What is Interstitial Cystitis & Painful Bladder Syndrome?
(Written by Jill Osborne, MA - Revision: October 30, 2010- Created: 1995)
Interstitial cystitis (IC), also known as bladder pain syndrome (BPS), painful bladder syndrome (PBS) or hypersensitive bladder syndrome (HBS), is a condition that results in "an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes." (2009 new American IC/BPS Guidelines).
The symptoms can vary greatly between individuals and even for the same person throughout the month, including an urgent need to urinate (urgency), a frequent need to urinate (frequency) and, for some, pressure and/or pelvic pain. People with severe cases of IC/PBS may urinate as many as 60 times a day, including frequent nighttime urination (nocturia).
Pain levels can range from mild tenderness to intense, agonizing pain. Pain typically worsens as the bladder fills and is then relieved after urination. Pain occurring after urination may relate to pelvic floor tension and/or muscle spasms. Pain may also radiate to the lower back, upper legs, vulva and penis. Women's symptoms may fluctuate with their menstrual cycle, often flaring during ovulation and/or just before their periods. Men and women may experience discomfort during or after sexual relations. During flares, patients may also experience the “IC Belly,” a sudden and random swelling of the lower abdomen.
When an IC bladder is examined using a procedure called hydrodistention with cystoscopy, physicians often find small, bleeding wounds, also known as petechial hemorrhages or glomerulations. These are usually caused by recurring irritation, such as coffee or soda. About ten percent of patients may have larger, more painful wounds, called Hunner’s Ulcers. Some patients with mild IC may have bladders that appear normal during a cystoscopy. IC patients rarely test positive for infection in standard urinalysis and urine cultures (1,2).
In recent years, there has been much debate about renaming IC. In the United States, we typically use the term interstitial cystitis (IC) or interstitial cystitis/bladder pain syndrome IC/BPS) though many believe that patients are being frequently misdiagnosed with overactive bladder and/or chronic prostatitis. In Europe, physicians appear to favor the term bladder pain syndrome (BPS). In Japan, the term hypersensitive bladder syndrome is generally used. We urge you not to become invested in any specific name but rather focus on symptoms. If someone has frequency, urgency, pressure and/or pain, they clearly require medical care and should be treated with compassion.
What Causes IC?
The cause of IC remains a mystery. Various research studies have explored the possibility that infection, epithelial links, epithelial permeability, mast cells, heredity and neuroinflammation may play a role in IC but, to date, there is no single cause that we can attribute to causing IC in ALL patients. Rather, it may be that IC has several different variations.
In a 2000-2001 ICN Research Survey, we asked patients how they believed their IC began. Some IC patients reported that their symptoms began after a traumatic event, such as a fall, car accident, pelvic surgery (i.e. hysterectomy or ovarian cyst removal), childbirth or chemical exposure in a swimming pool. Others believed that their IC began after a severe UTI or as a result of another medical condition, such as fibromyalgia. Some patients thought that their excessive drinking of sodas (diet & regular sodas), coffees and/or alcohol was the cause of their IC. The common factor in all of these events is their potential for irritating the bladder wall.
The biggest breakthrough, to date, occurred when researchers at the University of Maryland (led by Susan Keay) isolated a substance found almost exclusively in the urine of people with interstitial cystitis. They have named the substance the antiproliferative factor (APF), because it appears to block the normal growth of the cells that line the inside wall of the bladder. Thus, it may take longer for an IC patient to heal when their bladder is injured or irritated.
In Fall 2007, the National Institutes of Health launched the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to help uncover the genetic, biological and behavioral relationships of IC and it's related conditions (i.e. irritable bowel syndrome, etc.) This is a remarkable change of direction for the IC research movement. Many of the new discussions in the IC research movement are focusing on the concept of neuroinflammation and neurosensitization. It may be that once our body has sustained an injury, perhaps to any organ, it may create a cascade like effect of neurosensitization in nearby organs. IBS and IC, for example, both involve neurosensitization of the nerves in those organs and, in both cases, treatments are focused on reducing neuroinflammation. This could explain why coffee, a well known neurostimulatory agent, exacerbates both IC and IBS.
Other Bladder Conditions
IC can be easily confused with many different bladder diseases, such as a UTI, because the symptoms of frequency, urgency and/or pain are common to most bladder conditions. In fact, many IC patients and/or their physicians may mistakenly assume that they have recurring bladder infections despite the fact that their urine cultures are usually negative. Men with IC symptoms are often misdiagnosed as prostatitis or bladder outlet obstruction (1) patients.
The nebulous terms of urethritis, urethral syndrome, trigonitis, overactive bladder, lower urinary tract syndrome and painful bladder often add more confusion for patients, because the medical community itself continues to debate the precise definitions of each disease. Hanno (3), for example, refers to urethral syndrome as short-term lower urinary tract symptoms that resolve before a physician can perform formal diagnostic tests. Childs and Egan (4) refer to urethral syndrome patients as those who experience UTI symptoms but with no apparent infection.
As IC patients endure the diagnostic process and seek "a name" for their condition, it is often helpful to understand the other bladder conditions that IC can be mistaken for, such as:
- Urinary Tract Infections - The terms urinary tract infection (UTI), bacterial cystitis and cystitis are used interchangeably to describe bladder infections, if verified by urinalysis and/or urine cultures. Bladder infections can cause frequency, urgency, painful urination, abdominal pain, fever and other symptoms.
- Urethritis - Urethritis is used to describe an inflammation or infection of the urethra in men and women. Inflammation can be caused by direct trauma to the urethra or can be an irritation from spermicides, soaps, douches or bath oils. Some sexually transmitted diseases, such as chlamydia, can also cause a urethral infection and urethral discharge that may also be labeled as urethritis (5).
- Urethral Syndrome - As mentioned earlier, urethral syndrome can be used to describe the symptoms of a UTI when urinalysis fails to reveal infection. Some physicians, such as Hanno, believe that urethral syndrome is short, rather than long, term. Many IC patients, including the authors of this book, have received urethral syndrome diagnoses before the IC was actually discovered.
- Trigonitis - Trigonitis patients may experience similar symptoms of frequency, urgency and/or pain. Trigonitis is diagnosed when physicians discover that the trigone (a triangular portion of the bladder that contains the openings for both the ureters and the urethra) appears inflamed and/or has a "cobblestone like" appearance. Some urologists don't believe in trigonitis because they believe that the cobblestone appearance is normal to the trigone. Others believe that an inflammation of the trigone may have a direct role in urethral syndrome (4).
- Prostatitis - There are several types of prostatitis diagnosed in men, including bacterial prostatitis (acute and chronic), non-bacterial prostatitis, and prostatodynia. The latter two account for 95% of all prostatitis diagnoses and usually have symptoms of perineal (or nearby) pain, reduced urine flow (and related symptoms), and possibly impotence and pain before, during or after ejaculation (6).
- Dysuria & Nocturia - Dysuria describes pain with urination. Nocturia describes frequent urination during sleep or nighttime hours (7).
- Overactive Bladder Syndrome & Urge Incontinence - Overactive bladder syndrome and urge incontinence patients may have frequency, urgency and episodes of incontinence. It is theorized that overactive bladder is the result of a neurological dysfunction, or smooth muscle disease, of the bladder. It is called detrusor hyperreflexia when a neurological cause is known and detrusor instability when there is no neurologic abnormality (8).
- Interstitial Cystitis, Painful Bladder Syndrome, Bladder Pain Syndrome, Freqency-Urgency-Dysuria Syndrome - These terms are used interchangeably to describe urinary frequency, urgency and/or feelings of pain or pressure around the bladder, pelvis and perineum (9).
A History of IC
Once a patient has a diagnosis of interstitial cystitis, they are often frustrated by the lack of knowledge about IC in the medical community. Although the first IC case may have been recognized as early as the mid 1800's, it wasn't until 1987 that the US National Institutes of Health convened the first meeting to discuss IC. As such, patients face the unique challenge of becoming educators and advocates for the IC community as they spread the word that IC is, indeed, a disease that is worth care and treatment. In 1997, Christmas (10) wrote a comprehensive analysis of the history of IC, which documented the first investigators of IC, the earliest discussions of the possible causes, and early treatment preferences for this disease. Here are some fascinating highlights.
- 1800's: The first possible case of interstitial cystitis may have been reported in 1836 by Mercier (11). The term "interstitial cystitis" was first used in 1887 by Skene in his book Diseases of the Bladder and Urethra in Women (12).
- 1900's: In the early 1900's, investigators believed that two possible forms of bladder ulcers were present. Fenwick described bladder ulcers that appeared on the trigonal tissues (13). In 1914, Hunner documented the presence of ulcers on the bladder wall, other than the trigone. Hunner's work was pivotal in that it documented bladder epithelial damage and the related blood vessel transitions (14).
- 1930's: In the 1930's, Bumpus took the position that more of the bladder was involved than originally thought and that ulcer removal was not helpful. He utilized cystodistention as a treatment option, which became one of the more popular treatments during the 1940's (15). In 1937, as deep x-ray therapy (now known to contribute to various forms cancer) gained regrettable popularity, Kreutzmann explored x-rays as a means to treat IC, yet had no permanent cures in his patient study (16). In 1938, the relationship between IC and other diseases was first discussed by Fister (17), who compared IC with a connective tissue disorder, lupus erythematosus.
- 1940's: In the 1940's, the first "caustic" or "irritative" bladder instillations were utilized, such as anilyne dyes (18) and silver nitrate (19). In 1944, IC was first accepted as a disease that effected men (20). Hanno (3) believes that Hand's publication in 1949, the first comprehensive paper on the disease, was seminal to the study of IC. It included the first descriptions of small, discrete submucosal hemorrhages (now known as glomerulations) found during bladder distentions.
- 1950's - early 1980's: IC is mistakenly labelled as a psychiatric condition as various members of the medical community clung to the misguided belief that IC may have psychosomatic origins. Although a research study in 1953 first documented the presence of IC in children (21), IC was unfortunately labeled a "hysterical" disease of women in an article by Bowers, Schwartz and Leon (22). They suggested that a woman who had been under medical care from childhood to 29 years of age with severe IC, may have had "repressed hostility towards parental figures handled masochistically via bladder symptoms since infancy." Sadly, this appears to have contributed to an attitude of passiveness in patient care and physician training that has lasted throughout the following decades. This attitude was aptly demonstrated by Dr. Daniel Brookoff, as he explained 'The first time I heard of IC was in medical school twenty years ago. A famous professor was lecturing. At the end of his speech he said "There's this disease called interstitial cystitis. It is little old ladies and they have to urinate a lot. They're always in pain and they will drive you nuts. It's a psychiatric disease. It's all in their heads."'(23)
- 1970's: Two pivotal IC studies occurred in the late 1970's. Walsh (24) was the first to use the term "glomerulations" to describe the small petechial hemorrhages on the bladder wall described by earlier researchers. Messing and Stamey (25) altered the perception of IC irrevocably by recognizing glomerulations (in addition to ulcers) as the primary indicators of the disease and that diagnosis of IC should be done by exclusion.
- 1980's: The US National Institutes of Health (NIH) convened workshops in 1987 and 1988 to establish the first definition and research criteria for IC as a severe and potentially debilitating disease (26). In an effort to track the long term progress of IC patients, the NIH launched the Interstitial Cystitis Database (ICDB) studies in 1991, which offered many new insights into the history and characteristics of IC.
- 1990's: Although some sectors of the medical community still believe that IC does not exist, researchers and physicians now aggressively support the IC cause to encourage compassionate patient treatment. In 1994, Wein and Broderick spoke strongly to their peers on this matter. "In our opinion, the first "rule" in obtaining the maximum success possible in treating this difficult group of patients is that, if you as a physician do not believe that this disease exists or if you believe the symptoms are entirely psychosomatic, then you are doing neither the patients nor yourself a great service by trying or continuing to manage them.... It is necessary not only to be knowledgeable, but also to be sympathetic (and) empathetic..." (27)
- 2000's: IC is now accepted as one of the most challenging conditions known to the urology community. The NIH, as well as researchers around the world, are devoting millions of dollars towards research that is slowly, yet surely, revealing essential pieces to the IC puzzle. Research studies now flourish and cover topics such as epidemiology, diagnostic methods, new treatments and long term patient care. Medical journals such as Urology and the Journal of Urology are routinely publishing articles or special editions dedicated to interstitial cystitis. A search of PUBMED (28), the free medical research index on the web, currently reveals hundreds of studies on IC. The research is fertile, the funding is obtainable, and IC is slowly, but surely, gaining credibility.
- 2009: New American guidelines have been released selecting the name IC/BPS as the formal term to be used in the USA. New treatment guidelines were also released.
Doctors must rule out a UTI and other treatable conditions before considering a diagnosis of IC/PBS, including: prostatitis, chronic pelvic pain syndrome, pelvic floor dysfunction and bladder cancer. Luckily, IC/PBS is not associated with any increased risk in developing cancer.
Unfortunately, there is no definitive test for IC currently on the market, thus a diagnosis of IC/PBS in the general population is based on clinical symptoms, including the presence of pain, frequency and/or urgency. In recent years, diagnostic testing for IC has changed dramatically. (1) Previously, physicians performed a cystoscopy with hydrodistention of the bladder to comfirm a diagnosis of IC.
In recent years, clinicians have favored less invasive diagnostic methods, such as The PUF Questionnaire. Based upon those results, doctors may perform a brief Potassium Sensitivity Test to determine if the bladder wall is damaged. Hydrodistention of the bladder may be requested if a doctor wishes to perform a biopsy. A voiding diary can also be helpful.
Epidemiology of IC
Epidemiological and population based studies of IC are still not conclusive. Several report a fairly low incidence of IC while others, such as an epidemiology study conducted in 2005 by Dr. Matt Rosenberg, suggested that up to 12% of women in the US may have symptoms of interstitial cystitis. Previous studies by Oravisto (31), Held (32) and Koziol (33) have determined that:
- The average age of onset for IC is 40 years, with 25% of patients under the age of 30.
- A late deterioration of symptoms is unusual.
- Up to 50% of patients experience spontaneous remissions probably unrelated to treatment, with a duration ranging from 1 to 80 months.
- Patients with IC are 10 to 12 times more likely than controls to report childhood bladder problems.
- Patients with IC are twice as likely as controls to report a history of urinary tract infection; however, over half of all IC patients report fewer than one such infection per year before the onset of IC.
- 50% of IC patients have pain while riding in car.
- 63% of IC patients are unable to work full time.
- IC patients have suicidal thoughts 3-4 times above the national average.
- The quality of life of IC patients is worse than patients experiencing chronic renal failure and undergoing dialysis.
- IC related medical care cost in the US was $116.6 million in 1987 and IC related lost economic production was $311.7 million.
- Household size, marital status, sexual partners and education did not differ from the general population.
- Parsons L. Evaluating and Managing Interstitial Cystitis. New Jersey:University Research Associates, 1997
- Ho N, Koziol J, Parsons CL. Epidemiology of Interstitial Cystitis, in G. Sant (Ed.), Interstitial Cystitis. Philadelphia: Lippincott-Raven Publishers, 1997; 9-15
- Hanno P. Interstitial Cystitis and Related Diseases, in Campbell's Urology, 7th Ed. Philadelphia: W.B. Saunders Company, 1998; 631-662
- Childs S, Egan R. Microbiology and Epidemiology of Recurrent Lower Urinary Tract Infections. Infect Urol 1998;11(3):88-92
- University of Michigan Health System Health Topics 8/98. Available: http://www.med.umich.edu/1libr/topics/mens/ureth01.htm
- Prostatitis: Disorders of the Prostate, NIDDK Publication, 1998; Available: http://www.niddk.nih.gov/health/urolog/summary/prstitis/prstitis.htm
- Mirriam Webster Medical Dictionary 1997; Available: http://www.medscape.com/mw/medical.htm
- Payne C. Epidemiology, pathophysiology, and evaluation of urinary incontinence and overactive bladder. Urology 1998;51(2a suppl):3-10
- Interstitial cystitis. NIH Publication No. 94-3220, 1994; Available http://www.niddk.nih.gov/health/urolog/pubs/cystitis/cystitis.htm
- Christmas T. Historical Aspects of Interstitial Cystitis, in G. Sant (Ed.), Interstitial Cystitis. Philadelphia: Lippincott-Raven Publishers, 1997; 1-8
- Mercier, LA. Memoire sur certaines perforations spontanees de la vessie non decrites jusqu'a ce jour. Gaz Med Paris 1836;4:257-263
- Skene AJC. Diseases of the Bladder and Urethra in Women. New York: Wm Wood, 1887;167
- Fenwick EH. The clinical significance of the simple solitary ulcer of the urinary bladder. Br Med J 1896;1:113-1135
- Hunner GL. A rare type of bladder ulcer in women: report of cases. Trans south Surg Gynecol Assoc 1915;27:247-292
- Bumpus HC. Interstitial Cystitis: its treatment by over-distention of the bladder. Med Clin North Am 1930;13:1495-1498
- Kreutzmann HAR. The treatment of Hunner's ulcer with deep x-ray therapy. J Urol 1941;46:907-912
- Fister GM. Similarity of interstitial cystitis (Hunner ulcer) to lupus erythematosus. J Urol 1938:40:37-51
- Davis E. Aniline dyes in the treatment of Hunner ulcer. J Urol 1941;46:899-906
- Pool, TL, Rives HF. Interstitial cystitis: treatment with silver nitrate. J Urol 1944;51:520-525
- Cristol DS, Greene LF, Thompson GJ. Interstitial cystitis of men, a review of seventy-eight cases. JAMA 1944;126:825-828
- McDonald HP, Upchurch WE, Sturdevant CE. Interstitial cystitis in children. J Urol 1953;70:890-893
- Bowers JE, Schwarz BE, Leon MJ. Masochism and interstitial cystitis. Psychosom Med 1958;20:296-302
- Brookoff D. What's True is What Our Patients Tell Us. Presented at the 1997 Summit on Chronic Pain, Santa Rosa California. Available: http://www.sonic.net/jill/icnet/handbook/pain.html
- Walsh A. Interstitial Cystitis, in Campbell's Urology, 4th Ed. Philadelphia: W.B. Saunders Company, 1978;693-707
- Messing EM, Stamey TA. Interstitial cystitis, early diagnosis, pathology and treatment. Urology 1978;12:381-392
- Gillenwater JY, Wein AJ. Summary of the NIADDK workshop on interstitial cystitis, National Institutes of Health, Bethesda, MD. J Urol 1988:203-205
- Wein AJ, Broderick G. Interstitial Cystitis - Current and Future Approaches to Diagnosis and Treatment. Urologic Clinics of North America 1994;21:153-161
- Medline (National Library of Medicine) Available: http://www.ncbi.nlm.nih.gov/PubMed/
- Nigro D, Wein A. Interstitial Cystitis: Clinical and Endoscopic Features. In G. Sant (Ed.) Interstitial Cystitis Philadelphia: Lippincott-Raven, 1997;137-142
- Slade D, Ratner V, Chalker R. A collaborative Approach to Managing Interstitial Cystitis. Urology 1997;10-13
- Oravisto KJ. Epidemiology of interstitial cystitis. Ann Chir Gynaecol Fenniae 1975;64:75-77
- Held PJ, Hanno PM, Wein AJ, et al. Epidemiology of interstitial cystitis. In Hanno PM, Stasking DR, Krane RJ, Wein AJ (Eds.) Interstitial Cystitis. London: Springer Verlag, 1990;29-48
- Ho N, Koziol J, Parsons CL. Epidemiology of Interstitial Cystitis, in G. Sant (Ed.), Interstitial Cystitis. Philadelphia: Lippincott-Raven Publishers, 1997; 9-15
- Domingue GJ, Ghoneim GM. Occult Infection in Interstitial Cystitis, in G. Sant (Ed.), Interstitial Cystitis. Philadelphia: Lippincott-Raven Publishers, 1997; 77-86
- Keay S, Schwalbe RS, Trifillis AL, et al. A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls. Urology 1995;45:223-229
- Domingue GJ, Ghoneim GM, Bost KL, et al. Dormant microbes in interstitial cystitis. J Urol 1995;153:1321-1326
- Duncan JL, Schaeffer, AJ. Do Infectious Agents Cause Interstitial Cystitis. Urology 1997;49:48-51
- Pontari, M. Interstitial Cystitis Update. Infect Urol 1997;10(3):75-79,80
- Ghoneim GM, El Leithy T, Domingue G. Antimicrobial treatment for interstitial cystitis: Preliminary report. NIDDK/ICA Scientific Workshop, October 5-6, 1995, San Diego, Calif. Abstract, p 56.
- Maskell, R. Broadening the concept of urinary tract infection. Br J Urology 1995; 76:2-8
- Durier, JL. The application of anti-anaerobic antibiotics to the treatment of female bladder dysfunctions. Neurourol Urodyn 1992;11:418
- Parsons, CL. The role of the glycosaminoglycan layer in bladder defense mechanisms and interstitial cystitis. Int Urogynecol J 1993;4:373-379
- Hurst RE, Roy JB, Parsons CL. The role of glycosaminoglycans in normal bladder physiology and the pathophysiology of interstitial cystitis, in G. Sant (Ed.), Interstitial Cystitis. Philadelphia: Lippincott-Raven Publishers, 1997; 93-100
- Holm-Bentzen M, Jacobsen F, et al. Painful bladder disease-clinical and pathoanatomical differences in 115 patients. J Urol 1990;143:278-281
- Johannson SL, Fall M. clinical features, and spectrum of light microscopic changes in interstitial cystitis. J Urol 1989;143:1118-1124
- Theoharides TC, Sant GR. Bladder mast cell activation in interstitial cystitis. Semin Urol 1991;9:74-87
- Theoharides TC, Sant GR, El-Mansoury M, et al. Activation of bladder mast cells in interstitial cystitis: A light and electron microscopic study. J Urol 1995;153:629-636
- Elbadawi, A. Interstitial Cystitis: A critique of current concepts with a new proposal for pathologic diagnosis and pathogenesis. Urology 1997;49(5a):14-40
- Keay S, Zhang CO, Kagen D, et al. Concentrations of specific epithelial growth factors in the urine of interstitial cystitis patients and controls. J Urol 1997;158(5):1983-8
- Keay S, Zhange CO, Trifillis A, et al. Decreased 3H-thymidine incorporation by human bladder epithelial cells following exposure to urine from interstitial cystitis patients. J Urol 1996;156(6):2073-8
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A note from ICN Founder Jill Osborne - The IC community of researchers, scientists, patient groups, clinicians, physical therapists are working so very hard to find answers for us. I want you to carry hope in your heart. These professionals are dedicated, skilled and, most of all, care about IC patients both near and far. Whether the cure for IC/PBS comes from a european, asian or USA based researcher is not important. What is important is that we all collaborate and work together to find the cure. As Margaret Meade once said "Never doubt the power of a small group of committed people to change the world for, indeed, it's the only thing that ever has." As an IC patient, you are our ambassador. It's vital that you treat your physicians with respect, that you prepare carefully for your appointments and, most of all, that you try various treatments until you have success. Don't you dare give up. If I can do, so can you!