1. No category

Interstitial Cystitis Association
C M E / C E
M o n o g r a p h
Conquering IC:
Identification and Management Strategies
Contributing Authors
Eman A. Elkadry, MD
Jennifer Yonaitis Fariello, MSN, CRNP
Jeffrey G. Proctor, MD
www.ichelpcme.org
Developed in Cooperation with
A Continuing Education Company &
NPA
Conquering IC: Identification and Management Strategies
Table of Contents
CME/CE Information ..............................................................................................................................................2
Faculty and Disclosures.........................................................................................................................................3
Introduction..............................................................................................................................................................5
Identification of Interstitial Cystitis...................................................................................................................9
Management Strategies for IC .........................................................................................................................12
Support for Patients.............................................................................................................................................17
Conclusion ..............................................................................................................................................................18
References...............................................................................................................................................................19
❨1❩
Conquering IC: Identification and Management Strategies
CME/CE Information
TARGET AUDIENCE
This activity is intended for health care providers who
are involved in the diagnosis and treatment of
interstitial cystitis, including primary care providers,
urologists, obstetricians, and gynecologists.
SPONSOR
This activity is sponsored through an educational
collaboration by Interstitial Cystitis Association,
The France Foundation, American Urogynecologic
Society, and Nurse Practitioner Alternatives.
STATEMENT OF NEED
Interstitial cystitis is a complicated and poorly
understood urological condition, with over 4 million
Americans impacted by this syndrome. Without a
definitive diagnostic test, patients may go undiagnosed
and untreated for several years. This educational
initiative is designed to increase awareness about
interstitial cystitis and provide clinicians with strategies
for the diagnosis and management of this chronic
condition.
ACCREDITATION STATEMENT
The France Foundation is accredited by the
Accreditation Council for Continuing Medical Education
to provide continuing medical education for physicians.
EDUCATIONAL ACTIVITY LEARNING OBJECTIVES
Upon completion of this course, the participants should
be able to:
• Describe interstitial cystitis, including the
epidemiology, pathophysiology, and disease course
• Recognize signs and symptoms of IC, and employ
the appropriate assessments involved in establishing
an early diagnosis
• Identify appropriate individualized management
strategies for patients with IC
• Utilize tools and resources to educate, counsel and
support patients with the ongoing management of IC
Release Date: May 2013 • Expiration Date: May 31, 2015
Estimated Time to Complete Activity: 1 hour
CREDIT DESIGNATION
Physicians: The France Foundation designates this
enduring material for a maximum of 1.0 AMA PRA
Category 1 Credit(s)™. Physicians should claim only the
credit commensurate with the extent of their
participation in the activity.
Nurses: Nurse Practitioner Alternatives is accredited as a
provider of continuing nursing education by the
American Nurses Credentialing Center's Commission on
Accreditation.
Awarded 1.0 contact hours of continuing nursing
education for RNs and APRNs.
Accreditation does not imply endorsement by
Interstitial Cystitis Association, The France Foundation,
American Urogynecologic Society, Nurse Practitioner
Alternatives, or ANCC of recommendations or any
commercial products discussed in conjunction with the
educational activity.
METHOD OF PARTICIPATION / HOW TO RECEIVE CREDIT
There are no fees for participating in and receiving credit for this activity.
Review the activity objectives and CME/CE information.
Complete the CME/CE activity.
Request CME/CE credit by going to www.IChelpCME.org/monograph and complete steps 5, 6, and 7.
Complete the posttest.
Complete the CME/CE evaluation/attestation form, which provides each participant with the opportunity
to comment on how participating in the activity will affect their professional practice; the quality of the
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commercial bias; and his/her views on future educational needs.
7. Your CME/CE certificate will be available for download.
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❨2❩
Conquering IC: Identification and Management Strategies
Faculty and Disclosures
participating in this activity have disclosed to the
participants any significant financial interest or other
relationship with manufacturer(s) of any commercial
product(s)/device(s) and/or provider(s) of commercial
services included in this educational activity. The
intent of this disclosure is not to prevent a person with
a relevant financial or other relationship from
participating in the activity, but rather to provide
participants with information on which they can base
their own judgments. The Interstitial Cystitis
Association, The France Foundation, American
Urogynecologic Society, and Nurse Practitioner
Alternatives have identified and resolved any and all
conflicts of interest prior to the release of this activity.
CONTENT PLANNING COMMITTEE
CONTENT FACULTY
Eman A. Elkadry, MD
Fellowship Director
Division of Urogynecology
Female Pelvic Medicine and Reconstructive Surgery
Mount Auburn Hospital
Cambridge, Massachusetts
Clinical Instructor
Obstetrics and Gynecology
Harvard Medical School
Boston, Massachusetts
Jennifer Yonaitis Fariello, MSN, CRNP
Female and Male Pelvic and Sexual Medicine
The Pelvic and Sexual Health Institute
Philadelphia, Pennsylvania
ACTIVITY STAFF DISCLOSURES
The reviewers, staff, or other members at the
Interstitial Cystitis Association who control content
have no relevant financial relationships to disclose.
• Lee Claassen, CAE
• Rhonda L. Garrett
• Amy Lestition, CAE
• Anita Roach
• Linda Salin
Jeffrey G. Proctor, MD
Director of Interstitial Cystitis
Georgia Urology
Cartersville, Georgia
PLANNING STAFF
Wendy Scales, PhD
Medical Director
The France Foundation
Old Lyme, Connecticut
The planners, reviewers, editors, staff, or other
members at The France Foundation who control
content have no relevant financial relationships to
disclose.
• Melissa Austin
• Jennifer Green
• Lenna Levine
• Heather Tarbox, MPH
• Wendy Scales, PhD
Laurie Scudder, DNP, NP
Nurse Planner
President
Nurse Practitioner Alternatives
Ellicott City, Maryland
DISCLOSURES
It is the policy of the Interstitial Cystitis Association,
The France Foundation, American Urogynecologic
Society, and Nurse Practitioner Alternatives to ensure
balance, independence, objectivity, and scientific rigor
in all its sponsored educational activities. All faculty,
activity planners, content reviewers, and staff
The reviewers, staff, or other members at American
Urogynecologic Society who control content have no
relevant financial relationships to disclose.
• Michelle Zinnert, CAE
The planner and reviewer at Nurse Practitioner
Alternatives who controls content have no relevant
financial relationships to disclose.
• Laurie Scudder, DNP, NP
❨3❩
Conquering IC: Identification and Management Strategies
FACULTY DISCLOSURE
The following faculty has indicated she has no
relationships with industry to disclose relative to the
content of this CME/CNE activity:
• Jennifer Yonaitis Fariello, MSN, CRNP
DISCLAIMER
The Interstitial Cystitis Association, The France
Foundation, American Urogynecologic Society, and
Nurse Practitioner Alternatives present this
information for educational purposes only. The
content is provided solely by faculty who have been
selected because of recognized expertise in their field.
Participants have the professional responsibility to
ensure that products are prescribed and used
appropriately on the basis of their own clinical
judgment and accepted standards of care. The
Interstitial Cystitis Association, The France Foundation,
American Urogynecologic Society, Nurse Practitioner
Alternatives, and Centers for Disease Control and
Prevention assume no liability for the information
herein.
The following faculty have indicated they have
relationships with industry to disclose relative to the
content of this CME/CNE activity:
• Eman Elkadry, MD has served as a consultant,
and is a stock shareholder for Merck.
• Jeffrey G. Proctor, MD has served on the scientific
advisory board, and is a stock shareholder for
Urigen Pharmaceuticals, Inc. He has received
honoraria from Astellas Pharma US Inc, Janssen
Pharmaceuticals Inc, and Watson Pharmaceuticals
Inc.
UNAPPROVED USE DISCLOSURE
The Interstitial Cystitis Association, The France
Foundation, American Urogynecologic Society, and
Nurse Practitioner Alternatives require CME faculty
(speakers) to disclose to the attendees when products
or procedures being discussed are off-label, unlabeled,
experimental, and/or investigational (not FDA
approved); and any limitations on the information that
is presented, such as data that are preliminary or that
represent ongoing research, interim analyses, and/or
unsupported opinion. Faculty in this activity may
discuss information about pharmaceutical agents that
is outside of US Food and Drug Administration
approved labeling. This information is intended solely
for continuing medical education and is not intended
to promote off-label use of these medications. If you
have questions, contact the medical affairs
department of the manufacturer for the most recent
prescribing information.
SUPPORT ACKNOWLEDGMENT
This activity is supported by the Cooperative
Agreement Number 5U58DP002936-02 from
The Centers for Disease Control and Prevention.
Its contents are solely the responsibility of the authors
and do not necessarily represent the official views of
The Centers for Disease Control and Prevention.
PRIVACY POLICY
The France Foundation protects the privacy of
personal and other information regarding participants
and educational collaborators. The France Foundation
will not release personally identifiable information to a
third party without the individual's consent, except
such information as is required for reporting purposes
to the ACCME and ANCC.
The France Foundation maintains physical, electronic,
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Additional information regarding The France
Foundation’s Privacy Policy can be viewed at
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CONTACT INFORMATION
If you have questions about this educational activity,
please contact The France Foundation at 860-434-1650
or [email protected].
❨4❩
Conquering IC: Identification and Management Strategies
Introduction
Interstitial cystitis is generally thought of as
urinary urgency, frequency, and bladder pain.
Symptoms wax and wane, and can progress over
time, particularly when untreated. Symptoms
associated with interstitial cystitis range from
mild to severe. The 2011 American Urological
Association (AUA) guidelines refer to interstitial
cystitis/bladder pain syndrome (IC/BPS) as “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 in duration, in the absence
of infection or other identifiable causes.”1 This
definition comes from a 2008 international
consensus conference sponsored by the Society
of Urodynamics, Female Pelvic Medicine &
Urogenital Reconstruction.2 For clinical research
purposes, the term “interstitial cystitis” was used
only for those patients meeting very strict criteria
suggested by the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK).3
However, it was recognized that this strict
definition was not appropriate for clinical
practice, as 60% of patients would not in fact
meet such strict criteria, leaving them
misdiagnosed or undiagnosed.4 This condition
has also been referred to as “painful bladder
syndrome” and “hypersensitivity bladder
syndrome.” Various theories regarding the
etiology of IC will be discussed in subsequent
paragraphs. For the purposes of this review, we
will use “IC” as an umbrella term to encompass
the broad definition as reflected in the current
AUA guidelines.
The 2011 AUA guidelines refer to
interstitial cystitis/bladder pain
syndrome as “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 in
duration, in the absence of infection or
other identifiable causes”
Historically, IC has been an under-reported and
under-recognized condition. Varied definitions for
IC have complicated efforts to establish
prevalence estimates for this chronic condition.
Results from the third National Health and
Nutrition Examination Surveys (NHANES III)
indicated greater prevalence of IC in women vs.
men (850 per 100,000 women vs. 60 per 100,000
men).5 Using standard case definitions (one with
high sensitivity, and one with high specificity),
the RAND Interstitial Cystitis Epidemiology (RICE)
study (2-staged telephone-based survey)
concluded that between 2.7 and 6.5% of adult
women in the US (or 3.3 to 7.9 million) have
symptoms consistent with IC.6 Recent data
suggest that the prevalence of IC in men may be
higher than once thought. As part of the RAND
study, the prevalence of IC and chronic
prostatitis/chronic pelvic pain syndrome
(CP/CPPS) was evaluated in men by Suskind et al.7
These investigators recently reported that based
on their national sample, the prevalence of IC in
men was between 1.9 and 4.2% (for the high
specificity and high sensitivity definitions,
respectively), and the prevalence of CP/CPPS was
1.8%. These values translate into 2.1 million men
with IC in the US. Seventeen percent of the men
in the study met both the high specificity
definition of IC and the case definition of
CP/CPPS.
❨5❩
Conquering IC: Identification and Management Strategies
The economic burden associated with IC is
significant. In a case-control study of a Kaiser
Permanente managed care population, women
with an ICD-9 diagnosis of interstitial cystitis were
reported to have annual medical costs 2.4 fold
greater than matched controls ($7,100 vs. $2,994,
respectively).8 This large difference in annual
costs was largely attributed to outpatient and
pharmacy expenses. Direct and indirect costs
associated with IC and chronic pelvic pain (CPP)
combined are estimated to be over $2 billion per
year.9 Indirect costs associated with IC include
time away from work, inability to work full-time,
decreased productivity, and toll on family life and
personal relationships. A study by Clemens et al
reported that 1 in 5 women with IC reported
disease-related work absenteeism over a 3-month
time frame.10
It is not uncommon for patients to see 5–7
different clinicians (and receive various diagnoses
and treatments) prior to receiving a diagnosis of
IC. Patients are often misdiagnosed with recurrent
urinary tract infection (UTI) or vaginitis, even
when cultures have been negative. Untreated, IC
can impact all aspects of a patient’s life including
social, psychological, occupational, domestic,
physical and sexual effects. A case-control study
by Nickel et al indicated that women with IC
reported greater sleep dysfunction, depression,
anxiety, stress, catastrophizing, sexual
dysfunction, and social support dysfunction
compared with asymptomatic controls.11
Symptom severity was found to independently
predict worse quality of life on domains of bodily
pain, general health, and mental health in a study
of female patients with IC by El Khoudary et al.12
However, it is important to note that with early
identification, appropriate treatment, and
support, the majority of patients with IC have
satisfactory outcomes.
The etiology and pathophysiology of IC are not
fully understood. While there is no consensus on
Figure 1: Interstitial Cystitis Pathophysiology (Adapted from Sant et al16)
Urothelial Dysfunction
Mast Cell Activation
Inflammation
C-Fiber Upregulation
Spinal Cord and Central Nervous System “Wind-up”
Visceral Organ Hyperalgesia/Allodynia
Urinary
Gynecologic
Pelvic Musculoskeletal
System
❨6❩
Gastrointestinal
Conquering IC: Identification and Management Strategies
the event(s) or trigger(s) that initiate the
development of IC, there are a number of
elements that are thought to contribute to the
constellation of symptoms associated with IC.
Data from human, animal, and in vitro studies
suggest that urothelial dysfunction, mast cell
activation, neurogenic inflammation and central
sensitization contribute in an interrelated manner
to the pain and urinary symptoms associated
with IC (Figure 1).13,14,15,16,17
Urothelial cell membranes, cell adhesion
molecules, tight junctions, and
glycosaminoglycans (GAG) serve as a protective
barrier in normal bladder. Studies of bladder
surface function demonstrate that individuals
with IC have marked urothelial dysfunction
compared to healthy bladders. Disruption of the
protective urothelial barrier can result in
permeability changes in which urinary
solutes/noxious stimuli can cross the urothelium.
When such stimuli (including potassium ions)
contact underlying tissues, they trigger the
depolarization of sensory nerve fibers
(responsible for urgency) and C-fibers, and leads
to neurogenic inflammation. Activated
submucosal C-fiber afferents release Substance P,
which is involved in nociception and is an
inflammatory mediator that can activate mast
cells. In turn, activated mast cells release
vasoactive, inflammatory, and nociceptive
molecules including Substance P and nerve
growth factor, which can drive proliferation of
more nerve fibers, in a self-reinforcing cycle.
Chronic inflammation and activation of C-fibers
can lead to neural upregulation and even spinal
cord changes that may contribute to chronic
pelvic pain. It is important to point out that it is
not clear if bladder injury is a primary or
secondary event in the development of IC. Some
authors have suggested that neurogenic
inflammation from myofascial dysfunction can
secondarily affect the bladder and lead to this
syndrome.18
The inflammatory response in the submucosal
and detrusor layers of the bladder of patients
with IC is characterized by proliferation and
activation of mast cells.16 Activated mast cells
release histamine, kinins, proteases, leukotrienes,
cytokines (interleukin-6, tumor necrosis factor-α),
prostaglandins, and nitric oxide. These factors can
induce increased permeability, recruitment of
other immune cells, and local tissue damage, all
contributing to further urothelial dysfunction.
Unchecked, this ongoing inflammatory process
can result in fibrotic changes and poor
compliance of the bladder. Some theories have
suggested that IC is an autoimmune disorder
based on the greater prevalence of CD8+, CD4+
lymphocytes, B-lymphocytes, plasma cells, and
immunoglobulins in the bladders of patients with
IC compared with healthy bladders. Genetic
susceptibility for IC has been suggested by
studies showing increased prevalence of IC in first
degree relatives compared with the general
population, and concordance among
monozygotic versus dizygotic twins.19
Persistent inflammation and urothelial re-injury
are thought to contribute to the pain and lower
urinary tract symptoms associated with IC. The
cycle of inflammation-mast cell activationsensory nerve stimulation in the bladder results
in dorsal horn upregulation/central sensitization
and a visceral neuropathic pain syndrome
affecting the bladder and adjacent pelvic organs.
This scenario may help to explain the varied,
non-bladder pain syndromes often associated
with IC such as vulvodynia, dyspareunia, irritable
bowel syndrome, and pelvic floor dysfunction.
Afferent sensitization of one pelvic organ may
❨7❩
Conquering IC: Identification and Management Strategies
Figure 2: Comorbidities of Interstitial Cystitis (adapted from Nickel et al20)
P < 0.001
Irritable bowel syndrome
P < 0.001
Fibromyalgia
P = 0.008
Chronic fatigue syndrome
P < 0.001
Vulvodynia
P < 0.001
Migraine headache
P = 0.001
Tension headache
P = 0.048
Temporomandibular joint disorder
P < 0.001
Low back pain
0
10
20
30
40
50
Percent of Patients
IC (n = 207)
negatively impact adjacent structures (organ
“cross-talk”), without direct injury or insult to the
neighboring organ. Indeed, comorbidities
associated with IC are common, as illustrated in a
case-control study by Nickel et al (Figure 2). All of
Controls (n = 117)
these issues speak to possible muscle
hypertonicity playing a role locally in the pelvis as
well as remotely as with temporomandibular joint
disorder and migraines–suggesting a potentially
common mechanism in susceptible patients.
❨8❩
Conquering IC: Identification and Management Strategies
Identification of Interstitial Cystitis
As mentioned previously, IC is under-reported
and under-diagnosed. This may be due in large
part to the lack of a definitive diagnostic test for
IC, and also because of varied presentations. Men
and women with IC may experience a range of
symptoms (Table 1).
Recognition of IC early in the
disease course can translate into
earlier initiation of treatment prior
to the development of more
severe symptoms
According to some reports, patients may go
several years between onset of symptoms and
Table 1: Symptoms Associated with IC
• Pain, pressure, discomfort or unpleasant
sensation that typically worsens as the
bladder fills and/or in the morning
• Feeling of bladder fullness even when
the bladder is partially filled
• Spasms in or around the bladder
• Suprapubic pain or discomfort, pelvic
pain (lower abdominal pain),
sometimes extending to the lower part
of the back, the groin, and thighs
• In women, pain in the vagina and vulva
• In men, pain in the penis, testicles,
scrotum, and perineum
• Pain in the urethra and rectum
• Pain with sexual intercourse
(dyspareunia; pain with ejaculation)
• Pain may worsen with specific food,
drink, activity, or position
• Urinary frequency; nocturia
• Urinary urgency
Adapted from Meijlink21
diagnosis of IC.12 Recognition of IC early in the
disease course can translate into earlier treatment
and more rapid improvement prior to the
development of more severe symptoms. Early
intervention may also prevent central
sensitization and subsequent allodynia that can
occur with sustained sensory afferent
stimulation/activation in the bladder.
The diagnosis of IC is based primarily on
symptoms (pain, discomfort, or pressure
accompanied by urinary urgency/frequency for at
least 6 weeks in duration) in the absence of
identifiable infection, disease, or other disorder
causing the symptoms. IC may also be diagnosed
by the finding of Hunner’s lesions on cystoscopy.
The AUA guidelines advise that a basic
assessment for IC should include history, physical
exam, and laboratory tests in order to rule in
symptoms characteristic of IC and to rule out
other confusable disorders.1 A careful history is of
paramount importance in the diagnosis of IC. A
survey-based study of over 700 patients with IC in
the United Kingdom showed that most patients
reported urinary frequency, urinary urgency, and
nocturia (92%, 84%, and 87%, respectively).22
Clinicians need to ask the right questions and be
very attentive to patient responses.
❨9❩
Conquering IC: Identification and Management Strategies
Examples of questions that can aid in the
diagnosis of IC include the following:
• How do patients describe their voiding
patterns? Is there frequency during the day
and night?
• When is there urgency? Is there a persistent
urgency to void?
• When do patients have pain?
• Where is the pain?
• How do they describe pain (is it pressure,
burning, sharp pain, or general discomfort)?
• Are bladder symptoms worse in the morning
(specifically pain/pressure)?
• Is there any hematuria?
• Is there any dysuria?
• What is their flow like (steady stream or start
and stop)?
• Is there discomfort with bladder filling or
emptying?
• Do they feel like they empty their bladder when
they void?
• Is pain worse at specific points in the menstrual
cycle?
• Are there flares during allergy season or flares
associated with any foods?
• Are there certain activities that trigger bladder
symptoms or pain?
• Is there pain during and/or after intercourse?
• Have they had frequent culture negative
urinary or vaginal “infections?”
• Does stress cause a worsening of symptoms?
overactive bladder unresponsive to
antimuscarinic treatment, persistent vulvodynia,
persistent chronic prostatitis, and persistent
pelvic pain post-hysterectomy.
Elements of a physical exam and lab tests for IC
are summarized in Table 2.
Conditions that may be confused with IC due to
similarity of symptoms include chronic bacterial
cystitis, renal calculi, urethral diverticulum,
endometriosis, overactive bladder, chronic
bacterial prostatitis, vaginal infection,
postradiation cystitis, and bladder cancer. Clinical
scenarios when present that should alert
clinicians to consider IC include UTI symptoms
with negative cultures, unresolved endometriosis,
❨10❩
Table 2: Physical and Laboratory Exams
for Interstitial Cystitis
Physical Exam
• Abdominal exam
– Suprapubic tenderness
– Masses
– Hernias
• Pelvic exam (internal and external)
– Palpation of bladder base in females,
urethra in both sexes
– Kaufman Q-tip touch test
• Evaluation of pelvic floor muscles
(strength and tenderness on palpation)
• Musculoskeletal system
– Hip alignment
– Sacroiliac joint pain
– Pelvic structure
– Gait
• Brief neurological exam
• Evaluate for incomplete bladder
emptying–post void residual
Lab Tests
• Urinalysis
• Urine culture
• Cytology for patients with a history of
smoking, those with unevaluated
microhematuria, or greater than 45 years
old with urinary frequency and urgency
Conquering IC: Identification and Management Strategies
Voiding diaries (24 hour–3 day) are useful as part
of an initial evaluation for IC. Such information
can help to establish baseline information on
frequency, urgency, and void volumes.
Paper-based bladder diaries
(http://www.voicesforpfd.org/p/cm/ld/fid=60)
and an app for smartphones are available for this
purpose (BladderTrakHer at the iTunes Store).
Some clinicians also find it useful to have their
patients keep a food diary at the same time that
they are using a bladder diary, in order to identify
any association between specific foods and
symptoms. When there are unclear triggers to
pain, a “pain diary” may help to evaluate patterns
before or during a flare. Baseline pain and
symptom evaluation are important as reference
for the assessment of treatment effectiveness.
Two self-report questionnaires used for this
purpose are the O’Leary-Sant Symptom and
Problem Questionnaire (this questionnaire has
two parts: Interstitial Cystitis Symptom Index and
Problem Index [ICSI] and [ICPI]) and the Pelvic
Pain and Urgency/Frequency (PUF)
Questionnaire.23,24
While not required for the diagnosis of IC,
cystoscopy and urodynamic testing can aid in the
diagnosis of IC when either the results of other
evaluations are inconclusive, to exclude other
disease states, or to guide therapy.1 Evidence of
bladder cancer, vesical stones, urethral
diverticula, and intravesical foreign bodies may
be detected with cystoscopy. Hunner’s lesions
(inflammatory lesions specific for IC) or
glomerulations (pinpoint petechial hemorrhages
not pathognomonic for IC) may be visualized
with cystoscopy. Urodynamic testing may help to
detect detrusor overactivity or bladder outlet
obstruction. The potassium sensitivity test and
anesthetic challenge test are used by some
clinicians as a way to establish the bladder as the
location of the pain/discomfort experienced by
patients. Introducing a potassium solution into
the bladder may cause pain and/or urgency for
patients with urothelial injury or abnormal
permeability; if pain/urgency is encountered, the
bladder is rinsed, and a lidocaine-based cocktail is
introduced as a rescue therapy. This test is
controversial and not advocated in the current
AUA guidelines; however some clinicians find it is
useful and informative for selected patients.
Bladder instillation of an anesthetic cocktail can
calm pain and urgency in the bladder and may be
both diagnostic and therapeutic. There are many
different bladder instillation “cocktails” used.
Clinical Assessment Tools
Paper-based Bladder Diary: http://www.voicesforpfd.org/p/cm/ld/fid=60
BladderTrakHer App: https://itunes.apple.com/us/app/bladdertrakher/id589851942?ls=1&mt=8
Food Diary: http://www.ichelp.org/page.aspx?pid=572
O’Leary-Sant Symptom and Problem Questionnaire:
http://www.ichelp.org/document.doc?id=306
Pelvic Pain and Urgency/Frequency (PUF) Questionnaire:
http://www.ichelp.org/document.doc?id=16.5
❨11❩
Conquering IC: Identification and Management Strategies
Management Strategies for IC
A critical starting point for the management of IC
is communication with patients about realistic
expectations with treatment. It is important that
patients fully understand the chronic nature of
the condition, and that flares are part of the
cyclical nature of the syndrome. Treatment
strategies are intended to provide improvement
in symptoms and quality of life, but “cure” or
complete elimination of IC symptoms may not
occur. It may take several months of therapy
before patients start to feel better, and the more
severe the symptoms, usually the longer time to
improvement. Individualized, tailored multimodal
Table 3: Clinical Management Principles
for Interstitial Cystitis1
(adapted from 2011 AUA guidelines)
• Treatments are ordered from most to least
conservative; cystectomy is a treatment
option only after all other treatment
options have been exhausted and found
to be ineffective
• Initial treatment level depends on
treatment severity, clinician judgment,
and patient preferences
• Multiple, simultaneous treatments may be
considered if in the best interests of the
patient
• Ineffective treatments should be stopped
• Pain management should be considered
throughout the course of therapy with the
goal of maximizing function and
minimizing pain and side effects
• IC diagnosis should be reconsidered if no
improvement after multiple treatment
approaches
therapy, which may involve combining
treatments to optimize symptom management, is
common, as there is no single treatment
approach to which most patients will respond.
Clinical management principles for IC are
summarized in Table 3.
A critical starting point for the
management of IC is communication
with patients about realistic
expectations with treatment
First- through sixth-line treatments from the
2011 AUA treatment algorithm are included in
Figure 3.
Selection of first-line treatment options may be
based on each patient’s desires/preferences/
willingness to try, and the risk/benefit of each
therapy. In addition to education about IC and
treatment expectations, all patients should learn
about self-care practices and behavioral
modifications that may help to improve
symptoms. Coping strategies and general
relaxation techniques such as yoga and
meditation may help to minimize stress-related
triggers or flares. Dietary adjustments or an
elimination diet are useful to identify foods that
irritate the bladder and exacerbate symptoms.25
The Interstitial Cystitis Association has resources
for patients about the elimination diet.26,27 An IC
diet can be individualized depending on
patient-identified triggers. Over-the-counter
alkalizing agents such as calcium
glycerophosphate (Prelief ) provide benefits for
some patients to help offset acidic food-related
❨12❩
Conquering IC: Identification and Management Strategies
Figure 3: Treatment for Interstitial Cystitis1 (adapted from 2011 AUA Guidelines)
FIRST-LINE TREATMENTS
General relaxation/Stress Management • Pain Management
Patient Education • Self-care/Behavioral Modification
SECOND-LINE TREATMENTS
Appropriate manual physical therapy techniques • Pain Management
Oral: amitryptyline, cimetidine,hydroxyzine, pentosan polysulfate sodium*
Intravesical: DMSO*, heparin, lidocaine
THIRD-LINE TREATMENTS
Cystoscopy under anesthesia with hydrodistension • Pain Management
Treatment of Hunner’s lesions if found
FOURTH-LINE TREATMENTS
Neuromodulation • Pain Management
FIFTH-LINE TREATMENTS
Cyclosporine A • Intradetrusor onabotulinumtoxinA • Pain Management
SIXTH-LINE TREATMENTS
Diversion with or without cystectomy • Pain Management • Substitution cystoplasty
*FDA approved for IC
irritation. Constipation should be avoided in
patients with IC, as straining increases pressure
on the pelvic floor, and can exacerbate
symptoms. There may also be other activities or
stresses that patients identify as causing a flare of
symptoms. Patients may find comfort from local
application of heat or ice to tender areas. Bladder
retraining to increase bladder capacity and
manage urge are also valuable for patients with IC.
Multimodal treatment strategies are fundamental
in the management of IC, and may include
physical therapy (pelvic floor relaxation, with
myofascial release techniques in particular), stress
management, and pharmacological approaches.1
Referral to a pain clinic may be advised when pain
cannot be managed without narcotics. In a
retrospective chart review of patients with a
diagnosis of IC, Bassaly et al reported that 78%
❨13❩
Conquering IC: Identification and Management Strategies
had myofascial pain with at least one myofascial
trigger point, and 68% of their patient sample
had multiple trigger points.28 Myofascial trigger
points can refer pain to the perineum, vagina,
urethra, and rectum.29 For example,
pain/symptoms in the suprapubic region, urethra,
bladder, or perineum can be referred from the
levator ani anterior muscle; patients may
complain of urinary urgency and frequency,
painful urination, or dyspareunia. Manual
myofascial release techniques and trigger point
injections may help to resolve pain and relax
muscles and connective tissue restrictions.30
Individualized, tailored multimodal
therapy, which may involve combining
treatments to optimize symptom
management, is common, as there is no
single treatment approach to which
most patients will respond
Pharmacological treatment of IC includes both
oral and intravesical agents. Of the various
therapeutic agents, only oral pentosan
polysulfate sodium (PPS, Elmiron®) and
intravesical dimethyl sulfoxide (DMSO,
RIMSO-50®) are FDA approved for the treatment
of IC, all others are used off-label.31,32 Table 4
includes a summary of commonly used agents for
the management of IC. PPS is thought to help
restore urothelial barrier function in patients with
IC. Moldwin et al reviewed PPS in
placebo-controlled, double-blind studies in
patients with IC.33 Treatment with PPS (typically
300 mg/day) was associated with pain reduction
in 27–44% of patients compared with placebo
rates of 15–34% (37 vs. 21% overall for the studies
reviewed). Gastrointestinal disturbance is a
common side effect with PPS. Patients treated
with PPS should be educated about the time
required to reach full therapeutic effect, which
can take 3 to 6 months or longer. The tricyclic
antidepressant amitriptyline is commonly
included in the treatment algorithms for IC. In a
randomized, double-blind, placebo-controlled
study, Foster et al found no statistically significant
difference in overall symptom improvement
response rates between amitriptyline (55%) and
placebo (45%) in a 12-week study, however
subgroup analysis showed that patients who
were treated with at least 50 mg/day of
amitriptyline had significantly better response
rates relative to placebo (66 vs. 47%, P = 0.01).34 A
4-month placebo-controlled study showed that
treatment with amitriptyline (self-titration 25 mg
to 100 mg/day) was associated with significant
improvement in symptom scores, pain, and
urgency compared with placebo.35 Drowsiness,
dry mouth, and constipation are side effects
associated with amitriptyline; some patients
experience a “hangover” after use. Patients can
counter these side effects by altering the timing
when they take their medications, ie, taking them
between 5–7 PM instead of right before bed, as
well as taking a daily stool softener or flax seed oil
capsules. Antihistamine agents are used by many
clinicians for IC, particularly in patients with
allergy-related flares. In a 24-week study, Sant et
al showed that the combination of PPS (100 mg
TID) and hydroxyzine (50 mg daily) was
associated with a response rate of 40% compared
with controls (13%).36 In this study, treatment
with either hydroxyzine or PPS alone was not as
effective as the combination (23 and 28%
response rates, respectively). Hydroxyzine has
sedative effects, so patients are often advised to
take this treatment in the evening.
Direct application of medication to the bladder
with instillation therapy potentially minimizes
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Conquering IC: Identification and Management Strategies
Table 4: Pharmacological Treatment of IC
Treatment
Properties
Comments
Oral Agents
Pentosan polysulfate sodium
100 mg TID
Synthetic sulfated polysaccharide;
May require 3–6 months for
3–6% excreted in urine; theoretically symptom improvement
replenishes the urothelial GAG layer Side effects: minor GI disturbances
Amitriptyline
10 mg daily; gradually titrated
up to 100 mg
Tricyclic antidepressant with
analgesic properties
Side effects: drowsiness, nausea,
constipation; dry mouth, arrhythmia,
“vivid dreams”/nightmares, some
patients experience a “hangover”
Gabapentin
300-1200 mg TID
Anticonvulsant used for
neuropathic pain
Side effects: drowsiness, dizziness,
slight weight gain
Pregabalin
150 mg BID
Anticonvulsant used for
neuropathic pain
Side effects: drowsiness, dizziness,
slight weight gain, angioedema
Hydroxyzine
10 mg daily titrated up to 75 mg
Antihistamine
Side effects: sedation, weakness,
dizziness, dry mouth, constipation
Montelukast
10 mg daily
Antihistamine, leukotriene modifier
Side effects: headache, pharyngitis,
cough
Cyclosporine A
2-3 mg/kg/day divided in 2 doses
Immunomodulator
Side effects: nephrotoxicity,
hypertension, immunosuppression
Dimethyl sulfoxide (DMSO)
50% solution
Anti-inflammatory, analgesic,
smooth muscle relaxation
Side effects: garlic-like taste/odor
Heparin
10,000-40,000 units in 10 mL
sterile H2O
Anti-inflammatory and surface
protective
Side effects: dysuria, urethral/bladder
irritation
Lidocaine
1-2% solution
Analgesic
Side effects: dysuria, urethral/bladder
irritation, urinary retention
Intravesical Agents*
“Cocktails”
Anti-inflammatory, analgesic,
Heparin + lidocaine + bicarbonate; surface protective
Heparin + bicarbonate + steroid +
lidocaine
Side effects: dysuria, urethral/bladder
irritation, urinary retention
Bupivacaine (Marcaine)
0.5% solution
Side effects: dizziness,
lightheadedness, cardiotoxicity,
dysuria/bladder irritation, urinary
retention
Analgesic
*These agents are used individually or as “cocktails”
❨15❩
Conquering IC: Identification and Management Strategies
side effects due to limited systemic drug
absorption. However, these treatments do require
catheterization, which can cause urethral
irritation. Drugs administered by intravesical
installation are used individually or as “cocktails.”
A prospective, double-blind, cross-over,
placebo-controlled trial recently reported by
Parsons et al evaluated intravesical instillation of
alkalinized lidocaine and heparin in patients with
IC. Active treatment (heparin + lidocaine +
sodium bicarbonate) was associated with
significant improvement over 12 hours in pain
scores and symptom improvement (including
urgency) compared with controls (42 vs 21%,
P = 0.04; and 50 vs 13%, P = 0.01 respectively).37
Cystoscopy under anesthesia with
hydrodistension is a third-line therapy according
to the 2011 AUA guidelines for patients who have
persistent symptoms and have failed other
treatment approaches. This procedure serves 3
purposes: 1) evaluate for bladder tumors or
Hunner’s lesions; 2) hydrodistension serves as a
treatment with significant relief of symptoms for
some patients; and 3) distention allows disease
“staging” by determining the anatomic bladder
capacity.1 When Hunner’s lesions are noted on
cystoscopy, the AUA guidelines recommend
fulguration and/or injection with
triamcinolone.38,39 Sacral nerve stimulation and
intradetrusor injection of onabotulinumtoxinA
have been used to address urinary frequency and
urgency; however these approaches are not FDA
approved for patients with IC. Bladder
augmentation and cystectomy are considered
appropriate only for patients with severe disease,
refractory to all other treatment options. These
patients must be aware of and accept the
associated life-long changes.
❨16❩
Conquering IC: Identification and Management Strategies
Support for Patients
As stated previously, patient education about IC,
the disease course, and treatment expectations
are imperative to help patients manage this
chronic condition. A team approach in the office,
in which all staff understand the needs of patients
with IC will help to remove any perceived barriers,
and can reinforce the availability of the practice
to support patients with challenges and
management of flares. Patients should be
encouraged to include members of their support
network in appointments, where appropriate.
Patients will benefit from understanding
strategies for the management of flares, such as
application of ice or heat, warm baths, use of
vaginal suppositories (for example, valium +
baclofen + lidocaine prepared by a compounding
pharmacy), urinary analgesics, intravesical
instillations (performed in the office or at home),
oral analgesics, and trigger point injections into
abdominal or pelvic floor muscles.
Table 6: Non-Profit Patient
Resource Providers
• Interstitial Cystitis Association
www.ichelp.org
– ICA Update
– Support Groups
• American Urological Association
www.auanet.org
• National Institute of Diabetes and
Digestive and Kidney Diseases
www.kidney.niddk.nih.gov
• International Urogynecological Association
www.iuga.org
• National Vulvodynia Association
www.nva.org
• Urology Care Foundation
www.UrologyHealth.org
• American Association of Sexuality
Educators Counselors and Therapists
(AASECT)
www.aasect.org
Table 5: A Multidisciplinary Approach
to Interstitial Cystitis
• Nursing
• Physical therapy (pelvic floor specialists
trained in myofascial release)
• Nutrition consultation
• Pain clinic
• Gastroenterology
• Gynecology
• Urogynecology
• Urology
• Rheumatology
A multidisciplinary team is involved in the care of
patients with IC, and referral to specialists is
especially important for patients with persistent
symptoms (Table 5).
Numerous resources are available to educate and
support patients with IC, such as those included
in Table 6.
• Sex therapy
• Psychiatry/psychology/counseling
• Musculoskeletal specialty
❨17❩
Conquering IC: Identification and Management Strategies
Conclusion
Historically, IC has been an under-recognized
condition with a negative impact on quality of life
for affected patients. However, early recognition and
prompt initiation of treatment can improve pain,
symptoms, and overall outcomes. There are gaps in
our understanding of the pathophysiology of IC, and
as more is learned about this syndrome, hopefully
additional therapeutic agents will be incorporated
into treatment algorithms. There are many treatment
approaches for IC, and it is essential to consider new
modalities, multimodal therapies, and a
multidisciplinary approach when unsatisfactory
results are obtained with current treatment.
There is reason for optimism for patients with IC and
chronic pelvic pain syndromes. Research efforts are
ongoing to better understand the causes of these
conditions, improve diagnosis, and develop new
treatments. The Multidisciplinary Approach to the
Study of Chronic Pelvic Pain (MAPP) Research
Network is devoted to better understanding the
phenotypes, etiology, and natural history of urologic
chronic pelvic pain syndromes.40 Studies exploring
the potential relationships of IC/CP/CPPS with pain
disorders such as IBS, fibromyalgia, and chronic
fatigue syndrome are included in the MAPP
initiative. A system for clinically phenotyping
patients with urologic pelvic pain was developed by
There is reason for optimism
for patients with IC and chronic
pelvic pain syndromes
Shoskes et al, which can be used to guide and
optimize therapy.41 The “UPOINT” system includes
Urinary complaints, Psychosocial, Organ specific,
Infection, Neurogenic/systemic and Tenderness of
muscles domains. The diagnosis of IC would be
greatly facilitated by a definitive diagnostic test.
Research into clinically relevant biomarkers for IC is a
step toward this goal. Parsons et al have recently
reported a significant difference in the glycosylation
of Tamm-Horsfall protein in the urine of patients
with IC compared with controls.42 Investigation into
the role of antiproliferative factor (APF) and
associated signaling pathways in IC is ongoing.43 A
novel approach for treatment of IC involves
liposomal delivery of drugs to the bladder. Chuang
et al reported promising results of intravesical
liposomal PPS for patients with IC, which provides
the groundwork for larger, placebo-controlled
trials.44 With continued clinical interest, research, and
multidisciplinary efforts, advances can be
anticipated in the identification and management of
patients with IC.
Research Grant Resources
IC Research Funding Opportunities: http://www.ichelp.org/page.aspx?pid=559
ICA Pilot Research Program: http://www.ichelp.org/page.aspx?pid=457
AUGS Research Grant Programs: http://www.augs.org/p/cm/ld/fid=62
❨18❩
Conquering IC: Identification and Management Strategies
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❨21❩
Interstitial Cystitis Association
www.ichelpcme.org
Developed in Cooperation with
A Continuing Education Company &
NPA