Author: Jill Osborne, MA – ICN President & Founder – Revised: June 3, 2013 Created: 1995
What are the symptoms of interstitial cystitis?
Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as “An unpleasant sensation (pain, pressure, 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.” (1)
Pain is the hallmark symptom, particularly as the bladder fills with urine. Pain can also occur in the urethra, vulva, vagina, testicles, rectum and/or throughout the pelvis. Urinary frequency is found in 92% of patients with IC/BPS. Urgency is also common. IC patients struggling with urgency often rush to the restroom to avoid and/or reduce pain. In contrast, overactive bladder (OAB) patients struggling with urgency run to the restroom not to reduce discomfort but to avoid leakage and/or becoming incontinent. It’s not unusual for patients to struggle with sleep due to a constant urge to urinate (nocturia). Intimacy may also provoke pain and discomfort (dyspareunia).
Most IC bladders look normal when a simple cystoscopy is performed. However, when closely examined during a hydrodistention with cystoscopy, physicians often find small, bleeding wounds, also known as petechial hemorrhages or glomerulations. (AUA Video of Glomerulations) About five to ten percent of patients may have larger, more painful wounds known as Hunner’s Lesions. (AUA Video of Hunner’s Ulcers)
What are the causes of interstitial cystitis?
Bladder Wall Trauma – The cause of IC remains unclear. Some cases of IC/BPS begin with an identifiable trauma or injury to the bladder, such as a bladder infection. In one study, a proven UTI was initially identified in 18 to 36% of women though subsequent urine cultures are negative. (2) Chemical exposure, such as from ketamine use (3) or chemotherapy, can also result in bladder wall injury. Some patients believe that their excessive consumption of sodas (diet & regular sodas), coffees and/or alcohol is the cause of their IC.
Genetics – A genetic connection has been observed in some patients who have first degree relatives also diagnosed with IC.(4)
A Systemic Disorder – For patients struggling with IC and other pain syndromes (irritable bowel syndrome (IBS), vulvodynia, prostatitis, chronic fatigue and anxiety disorder), a systemic condition may underly their health problems. It has been suggested that “IC/BPS is a member of a family of hypersensitivity disorders which affects the bladder and other somatic/visceral organs.” (1)
Pelvic Organ “Cross Talk” – Pelvic nerve pathways can also contribute to bladder irritation. Research studies have demonstrated that 40 to 50% of IBS patients have symptoms of IC while up to 52% of IC patients also have symptoms consistent with IBS. (5) Bowel-bladder nerve “cross sensitization” was proven by Pezzone, who demonstrated that direct bowel irritation caused bladder irritation and vice versa. When long-term chronic bowel irritation occurred, some of the familiar symptoms of IC also occurred, such as increased frequency and decreased urinary volume.(6) He determined that the outgoing (afferent) nerves of the bladder and the bowel combine at the dorsal root ganglia, providing ample opportunity for “cross talk.” Dr. Pezzone believes that chronic pelvic pain can develop after an acute injury or chronic irritation to one of the pelvic organs (bladder, bowel, reproductive), nerves or perhaps even the skin. If the irritation/inflammation persists, the other organs and muscles then become involved through this “cross talk” sensitization pathway. Researchers and clinicians agree that treatment should be focused on calming and soothing every condition that is producing pain and/or discomfort.
Pelvic Floor Dysfunction – The health of the pelvic floor muscles is also a factor. Some IC patients report that their symptoms began immediately after pelvic floor muscle trauma, including: childbirth, athletic injury, or riding a bicycle / motorcycle. For years, urologists have described finding tight muscles during examinations of IC patients. Now known as pelvic floor dysfunction, these tight muscles can cause a “burning sensation” in the pelvis and make urination, defecation and intimacy difficult and painful. PFD patients may not experience pain as the bladder fills with urine. Their discomfort is often more chronic, with duller levels of consistent pain that can worsen with sitting.
AntiProliferative Factor (APF) – One of the biggest research breakthroughs IC/BPS, the antiproliferative factor (APF). It appears to block the normal growth of the cells that line the inside wall of the bladder.(6) APF may be part of an inflammatory reaction. Researchers are developing a diagnostic urine test using APF as a marker.
How is a diagnosis of IC made?
In 2011, the American Urological Association (AUA) issued Guidelines for the Diagnosis and Treatment of IC/BPS (1). These guidelines suggest that the physician first perform a thorough history and physical examination of the patient. Symptoms should be present at least six weeks in the absence of infection and positive urine cultures. An examination of the pelvis and pelvic floor muscles should be completed to look for areas of tenderness and/or painful trigger points. Several conditions should be ruled out, including bladder infection, bladder stones, vaginitis, prostatitis and, in patients with a history of smoking, bladder cancer.
In a dramatic change, the AUA does NOT recommend additional invasive testing, such as cystoscopy, urodynamics and hydrodistention, UNLESS the diagnosis is in doubt.(1) Rather, they encourage the use of more simple, benign methods. Parsons, for example, developed a brief diagnostic survey, the PUF Questionnaire that is used in many clinics around the world and is particularly effective in discriminating between bladder vs. reproductive tract patient. (7) A simple “anesthetic challenge,” the instillation of a numbing agent into the bladder, can also quickly determine if the bladder wall is the source of the pain and/or discomfort.
If additional testing is required, a cystoscopy is usually the first suggested. A minor procedure performed in a doctors office, it allows the physician to look at the bladder to rule out other conditions that can mimic IC symptoms, such as bladder cancer or stones. In general, most IC patients have a normal cystoscopy because it does not allow for a close examination of the bladder wall.
Hydrodistention with cystoscopy, a more difficult procedure requiring anesthesia and outpatient care, may reveal the presence of glomerulations and Hunner’s ulcers on the bladder wall. Please note that the AUA discourages “high pressure, long duration” hydrodistentions in favor of “low pressure, short duration” procedures which can greatly minimize the risk of bladder trauma or rupture.(1)
A finding of glomerulations are suggestive of, but not specific to, a diagnosis of IC because they can occur in other bladder conditions as well. Hunner’s ulcers, on the otherhand, confirm a diagnosis of IC. In an acute phase, these ulcers appear “as an inflamed, friable, denuded area.”(1) In a chronic phase, they are identified as a “blanched, non-bleeding area.”(1)
The ICN supports the use of the UPOINT System for the Clinical Phenotyping of Chronic Pelvic Pain developed by Nickel, Shoskes and Rackley. (8) When released in 2009, it revolutionized the diagnosis of pelvic pain by evaluating each patient based upon their own unique symptoms along six parameters, including bladder symptoms, organ specific findings (i.e. ulcers) , the presence of IBS & other related conditions, the health of the pelvic floor muscles, the presence of anxiety / depression and/or the presence of any confirmed infection. This “whole body” approach has gained substantial momentum since it was released and phenotyping is now a hot topic in research circles. At AUA 2013, two courses were taught on pelvic pain that encouraged physicians to assess and treat every condition contributing to chronic pain.
Prevalence and Epidemiology
Once considered a rare condition, IC/BPS affects millions of men and women around the world. In the USA alone, an estimated 3.2 to 7.9 million women (2.7 to 6.5% of women) (9) and 1 to 4 million men (10) have symptoms. Researchers believe that many more men may have been incorrectly diagnosed with chronic prostatitis, thus making its incidence much higher. Researchers have uncovered a substantial overlap of IC with other painful disorders, such as IBS, vulvodynia, chronic fatigue, TMJ and others. An estimated 79% of IC patients may struggle with IBS. (11) Studies by Oravisto (12), Held (13), Ho (14), Watkins (15) and Clemens (16) 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.
- 52% of women with IC reported panic attacks and over 30% reported depression.
- IC patients pay twice as much out of pocket for direct medical care when compared with someone without the condition.
History & Names Associated with Interstitial Cystitis
For more than a century, IC was thought to be a rare, bladder specific disease that affected only women. Through slow, steady research and several false starts, IC is now considered a pelvic pain syndrome strongly linked to the bladder, the pelvic floor muscles, the bowel, the reproductive tract and/or the nervous system. Let’s take a look at the history.
In 1836, Dr. Joseph Parrish, a surgeon in Philadelphia, was the first to document cases of severe bladder dysfunction which he labeled as “tic doloureux of the bladder.” (17) Fifty years later, Skene coined the term “interstitial cystitis” to describe what he thought was inflammation of the bladder wall that had destroyed the mucus membrane.(18) Technology arrived in the early 1900‘s with the development of the first cystoscope, an instrument that allowed physicians to look inside the bladder. In 1918, Guy Hunner MD reported that he had observed red, bleeding areas in the bladder wall of patients that he believed were ulcers, thus coining the term “Hunner’s Ulcers.” (19) For the following sixty years, urologists believed that all IC bladders were ulcerated, a finding which was later disproven. Only a small percentage of patients have these more intense areas of inflammation, now also known as “Hunner’s lesions.” (20)
In 1944, Cristol published the first study of men with IC, documenting 78 cases. (21) In 1949, Hand was the first to provide an in-depth description of the bladder wall in patients with IC symptoms. He found “small, discrete submucosal hemorrhages… dot-like bleeding points” in bladders.(22) These later became known as “glomerulations.” (23) In 1953, the first paper was published showing that children could have IC. (24)
IC patients experienced a profound setback in 1958 when three clinicians 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.” (25) This led to the misperception that IC was a mental disorder that, sadly, was taught in medical schools through the 1980‘s. Some patients still face physicians who tell them that IC is “all in your head” despite millions of dollars in research proving that IC is a serious and often disabling pelvic disorder.
In the late 1970‘s, a paradigm shift occurred. Rather than focusing on ulcers, Messing and Stamey proposed that bladder symptoms AND the presence of glomerulations on the bladder wall were the hallmarks of IC. (26) They also suggested that a diagnosis should be made through the exclusion of other diseases.
In 1987, the US National Institutes of Health (NIH/NIDDK) created their first working definition of IC, requiring that patients have either glomerulations or ulcers on the bladder along with symptoms of bladder pain or urinary urgency.(27) These very strict criteria were meant only for use in research studies yet became a defacto definition of IC in the USA. They excluded, for example, patients who had symptoms less than nine months, patients who urinated less than 8 times per day and patients under the age of 18. It was later determined that 60% of the patients who had IC wouldn’t qualify using these criteria. (28) As a result, the research community began focusing more on symptoms rather than specific bladder wall findings.
In 2002, the International Continence Society triggered fierce debate by selecting the first new name in eighty years, “painful bladder syndrome (PBS).” (29) Many felt that term IC did not accurately describe the condition because IC does not involve the interstitial layers of the bladder wall. Some patients have no visible bladder wall damage. In 2003, the international IC community agreed and suggested “interstitial cystitis / painful bladder syndrome (IC/PBS). (30) In 2004, researchers from several nations voted to reverse the names, placing painful bladder syndrome first, (PBS/IC). (31)
In 2006, the European ESSIC Society proposed yet another radical change. They began using the term “bladder pain syndrome (BPS)” to conform with the taxonomy of other similar pain syndromes and also applied a new rating scale based upon the results of a hydrodistention and tissue biopsy. Grade 1 patients have a normal bladder, Grade 2 patients have glomerulations and Grade 3 patients have Hunner’s lesions. If a biopsy from the bladder was normal, the grade would also include a designation of A. If the biopsy was inconclusive, it would be receive a B score. If the biopsy showed signs of inflammation, mastocystosis, granulation and/or fibrosis, it would receive a score of C. Thus, the mildest patients would receive a score of BPS 1A, and the most severe BPS 3C. (32)
Physicians in Japan, Taiwan and Korea took a different approach. They chose to use the terms “hypersensitive bladder syndrome (HBS)” and interstitial cystitis (IC) in their national guidelines which are still in use today. (33)
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 its related conditions (i.e. irritable bowel syndrome, etc.) New discussions in the IC research movement now focus on the concept of neuroinflammation and neurosensitization. It may be that once our body has sustained an injury, it may create a cascade like effect of neurosensitization in nearby organs.
In 2011, the American Urological Association chose to use the name “Interstitial Cystitis/ Bladder Pain Syndrome (IC/BPS),” due, in great part, to concerns raised about health and disability insurance plans that had already recognized IC as a condition to be covered. The AUA diagnostic criteria focuses almost entirely on symptoms. (34)
As if that weren’t confusing enough, because IC/BPS often co-exists with and may be related to prostatitis, some researchers (including the US National Institutes of Health) classify IC and chronic prostatitis as a “urologic chronic pelvic pain syndrome (UCPPS).” (35)
Others include IC, IBS, endometriosis, pelvic floor dysfunction, vulvodynia and prostatodynia collectively in the term “chronic pelvic pain syndrome (CPPS).” This was reflected at the 2013 annual meeting of the AUA, where two new courses were offered that trained urologists in the diagnosis of chronic pelvic pain. A very strong emphasis was placed on the examination of the pelvic floor muscles and the use of physical therapy as an important treatment modality. The International Adhesions Society has also coined the term “complex abdominal and pelvic pain syndrome (CAPPS).” (36)
- Hanno PM, et al. AUA Guidelines for the diagnosis and treatment of IC/BPS J Urol. 2011;185(6):2162-2170
- Porru D, Politano R, Gerardini M et al: Different clinical presentation of interstitial cystitis syndrome. Int Urogynecol J Pelvic Floor Dysfunct 2004; 15:198.
- Tsai TH et al. Ketamine-associated bladder dysfunction. Int J Urol. 2009 Oct;16(10):826-9. Epub 2009 Jul 29.
- Warren JW, et al.Prevalence of interstitial cystitis in first-degree relatives of patients with interstitial cystitis. Urology. 2004 Jan;63(1):17-21.
- Pezzone M. Chronic Pelvic Pain and the Overlap of Chronic Pelvic Pain Disorders. International Foundation for Functional Gastrointestinal Disorders. 2007
- Keay S, Warren JW. A hypothesis for the etiology of interstitial cystitis based upon inhibition of bladder epithelial repair. Med Hypotheses. 1998 Jul;51(1):79-83.
- Parsons CL, et al. Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology. 2002 Oct;60(4):573-8.
- Nickel JC, Shoskes D. Phenotypic approach to the management of chronic prostatitis/chronic pelvic pain syndrome. Curr Urol Rep. 2009 Jul;10(4):307-12.
- Berry, et al. Prevalence of Symptoms of Bladder Pain Syndrome in Adult Females in the US. The Journal of Urology, v. 186, no. 2, Aug. 2011, p. 540-544
- Suskind, A., et al. The Prevalence and Overlap of IC/BPS and CP/CPOS in Men. The Journal of Urology, v. 189, no. 1, Jan. 2013, p. 141-145
- Bullones Rodriguez, MA, et al. Evidence for overlap between urological and nonurological unexplained clinical conditions. J Urol. 2013 Jan;189(1 Suppl):S66-74.
- 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
- Watkins K, et al. Depressive Disorders and Panic Attacks in Women with Bladder Pain Syndrome/Interstitial Cystitis: A Population-Based Sample. General Hospital Psychiatry, v. 33, no. 2, Mar.-Apr. 2011, p. 143-149
- Clemens JQ, et al. Urologic Diseases In America / Edited By Litwin and Saigal (Washington, D.C. : US Department of Health and Human Services, Public Health, NIH, NIDDK, 2007), Chapter 4, p. 125-154, NIH Pub. no. 07-5512
- Parrish J. Tic doloureux of the urinary bladder. Practical observations on strangulated hermia and some of the diseases of the urinary organs. Philadelphia: Key and Biddle: 1836. p. 309-13
- Skene AJC. Diseases of the bladder and urethra in women. New York: William Wood: 1887
- Hunner GL. A rare type of bladder ulcer in women; report of cases. JAMA. 1918; 70(4):203-212
- van de Merwe J, et al. Diagnostic critera, classification and nomenclature for PBS/IC: an ESSIC proposal. Eur. Urol. 2008;53:60-7
- Cristol DS, Greene LF, Thompson GJ. Interstitial cystitis of men, a review of seventy-eight cases. JAMA 1944;126:825-828
- Hand JR. Interstitial cystitis: report of 223 cases (204 women and 19 men) J. Urol. 1949;61:291-310
- Walsh A. Interstitial cystitis, In: Harrison JH, et al. editors Campbell’s Urology. 4th ed. WB Saunders; 1978. p. 693-707.
- 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
- Messing EM, Stamey TA. Interstitial cystitis, early diagnosis, pathology and treatment. Urology 1978;12:381-392
- Gillenwater JY, et al. Summary of the NIADDK Diseases Workshop on Interstitial Cystitis, NIH. J UROL. 1988;140(1):203-206
- Hanno P, et al. The diagnosis of IC revisited: lessons learned from the NIH IC Database Study. J Urol. 1999;161(2):553-7
- Abrams P, et al. The standardisation of termination of lower urinary tract function: report from the standardisation subcommittee of the ICS. Neurouol Urodyn. 2002;21:167-78
- Ueda T, et al. Interstitial cystitis and frequency-urgency syndrome (OAB syndrome). Int J Urol2003;10(Suppl):S39-48
- Hanno P, et al. International consultation on IC – Rome. September 2004/Forging an international consensus: progress in PBS/IC. Int Urogynecol J Pelvic Floor Dysfunct. 2005;16 Suppl 1:S2-34
- van de Merwe J, et al. Diagnostic criteria, classification and nomenclature for PBS/IC: an ESSIC proposal. Eur Urol. 2008;53(1):60-7
- Homma Y, et al. Clinical guidelines for the IC and HBS. Int. J Urol. 2009;16(7):597-615
- Hanno P, et al. AUA guidelines for the diagnosis and treatment of IC/BPS. J Urol. 2011;185(6):2162-70
- Defining the Urologic Chronic Pelvic Pain Syndromes: A New Beginning – NIDDK conference, June 16-17, Bethesda MD 2008
- Echenberg R. IC’s Role in CAPPS. BrightTalk Webinar April 4, 2013 – https://www.brighttalk.com/community/medical-research/webcast/9263/68467