Committee 19 Bladder Pain Syndrome International Consultation on Incontinence Chairman P. H ANNO (USA) Members A. LIN (Taiwan), J. NORDLING (Denamark), L. NYBERG (USA), A. VAN OPHOVEN (Germany), T. UEDA (Japon) 1459 CONTENTS INTRODUCTION X. NEUROMODULATION I. NOMENCLATURE/ HISTORY/ XI. PAIN EVALUATION AND TAXONOMY TREATMENT II. EPIDEMIOLOGY XII. SURGICAL THERAPY III. AETIOLOGY XIII. CLINICAL SYMPTOM SCALES IV. PATHOLOGY XIV. OUTCOME ASSESSMENT V. DIAGNOSIS XV. PRINCIPLES OF MANAGEMENT VI. CLASSIFICATION XVI. FUTURE DIRECTIONS IN RESEARCH VII. CONSERVATIVE TREATMENT XVII. SUMMARY (figure 10) VIII. ORAL THERAPY REFERENCES IX. INTRAVESICAL / INTRAMURAL THERAPY (Table 5) 1460 Bladder Pain Syndrome International Consultation on Incontinence P. H ANNO, A. LIN, J. NORDLING, L. NYBERG, A. VAN OPHOVEN, T. UEDA 2. DEFINITION INTRODUCTION Bladder Pain Syndrome (BPS) is a clinical diagnosis that relies on symptoms of pain in the bladder and or 1. EVIDENCE ACQUISITION pelvis and other urinary symptoms like urgency and The unrestricted, fully exploded Medical Subject frequency. Based on the evolving consensus that Heading (MeSH) ‘‘interstitial cystitis’’ (including all BPS probably is strongly related to other pain related terms as ‘‘painful bladder syndrome,’’ “bladder syndromes like Irritable Bowel Syndrome, Fibromyalgia pain syndrome”, or different terms such as ‘‘chronic and Chronic Fatigue Syndrome, the European Society interstitial cystitis,’’ etc.) were used to thoroughly for the Study of Bladder Pain Syndrome/ Interstitial search the PubMed database (http://www.ncbi. Cystitis (ESSIC) recently published a comprehensive nlm.nih.gov/PubMed/) of the US National Library of paper on definition and diagnosis of BPS [1]. Medicine of the National Institutes of Health; 1795 BPS was defined as chronic (>6 months) pelvic pain, hits were retrieved. After exclusion of uncommon pressure, or discomfort perceived to be related to the languages (other than English, French, German, urinary bladder accompanied by at least one other Italian, Japanese, Spanish, Swedish) and by limiting urinary symptom such as persistent urge to void or the publications to the time period January 2004 to May frequency. Confusable diseases as the cause of the 2008, 512 publications resulted. symptoms must be excluded. Further documentation Abstracts if available and titles of the 512 hits were and classification of BPS might be performed reviewed, focusing on (but not limited to) clinical trials, according to findings at cystoscopy with hydro- randomised controlled trials, meta-analyses, scientific distension and morphological findings in bladder guidelines, and core clinical journals. The literature biopsies. The presence of other organ symptoms as update thus achieved was added to the pre-existing well as cognitive, behavioural, emotional, and sexual database, covering the time period before and during symptoms should be addressed. 2004 (generated for the 2004 ICI Incontinence This definition has been broadly accepted although guideline, published 2005) that was established actual wording differs somewhat [2]. Because omitting according to the same protocol. the name “Interstitial Cystitis” might cause serious Rating of the level of evidence and grade of problems in different health systems by affecting recommendation was performed according to the reimbursement, the possibility of patients gaining Oxford Scale. disability benefits, and so forth, the name Bladder Pain Syndrome/ Interstitial Cystitis (BPS/IC) could be The committee believes that the Oxford system for used in parallel with BPS for the time being. In this categorizing levels of evidence is primarily relevant only chapter the term Bladder Pain Syndrome largely for the sections on treatment, which follow. While the replaces the older Interstitial Cystitis term, but committee’s opinions will be expressed, where the two are essentially interchangeable as there applicable, regarding evidence and conclusions for is no accepted definition that clearly delineates the other areas, including diagnosis, aetiology, and interstitial cystitis syndrome from bladder pain pathophysiology, use of the Oxford system in this syndrome. The Consultation believes the latter context is more open to interpretation. term more appropriately describes the disorder. 1461 Historically, definitions of IC have moved from a severe clear objective diagnostic criteria or pathophysiological inflammatory bladder disease to a condition described explanation, countless theories have been put forward primarily by symptoms (table 1) [2]. without adding much to the delineation or under- standing of the disease. The International Continence Society [9] (ICS) used the term Painful Bladder Syndrome (PBS) defined as In practice, patients with symptoms of BPS are “ the complaint of suprapubic pain related to bladder screened to exclude other relevant diagnoses or filling, accompanied by other symptoms such as confusable diseases [1], and a focused evaluation is increased daytime and night-time frequency, in the performed at the discretion of the physician or centre. absence of proven urinary infection or other obvious This evaluation might include cystoscopy under local pathology”. ICS reserved the diagnosis Interstitial or general anaesthesia, bladder distension with Cystitis (IC) to patients with “typical cystoscopic and registration of bladder capacity and/or the presence histological features”, without further specifying these. of glomerulations and Hunner’s lesion. Bladder wall It has however been shown, that only a fraction of biopsies might be obtained and evaluated for patients believed by experts to have BPS fulfil this inflammation, ulcer, fibrosis, mast cells etc. The definition [10]. evaluation might also include urodynamics with registration of bladder capacity, compliance and The condition will therefore in the remainder of this bladder stability [11]. One view of the relationship of chapter be referred to as BPS. As the terminology is BPS with OAB is graphically depicted in Figure 1 in flux, some of the older literature may be discussed [12]. The 14% incidence of urodynamic detrusor using the original terminology in the interests of clarity. overactivity in the BPS [13] patients is probably close Logically “interstitial cystitis” should include some to what one might expect in the general population if form of demonstrable inflammation in the bladder studied urodynamically [14]. wall, while “bladder pain syndrome” should include pain In the end, these investigations might prove to be in the region of the bladder. The diagnosis of BPS is normal and the patients are identified as having BPS based on exclusion of other diseases in the bladder, as a diagnosis of exclusion. The relevance of urethra, and other pelvic organs including the urodynamic, cystoscopic and histological findings is musculoskeletal system. As with other diseases without further obscured, because the methodology by which these results is obtained is rarely comparable and it Table 1. Historical definitions of interstitial cystitis is therefore recommended to use the standardisations described by ESSIC [1]. • 1887 Skene [3] : An inflammation that has destroyed the mucous membrane partly or wholly and extended to the muscular parietes. I. NOMENCLATURE/ HISTORY/ TAXONOMY • 1915 Hunner [4]: A peculiar form of bladder ulceration whose diagnosis depends ultimately on its resistance to all ordinary forms of treatment in patients with 1. HISTORICAL NOTES frequency and bladder symptoms (spasms). Recent historical reviews confirm that interstitial cystitis • 1951 Bourque [5] : Patients who suffer chronically was recognized as a pathologic entity during the 19th from their bladder; and we mean the ones who are century [15,16]. In his textbook Practical Observations distressed, not only periodically but constantly, having on Strangulated Hernia and Some Diseases of the to urinate at all moments of the dav and of the night Urinary Organs, Joseph Parrish, a Philadelphia suffering pains every time they void. surgeon, described 3 problematic cases of recurrent, • 1978 Messing and Stamey [6]: Nonspecific and highly severe lower urinary tract symptoms in which he made subjective symptoms of around-the-clock frequency, repeated attempts to locate a bladder stone, which was urgency, and pain somewhat relieved by voiding when the most common source for these symptoms in early associated with glomerulations upon bladder distention 19th century America [17]. As Teichman et al have under anesthesia. convincingly argued, these patients displayed all of the clinical hallmarks of IC including chronic frequency, • 1990 Revised NIDDK Criteria: Pain associated with urgency, dysuria and pelvic pain in the absence of the bladder or urinary urgency, and, glomerulations demonstrable pathology [18]. Although he used the or Hunner’s ulcer on cystoscopy under anesthesia in patients with 9 months or more of symptoms, at least term repeatedly in his manuscript, Parrish did not 8 voids per day, 1 void per night, and cystometric elaborate upon the clinical definition of “tic doloureux,” bladder capacity less than 350cc [7]. likely because contemporaneous physicians would have been familiar with the concept. However, Parrish • 1997 NIDDK Interstitial Cystitis Database Entry attributed the term Tic doloreux to his mentor, Dr. Criteria: Unexplained urgency or frequency (7 or more Phillip Syng Physick, who had applied it to patients voids per day), OR pelvic pain of at least 6 months with severe lower urinary