You are here: IC Network > Patient Handbook > What is IC?
About Interstitial Cystitis
"I first had bladder symptoms when I was 13
years old and was very quickly diagnosed with urethral syndrome. After
three years, the symptoms gradually went away and I lived a normal life
as an athlete, student and young professional. My journey into the world
of IC began at the age of 32. One late winter night, I woke up with
intense frequency, urgency and, for the first time, pain. It took
another year before I received my first diagnosis of IC." - J.
Osborne
Introduction
New urology patients are often confused by the
various terms used to describe bladder conditions and symptoms, such as
urinary tract infection (UTI), bacterial cystitis, urethritis, urethral
syndrome, trigonitis, prostatitis, dysuria, nocturia, overactive bladder,
interstitial cystitis, painful bladder syndrome and
frequency-urgency-dysuria syndrome. This chapter discusses IC, some of the
common bladder diseases often confused with IC, its early history,
diagnostic criteria and possible causes.
Interstitial Cystitis
Interstitial cystitis is a chronic, and
often severe, inflammation and/or injury to the bladder wall. Primary symptoms are urinary frequency, urgency, and, for some,
severe lower abdominal or perineal pain. However, IC patients rarely test
positive for infection in standard urinalysis and urine cultures (1).
Unfortunately, there is no definitive diagnostic test for IC. A
diagnosis is usually based upon a patient's symptoms, a cystoscopic
examination of the bladder under anesthesia and exclusion of other bladder
diseases. During the cystoscopy urologists carefully examine the bladder
wall for signs of IC, including small petechial hemorrhages (aka
glomerulations or small wounds) and/or larger Hunner's Ulcers.
Ho, Koziol and Parsons (2) classify IC patients into two distinct
categories. The great majority of patients are diagnosed with "early
non-ulcerative" IC, as identified by the presence of glomerulations during
cystoscopy. An estimated 5% to 10% of IC patients are believed to have the
second, more severe, "classic ulcerative" IC, as demonstrated by the
presence of Hunner's Ulcers and glomerulations during cystoscopy. These
patients may also have reduced bladder capacities and stiffened bladder
walls.
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 Urethritis Urethral Syndrome Trigonitis Prostatitis Dysuria & Nocturia Overactive Bladder Syndrome & Urge
Incontinence Interstitial Cystitis, Painful Bladder Syndrome,
Freqency-Urgency-Dysuria Syndrome
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.
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.
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.
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."
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.
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.
Other Diseases of the Bladder
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 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 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).
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 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).
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 describes pain with urination.
Nocturia describes frequent urination during sleep or nighttime hours (7).
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 and frequency-urgency-dysuria syndrome, are used
interchangeably to describe urinary frequency, urgency and/or feelings of
pain or pressure around the bladder, pelvis and perineum. IC patients
usually have additional findings of small hemorrhages (called
glomerulations) or ulcers within the bladder. In addition, patients may
have a decreased bladder capacity and painful sexual intercourse. Women
may flare during their menstrual cycle. Men may have scrotal or penis pain
(9).
Is IC Progressive?
This is often the first question that an IC
patient asks. However, there is no easy answer. Hanno (3) states that IC
does not progress continuously but reaches its final stage rapidly and
then continues without significant change in symptomology. Parsons (1)
believes that patients diagnosed with infection, urethral syndrome and/or
IC may represent the same disease process, yet are caught in the early,
mid or later stages of the disease.
In our experience, many patients who struggle with symptoms are those who have not modified their diets to remove those foods and/or beverages that we know can badly irritate the bladder, such as coffees, teas, green teas, sodas, etc. Diet modification is the foundation for IC therapy and recovery. Learn more about diet.
The 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.
The 1800's: The Early Years
It appears that 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 - 1950: The Formative Years
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).
1951-1987: The Dark Years
From the 1950's to the 1980's, it
appears that IC research slowed as various elements 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 his own experience during his early
medical training (23).
1987 to Present: Years of Growth, Credibility and New
Breakthroughs
With encouragement from the Interstitial Cystitis
Association, 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 continue to
reveal new insight into the history and characteristics of IC.
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).
In 1998, 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 tens of thousands 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 Medline (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.
Diagnostic Testing
A diagnosis of interstitial cystitis based primarily on a patients symptoms, as well as the exclusion of other potential conditions which can mimic IC. Diagnostic methods have changed dramatically in the past five years with the addition of several new, less invasive tools, including the PUF Questionnaire and the Potassium Sensitivity Test. A diagnosis of IC is no longer based upon the NIDDK Diagnostic Criteria of IC, which had required a hydrodistention and cystoscopy, though research studies may still require that this test be performed.
The Epidemiology of IC
New epidemiology studies conducted in 2005 by Dr. Matt Rosenberg now suggest 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.
The Origins of IC
Researchers have yet to agree on a common cause for IC, however several research studies are currently exploring potential origins, including infection, epithelial permeability, mast cells and other theories. Please note that there is no consensus on one origin for IC. As such, many believe that IC is actually a syndrome, perhaps with a variety of different origins.
1. Infection
Given the similarity in symptoms between bacterial cystitis and interstitial cystitis, it is only natural that our thoughts would turn to infection as a source for our symptoms. In 1915, Hunner was the first to theorize that a bacterial infection as a cause of IC. Yet, decades later, IC patients still routinely test negative for infection in standard urinalysis. How then could an infection be present?It has been suggested that some patients may have infections of
"fastidious" bacteria in their bladders, such that the bacteria may adhere
to, or are imbedded in, the bladder wall. In these cases, urinalysis may
not demonstrate the presence of these bacteria.It is worth noting that no research studies have conclusively proven
that a single, or class of, bacteria is the cause of IC. Yet, studies
continue to reveal that low levels of bacteria have been found in the
urine of IC patients (34).
Neurogenic inflammation appears to be gaining respect among a subgroup
of IC researchers. Neurogenic inflammation implies that nerves themselves
can generate some degree of inflammation. As mentioned above, Elbadawi
believes that the mast cells may actually be triggered by some type of
nerve dysfunction (48). Autoimmunity and the consideration of IC as an
autoimmune disorder continue to be controversial and too complex to
discuss in this workbook. For additional information, we suggest that you
refer to Hanno (3).
(2) Epithelial Permeability-Leaks
C. Lowell Parsons (42-43), of
the University of California, San Diego, is at the forefront for research
of the GAG layer and epithelial permeability. He hypothesized that IC
patients may have a defect in the epithelial permeability barrier of the
bladder surface GAG layer, leading to irritative components of urine
penetrating into the more sensitive layers of the bladder wall. As such, a
great deal of research effort has been placed into the development of
protective bladder coatings, such as Elmiron® and Cystistat®, which would
coat the bladder and, ideally, reduce irritation.
(3) Mast Cells
There is evidence that mast cells are involved in
IC, although it may be in a secondary role rather than as a direct cause
of IC. Mast cells release histamine in a process called degranulation,
which can cause localized pain and irritation in tissues where the mast
cells are present. Bentzen et al. (44) discovered that patients with a
higher level of mast cells in their bladder tissues experienced more
bleeding and a reduced bladder capacity. Johannson and Fall's (45)
research demonstrated that mild IC patients did not have elevated mast
cell counts and that they appear to be increased only in patients with
classic IC. Using an electron microscope, Theoharides & Sant (46-47)
confirmed that the mast cells in IC patients are more likely to be
degranulated or activated than in other conditions, clearly demonstrating
local irritation of bladder tissues. Elbadawi (48) believes that mast
cells play an important role in his own proposed neuroinflammatory
reactions in IC. Research continues to evaluate the role of the mast cell
in IC.
(4) Other Causes
Urine abnormalities, perhaps the presence of an
irritant in the urine, offer yet another possible explanation of IC. Keay
et al. (49) assessed various urine growth factors and discovered that IC
patients had unusual variations in contrast to the normal population. In
another study, Keay et al. (50) may have identified a protein (the antiproliferative factor) found in IC
patients that may inhibit growth of the bladder epithelium. Both cases, as
well as additional studies, apparently add credibility and interest to
this line of research.
References
Due to the length of these files, we've had to assemble
all of the references on their own page. You can read them BY CLICKING
HERE!