Interstitial cystitis (IC) is a chronic, inflammatory disorder of the urinary bladder characterized by variable degrees of urinary urgency, frequency and bladder pain. IC is a neglected chronic debilitating disease. Though first recognized as a pathological entity in 1887, it remained a largely unaccepted disease for 100 years. Physicians did not believe that such a condition existed and patients were consequently shunted from one consultant to another. The biggest problem with disease is that although the patient suffers severely from it, there are no symptoms, signs or investigations that are diagnostic for IC. To complicate the matter still further, there is no clue to its etiology, its pathology is unknown and no treatment has been found to cure the disease. IC has baffled the scientists and every effort to find a solution has only complicated our understanding of it.
In 1987, the NIDDK formed a consensus definition of IC. The criteria were revised in 1988. The NIDDK established guidelines specifically for research purposes and these guidelines have remained the de facto definition for interstitial cystitis to the present day. The aim of drawing up these guidelines was to have an international standard to enable a comparison of patients in different geographical areas. Today, some 17 years after these research guidelines were first drawn up, the original aim has not been fulfilled. The guidelines has not served its purpose since it was basically a concept of exclusions and not based on evidence. Very few patients with interstitial cystitis fulfilled the criteria and for every patient diagnosed with IC, many remained undiagnosed. Hanno et al. proved this point by analyzing patients who were enrolled in the multi-centre Interstitial Cystitis database (ICDB) study.
With an increase in knowledge about the disease and the endeavors of patient support organizations such as the ICA (Interstitial Cystitis Association) and IICPN (International Interstitial Cystitis Patient Network), by 2002 it became evident that there is an urgent need to define the disease. It is also clear now that the 1987 NIH criteria need to be changed since accepting them will lead to under-diagnosis. Awareness of the disease has increased all over the world and it is now clear that the disease which was initially considered as prevalent in western world only is now a global disease.
The year 2003 was a milestone in the history of IC as two very important workshop were organized aimed at reaching some consensus on various aspects of IC. The first meeting was held in Japan in March 2003 and was attended by 25 international urologist and a similar number of Japanese urologists. This meeting was an attempt to gather opinion of urologists from all over the world on different aspects of IC. It set the ball rolling and clearly demonstrated that it is very difficult to define the disease and establish criteria. Another workshop was held in Copenhagen in May 2003 and attended by 22 researchers from European countries and one from India. At this European meeting no attempt was made to define the disease, but rather to reach consensus regarding history taking, physical examination, investigations, cystoscopy finding and biopsy reading. It was agreed that an attempt should be made to evaluate the IC patients in the same standard way and this workshop was a big success. The October 2003 IC International Symphosium held in Washington also discussed definition and criteria in detail.
Interstitial cystitis is one of the most controversial diseases around. Physician do not even agree whether it actually exist, what they may agree on is that it is difficult to diagnose and if diagnosed that it is difficult to prove and, if proven, that it is difficult to treat. The disease is unique in the sense that although IC patients are numerous there is no internationally accepted definition and standard criteria do not exist. In 1987, NIDDK criteria were issued for research purpose and they served as a de facto definition since no clinical guidelines were available. It soon became apparent, however, that these guidelines were inadequate and that they conceal more than they reveal. It has been estimated that if the guidelines are strictly followed, around 60% of patients will fail to be diagnosed.
In the ICDB study it was demonstrated that the disease is under-diagnosed. It is generally believed that IC should be suspected in bacteria cystitis patients who do not respond to antibiotic therapy. Patient with OAB who do not respond to anticholinergics should also be suspected of having IC. Furthermore, there is every chance that patients with chronic abacterial prostatits may also be suffering from IC. A cystoscopic appearance of IC was found in 10% of men with symptoms of non bacterial prostatits and prostatodynia when scopes under anaesthesia. In 2004 there is a substantial difference of opinion concerning the concept that IC is the same as abacterial prostatitis, although there is growing evidence favoring both as the same disease.
Symptoms
The symptoms of IC patients are by no means uniform. These symptoms are related to urological, gynecological, gastrointestinal and pelvic floor organs. They may originate from the bladder, urethra, prostate, vagina, uterus, rectum and pelvic floor muscles. Furthermore, in some patients a systemic or generalized disease may affect any part of the body, including the symptoms of IC in the bladder. Studies have been carried out into the possible relationship between IC and systemic autommune diseases such as SLE (“Lupus cystitis”), Sjogren’s syndrome etc.
Some IC patients have symptoms of pain, urgency and frequency, some may experience pain as their main symptom with minimum frequency and urgency, while other patients may complain of only frequency and urgency. Absence of nocturia has been considered to be an exclusion criterium in the NIDDK guidelines, but many IC patients may in fact have no nocturia. In other words, patients can have a variety of different symptom combinations. In 2004 it is now becoming clear that pain is most important symptom of IC. Nocturia is not essential for the diagnosis of IC. It is also believed that patients with normal frequency but with pain and urgency can also have IC. This is indicates that IC patients can present with a wide range of different permutations and combinations of symptoms.
Different patients define the sensation of pain differently. Some of the patients will talk of pain, some will speak of burning and some will say the feel discomfort. These symptoms may or may not be relieved by micturition. In 2004 the researchers feel that IC should be suspected in all those patients who come with urinary discomfort, supra pubic pressure or heaviness or burning micturition with or without pain. It is very disappointing to note that the NIDDK criteria do not make any reference to the different types of pain or its severity.
Taking a look at the severity of symptoms and the suffering of the patients, it is not understood why we should wait for 9-12 months to diagnose IC. The consensus in 2004 is 3 months. IC should be suspected in a patient if the symptoms are present for 3 months. This very significant point should be borne in mind when the criteria for the disease are drawn up in the future. This will go a long way towards decreasing the suffering of IC patients.
Investigations
Any article written on IC will list numerous investigations, but none will mention the minimum investigations needed or their significance. IC is currently diagnosed on the basis of clinical features. The recommended tests include urinalysis, urine culture, cytology, uridynamics and Cystoscopy under anesthesia with bladder distension. In 2004 there is consensus about the need for urine analysis, urine culture and a voiding diary. It is believed that urodynamics do not serve any fruitful purpose and can better be omitted. Cystoscopy under anesthesia is the most controversial investigation as there are some who believe it to be most who do not think it necessary at all and feel that a diagnostic office cystoscopy can be performed under local anesthesia to rule out malignancy in patients who have haematuria. It is also clear whether investigations such as X-ray KUB and USG KUB, urinary cytology should be performed or not as these tests rule out other disease.
Glomerulations / Hunners Ulcer Confusing Terminology
Glomerulations have long been considered the hallmark of IC. If certain conditions are excludes, the presence of glomerulations will point to a diagnosis of IC. However, many IC patients will not have glomerulations on cystoscopy and hydrodistension. Glomerulations have also been found in normal women undergoing tubal ligation. Although the term glomerulations is associated with IC, there is no correlation between them and the degree of histological inflammation and symptoms. In 2004, there is increasing consensus that the term Hunner’s ulcer and glomerulations should be dropped as they create more confusion. At the Copenhagen European workshop, these two terms have been omitted from the description of the cystoscopic findings.
Copenhagen Cystoscopic classification of bladder
mucosa (May 2003)
Grade 0 = normal mucosa
Grade I = petechiae in at least two quadrants
Grade II = large submucosal bleeding
Grade III = diffuse global mucosal bleeding
Grade IV = mucosal disruption, with or without bleeding/oedema
Disease underdiagnosed:
As the disease under-diagnosed, there is a need to change and expand the definition of IC. Others have also raised similar concerns. It is believed that until the cause(s) of and the risk factors for IC are known, a more inclusive definition of this symptom complex may be appropriate to allow a more accurate assessment of its prevalence in the general population. IC is grossly under-diagnosed in Europe because outdated criteria are applied for the diagnosis.
Is IC limited to the bladder?
It is difficult to believe that we are dealing with a disease where we are not sure of the organ where the symptoms originate. Nor are we confident that IC is a disease or whether it may be a syndrome. Even in 2004 it is not clear if the disease is limited to bladder only or involves other pelvic organs.
Change of Nomenclature : IC / CPPS
At a recent of BAUS (2000) it was proposed that the term “painful bladder syndrome” might be more appropriate. But again there are conflicting views on this issue too. Painful bladder syndrome may be a different entity to IC or it may be the same entity but with different grade of severity. The pain may stem from the bladder or from the different organs of the pelvis. In some patients, the pain is mediated by more centralized pain mechanisms in the spinal cord. In such patients the entire pelvis is painful and the symptoms worsen with urination and sexual intercourse. It is difficult to determine whether the pain is coming from bladder or not, as even removal of the bladder in some IC patients failed to lead to resolution of pain. Some IC patients appear to present with more than one pain syndrome in the urogenital region. Some scientists do not want to change the name of the diseases as the term interstitial cystitis has become very well-known. The terminology is a misnomer as it denotes inflammation which may or may not be present in a case of IC. IC is also considered to be part of a CHRONIC PELVIC PAIN SYNDROME and it is possible that IC may be known by the terminology IC/CPPS in future. In Washington people were in favour of IC/PBS terminology. The final chapter in nomenclature has not been written yet.
Subtype of IC
Though the disease has not been defined, it has two subtypes: ulcerative (Hunner’s ulcer) and non-ulcerative types. Ulcerative or classic IC is considered to be a rare type accounting for 5-10% of cases. It is claimed that the two subtypes differ in clinical presentation, age distribution, histopathological and immunological findings and response to treatment. In 2004 there is concern about the terminology Hunner’s ulcer. Scientists are of the opinion that this terminology should be scrapped. There are some researchers who believe in Hunner’s ulcers and some who swear that they have never seen Hunner’s ulcers in a single patient. The terms Hunner’s ulcer and glomerulations have not been used in the Copenhagen cystoscopic classification. This also raises a question about the existence of two subtypes of the disease.
Potassium sensitivity test
The potassium sensitivity test was introduced in 1994. This test has been shown to be positive in 75% of patients with IC and is also positive in patients with detrusor instability, radiation cystitis and bacterial cystitis. The potassium sensitivity test is not very popular. In 2004 the consensus is that it can be included as an optional test.
IC in children
Patients under the age of 18 years were automatic exclusion in the 1987 NIDDK research criteria. The diagnosis of IC in children is controversial. 25% of IC patients report that they had chronic urinary tract problems in childhood. Children do indeed present with dysfunctional voiding. There is no theoretical reason why IC cannot exist in children. In 2004 it is agreed that IC can present in children and exclusion criteria based on age dose not hold true.
In 2004 author’s criteria for diagnosis of IC.
Patients presenting with pain, frequency, urgency in various permutations and combinations.
- Nocturia may or may not be present.
- These symptoms are present for at least 3 months.
- X-RAY KUB, USG (KUB) are normal and urine culture is negative.
- Under anaesthesia, cystoscopy finding ranging from GRADE 0 TO GRADE 4 (COPENHAGEN CLASSIFICATION).
- No disease identified on bladder biopsy (i.e carcinoma in situ, tuberculosis).
- Diagnosis of IC should also be entertained in a patient who has culture positive urine but in whom the symptoms do not disappear after adequate treatment with a suitable antibiotic.
Conclusion
In 2004 there is consensus that a big change is needed in the IC world. There is a need to draw up a definition and establish the criteria for the disease. It is also believed that the new definition and criteria should be evidence-based and should not be only opinion-based. All the researchers agree that it is very difficult task but that a start has to be made. 2003 was really a landmark in the history of IC. Until the final diagnostic criteria are established, there is a need to work together. There is a need to follow a common algorithm so that a large amount of data can be collected and compared. There should be a working algorithm for history taking, physical examination, investigations cystoscopy, biopsy and treatment. We should also establish an INDIAN ALGORITHM for the disease and review it periodically.
