Int. Meeting to Assess Areas of Consensus, Disagreement Regarding Interstitial Cystitis, Bladder Pain Syndrome

Newswise — Over the last 6 years there have been ongoing efforts around the world to standardize nomenclature, definition, and evaluation of interstitial cystitis/bladder pain syndrome/painful bladder syndrome. The convergence this year of several new projects stimulated an effort to bring together thought leaders from around the world to give a snapshot of current thinking with regard to this disorder. The Society for Urodynamics and Female Urology brought together thought leaders* from Europe, Asia, and the United States to Miami on February 27th, and a broad, structured discussion ensued. What has become a very political question of nomenclature was intentionally not addressed in this meeting.

National Institutes of Health Perspective

Drs Leroy Nyberg and John Kusek from the National Institute of Diabetes, Digestive, and Kidney Disorders described current NIDDK efforts and their rationale. Published studies now demonstrate that the "phenotype" of the person with IC is still cloudy and needs to redefined. Questions such as: what is the relationship of glomerulations to IC; can specific biomarkers be identified and what do they mean for IC; what factors are in common in persons with IC and other co-morbid conditions such as irritable bowel syndrome, Fibromyalgia, etc,; what do biopsies contribute to the understanding of IC; and are there differences between persons in early onset of IC and long-term IC. The NIDDK plans to address those issues and others in upcoming workshops with an ultimate goal of establishing a revised, evidenced-based research definition of IC.

The NIDDK released a funding solicitation in the fall of 2007 to establish a multi-disciplinary approach to the study of chronic pelvic pain (MAPP), with a primary focus on IC/PBS and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) " the two most common urologic pelvic pain syndromes in the United States. It is envisioned that research conducted by the MAPP Research Network will be multi-disciplinary, highly collaborative and focus on basic, translational, and clinical aspects of both IC/PBS and CP/CPPS. The ultimate goal of this effort will be to increase our understanding of the fundamental pathophysiology, biologic and behavioral risk factors, natural history, and genetics of IC/PBS and CP/CPPS, thus providing a knowledge base for the future development of effective prevention and treatment strategies. A unique aspect of this Network is the identification and characterization of pathological and physiological associations between IC/PBS and CP/CPPS and selected co-morbid illnesses including irritable bowel syndrome, chronic fatigue syndrome, fibromylagia, headache, and vulvodynia.

The Perception of Pain

Drs. Mauro Cervigni from Rome, Alex Lin from Taipei, Tomohiro Ueda from Kyoto, and Quentin Clemens from Ann Arbor discussed pain. European perceptions are largely guided by the definitions and taxonomy established by the International Continence Society (ICS), the International Association for the Study of Pain (IASP), European Association of Urology (EAU), and the European Society for the Study of Interstitial Cystitis (ESSIC). Bladder Pain Syndrome / Interstitial Cystitis (BPS/IC) is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder accompanied by at least on other urinary symptom such as persistent urge to void or urinary frequency.

In Taiwan, pain is not a perquisite criterion for diagnosing IC. Glomerulations or an ulceration on cystoscopy in conjunction with urgency make the diagnosis even if there is no complaint of pain. Japanese patients often do not recognize the sensations of pressure and discomfort as pain, and that is one of the reasons that the diagnosis has not been made in Japan as often as in Western countries.

Clemens pointed out that pain is notoriously difficult to measure. Perceptions of pain may be influenced by situational, emotional, and cultural factors. Work must be done to identify the types of descriptors most relevant to the condition under study. For example, some IC/BPS patients may experience their symptoms as a sensation of burning, pressure or discomfort in the pelvic region, rather than pain. Epidemiologic studies suggest there are additional men and women with IC/BPS symptoms who have not been diagnosed, or who have not sought care for their symptoms. The pain characteristics may be different in these individuals than those seen in physician offices. It needs to be determined if we should attempt to include or acknowledge these 'nonpatients' in a definition of IC/BPS.

Perception of Frequency and Urgency

Jane Meijlink from the Netherlands expressed the frustration of patients. Bearing in mind that some patients may express little or no pain but still have high levels of frequency, it may be deduced that the driving factor for urge/urgency/frequency must be something more than pain alone. Urgency has only become a controversial topic in relation to PBS/IC in recent years, largely due to ICS terminology and definition issues. Previously it was taken for granted that IC patients had a problem with an urgent need to find a toilet, hence the "Can't Wait" toilet cards issued by patient organizations to their members.

Urgency, she went on, in PBS/IC is an urgent or pressing need to find a toilet due to increasing pain, discomfort, or urge sensation that becomes impossible to tolerate any longer, and may in some patients be accompanied by an increasing feeling of malaise and/or nausea. Some patients find that having to postpone urination leads to retention or difficulty in getting the urine flow started.

Dr. Tomoe noted that in Japan, urgency is commonly used to describe the overactive bladder, as per ICS definitions. "It might be better to add the phrase "fear of leakage" after "which is difficult to defer" in the ICS definition of urgency. In most bladder pain syndrome (BPS)/IC, incontinence is uncommon and the patients have no fear of leakage." Regarding " frequency" , when OAB patients drink more, urinary frequency increases in proportion to the urine volume and urgency occurs with high frequency, sometimes with urgency urinary incontinence. On the other hand in BPS/IC, as the irritability to the bladder decreases by urinary dilution, the sensation of discomfort or pain tends to be softened and the patients urinate with ease, so urinary frequency is not always in proportion to the urine volume.

Similar thoughts came from Dr. J.G. Lee of Korea. Both urologists felt that the urgency definition of the International Continence Society was unclear and served to confuse the overactive bladder and BPS/IC diagnosis.

Dr. Whitmore from the United States made several suggestions. Voiding diaries and urodynamic studies recordings of cystometric bladder sensation might include pain/pressure/discomfort as a parameter for bladder filling. An evaluation of sensory urgency and urethral instability may warrant re-investigation. Updated technology for quantitative sensory threshold testing may be useful in further defining filling bladder sensations. Education to providers on questioning regarding urgency/urge needs to be updated. OAB dry patients should be followed over time to see if they develop urgency urinary incontinence or IC/PBS. Standardized testing of pelvic floor muscles will aid in distinguishing low tone from high tone pelvic floor muscle dysfunction, which may increase our understanding of the bladder response to pelvic floor muscle dysfunction. A suggested list of validated questionnaires should be provided to all patients with frequency and urgency/urge to aid in distinguishing between OAB and IC/PBS with longitudinal follow-up.

Dr. Magnus Fall of Sweden presented the European view in this way: Pain and urinary frequency are the cardinal symptoms, and are typically very marked. There is always nocturia. The character of pain is the key to disease. Pain is typically related to the degree of bladder filling, increasing with increasing bladder content, located suprapubically, sometimes radiating to the groins, vagina, rectum or sacrum, and is relieved by voiding but soon returns. Symptoms are not always typical and do not tell too much of aetiology. That was the reason of proposing a classification system aimed at replacing the old-fashioned terminology based on spurious assumptions of cause, as in the 2004 EAU guidelines on chronic pelvic pain and brought further by the ESSIC proposals. This was to make clear that where the pain is perceived one would not always find pathology. The definitions were based on the terminology report by the International Continence Society and used the axial structure of the International Association for the Study of Pain classification49. Pain syndrome terms were introduced to emphasise that multiple mechanisms may be involved, both physical and psychological. The challenge is to identify (when possible) well-defined entities with discriminative symptoms, founded on robust diagnostic signs.

Overactive Bladder, Urgency Frequency Syndrome and the Relationship to IC/BPS

Dr. Dmochowski from the United States went into the complexity involved in this difficult topic. Urinary urgency/frequency are non-specific responses of the lower urinary tract to noxious stimuli (specific or non-specific) and not useful, per se, for segregating the two syndromes. Therefore urgency/frequency exists as a key component to each urologic syndrome, but is not explicitly or uniquely related to either entity. The definition of frequency is similar between the two entities of Painful Bladder Syndrome /Interstitial Cystitis and OAB, that being a urinary voiding number greater than 8 voids/24hr, and with nocturia usually associated with the global presentation. However, the definition and parameters of urgency, and even the utility of the term across languages have come under significant scrutiny as researchers have attempted to standardize this term.

Dmochowski believes it is vital that some unanimity of opinion be attained both in the definition of urgency and the assessment of this symptom so that the effect of this component of the urgency/frequency syndrome can be defined at baseline and also after intervention for symptomatic patients who experience either the OAB or Painful Bladder Syndrome /Interstitial Cystitis, or who may have symptoms which span both syndromes.

Dr. Ueda reported a distinctly different approach in Japan. The Society for Interstitial Cystitis Japan (SICJ) has proposed to use "Hypersensitive bladder syndrome (HBS) or Irritable bladder syndrome (IBS) " to express the meaning of IC symptoms as bladder hypersensitivity. They consider this terminology more desirable because IC patients do not always exhibit apparent pain symptoms, and often describe their symptoms as pressures or discomfort rather than pain. In addition, among those diagnosed with OAB, the clinical diagnosis of HBS/IC should be considered when cystoscopic findings prove bladder pathology, which has reportedly showed positive correlations with IC symptoms despite the remaining doubt as to their specificity.

Dr. Mishra's experience in India led him to conclude that patients presenting with only urgency frequency and incontinence without any pain element can be considered to be suffering from overactive bladder. Patients with PBS/ IC may present with only urgency and frequency with the pain component developing later. This means in all patients with frequency and urgency, IC should be suspected as one of the differential diagnoses if the patient does not improve.

Chronic Pelvic Pain Syndrome (CPPS) NIDDK Type 3 (Non Bacterial Prostatitis) and BPS/IC

Dr. Doggweiler from the United States led off the discussion with a review. She concluded that CPPS and IC have similar symptomatology and may respond to similar treatments. We should at least evaluate these patients for "both" diagnoses and possibly also for other often associated diseases and treat the whole person adequately, keeping in mind that this "disease" or "symptom complex" is still poorly understood and that we need to treat the person affected by it and not only the diagnosis.

Dr Tomoe stated the Japanese view that with CPPS the origins of the various symptoms including pain are in the prostate, but in IC they come from the bladder. Cystoscopy with hydrodistension is the most useful technique in order to differentiate male IC from CPPS.

In frequency volume charts, bladder volume often decreases in men with IC compared with CPPS. Although many males suffering from CPPS can be patient about going to the toilet, even if they feel very uncomfortable, IC patients cannot.

Dr. Fall presented a European view. In the European Association of Urology guidelines for chronic pelvic pain prostate pain syndrome (PPS) is defined as persistent or recurrent episodic prostate pain, associated with symptoms suggestive of urinary tract and/or sexual dysfunction, with no proven infection or other obvious pathology. There is no doubt an overlap between BPS and PPS. Although there is a marked female predominance for BPS, the diagnosis must also be considered in men presenting relevant symptoms. In fact, it has been argued that many men diagnosed with chronic prostatitis/PPS may present signs consistent with the NIDDK criteria of BPS/IC and that these diagnoses are interrelated. On the other hand, differences in urinary markers suggest that BPS/IC and PPS may be different disorders with distinct pathophysiologies. A general remark is that if pain is poorly localized, or is perceived in 3 or more sites, the patient would be regarded as suffering from chronic pelvic pain syndrome. Then there is no need for further end-organ subdivision, recognizing that poor localization suggests overlapping mechanisms that call for involvement of the multidisciplinary pain team.

Interstitial Cystitis Association (ICA) Perspective

Libby Mullin gave the ICA viewpoint. She warned against focusing solely on bladder pain as the main symptom of this condition, as it would exclude patients with urinary urgency and pelvic pressure. While urgency may need to be further defined as it applies to IC patients (as opposed to urge incontinence patients), excluding urgency altogether will not solve this dilemma. Refining/redefining urinary urgency in IC is key. She stated the position of the patient organization that a change from the name "interstitial cystitis/painful bladder syndrome" was unwarranted at this time, and that whatever name is chose, IC should be a part of it.

Nursing Perspective

Diane Newman raised the issue of a team approach to care, and sited the following professional and consumer organizations that might be of help:

American Urological Association Foundation

Society of Urologic Nurses and Associates (SUNA)

Association of Reproductive Health Professionals (ARHP)

National Women's Health Information Center, U.S. Department of Health and Human Services, Office on Women's Health

National Vulvodynia Association

Interstitial Cystitis Association

The Interstitial Cystitis Network

The Wellness Interactive Network

International Painful Bladder Foundation

Diagnosis of IC/BPS

Dr. Chris Payne led a discussion of this controversial topic and facilitated development of consensus. Dr. Burks said that in the United States symptoms and exclusion criteria will continue to be the hallmarks of the disease until we have a validated marker. He believes that BPS plus the inclusion of hydrodistention findings of glomerulations or Hunner's lesion defines interstitial cystitis. Dr. M.H. Lee from Taiwan agreed that the minimal criteria are to be symptom- based for practical purposes, the definitive criteria using optional measures to collect homogenous patients for studies.

Dr. J.G. Lee outlined Korean criteria as follows:

Minimal Diagnostic Criteria

If a patient shows some of the following symptoms and there is no other disease or condition which can explain them, PBS/IC is likely to be present and low invasive treatments including conservative therapy and oral medication therapy can be started.

* Urinary frequency, unresponsive to anticholinergic and antibacterial drugs, persisting more than 3 months. * Bladder discomfort or pain that worsens as the bladder fills with urine, and lessens as it empties. * Average voided volume per micturition is less than 200ml estimated from the frequency-volume chart. * Maximum bladder capacity is less than 250ml with the absence of detrusor overactivity on cystometry.

Definitive Diagnostic Criteria

When all of the following three conditions are met, IC is clinically diagnosed.

* Presence of the symptoms including urinary frequency, increased need to urinate, urinary urgency, bladder discomfort, bladder pain, etc. * Hunner's ulcer or hemorrhage after hydrodistension is observed in the bladder. * Absence of other diseases which explain the above symptoms or findings.

CONFERENCE CONCLUSIONS

A broad discussion of conference results and conclusions is in preparation for publication. Highlights of the conclusions are the following:

PAIN

Pain, pressure, discomfort all refer to the same idea that we are addressing in a clinical definition, and all require assessment. In the event that pain is not elicited on initial questioning, it should be sought out as a corollary of the patient's other symptoms (frequency, urgency) so as not to under-diagnose IC/BPS/PBS.

FREQUENCY

Frequency is a symptom, not a number. Nocturia is also important. Both are patient perceptions. One needs to consider frequency in conjunction with volume voided.

URGENCY

Urgency is a clinical tool. Perceptions of urgency may differ among patients, physicians, and the International Continence Society. The group suggested that urgency should be further categorized as to "type" , and recommended further research to improve understanding and to better measure urgency in BPS/IC/PBS.

BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME DEFINITION

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.

It seems that the world is moving to a presumptive diagnosis based on history and physical examination, and relying on invasive procedures for more complex cases, although this is by no means a universal opinion, being more prevalent in the United States and Asia than in Europe. The name of the disease remains an area of contention around the world.

Reported by Philip M. Hanno, MD, a Contributing Editor with UroToday.

*Conference Attendees:

USADavid BurksQuentin ClemensRoger DmochowskiRagi DoggweilerPhilip HannoJohn KusekLeroy NybergChristopher PayneKristene Whitmore

EUROPEMauro Cervigni: ItalyMagnus Fall: SwedenClaus Riedl: AustriaJoop Van de Merwe: NetherlandsArndt van Ophoven: Germany (contributor but unable to attend)

ASIAHikaru Tomoe: JapanTomohiro Ueda: JapanNagendranath Mishra: IndiaMing Huei Lee: TaiwanAlex Lin: TaiwanJeong Gu Lee: Korea

SPECIAL REPRESENTATIVESJane Meijlink: Netherlands, International Painful Bladder FoundationLibby Mullin: USA, Interstitial Cystitis AssociationDiane Newman: USA