria in the urine that may be causing PBS/IC-like symptoms. 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 a sample of urine "midstream" in a sterile container. White and red blood cells and bacteria in the urine suggest an infection of the urinary tract that can be treated with antibiotics. If urine is sterile for weeks or months while symptoms persist, a doctor may consider a diagnosis of PBS/IC.

    Culture of prostatic secretions. In men, the doctor can obtain a sample of prostatic fluid. This fluid is examined under the microscope for signs of an infection such as red and white blood cells and also can be cultured for bacteria. Prostatic infections can be treated with antibiotics.

    Potassium sensitivity test. A test known as the intravesical potassium sensitivity test (PST) has been developed to evaluate the leakiness of the protective lining of the bladder. Some experts recommend its use in the evaluation of PBS/IC, but it is not used routinely for this purpose because the results are not specific for PBS/IC; abnormal results can also be due to other conditions. The test also can be painful. Many people with PBS/IC have an abnormal PST suggesting an overly leaky urothelium (bladder lining). In the PST test, two different solutions (sterile water and a solution of potassium) are instilled separately into the bladder. The patient rates the severity of pain and/or urgency that occur when each solution is instilled. Using a scale of 0 to 5, the test is considered abnormal (positive) if the potassium solution induces at least a pain level of "2" and causes more pain than the sterile water.

    Lidocaine instillation. Filling the bladder with a solution containing the local anesthetic drug lidocaine has been described as an "anesthetic bladder challenge." Improvement of symptoms after lidocaine has been instilled into the bladder suggests PBS/IC. However, like the potassium sensitivity test, this test is not specific for PBS/IC and is not routinely performed.

    Cystoscopy under anesthesia with bladder distension. 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 source of light - to look 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 distension is painful in PBS/IC patients, before the doctor inserts the cystoscope through the urethra into the bladder, the patient must be given either regional or general anesthesia. Cystoscopy with distension of the bladder with fluid can detect inflammation, a thick and stiff bladder wall, and Hunner's ulcers. After the fluid has been drained from the bladder, small red spots, called glomerulations, that represent enlarged blood vessels and pinpoint areas of bleeding can be seen in the bladder's lining.

    The doctor may also determine a patient's bladder capacity -- the maximum amount of liquid or gas the bladder can hold under anesthesia. (Without anesthesia, capacity is limited by either pain or a severe urge to urinate.) Most people without PBS/IC have normal or large maximum bladder capacities under anesthesia. A small bladder capacity (due to scarring) under anesthesia helps to support the diagnosis of PBS/IC.

    Before the relatively recent development of the PST, cystoscopy was the best diagnostic test available for PBS/IC. However, cystoscopy has its limitations. Ulcers are generally not observed in mild or early cases of PBS/IC, and glomerulations have been observed in normal individuals without symptoms of PBS/IC. Due to these limitations, cystoscopy is recommended only to exclude other possible causes of symptoms and not as the definitive diagnostic measure in PBS/IC.

    One important note is that the distension often performed with cystoscopy may lead to relief of symptoms in some patients with PBS/IC, which generally lasts from several weeks to months following the procedure.

    Biopsy. A biopsy is a microscopic examination of a small sample of tissue. Samples of the bladder and urethra may be removed during cystoscopy and examined with a microscope later. A biopsy helps to exclude bladder cancer. It also may confirm the presence of mast cells or inflammation of the bladder wall that are consistent with a diagnosis of PBS/IC. Nevertheless, there is nothing on the biopsy that can make an absolute diagnosis of PBS/IC.

    What is the treatment for interstitial cystitis?

    Diet

    (Please see the later discussion of diet, "Are lifestyle modifications of value in managing interstitial cystitis?")

    Oral medications

    Oral medications that may be used to treat PBS/IC include antidepressants of the tricyclic group such as amitryptiline (Elavil). This is not due to a belief that PBS/IC is a psychological condition; rather, tricyclic antidepressants can help reduce the hyperactivation of nerves within the bladder wall. The antiseizure medication gabapentin (Neurontin, Gabarone) also has been used to treat nerve-related pain and has sometimes been used to treat the pain of IC/PBS. Oral antihistamines also may be prescribed to help reduce allergyic symptoms that may be worsening the patient's PBS/IC.

    For patients who may not respond well to amitryptiline, another type of oral medication that can be used is the heparinoid (heparin-like) drug pentosan polysulfate sodium (PPS; brand name Elmiron). PPS is chemically similar to the substance that lines the bladder, and it is believed that PPS assists in the repair or restoration of the lining tissues in the bladder. Even after therapy with PPS has begun, patients may still experience symptoms for some time because the sensory nerves in the bladder have been hyperactive, and it takes time for the nerves to return to their normal state of activation. Therefore, doctors recommend giving up to one year of PPS treatment in mild PBS/IC (and two years in severe PBS/IC) before deciding if the drug is effective or not. Between one-third and two-thirds of patients will improve after three months of treatment.

    For those individuals who are unable to sleep well because of the discomfort of PBS/IC, antihistamines such as hydroxyzine can be given to facilitate sleep.

    Aspirin (Bayer) and ibuprofen (Advil) are sometimes used as a first line of defense against mild discomfort. However, they may make symptoms worse in some patients. Over-the-counter forms of phenazopyridine hydrochloride (Azo-Standard, Prodium, and Uristat) may provide some relief from urinary pain, urgency, frequency, and burning. Higher doses of the drug are available by prescription as Prodium and phenazopyridine (Pyridium).

    Bladder distension

    As mentioned previously, because some patients have noted an improvement in symptoms after bladder distension done to diagnose PBS/IC, bladder distension (termed hydrodistension) sometimes is used for therapy of PBS/IC. Bladder distension helps reduce symptoms in many patients with interstitial cystitis. (Studies have shown an improvement in 40-80% of patients.) When it is effective, the relief of symptoms persists for several weeks to months after the procedure. It is usually performed under anesthesia or heavy sedation, and some patients have a temporary worsening of symptoms following the procedure.

    Bladder instillation (intravesical therapy)

    This procedure may also be called a bladder wash or bath. During a bladder instillation, the bladder is filled with a solution that is held for varying periods of time, from a few seconds to 15 minutes, before being drained through a narrow tube called a catheter.

    In severe cases of PBS/IC, intravesical solutions may be administered along with oral PPS to provide relief until the oral medication has had time to take effect.

    Drugs that have been used for bladder instillations include dimethyl sulfoxide (DMSO, RIMSO-50), heparin, sodium bicarbonate, PPS, and hydrocortisone (a steroid).

    Other surgical therapies for interstitial cystitis

    In severe cases of PBS/IC that do not respond well to oral medications or to bladder distension or instillation, more invasive surgical procedures may be attempted. A procedure known as sacral neuromodulation has been shown to be effective in controlling symptoms in some people with PBS/IC. The term "neuromodulation" refers to an alteration of the nervous system. In sacral neuromodulation, a device is implanted that allows for electrical impulses to stimulate the nerves in the sacral (lower back) area. Sacral neuromodulation is believed to work by inhibiting the hyperactive signals from the sensory nerves within the bladder wall. For sacral neuromodulation, a wire from an electrical impulse generator is implanted in the sacral region of the spinal column. If there is relief of symptoms, the impulse generator can be implanted beneath the skin in the region of the buttocks. A remote control programmer allows the patient to adjust the impulse frequency and power to provide optimal relief of symptoms.

    Therapies that also have been used include transcutaneous electrical nerve stimulation (TENS), a form of neuromodulation that does not involve surgical placement of wires or an impulse generator. With TENS, mild electric pulses enter the body for minutes to hours two or more times a day either through wires placed on the surface of the lower back or the suprapubic region, between the navel and the pubic hair, or through special devices inserted into the vagina in women or into the rectum in men. It is believed that the electric pulses may increase blood flow to the bladder, strengthen pelvic muscles that help control the bladder, and trigger the release of hormones that block pain. TENS is generally more effective in reducing pain than in reducing urinary frequency.

    Other surgical procedures that may rarely be performed to treat severe PBS/IC include peripheral denervation (disrupting the nerves to the bladder wall), bladder augmentation to increase bladder capacity, and cystectomy (bladder removal) with diversion, or re-routing, of urine flow.

    Are lifestyle modifications of value in the management of interstitial cystitis?

    Diet

    There is no scientific evidence linking diet to PBS/IC, but doctors and patients believe that certain foods, including alcohol, spices, chocolate, and caffeinated and citrus beverages, may contribute to bladder irritation and inflammation. Foods containing acid, for example, carbonated beverages, tomatoes, vitamin C, citrus fruits and beverages, vinegar, cranberries, strawberries, grapes, guava, mango, and pineapple also are believed to aggravate PBS/IC. Other foods that may increase symptoms because they contain the natural chemical tyramine include wine, beer, cheese, nuts, yogurt, bananas, soy sauce, chicken livers, raisins, sour cream, avocados, canned figs, corned beef, fava beans, brewers' yeast, and chocolate.

    Some patients with PBS/IC also have noticed a worsening of symptoms after eating or drinking products containing artificial sweeteners. Patients may try eliminating such products from their diet and, if there is a reduction of symptoms, they can reintroduce them one at a time to determine which product seems to be aggravating their symptoms.

    Smoking

    Many PBS/IC patients feel that smoking worsens their symptoms. (Because smoking is the major known cause of bladder cancer, one of the best things a smoker can do for the bladder is to quit smoking.)

    Exercise

    Many PBS/IC patients feel that regular exercise helps relieve symptoms and, in some cases, hastens remission.

    Bladder training

    People who have found some relief from pain may then be able to reduce frequency using bladder training techniques. Methods vary but basically the patient decides to urinate at designated times and uses relaxation techniques and distractions to help keep to the schedule. Gradually, the patient lengthens the time between urinations. A diary usually is helpful in keeping track of progress.

    Source: http://www.rxlist.com

    (Please see the later discussion of diet, "Are lifestyle modifications of value in managing interstitial cystitis?")

    Source: http://www.rxlist.com

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