Infection/Inflammation Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome: AUA Guideline Amendment Philip M. Hanno, Deborah Erickson, Robert Moldwin* and Martha M. Faraday From the American Urological Association Education and Research, Inc., Linthicum, Maryland Purpose: The purpose of this amendment is to provide an updated clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain Abbreviations and Acronyms syndrome based upon data received since the publication of original guideline ¼ in 2011. AE adverse event Ò ¼ Materials and Methods: A systematic literature review using the MEDLINE BPS bladder pain syndrome database (search dates 1/1/83-7/22/09) was conducted to identify peer-reviewed BTX-A ¼ botulinum toxin A publications relevant to the diagnosis and treatment of IC/BPS. This initial re- CP ¼ chronic prostatitis view yielded an evidence base of 86 treatment articles after application of in- CPPS ¼ chronic pelvic pain clusion/exclusion criteria. The AUA update literature review process, in which syndrome an additional systematic review is conducted periodically to maintain guideline GTM ¼ global therapeutic currency with newly published relevant literature, was conducted in July 2013. massage This review identified an additional 31 articles, which were added to the evidence IC ¼ interstitial cystitis base of this Guideline. MPT ¼ myofascial physical Results: Newly incorporated literature describing the treatment of IC/BPS therapy was integrated into the Guideline with additional treatment information pro- Qol ¼ quality of life vided as Clinical Principles and Expert Opinions when insufficient evidence UTI ¼ urinary tract infection existed. The diagnostic portion of the Guideline remains unchanged from the original publication and is still based on Expert Opinions and Clinical Principles. Accepted for publication January 16, 2015. Conclusions: The management of IC/BPS continues to evolve as can be seen by The complete guideline is available at http:// an expanding literature on the topic. This document constitutes a clinical www.auanet.org/education/guidelines/ic-bladder- pain-syndrome.cfm. strategy and is not intended to be interpreted rigidly. The most effective This document is being prined as submitted approach for a particular patient is best determined by the individual clinician independent of editorial or peer review by the and patient. As the science relevant to IC/BPS evolves and improves, the stra- Editors of The Journal of UrologyÒ. * Financial and/or other relationship with tegies presented will require amendment to remain consistent with the highest Taris Biomedical, Urigen Pharmaceuticals and standards of care. Afferent Pharmaceuticals. For another article on a related Key Words: cystitis, interstitial; pelvic pain; urodynamics; topic see page 1676. lower urinary tract symptoms; urinary bladder diseases INTRODUCTION while minimizing adverse events THIS guideline’s purpose is to provide and patient burden. The strategies direction to clinicians and patients and approaches recommended in regarding how to recognize intersti- this document were derived from tial cystitis/bladder pain syndrome, evidence-based and consensus-based conduct a valid diagnostic process, processes. IC/BPS nomenclature is a and, approach treatment with the controversial issue; for the purpose goals of maximizing symptom con- of clarity the Panel decided to refer trol and patient quality of life to the syndrome as IC/BPS and to 0022-5347/15/1935-1545/0 http://dx.doi.org/10.1016/j.juro.2015.01.086 THE JOURNAL OF UROLOGY® Vol. 193, 1545-1553, May 2015 www.jurology.com j 1545 © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH,INC. Printed in U.S.A. 1546 AUA GUIDELINE AMENDMENT consider these terms synonymous. This document construct the majority of the treatment portion of the provides an overview of the amendments made to algorithm. the 2011 Guideline and should, therefore, be viewed The initial and update reviews revealed insufficient in conjunction with the full Guideline available at publications to address IC/BPS diagnosis and overall http://www.auanet.org/education/guidelines/ic-bladder- management from an evidence basis and, therefore, the diagnosis and management portions of the algorithm pain-syndrome.cfm. The updated algorithm reflects (see figure) are provided as Clinical Principles or as these changes as well (see figure). Expert Opinion with consensus achieved using a modified Delphi technique if differences of opinion emerged.1 For a complete discussion of the methodology and evidence METHODOLOGY grading, please refer to the unabridged version of this An initial systematic review was conducted to identify Guideline. published articles relevant to the diagnosis and treatment of IC/BPS. Literature searches were performed on English language publications using the MEDLINE database from January 1, 1983 to July 22, 2009 using the BACKGROUND terms “interstitial cystitis,” “painful bladder syndrome,” Definition “bladder pain syndrome,” and “pelvic pain” as well as key The bladder disease complex includes a large group words capturing the various diagnostic procedures and of patients with bladder and/or urethral and/or treatments known to be used for these syndromes. With pelvic pain, lower urinary tract symptoms and regard to treatment, a total of 86 articles from the original literature searches met the inclusion criteria, and an sterile urine cultures, many with specific identifi- additional 31 relevant studies were retrieved as part of able causes. IC/BPS comprises a part of this com- the update literature review process. The Panel judged plex. The Panel used the IC/BPS definition agreed that these were a sufficient evidence base from which to upon by the Society of Urodynamics, Female Pelvic Interstitial cystitis/bladder pain syndrome algorithm AUA GUIDELINE AMENDMENT 1547 Medicine & Urogenital Reconstruction: “An un- it may be greatly under diagnosed in the male pleasant sensation (pain, pressure, discomfort) population.” perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of Typical Course and Comorbidities more than six weeks duration, in the absence of IC/BPS is most commonly diagnosed in the fourth infection or other identifiable causes.”2 This defini- decade or after, although the diagnosis may be tion was selected because it allows treatment to delayed depending upon the index of suspicion for begin after a relatively short symptomatic period, the disease and the criteria used to diagnose it.7 A preventing treatment withholding that could occur history of a recent culture proven UTI can be iden- with definitions that require longer symptom du- tified on presentation in 18% to 36% of women, rations (i.e. six months). Definitions used in although subsequent cultures are negative.8,9 research or clinical trials should be avoided in Initially it is not uncommon for patients to report a clinical practice, as many patients may be mis- single symptom such as dysuria, frequency or pain, diagnosed or diagnosis and treatment may be with subsequent progression to multiple symp- delayed if these criteria are used.3 toms.10,11 Symptom flares, during which symptoms suddenly intensify for several hours, days or weeks, IC/BPS Symptoms are not uncommon. There is a high rate of prior pelvic Since the original publication of this Guideline, surgery (especially hysterectomy) and levator ani three papers reported data from the RICE (RAND pain in women with IC/BPS, suggesting that trauma Interstitial Cystitis Epidemiology) study.4e6 One or other local factors may contribute to symptoms.12 of the RICE study objectives was to develop an It is important to note, however, that the high IC/BPS case definition for use in epidemiological incidence of other procedures, such as hysterectomy studies that had known sensitivity and specificity. or laparoscopy, may be the result of a missed diag- Berry et al reported findings from a literature re- nosis and does not necessarily indicate that the view, a structured expert panel process and a tele- surgical procedure itself is a contributing factor to phone interview validation study to derive an symptoms. It is also common for IC/BPS to coexist IC/BPS definition.4 They note that none of the with other unexplained medical conditions, such as existing epidemiological definitions had high sensi- fibromyalgia, irritable bowel syndrome, chronic fa- tivity or high specificity. As a result of this process, tigue syndrome, Sjogren’s syndrome, chronic head- two definitions emerged, one with high sensitivity aches and vulvodynia.13,14 These associations that correctly identified IC/BPS cases 81% of the suggest that there may be a systemic dysregulation time (with 54% specificity) and one with high spec- in some patients. Finally, patients with IC/BPS ificity that correctly excluded nonIC/BPS cases frequently exhibit mental health disorders, such as 83% of the time (with 48% sensitivity). The defini- depression and anxiety. While these symptoms may tions are captured in an 11-item questionnaire. be reactive in some IC/BPS patients, there is also See the Appendix for definitions, which the Panel some evidence that there may be a common biolog- notes that these are epidemiological case definitions ical mechanism involved. and are not appropriate for use as diagnostic criteria. Conceptualizing IC/BPS Berry et al used the questionnaire to determine It is not known whether IC/BPS is a primary prevalence of IC/BPS among adult females in the bladder