Information on the following diseases can be found in the Related Disorders section of this report:

• Cystitis (General including acute, radiation, and drug induced cystitis)
• Cystitis Colli
• Cancer of the Bladder (Carcinoma In Situ of the Bladder)
• Endometriosis
• Prostatitis
• Reiter's Syndrome

Symptoms of interstitial cystitis include bladder pain, pain or pressure above the pubic area, urinary urgency and frequency, and waking numerous times at night to urinate (nocturia). Affected individuals may also experience urethral, vaginal, penile, and/or rectal pain, as well as pain that radiates down the thighs. Sexual intercourse may be very painful. In addition, some patients may experience muscle and joint pain, vulvar pain, migraines, allergic reactions, gastrointestinal problems, and depression. Symptoms can range from mild to severe and may be exacerbated by stress.

Most individuals with interstitial cystitis only exhibit abnormalities of the bladder. However, in some cases, additional symptoms such as joint pain, headaches, and additional gastrointestinal abnormalities may also be present. In some cases, interstitial cystitis may be associated with other disorders such as irritable bowel syndrome.
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The exact cause of interstitial cystitis is not known. Some studies suggest that it may be an autoimmune disease of the bladder's connective tissue. Autoimmune disorders are caused when the body's natural defenses against "foreign" or invading organisms (e.g., antibodies or lymphocytes) begin to attack healthy tissue for unknown reasons.

Research at the University of Maryland has revealed that bladder cells of interstitial cystitis patients produce high levels of a toxin called APF, or antiproliferative factor. APF appears to decrease levels of a growth factor called HB-EGF that helps repair a damaged bladder lining. This discovery may lead to a faster urine test for IC, but it may also help in the understanding of the root cause of IC.

Many people with interstitial cystitis have a history of allergies, but few report having had many infections of the urinary tract. Some research suggests that interstitial cystitis may be associated with abnormalities of the very thin top layer of protective mucous that lines the walls of the bladder (glycosaminoglycan or GAG layer). Defects in this lining may lead to the development of chronic inflammation or ulceration. Other studies are investigating the role of certain substances that are essential to maintain the health of the bladder (glycosaminoglycan uronates). There is some evidence that certain uronates may be deficient in certain people with interstitial cystitis.

Other suspected causes of interstitial cystitis include bacterial or viral agents which have yet to be indentified in the laboratory; defects in the bladder lining (the so-called "leaky bladder syndrome"); toxic substances in the urine; bladder irritation caused by substances such as histamine released into the bladder wall by mast cells; bladder-specific immune dysfunction; and a neuroinflammatory disorder. To date, none of these possible causative factors has been proven or eliminated.

Interstitial cystitis affects approximately 450,000 individuals in the United States. Some estimates suggest that the interstitial cystitis affects more than 700,000 people. Because the condition is underdiagnosed, determining the true frequency in the general population is difficult.

Interstitial cystitis can affect anyone at any age, including children and teenagers; however, the average age of onset is 40 years, with 25 percent of the patient population under the age of 30. Ninety percent of affected individuals are women, although some studies have suggested that some men who are diagnosed with nonbacterial prostatitis may actually have interstitial cystitis.
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Symptoms of the following disorders can be similar to those of Interstitial Cystitis. Comparisons may be useful for a differential diagnosis:

Cystitis is a very common inflammatory bladder disease characterized by painful and frequent urination. Blood may be present in the urine (hematuria). Pain and pressure may be present in the pelvic and genital area. Acute Cystitis may occur because of a bacterial infection of the lower urinary tract, radiation therapy, or treatment with certain immunosuppressant drugs (i.e., cyclophosphamide) used in cancer therapy. In radiation-induced Cystitis, cysts may form in the interior walls of the bladder.

Cystitis colli (cystanchenitis) is an acute inflammatory condition of the neck of the bladder. The symptoms are similar to those of Interstitial Cystitis and may include painful and frequent urination accompanied by pain in the pelvic area.

Cancer of the bladder (carcinoma in situ) is characterized by malignant growths on the bladder walls that may destroy the mucous lining of the bladder. Symptoms may include pain and pressure in the pelvis and genitals accompanied by frequent and painful urination. Blood may be present in the urine. Bladder cancer is diagnosed through a biopsy of bladder tissue.

Endometriosis is a common gynecological condition that affects women and is characterized by the inability to shed the tissue that normally lines the uterus before menstruation. This excess tissue may sometimes spread to other areas of the body, including the bladder. Symptoms may include lower back pain, pain in the thighs, repeated miscarriages, and/or infertility. When endometrial tissue spreads to the bladder, the symptoms can be similar to those of Interstitial Cystitis, including frequent and painful urination. (For more information on this disorder, choose "Endometriosis" as your search term in the Rare Disease Database.)

Prostatitis is a common infection of the prostate gland in males. Acute bacterial Prostatitis is characterized by chills, high fever, low back pain, and/or painful joints. The primary symptoms a frequent urge to urinate, accompanied by difficult and painful urination. Inflammation of the bladder (acute cystitis) usually accompanies Acute Prostatitis. Males with chronic bacterial Prostatitis experience frequency and urgency of urination, pain and burning sensations during urination, and excessive urination at night. (For more information on this disorder, choose "Prostatitis" as your search term in the Rare Disease Database.)

Reiter's Syndrome is a rare disorder characterized by arthritis, inflammation of the urinary tract (nongonococcal urethritis) and the mucous membranes that line the eyes (conjunctivitis). Symptoms may include painful urination, abdominal pain, cramping, and/or diarrhea. Painful and swollen joints (arthritis), as well as other symptoms, may appear 4 days to 4 weeks later. (For more information on this disorder, choose "Reiter" as your search term in the Rare Disease Database.)

Other conditions that can cause painful and frequent urination include kidney diseases, stones in the kidney or bladder (calculi), sexually transmitted diseases, diabetes, and multiple sclerosis.

Diagnosis
The diagnosis of interstitial cystitis may be confirmed by a thorough clinical evaluation, detailed patient history, and a variety of specialized tests (i.e. urine culture to rule out bacterial infection and/or cystoscopy with hydrodistention). A cystoscopy uses a special instrument known as a cystoscope to examine the internal bladder. In interstitial cystitis, cystoscopy usually reveals abnormally thick bladder walls and areas of inflammation. During cystoscopic examination, the physician may also see areas of bleeding and deep scars (fibrosis) within the mucous lining of the bladder. Inflammatory changes that may also be seen include the replacement of muscle by fibrous tissue, an abnormally thin and patchy mucous layer, an increase in the number of blood vessels, and degeneration of the blood vessels around the bladder.

Specialized white blood cells (mast cells), which are associated with inflammation, may be present within the mucous lining of the bladder. Measurement of urinary volume typically reveals a decreased volume of urine that is passed during each urination. People with interstitial cystitis should have a biopsy of the bladder to rule out the possibility of an early cancer (carcinoma in situ) in the bladder.

Treatment
The orphan drug sodium pentosan polysulphate (Elmiron) has been approved by the Food and Drug Administration (FDA) as a treatment for individuals with interstitial cystitis. Elmiron is an oral medication that may help restore the delicate protective lining of the bladder walls (GAG layer). Elmiron is manufactured by Alza Corporation.

Several other therapies may help relieve the symptoms of interstitial cystitis, but none are considered curative. The symptoms are not helped by antibiotic therapy since there is no bacterial infection. One method of treatment for interstitial cystitis is bladder distention with water (hydraulic distention). This procedure may be done under local or general anesthesia. Approximately 30 percent of people with this disorder experience some short-term relief from this procedure. Repeated bladder distentions may be done to try to increase the urinary capacity of the bladder.

In another procedure, the interior walls of the bladder may be "washed" (lavage) with dimethyl sulfoxide (DMSO). A tube is placed inside the bladder (catheter) and the solution is held in the bladder for approximately 15 minutes. Treatments of DMSO are given once or twice a week for several weeks. Other drugs that may be used instead of DMSO include cortisone acetate and silver nitrate. Oxychlorosene sodium (Clorpactin) is another medication that can be placed directly into the bladder to treat inflammation. Since this is an extremely painful procedure, it is generally done in a hospital under general anesthesia. Electrofulguration, or the destruction of bleeding ulcers with an instrument that delivers an electrical current to the affected area within the bladder, may temporarily relieve some symptoms of interstitial cystitis and allow ulcerations to heal.

Other medications used to treat interstitial cystitis include tricyclic antidepressants; antispasmodics (Urised); anticholinergics (Detrol, Ditropan XL, Levsin); H2 Blockers such as cimetidine (Tagamet) or ranitide (Zantac); urinary alkalinizing agents, Bicitra and Polycitra-K; adrenergeric blockers, Cardura, Flomax and Hytrin; muscle relaxants; and if pain is severe opioid analgesics. Short-acting analgesics such as Vicodin and Percocet may be used to treat moderate, intermittent interstitial cystitis pain. OxyContin MS-contin and Duragesic are long-acting analygesics that may be useful in treating severe interstitial cystitis pain. Cromolyn sodium (Gastrocrom), a mast cell inhibitor, may also help to relieve symptoms in some patients.

When the urogenital pain associated with interstitial cystitis is severe, a special device known as a transcutaneous electrical nerve stimulator, or TENS unit, may be used to alter nerve transmissions to the bladder and help to block pain impulses. Other severely affected individuals may have pain medications administered directly into the spinal column (lumbar epidural block).

When the symptoms of interstitial cystitis do not respond to bladder lavage or drug therapy, surgery may be performed to increase the size of the bladder. In one surgical procedure known as ileocystoplasy or sigmoidplasty/uretosigmoidostomy, the size of the bladder is increased using tissue from the intestine. In very severe cases, it may be necessary to remove the bladder (cystectomy) and shift urine flow into the small or large intestine.
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Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.

As of December 2006, there were 14 clinical studies listed on www.clinicaltrials.gov related to interstitial cystitis. One is a Phase III clinical trial investigating the use of two doses of the orphan drug Elmiron, which was approved earlier for the relief of bladder pain or discomfort associated with interstitial cystitis. This multi-center study is sponsored by Johnson & Johnson Pharmaceutical Research & Development.

Because interstitial cystitis tends to run in some families, the possibility of genetic susceptibility is being studied in research sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. This national study is being conducted by telephone and mail. It is not necessary to leave one's home to participate. The University of Maryland School of Medicine is partnering with the NIDDK on this study. Families with two or more blood relatives with interstitial cystitis are being sought for this study, which is called the Maryland Genetics of Interstitial Cystitis Study (MaGIC). For information, contact Linda Horne at (877) 788-3942 or studyic@medicine.umaryland.edu.

Botulinum toxic A (Botox) is also being studied as a possible treatment for IC. This Phase IV study is sponsored by the University of Washington and the Paul Allen Foundation. For information, contact Sharon Downing, RN, at (206) 598-0850 or sdowning@u.washington.edu.

The Interstitial Cystitis Clinical Research Network (ICCRN) was formed in 2003 by the National Institute of Diabetes and Digestive and Kidney Diseases. It is a part of the U.S. Department of Health and Human Services, and has an array of information on current (2006) clinical trials and other investigative work for interstitial cystitis. One of these trials is studying the effectiveness of amitriptyline (Elavil) in treating painful bladder syndrome, which includes interstitial cystitis. Researchers are investigating whether the drug works to block nerve signals that trigger pain in the bladder and may also decrease muscle spasms in the bladder, helping to cut both pain and frequent urination. For a listing of ICCRN centers, go to www.niddk.nih.gov/patient/iccrn.htm#2.

HARRISON'S PRINCIPLES OF INTERNAL MEDICINE, 14th Ed.: Kurt J. Isselbacher, M.D. et al., Editors; McGraw-Hill, Inc., 1998. Pp. 264-65.

INTERNAL MEDICINE, 4th Ed.: Jay H. Stein, Editor-In-Chief; Mosby-Year Book, Inc., 1994. P. 2607.

Held PJ, et al., Epidemiology of interstitial cystitis. In Interstitial Cystitis; P.M. Hanno et al., Editors; Springer-Verlang, 1990. Pp. 29-48.

JOURNAL ARTICLES
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Curhan GC, et al., Epidemiology of interstitial cystitis: a population based study. J Urol. 1999;161:549-552.

Hanno PM, et al., The diagnosis of interstitial cystitis revisited: lessons learned from the national institutes of health interstitial cystitis database study. J Urol. 1999;161:553-7.

Theoharides TC, et al., Hydroxyzine therapy for interstitial cystitis. Urol. 1997;49:108-10.

Alagiri M, et al., Interstitial cystitis: unexplained associations with other chronic diseases and pain syndromes. Urol. 1997;49:52-7.

Pontari M, Interstitial cystitis update. Infect Urol. 1997;10:75-9.

Miller JE, et al., Prostatodynia and interstitial cystitis: one and the same? Urol. 1995;45:587-90.

Irwin PP, et al., Lumbar epidural blockage for management of pain in interstitial cystitis. Br J Urol. 1993;71:413-6.

Koziol JA, et al., The natural history of interstitial cystitis: a survey of 374 patients. J Urol. 1993;149:465-9.

Hurst RE, et al., Urinary glycosaminoglycan excretion as a laboratory marker in the diagnosis of interstitial cystitis. J Urol. 1993;149:31-5.

Ratner V, et al., Interstitial cystitis: a bladder disease finds legitimacy. J Women's Health. 1992;1:63-8.

Christmas TJ, et al., Characteristics of mast cells in normal bladder, bacterial cystitis and interstitial cystitis. Br J Urol. 1991;68:473-8.

Nurse DE, et al., Problems in the surgical treatment of interstitial cystitis. Br J Urol. 1991;68:153-4.

Parsons CL, et al., Successful treatment of interstitial cystitis with sodium pentosanpolysulfate. J Urol. 1983;130:51-3.

Worth PH, The treatment of interstitial cystitis by cystolysis with observations on cystoplasty. A review after 7 years. Br J Urol. 1980;52:32.