Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.
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 1½ 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 (for example, sodium and potassium) and waste products, but it is free of bacteria, viruses, and fungi. The wall of the bladder is isolated from urine and toxic substances by a coating on the inside lining of the bladder that discourages bacteria from attaching and growing on the bladder wall.
Interstitial cystitis (IC) refers to a clinical syndrome characterized by symptoms including chronic urinary urgency (feeling the need to urinate immediately) and frequency (frequent urination). Pelvic pain may or may not be present. Since the wall of the bladder is inflamed, this can lead to pain and soreness in the bladder and pelvic areas.
Interstitial cystitis (IC) is a term that has been used to refer to a clinical constellation of symptoms characterized by chronic urinary urgency (feeling the need to urinate immediately) and frequency (frequent urination), usually with suprapubic discomfort or pressure that usually is 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. In 2006, the European Society for the Study of IC/BPS suggested the use of the term bladder pain syndrome (BPS) for these patients.
The American Urological Association (AUA) guidelines use the following definition for IC/BPS:
IC/BPS is an unpleasant sensation (pain, pressure, and discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six weeks duration, in the absence of infection or other identifiable causes.
Estimates of the number of people affected by IC/PBS 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 a lack of consistency about the diagnosis of IC/PBS, 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. IC/PBS 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 IC/PBS.
Observations from cystoscopy (visual examination of the inside of the bladder via a camera) have found that two patterns exist for IC, ulcerative and nonulcerative, depending upon the presence or absence of ulcerations, breaks 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 IC/PBS 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.
No one knows what causes IC/PBS, 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 IC/PBS 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 IC/PBS 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 any toxic contents in urine. Researchers have found that this protective layer of the bladder is "leaky" in about 70% of IC/PBS patients and have hypothesized that this may allow substances in urine to pass into the bladder wall where they might trigger IC/PBS directly or by making these patients susceptible to other 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 IC/PBS 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 IC/PBS.
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 tissue and enter the muscle layers of the bladder where it can cause damage and promote inflammation.
Researchers have isolated a substance known as anti-proliferative 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 IC/PBS. Research is under way to clarify the potential role of APF in the development of IC/PBS.
Increased activation of sensory nerves (neurologic hypersensitivity) in the bladder wall is also thought to contribute to the symptoms of IC/PBS. In addition, cells known as mast cells within the bladder wall, which play a role in the body's inflammatory response to injury, release chemicals that are believed to contribute to the symptoms of IC/PBS.
Other theories about the cause of IC/PBS are that it is a form of autoimmune disorder (in which the body's own immune system attacks the body) or that infection with an unidentified organism may be producing the damage to the bladder and the accompanying symptoms.
Because the cause of IC/PBS is poorly understood, there are no definite risk factors for developing the condition. However, women are more likely than men to develop IC/PBS.
Some associations with other medical conditions are seen with IC/PBS. Women with IC/PBS are more likely to have had frequent urinary tract infections (UTIs) and to have had previous gynecologic surgery than women without IC/PBS. Certain chronic illnesses have been described as occurring more frequently in people with IC/PBS than in the general population. Examples of these associated illnesses 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 IC/PBS than in the general population, there is no evidence that any of these conditions is the cause of IC/PBS.
The symptoms of IC/PBS vary greatly from one person to another but have some similarities to those of a urinary tract infection. They include
Most people suffering from IC/PBS 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 IC/PBS 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.
Urologists are physicians that specialize in diagnosis and treatment of diseases of the urinary tract, including interstitial cystitis. Some gynecologists also may treat patients with interstitial cystitis.
Because the symptoms of IC/PBS are similar to those of other disorders of the urinary system and because there is no definitive test to identify IC/PBS, doctors must exclude other conditions before making a diagnosis of IC/PBS. 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, and biopsy of the bladder wall and, in men, laboratory examination of prostatic secretions.
Physical examination of an individual with IC/PBS 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 IC/PBS.
Urinalysis and urine culture: These tests can detect and identify the most common bacteria in the urine that may be causing IC/PBS-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 IC/PBS.
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 IC/PBS, but it is no longer used routinely for this purpose because the results are not specific for IC/PBS; abnormal results can also be due to other conditions. The test also can be painful. Many people with IC/PBS 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 IC/PBS. However, like the potassium sensitivity test, this test is not specific for IC/PBS 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 IC/PBS 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 (visually or with biopsies), 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 also may 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 IC/PBS have normal or large maximum bladder capacities under anesthesia. A small bladder capacity (due to scarring) under anesthesia helps to support the diagnosis of IC/PBS.
Before the relatively recent development of the PST, cystoscopy was the best diagnostic test available for IC/PBS. However, cystoscopy has its limitations. Ulcers are generally not observed in mild or early cases of IC/PBS, and glomerulations have been observed in normal individuals without symptoms of IC/PBS. Due to these limitations, cystoscopy is recommended only to exclude other possible causes of symptoms and not as the definitive diagnostic test for IC/PBS.
It is important to note that the distension often performed with cystoscopy may lead to relief of symptoms in some patients with IC/PBS, 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 IC/PBS. Nevertheless, there is nothing on the biopsy that can make an absolute diagnosis of IC/PBS.
Oral medications that may be used to treat IC/PBS include low doses of antidepressants of the tricyclic group such as amitryptiline (Elavil). This is not due to a belief that IC/PBS 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 allergic symptoms that may be worsening the patient's IC/PBS.
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 protection of the inner lining cells of the bladder. Even after therapy with PPS has begun, patients may still experience symptoms for some time because the sensory nerves in the bladder may 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 IC/PBS (and two years in severe IC/PBS) 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 IC/PBS, antihistamines such as hydroxyzine can be given to facilitate sleep.
Aspirin 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).
As mentioned previously, because some patients have noted an improvement in symptoms after bladder distension done to diagnose IC/PBS, bladder distension (termed hydrodistension) sometimes is used for therapy of IC/PBS. 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 because of discomfort, and some patients have a temporary worsening of symptoms following the procedure.
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 IC/PBS, intravesical solutions may be administered along with oral PPS to provide relief until the oral PPS 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).
In severe cases of IC/PBS 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 IC/PBS. 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 IC/PBS include peripheral denervation (disrupting the nerves to and from the bladder wall), bladder augmentation to increase bladder capacity, and cystectomy (bladder removal) with diversion, or re-routing, of urine flow into an artificial bladder formed from a loop of intestine.
There are a number of home remedies and self-care techniques that many people have found to be of benefit in controlling the symptoms of interstitial cystitis/painful bladder syndrome. These include limiting the consumption of certain foods, smoking cessation, exercise, and bladder training. These methods are described in more detail in the section below.
There is no scientific evidence linking diet to IC/PBS, 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 IC/PBS. 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 IC/PBS 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.
Many IC/PBS 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.)
Many IC/PBS patients feel that regular exercise helps relieve symptoms and, in some cases, hastens remission.
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.
IC/PBS is a chronic condition that is characterized by periods of relapse and remission. Doctors do not fully understand why the symptoms worsen at particular times or disappear and then reappear months or years later. Symptoms may be mild or severe and may vary in intensity even in the same individual over time. There is no cure for IC/PBS, and treatments are directed at reducing the severity of symptoms.
There has been no treatment that has been shown to be effective in slowing the progression of the disease or in preventing recurrences.
Because the cause is poorly understood, there are no known strategies for preventing IC/PBS. However, some self-care measures may help reduce the severity of symptoms (see section on home remedies).
Interstitial Cystitis Association of America
110 North Washington Street, Suite 340
Rockville, MD 20850
Phone: 1-800-HELP-ICA (435-7422) or 301-610-5300
Fax: 301-610-5308
Email: [email protected]
Internet: http://www.ichelp.org
American Urogynecologic Society
2025 M Street NW., Suite 800
Washington, DC 20036
Phone: 202-367-1167
Fax: 202-367-2167
Email: [email protected]
Internet: http://www.augs.org
European Society for the Study of Interstitial Cystitis
http://www.essic.eu
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Gabapentin (Neurontin, Gralise, Horizant, Fanatrex FusePag) is a drug prescribed for the treatment of seizure disorders, nerve damage from shingles and postherptic neuralgia. Off label uses of gabapentin include treatment for:
Common side effects include:
Adverse reactions and serious side effects include:
Gabapentin is available as capsules as 100, 300, and 400 mg; tablets as 100, 300, 400, 600, and 800 mg; and as a solution of 250 mg/5 ml. The exact dosage depends upon the condition being treated. It is not known if this drug is safe to take during pregnancy. It is secreted in breast milk, so mothers who are breastfeeding should consult their OB/GYN or other health care professional and only use this gabapentin if the benefits outweigh the risks to the fetus. Gabapentin is not a narcotic (opioid), however, it does share signs and symptoms associated with drug abuse and addiction. Patients taking this drug may experience withdrawal symptoms like goosebumps, sweating, vomiting, and nausea. Gabapentin was approved by the FDA in 1993.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce mild to moderate pain, inflammation, and fever. Ibuprofen works by blocking an enzyme that makes prostaglandin (a hormone-like substance that participates in a variety of body functions), which results in lower levels of prostaglandins in the body. Lower levels of prostaglandins reduce pain, inflammation, and fever.
Ibuprofen is prescribed to treat diseases and conditions that cause mild to moderate pain, fever, and inflammation. For example, Pain from strains and sprains; pain from cuts, scrapes, and puncture wounds; muscle aches and pains; tooth pain; common cold; mild headache; some arthritis conditions; joint pain; and to reduce fever.
Common side effects of ibuprofen include, diarrhea, constipation, nausea, heartburn, belly pain, drowsiness, headaches, tinnitus (ringing in the ears), and mild rash.
More serious side effects and adverse effects include, increased bleeding after injury, stomach ulcers, impaired kidney function, severe allergic reaction (anaphylaxis), blood clots, heart attack, heart failure, and high blood pressure.
The maximum dose prescribed under a doctor's care is 3.2 g daily. Otherwise, the over-the-counter (OTC) maximum daily dose is 1.2 g daily. Dosage depends upon the age, weight, and any current medical conditions of the patient. Several drugs interact with ibuprofen so check with your doctor, pharmacist, or other health care professional with questions in regard to this drug. Doctors don't know if it is safe to take ibuprofen if your are pregnant, therefore it is not recommended if you are pregnant. According to the American Academy of Pediatrics, ibuprofen is safe to take while breastfeeding.
REFERENCE: FDA Prescribing Information.
There are numerous causes of pelvic pain in women and men. Causes of pelvic pain in women and men include:
Treatment of pelvic pain depends upon the cause.
Pulmonary fibrosis is scarring throughout the lungs. Pulmonary fibrosis can be caused by many conditions including chronic inflammatory processes, infections, environmental agents, exposure to ionizing radiation, chronic conditions, and certain medications. Symptoms include
Treatment options are dependent on the type of pulmonary fibrosis; lung transplant and/or medications are options.
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