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Interstital Cystitis
Overview
Interstitial cystitis (IC) is a chronic inflammatory condition of the bladder that causes frequent, urgent, and painful urination and pelvic discomfort. The natural lining of the bladder (epithelium) is protected from toxins in the urine by a layer of protein called glycoaminoglycan (GAG). In IC this protective layer has broken down, allowing toxins to irritate the bladder wall. The bladder then becomes inflamed and tender and does not store urine well.
Unlike inflammation of the bladder caused by bacterial infection (cystitis), which is associated with urinary tract infections (UTI) and usually treated with antibiotics, no infectious agent has been found in IC. Though not curable, IC is treatable and most patients find some relief with treatment and lifestyle changes.
Incidence and Prevalence
According to the National Institutes of Health (NIH), IC affects about 700,000 people in the United States, 90% of which are women. The average age of onset is 40 years. Although only 25% of cases involve people under age 30, the number of children affected by IC may be greater than commonly believed. IC is often misdiagnosed, and sufferers may see several doctors over the course of years before a diagnosis is made. Increasing awareness of the disease is helping to speed diagnosis and treatment.
Causes and Risk Factors
IC is a poorly understood disease with unknown causes. Although no bacteria or viruses (pathogens) have been found in the urine of IC sufferers, an unidentified infectious agent may be the cause. Others believe that IC occurs with ischemia (tissue death) or a deficiency of GAG in the epithelium. It may be an autoimmune disease, in which the immune system attacks healthy cells, perhaps following a bladder infection. Spasms of the pelvic floor muscles may also contribute to the IC symptoms. It is likely that several factors cause the condition.
Other conditions associated with IC include the following:
• Asthma
• Endometriosis
• Food allergies
• Hay fever (pollen allergy)
• Incontinence
• Irritable bowel syndrome
• Lupus
• Migraine
• Rheumatoid arthritis
• Sinusitis
The connection between IC and these conditions is not understood.
IC may occur following gynecological surgery. Some evidence suggests an increased risk for IC in Jews; and studies of mothers, daughters, and twins who suffer from it suggest a hereditary risk factor.
Signs and Symptoms
Interstitial cystitis manifests differently in patients. For instance, some people experience chronic pelvic pain, while others do not. Symptoms may intensify as the bladder fills and diminish after urination. Classic symptoms include the following:
• Frequency— urination may exceed 60 times in a 24-hour period
• Pain — chronic pelvic, vulvar, urethral, or abdominal discomfort during urination and sex
• Urgency— sensation of having to urinate immediately, often accompanied by bladder pain, pressure, or spasm
Symptoms usually worsen within the first 5 years and then level off. Patients with IC typically experience periods of symptom flare, or intensification, followed by periods of remission, when symptoms abate.
For men, symptoms may include pain and inflammation of the prostate (prostatitis). Women may suffer increased vulvar pain. Both men and women may experience pain in the perineum (space between the vagina or scrotum and the anus) and painful or uncomfortable sex, including intercourse and touching. For some men, ejaculation may be painful.
Complications
Because of its chronic nature, frequently delayed diagnosis, and the lack of a cure, IC causes psychological and social problems that can affect family, work, and lifestyle:
• Anxiety
• Depression
• Difficulty traveling
• Fatigue
• Inability to enjoy usual activities
• Insomnia
• Panic
• Weight fluctuation and eating disorders
Diagnosis
To diagnose IC, diseases that cause similar symptoms must be ruled out. Urine culture and urinalysis are performed to test for bacteria and signs of infection. In men, prostatic fluid may also be cultured.
A cystoscopy with hydrodistention, performed under general anesthesia, is the standard diagnostic procedure for IC. The bladder is filled to capacity with water (commonly) or gas. This allows a urologist to examine the epithelium with a small, telescopic fiber-optic camera, or scope, that is inserted through the urethra to the bladder. Glomerulations (tiny hemorrhages that are the telltale sign of IC) are revealed only while the bladder is distended. These hemorrhages are present in 95% of IC cases.
Less frequently, epithelial ulcerations (Hunner’s ulcers), lesions, and scars are found. Hunner’s ulcers are indicative of IC, though hydrodistention is not needed to see them. A biopsy, in which a tissue sample is removed and analyzed, is performed to distinguish between ulcers and cancer and to evaluate the presence of mast cells, which are sometimes seen in abundance in IC-affected bladders. Some IC sufferers do not have epithelial glomerulations or ulcers. Cystoscopy may also reveal bladder stones, which can cause symptoms similar to IC.
Cystoscopy and hydrodistension are performed under anesthesia because distending the bladder of an IC sufferer is painful and otherwise causes urgent urination. However, hydrodistension may have therapeutic effects. Some patients repeat the procedure occasionally as treatment for IC because it may temporarily alleviate pain and pressure.
The potassium chloride (KCl) sensitivity test (Parsons test) is an experimental procedure used occasionally to test for IC and evaluate a patient's potential response to treatments such as Elmiron® that work on the bladder lining. A catheter is used to instill the bladder with a potassium chloride solution. The KCl solution is thought to reveal deficiencies in the GAG layer of the bladder wall. The test is painful and may be only 60% to 75% accurate. It is not yet widely accepted as a diagnostic test for IC.
Differential Diagnosis
Several diseases and conditions have symptoms similar to IC. They may be ruled out, diagnosed instead of IC, or found to be coexistent:
• Bladder stones (urolithiasis)
• Carcinoma of the bladder in situ
• Gynecological disorders (endometriosis, ectopic pregnancy, fibroids, ovarian tumor)
• Inflammation of the bladder (caused by chronic low-grade bacterial cystitis, cyclophosphamide cystitis, tuberculosis cystitis, radiation cystitis)
• Kidney disease (renal tuberculosis)
• Neurological disorders (multiple sclerosis)
• Pelvic floor dysfunction (PFD)
• Prostatitis (men)
• Sexually transmitted diseases (e.g., genital herpes, chlamydia)
• Surgical adhesions
• Urethrocele (bladder hernia into the vagina) or cystocele (tissue growth around the urethra)
Treatment
There is no cure for IC; the goal of treatment is to relieve symptoms. Often, treatment effectiveness wanes and a replacement must be found through trial and error. Most patients who suffer from IC find relief, usually with multiple, complementary treatments.
Types of treatment include the following:
• Biophysical techniques – behavioral changes, stress management, dietary changes
• Medications
• Surgery
Biophysical Techniques
Biophysical techniques used to control IC symptoms include bladder retraining, transcutaneous electrical nerve stimulation (TENS), stress reduction with biofeedback, diet modification, and exercise. Physical therapy for the pelvic floor muscles may help decrease pain and spasms. Bladder retraining is a self-help process in which patients learn to control their urge to urinate. The theory behind bladder retraining is that the bladder muscle actually weakens with frequent urination because it is not allowed to distend fully. Patients with IC experience the impulse to urinate frequently because they have pain or urgency as the bladder fills. Bladder retraining programs vary. Generally, the patient schedules times for urination (a voiding schedule) and uses a series of relaxation techniques and distractions to help keep the schedule. The interval is progressively lengthened, thus strengthening the bladder muscle. Bladder retraining may be complicated by severe pain.
Transcutaneous electrical nerve stimulation (TENS) TENS involves the application of mild electric pulses to the body for minutes or hours a day. It is believed that the electric pulses increase blood flow to the bladder, strengthen pelvic muscles that aid in control, and trigger the release of pain-blocking hormones. TENS therapy may help with IC pain, though it may take a couple of months before any benefit is realized. A TENS device is worn outside of the body, usually near the sacral nerve.
Sacral Nerve Stimulation
The InterStim® device, used traditionally to treat bladder-control problems, is being used experimentally in preclinical trials to evaluate its effects on IC. It is implanted under the skin of the lower back, near the sacral nerve, where it delivers electrical pulses to the nerves involved in bladder function. It may help control frequency and urgency associated with IC, although the Food and Drug Administration (FDA) has not approved it for IC therapy.
Stress reduction techniques, biofeedback, and exercise may reduce the occurrence of flares by strengthening the muscles of the pelvic floor. For some, exercise exacerbates symptoms by irritating an already tender bladder or sore abdomen.
Diet
Many people find that eliminating acidic, spicy, and sugary foods, as well as dairy products from their diet helps to control symptoms. The Interstitial Cystitis Association (ICA) provides a list of foods that may be problematic:
• Beverages — hard liquor, beer, wine, carbonated drinks, coffee, tea, cranberry juice
• Carbohydrates and grains — rye and sourdough bread
• Condiments — seasonings, mayonnaise, miso, soy sauce, salad dressings, vinegar
• Dairy products — aged cheese, sour cream, yogurt, chocolate, milk
• Fruits — apples, apricots, avocados, bananas, cantaloupes, citrus fruits, cranberries, grapes, nectarines, peaches, pineapples, plums, pomegranates, rhubarb, strawberries, fruit juices
• Meats and fish — aged, canned, cured, processed, or smoked meats and fish, anchovies, caviar, chicken liver, corned beef, meats containing nitrates or nitrites (e.g., ham, bacon)
• Nuts
• Others substances — tobacco, caffeine, diet pills, junk food, cold and allergy medication containing ephedrine or pseudoephedrine, vitamins that contain fillers (especially aspartate), tofu
• Preservatives and additives — benzol alcohol, citric acid, monosodium glutamate, aspartame (Nutrasweet®), saccharine, artificial ingredients and colors
• Vegetables — favabeans, lima beans, onions, tomatoes
Most IC patients have the least amount of trouble with rice, potatoes, pasta, vegetables, and chicken. Foods from the above groups that may be tolerable include the following:
• Beverages — decaffeinated and acid-free coffee and tea, certain herbal teas
• Carbohydrates and grains — breads other than rye and sourdough, rice
• Condiments — garlic
• Dairy products — cottage cheese, white chocolate
• Fruits — melon other than cantaloupe, pears
• Nuts — almonds, cashews, pine nuts
• Vegetables — fresh, homegrown potatoes and tomatoes
Some find that over-the-counter dietary aids such as Prelief®, which helps to make food less acidic, allow them to eat many foods that would otherwise be intolerable.
Smoking worsens symptoms for some people; symptoms improve for many after quitting.
Surgery
Surgery is typically performed only when other treatments fail to provide relief. It may be ineffective and may worsen IC symptoms.
Laser burning (fulguration) and surgical removal (resection) are two methods used to remove Hunner’s ulcers from the bladder in ulcerative IC. They are performed with a cystoscope inserted through the urethra under general anesthesia.
Urostomy involves creating a tube in the abdomen from intestinal tissue, rerouting the tubes that carry urine from the kidneys (ureters) to the tube, and connecting it to an opening (stoma) in the abdomen. Urine then drains continuously into a collection bag that can be emptied as necessary. Alternatively, an internal pouch, known as a Koch, Florida, or Indiana pouch, may be constructed from intestinal tissue to hold urine from the ureters. The patient periodically drains the pouch through the stoma with a self-administered catheter.
Bladder removal (cystectomy) may be performed with urostomy and internal pouch procedures.
Augmentation cytoplasty is performed rarely in cases where heavily scarred portions of the bladder need to be removed, though it is not considered a standard treatment. A section of intestinal tissue may be cut and shaped to replace the damaged portion of the bladder. It is attached to the remainder of the natural bladder so that urine can be stored and expelled through the urethra.
A relatively new procedure known as orthotopic diversion involves the removal of the entire bladder and the creation of a new one from intestinal tissue. The new bladder is connected to the urethra and works like a natural bladder. This allows people to urinate through the urethra without the use of catheters or collection devices.
Urgency, frequency, and phantom pelvic pain may remain following surgery, even if the bladder is removed. Possible risk factors and side effects, combined with the irreversible nature of these procedures make many surgeons reluctant to perform them and many patients wary of their effects. There is a risk for IC to develop in transplanted intestinal tissue, including that used to create an internal pouch. Normal urination may be impossible or difficult and self-catheterization may be necessary. Also, there is a risk for urinary incontinence (involuntary urination), especially with orthotopic diversion.
Some research suggests that putting urine in contact with intestinal tissue is risky. Infections, disturbances in metabolism, and problems with the mucosal lining of the bowel tissue may occur. Long-term kidney damage is also associated with these procedures.
Medications
Medications used to treat IC are administered by different methods. They include:
• Local medication – medication instilled directly into the bladder via a catheter
• Systemic medication – drugs taken orally
• Chronic pain medications
Local Medication
Dimethyl Sulfoxide (DMSO, Rimso-50®) may be instilled (intravesical) through the urethra and directly into the bladder via a catheter. It is the only FDA-approved instillation treatment for IC. It enters the bladder wall and reduces inflammation, pain, and painful muscle contractions; it may be mixed with heparin, steroids, or other local anesthetics. It may leave a garlicky taste and smell on the skin and in the breath for up to 72 hours. Heparin is similar to GAG and may help to repair problems caused by GAG deficiency in the bladder.
Blood, liver, and kidney tests are required every 6 months during DMSO therapy.
Hyaluronic acid (Cystistat®) and Bacille Calmette-Guérin (BCG) are undergoing clinical trials for IC treatment and are not widely available in the United States. Similar to heparin and GAG, Cystistat may help to repair a deficient bladder lining. BCG is a weakened form of cow tuberculosis (Mycobacterium bovis), which is used in tuberculosis vaccine in some European countries. Research shows that it may stimulate the immune system and improve the cellular makeup of the epithelium. The risk factors of BCG treatment are not fully understood, but may include inflammatory response in the bladder, tuberculosis-like chest infection, and the development of fibrous lumps (granulomas) in the bladder.
Silver nitrate and sodium oxychlorosene (Clorpactin®) were once used for instillation but are now considered outdated, because they cause irritation and greater risk for complications in the abdomen.
Temporary worsening of symptoms can occur up to 36 hours after any instillation treatment. Chemical cystitis is also a possible side effect.
Systemic Medication
Pentosan polysulfate sodium (Elmiron®) is the only oral medication approved by the Food and Drug Administration (FDA) for IC. It is thought to prevent irritating elements in the urine from affecting the cells that line the bladder, but its precise method of action is unknown. Since Elmiron is chemically similar to glycosaminoglycan (GAG), it helps to rebuild the epithelium by coating the bladder wall. It may take up to 6 months to provide relief from symptoms. Elmiron must be taken on a long-term basis to keep symptoms from recurring. Side effects include gastrointestinal discomfort and reversible hair loss, but these are uncommon.
Hydroxyzine (Vistaril®, Atarax®) is an antihistamine and mild antianxiety drug. It prevents mast cell degranulation, which is thought to play a role in IC, particularly in patients who have a history of allergies, migraine, and irritable bowel syndrome. Hydroxyzine decreases nighttime urination (nocturia), frequency, pain, and bladder pressure. Side effects include dry mouth and sedation.
Oxybutynin chloride (Ditropan XL®) , Detrol®, and a combination of atropine, hyoscyamine, methenamine, methylene blue, phenyl salicylate, and benzoic acid (Urised®) may reduce bladder spasms that cause frequency, urgency, and nighttime urination. Valium and other muscle relaxants may also be used to reduce spasms associated with IC.
Amitriptyline (Elavil®) and doxepin (Sinequan®) are tricyclic antidepressants that help to block pain, calm bladder spasms, and reduce inflammation; they may be useful in small doses.
Chronic Pain Medications
A typical IC treatment regimen includes medication for chronic pain:
• Anticonvulsant drugs – Tegretol®, Neurontin®
• Benzodiazepines – Xanax®, Ativan®
• Narcotics – Vicodin®, Percocet®
• Nonsteroidal anti-inflammatory drugs (NSAIs) – Advil®, Aleve®, Vioxx®, Celebrex®
• Trycyclic and SSRI antidepressants –Tofranil®, Prozac®
Generally, these are calming drugs. Benzodiazepines, for example, are used to treat anxiety; they are now thought to exert analgesic effects and reduce pelvic floor muscle spasm. Antidepressant medications affect levels of neurotransmitters in the brain, which are responsible for mood, concentration, and the ability to manage difficult situations. They, too, are used for their pain-blocking effects. IC sufferers typically have sensitivities to foods and drugs, which may be activated by these medications. It may be necessary to take them initially in small doses. Some may be combined, under the supervision of a physician, to control severe pain.
Many of these drugs carry a risk for kidney and liver dysfunction, and some require routine monitoring and blood tests. Pregnant women should consult their physicians before taking them.
Interstitial cystitis (IC) is a chronic inflammation of the urinary bladder. Naturopathic treatment involves inhibiting the inflammatory process by removing inflammatory and irritating foods from the diet, taking nutritional supplements, and using herbal support.
Nutrition
The importance of nutrition cannot be overstated and changing to a healthy diet may help relieve symptoms.
• Eliminate food sensitivities, which are often the cause of chronic inflammatory conditions. To determine food sensitivities, use an elimination and challenge diet.
• Eat whole, fresh, unrefined, and unprocessed foods. Include fruits, vegetables, whole grains, beans, seeds, nuts, olive oil, and cold-water fish (salmon, tuna, sardines, halibut, and mackerel).
• Avoid sugar, dairy products, refined foods, fried foods, junk foods, some beans (fava, lima, black, soy) and caffeine. Coffee, chocolate, alcohol, carbonated drinks, citrus fruits, and tomatoes often worsen symptoms.
• Drink ? of your body weight in ounces of water daily (e.g., if you weigh 150 lbs, drink 75 oz of water daily).
Supplements
• Calcium citrate alkalinizes the urine, which decreases irritation to the bladder.
• Bromelain provides anti-inflammatory action. Take away from food.
Herbal Medicine
Herbal medicines usually do not have side effects when used appropriately and at suggested doses. Occasionally, an herb at the prescribed dose causes stomach upset or headache. This may reflect the purity of the preparation or added ingredients, such as synthetic binders or fillers. For this reason, it is recommended that only high-quality products be used. As with all medications, more is not better and overdosing can lead to serious illness and death.
The following herbs may be used to treat IC:
• Gotu kola (Centella asiatica) — Take 30 mg standardized extract triterpenes 3 times a day. It enhances the integrity of connective tissue by stimulating production of glycosaminoglycans, which are an integral component of the protective mucous layer in the bladder.
Herbs to consider as a tea:
• Buchu (Barosma betulina) — A soothing diuretic and antiseptic for the urinary system.
• Cleavers (Galium aparine) — Traditionally used as a urinary tract tonic.
• Corn silk (Zea mays) — Has soothing and diuretic properties.
• Horsetail (Equisetum arvense) — An astringent and mild diuretic with tissue-healing properties.
• Marshmallow root (Althea officinalis) — Has soothing demulcent properties. It is best taken as a cold infusion; soak the herb in cold water for several hours, strain, and drink.
• Usnea (Usnea barbata) — Has soothing and antiseptic properties.
Homeopathy
A trained homeopathic practitioner is needed to diagnose and prescribe a deep-acting, constitutional remedy. The standard dosage for acute symptom relief is 3 pellets of 30C every 4 hours until symptoms resolve. Lower potencies, such as 6X, 6C, 30X, may be given every 2 to 4 hours. If the right remedy is chosen, symptoms should improve shortly after the second dose. If there is no improvement after 3 doses, a different remedy is given.
The following remedies may be effective in treating IC:
• Apis mellifica — Indicated for stinging pain that is worse with heat.
• Cantharis — Indicated for intolerable urgency with burning, scalding urination.
• Staphysagria — Indicated for a urinary tract infection that is the result of sexual intercourse.
• Sarsaparilla — Indicated for pain that burns after urination has stopped.
Physical Medicine
Castor oil packs can be applied for IC that has associated bladder cramping or pelvic discomfort.
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