Guidelines
Guideline of guidelines: bladder pain syndrome
Sachin Malde*, Stefano Palmisani†, Adnan Al-Kaisy† and Arun Sahai*
*Departments of Urology and †Pain Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
Objectives
Bladder pain syndrome (BPS) is a debilitating condition
which can be difficult to diagnose and treat due to the lack of
consensus on aetiology, definition, and management. The aim
of this review is to summarise the findings from major
national and international guidelines on the management of
BPS, highlighting areas of disagreement and uncertainty.
Methods
We performed a Medline/PubMed search from 1st January
2000 to 31st December 2017 in order to identify relevant
guidelines addressing BPS/interstitial cystitis. We also
manually searched the websites of major national and
international societies. The following guidelines were included
in this review: European Association of Urology, American
Urological Association, International Society for the Study of
BPS, International Consultation on Incontinence,
International Continence Society, East Asian guideline, Royal
College of Obstetricians and Gynaecologists/British Society of
Urogynaecology, and the Canadian Urological Association.
Results
There is disagreement between guidelines on the exact
definition of BPS and the nomenclature to use to describe
this condition. However, all agree that the diagnosis is
dependent on the presence of pain, pressure, or discomfort,
in addition to at least one urinary symptom, in the absence
of other diseases that could cause pain. Exclusion of other
pathology that could cause similar symptoms requires
Introduction
Bladder pain syndrome (BPS) is a severely debilitating,
chronic disorder of unknown aetiology that has a significant
negative impact on quality of life. A community-based study
in women in the USA reported a high prevalence rate of BPS
of 2.7%–6.5% [1]. Despite this, there is still a lack of
consensus worldwide on how to define the condition, the
nomenclature to use, and how to treat patients optimally.
This is reflected in the considerable variation in management
worldwide, and the divergent recommendations in national
and international guidelines. The aim of the present review
was to summarize the key findings from the numerous major
© 2018 The Authors
BJU International © 2018 BJU International | doi:10.1111/bju.14399
Published by John Wiley & Sons Ltd. www.bjui.org
thorough evaluation, and is recommended in all guidelines.
There is also disparity in the recommended diagnostic
investigation of BPS, with hydrodistension and bladder biopsy
either recommended, considered optional, or not
recommended, by different guidelines. It is accepted that BPS
can be diagnosed clinically, without invasive investigation, but
cystoscopy and diagnostic hydrodistension aids sub-typing of
patients and may help direct treatment strategies. Patients
should be phenotyped in order to direct multimodal
treatment (including behavioural, physical, emotional, and
psychological therapy), and treatments should follow a
stepwise approach starting with the most conservative.
Although widely performed, hydrodistension as a therapeutic
strategy has a limited evidence base and is unlikely to provide
long-term resolution of symptoms
Conclusion
There are multiple national and international guidelines for
the diagnosis and management of BPS, and this review has
highlighted the differences in nomenclature, definitions, and
recommended diagnostic tests between guidelines. The overall
evidence base for the majority of treatments for BPS/IC is of
low-quality, and larger randomised trials are required to more
accurately inform guideline recommendations and clinical
management of this complex group of patients.
Keywords
Bladder pain syndrome, Interstitial cystitis, Chronic pelvic
pain, Guidelines
guidelines for BPS, highlighting areas of disagreement and
uncertainty.
Throughout the literature, a range of terms are used
interchangeably to describe this condition, including BPS,
painful bladder syndrome (PBS), interstitial cystitis (IC), and
combinations of these terms (IC/PBS, IC/BPS, BPS/IC and
IC/BPS) [2]. A working group from the ICS has recently
attempted to standardize the terminology in chronic pelvic
pain syndromes, and has distinguished between hypersensitive
bladder, IC/BPS, and IC with Hunner lesion [3]. It is now
thought, however, that IC with Hunner lesion represents a
different disease process, requiring different management
strategies, and there is debate about whether this should now
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Table 1 Definitions of bladder pain syndrome/interstitial cystitis.

IASP The occurrence of persistent or recurrent pain perceived in the urinary bladder region, accompanied by at least one other symptom, such as pain
worsening with bladder filling and daytime and/or night-time urinary frequency. There is no proven infection or other obvious local pathology. BPS
is often associated with negative cognitive, behavioural, sexual or emotional consequences as well as with symptoms suggestive of lower urinary tract
and sexual dysfunction.
ESSIC Chronic pelvic pain, pressure or discomfort of >6 months’ duration, perceived to be related to the urinary bladder, accompanied by at least one other
urinary symptom such as persistent urge to void or urinary frequency. Confusable diseases as the cause of the symptoms must be excluded. The
presence of other organ symptoms as well as cognitive, behavioural, emotional and sexual symptoms should be addressed.
AUA An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with LUTS of >6 weeks’ duration, in the
absence of infection or other identifiable causes.
EAU Persistent or recurrent pain perceived in the urinary bladder region, accompanied by at least one other symptom, such as pain worsening with bladder
filling and daytime and/or night-time urinary frequency. There is no proven infection or other obvious local pathology. BPS is often associated with
negative cognitive, behavioural, sexual or emotional consequences, as well as with symptoms suggestive of lower urinary tract and sexual dysfunction.
ICI Men or women with pain, pressure, or discomfort that they perceive to be related to the bladder with at least one urinary symptom, such as frequency
not obviously related to high fluid intake, or a persistent urge to void
East Asian Guideline IC is defined by HSB symptoms and bladder pathology after excluding other diseases explaining symptoms. Bladder pathology is either a Hunner lesion
or mucosal bleeding after distension. HSB is defined as the presence of hypersensitive bladder symptoms (discomfort, pressure or pain in the bladder
usually associated with urinary frequency and nocturia) but no proven bladder pathology or other explainable diseases.
CUA Uses the same definition as the AUA guideline.
ICS A compelling need to urinate, due to pain or an unpleasant sensation, that is difficult to defer.

BPS, bladder pain syndrome; CUA, Canadian Urological Association; EAU, European Association of Urology; ESSIC, International Society for the Study of BPS: HSB, hypersensitive
bladder; IASP, International Association for the Study of Pain; ICI, International Consultation on Incontinence.

Table 2 National Institute of Diabetes and Digestive and Kidney Diseases

diagnostic criteria for interstitial cystitis.
be completely separated from BPS. In the present review, we
will use the term referred to by the guideline that is being
discussed.
Methodology
We performed a Medline/PubMed search for the period 1
January 2000 to 31 December 2017 to identify relevant
guidelines addressing BPS/IC. We also manually searched the
websites of the following national and international societies
to identify relevant guidelines for inclusion in this review: the
AUA, European Association of Urology (EAU), International
Society for the Study of BPS (ESSIC), Societe Internationale
d’Urologie, ICS, BAUS, Canadian Urological Association
(CUA), Japanese Urological Association, Urological Society of
India, Urological Society of Australia and New Zealand,
International Association for the Study of Pain (IASP), British
Pain Society, and British Society of Urogynaecology (BSUG).
Guidelines from the British Pain Society were not included in
the present review as, although they offer general guidance on
pelvic pain, they do not focus specifically on bladder pain
syndrome. The following guidelines were included in the
review: EAU [4], AUA [5], ESSIC [6,7], International
Consultation on Incontinence (ICI) [8], ICS [3], East Asian
guideline [9,10], Royal College of Obstetricians and
Gynaecologists/BSUG [11] and the CUA [12].
To be diagnosed with IC, patients must have either glomerulations on cystoscopic
examination or a classic Hunner ulcer, and they must have either pain associated
with the bladder or urinary urgency.
An examination for glomerulations should be undertaken after distention of the
bladder under anaesthesia to 80 to 100 cm H2O for 1–2 min. The bladder may be
distended up to two times before evaluation. The glomerulations must be diffuse
(present in at least three quadrants of the bladder) and there must be at least 10
glomerulations per quadrant. The glomerulations must not be along the path of
the cystoscope (to eliminate artefact from contact instrumentation).
Presence of any one of the following excludes a diagnosis of interstitial cystitis:
1. Bladder capacity of >350 mL on awake cystometry using either a gas or liquid
filling medium;
2. Absence of an intense urge to void with the bladder filled to 100 mL of gas or
150 mL of liquid filling medium;
3. Demonstration of phasic involuntary bladder contractions on cystometry using
the fill rate just described;
4. Duration of symptoms <9 months;
5. Absence of nocturia;
6. Symptoms relieved by antimicrobial agents, urinary antiseptic agents,
anticholinergic agents, or antispasmodic agents;
7. Frequency of urination while awake of <8 times per day;
8. Diagnosis of bacterial cystitis or prostatitis within a 3-month period;
9. Bladder or ureteric calculi;
10. Active genital herpes;
11. Uterine, cervical, vaginal or urethral cancer;
12. Urethral diverticulum;
13. Cyclophosphamide or any type of chemical cystitis;
14. Tuberculous cystitis;
15. Radiation cystitis;
16. Benign or malignant bladder tumours;
17. Vaginitis;
18. Age <18 years.

IC, interstitial cystitis.

Results
Definition and Nomenclature
The nomenclature for BPS has undergone a number of
changes over the past century, with the term ‘interstitial
cystitis’ (originally thought to describe a true inflammatory
end-organ bladder disorder) being increasingly replaced by
the term ‘bladder pain syndrome’ (a primary pain syndrome
with symptoms perceived to be related to the bladder). As
mentioned above, however, it is increasingly being considered
that IC (defined by the presence of Hunner’s lesions)

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Table 3 Summary of specific recommendations for diagnostic evaluation.

Diagnostic test EAU AUA ICI ICS East Asian RCOG CUA

History U U U U U U U
Physical examination U U U U U U U
Urine analysis U U U U U U U
Urine culture U U U U U U U
Urine cytology U* U* U* U* U U* U*
Symptom scores U U – U U U U
Food diary – – – – – U –
Frequency–volume chart – U U U U U U
Uroflowmetry – – – U – – –
Post-void residual urine volume – U – U U – U†
Cystoscopy U – U† U U – U
Diagnostic hydrodistension U – U† U U NR U†
Bladder biopsy U – U† – U† NR NR
Pelvic imaging – – – – U† – U†
Urodynamics – – U† U† U† – NR
Potassium sensitivity test – – NR – NR NR
Intravesical local anaesthetic challenge – – – U† – – U†

CUA, Canadian Urological Association; EAU, European Association of Urology; ICI, International Consultation on Incontinence; NR, not recommended; RCOG, Royal College of
Obstetricians and Gynaecologists. All guidelines recommend exclusion of other specific diseases, and so the relevant diagnostic test required to exclude a differential diagnosis should
be performed if clinical suspicion exists. *In high-risk groups. †Optional in select patients.

represents a distinct disease process, with different
pathological and endoscopic features, and different responses
to therapy. The different definitions are highlighted in
Table 1. The EAU guideline recommends use of the term
BPS. The EAU incorporates the negative psychological,
emotional and sexual consequences associated with BPS in
their definition, and advise against the use of older terms
such as ‘interstitial cystitis’, ‘painful bladder syndrome’, and
‘PBS/IC’ or ‘BPS/IC’.
The ESSIC guideline also prefers the term BPS, but recognizes
that omitting the term IC may affect reimbursement in
certain health services, so it was decided that the term BPS/IC
could be used. The ESSIC definition requires symptoms to be
present for >6 months. It has been reported that many
patients describe a sensation of pressure or discomfort, but
report this as urge rather than pain [13]; therefore, the term
‘persistent urge’ is included in the ESSIC definition, and
patients that complain of a pressure or discomfort are
considered as having BPS.
Recognizing the controversy around nomenclature, the AUA
guidelines panel decided to use the term IC/BPS and consider
these terms synonymous. The definition used is the one
agreed on by the Society for Urodynamics and Female
Urology, with a requirement for presence of symptoms for
>6 weeks [14]. The inclusion of a shorter timeframe allows
the diagnosis to be made sooner and treatment to begin more
rapidly.
The ICI committee agreed that the term BPS fits in well with
the taxonomy of the IASP, and recommended that this term
be used. The ICI also suggest that the term IC should be
reserved for patients who have a Hunner lesion, and this
should signify a distinct disease, separate from BPS.
The East Asian guideline is the only guideline that uses the
terms IC and hypersensitive bladder syndrome (HSB). The
term HSB was introduced as it was felt to be broader than a
‘pain syndrome’, including patients who complained of
pressure or discomfort rather than pain. As opposed to the
North American and European guidelines, which identify pain
as the key symptom, the Asian guidelines emphasize frequency/
urgency as the predominant complaint, incorporating both
HSB and overactive bladder as subgroups, and with PBS
representing a distinct subgroup of HSB with pain.

Table 4 International Society for the Study of Bladder Pain Syndrome (BPS) classification of BPS subtype based on cystoscopy with hydrodistension and
bladder biopsy results.

Biopsy Cystoscopy with hydrodistension

Not performed Normal Glomerulations* Hunner lesion†

Not performed XX 1X 2X 3X
Normal XA 1A 2A 3A
Inconclusive XB 1B 2B 3B
Positive‡ XC 1C 2C 3C

*Cystoscopy: glomerulations grades 2–3. †With or without glomerulations. ‡Histology showing inflammatory infiltrates and/or detrusor mastocytosis and/or granulation tissue and/
or intrafascicular fibrosis.

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Table 5 Summary of grades of recommendation for different treatment options for BPS/IC

Treatment EAU AUA ICI East Asian RCOG CUA

© 2018 The Authors

Conservative
Multimodal therapy (pain management, behavioural, psychological, educational) A Clinical Principle C B – A
Stress management – Clinical Principle C B D B
Dietary advice C Clinical Principle C B D B
Physiotherapy A Standard C C B B
Acupuncture – – – C D B
Trigger point injections into pelvic floor – –– – – – D
Transcutaneous electrical nerve stimulation (TENS) – – – C – –

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Oral therapies
Gabapentin – – C – – C
Amitriptyline A Option B B B B
Cimetidine Limited value Option C C B B
Hydroxyzine – Option D C NR B
Oral pentosan polysulphate A Option D B NR D
Oral pentosan polysulphate + subcutaneous heparin A – – – – –
Antibiotic regimes – NR D NR NR –
Sulphatast tosilate – – D C – –
Long–term glucocorticoids NR NR – NR NR –
Intravesical therapies
DMSO NR Option B B C B
Intravesical pentosan polysulphate A – D C – C
Intravesical hyaluronic acid B – D C B C
Intravesical chondroitin sulphate B – D C D D*
Heparin C Option C C D C
Lignocaine A† Option C C B B
Oxybutynin Limited value – D C – C
BCG NR NR NR NR NR NR
Capsaicin/resiniferatoxin – – NR NR NR NR
Cystoscopic techniques
Hydrodistension (short–duration low–pressure) NR Option C B D C
Fulguration of ulcers B Recommendation C B Recommended B
Injection of triamcinolone to ulcers – Recommendation – – – –
Other treatments
BTX-A C Option D C B C
BTX-A + hydrodistension A – – – – –
SNM B Option C C D C
Cyclosporin A – Option – C D C
Major surgery: all recommend as option of last resort
Urinary diversion or substitution cystoplasty  cystectomy A Option C C D C

BTX-A, botulinum toxin A; CUA, Canadian Urological Association; EAU, European Association of Urology; ICI, International Consultation on Incontinence; NR, not recommended; RCOG, Royal College of Obstetricians
and Gynaecologists; SNM, sacral neuromodulation. *As part of multimodal therapy. †With sodium bicarbonate.

The ICS recognize that patients may perceive and experience
pain in different ways, and distinguish between hypersensitive
bladder, IC/BPS, and IC with Hunner lesion.
All guidelines agree that this condition is a diagnosis of
exclusion, and all require the presence of pain, pressure or
discomfort, in addition to at least one urinary symptom. The
increase of pain on bladder filling is not always present, and
so has been left out of most of the guidelines’ definitions. The
extensive National Institute of Diabetes and Digestive and
Kidney Diseases diagnostic criteria for IC (Table 2) were
primarily designed to assess eligibility for research trials, and
were shown to be too restrictive for clinical use, leading to
under-diagnosis [15,16]. They are not, therefore, routinely
used in clinical practice.
Diagnosis
The ICI has attempted to create a guideline that is
harmonious with the different international guidelines.
Importantly, it is widely accepted that the diagnosis of BPS
can be made clinically and no invasive investigations (e.g.
cystoscopy, urodynamics) are required prior to making the
diagnosis or initiating treatment.
History
The diagnosis of BPS can be challenging because of the wide
variation in presenting symptoms and lack of clear diagnostic
criteria. There is a lack of high-quality evidence regarding
evaluation and investigation, and therefore the
recommendations on diagnosis are based primarily on expert
opinion (Table 3). BPS is a diagnosis of exclusion, and all
guidelines recommend a thorough history, a physical
examination and laboratory tests to aid diagnosis and exclude
specific diseases that may cause pelvic pain. A thorough
history should include assessing the characteristics of the
pain, any triggers (such as dietary factors) associated LUTS,
and any symptoms related to the other pelvic organs. The
EAU guideline states that the nature of the pain is important,
with the following features key to disease definition: symptom
location (suprapubic); symptom descriptors (pain, pressure or
discomfort); and exacerbating factors (increases with
increasing bladder content, relieved by voiding, and
aggravated by food or drink) [17]. The East Asian guidelines
note that a significant number of patients do not complain of
pain [18,19], therefore, symptoms of discomfort or pressure
should also be sought. Medical and surgical history, as well as
drug history (including ketamine use), should be elicited to
exclude any other specific diseases or medications that cause
pelvic pain. The ESSIC guidelines suggest that special
emphasis be given to previous pelvic operations, previous
UTI, previous pelvic radiation treatment, and autoimmune
diseases. The EAU guideline highlights the importance of
Bladder pain syndrome
taking a history about the function of all organs in the pelvic
area systematically, including cognitive, behavioural, sexual
and emotional consequences (grade A). The AUA guideline
also states that symptoms should be present for at least
6 weeks, and in women the relationship of the pain to
menstruation should be sought.
Physical Examination
A detailed physical examination of the abdomen, pelvis,
genitalia, and prostate in men, should be performed, with
specific attention paid to areas of tenderness. A
musculoskeletal and focused neurological examination should
be included, and pelvic floor muscle examination for
tenderness and trigger points should be included as this may
have a bearing on diagnosis and treatment. This is
recommended by all guidelines.
Frequency Volume Chart and Symptom Scores
Patients with BPS typically have lower voided volumes and higher
voiding frequency compared with asymptomatic patients, and
therefore the use of a frequency volume chart is recommended in
the initial evaluation. The AUA guideline recommends a
minimum 1-day frequency volume chart, whilst the ESSIC
guideline recommends a 3-day chart. The Royal College of
Obstetricians and Gynaecologists (RCOG) guideline also
recommends the use of a food diary to identify dietary triggers.
The use of a validated symptom and quality-of-life scoring
instrument is recommended for initial assessment and follow-
up, and the O’Leary–Sant Interstitial Cystitis Symptom and
Problem Index (ICSI/ICPI) is highlighted by most guidelines.
No specific recommendation is made about which symptom
score to use, but the CUA guideline recommends the use of
the ICSI/ICPI, Bladder Pain/Interstitial Cystitis Symptom
Score (BPIC-SS), or the Pelvic Pain and Urgency/Frequency
(PUF) score to grade severity of symptoms and assess
response to treatment. ESSIC and RCOG guidelines also
recommend the use of a visual analogue scale to assess pain
severity (grade D).
Laboratory Examination
There is agreement among all guidelines that urine dipstick
and urine culture should be performed to exclude UTI, and
culture for tuberculosis should be included if sterile pyuria
is present (Table 3). Urine cytology is specifically mentioned
by the EAU, AUA, ESSIC, RCOG and CUA guidelines, and
should be tested in patients who are at high risk of
urothelial malignancy. The ESSIC, RCOG and CUA
guidelines also state that testing for ureaplasma and
chlamydia in women could be considered, especially in
symptomatic patients with negative urine cultures and
pyuria (grade C, level of evidence 4).
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Fig. 1 Diagnostic and management algorithms from the different guidelines.
Chronic Pelvic Pain
Physical
History
examination
yes
Symptom of a well
known disease
no
Gastro-
Urology Gynaecology
enterology
Phenotype and proceed according to Chronic Pelvic Pain Guideline.
EAU guideline diagnostic algorithm [4]
Cystoscopy
Although there are no widely accepted diagnostic cystoscopic
features for BPS, the EAU (grade A), ESSIC, RCOG, East
Asian, and CUA (grade C) guidelines all recommend that
cystoscopy be performed as part of the initial evaluation in
order to exclude other underlying pathology that may mimic
BPS. The AUA and ICI guidelines suggest that cystoscopy is
optional as a diagnostic test for IC/BPS, but should be
performed if another pathological process is suspected;
however, the ICS standardization working group has
recommended cystoscopy and hydrodistension to identify
Hunner’s lesions and to sub-classify patients according to the
ESSIC classification. Cystoscopy without hydrodistension may
reveal reduced bladder capacity in patients with BPS, as well
as the presence of Hunner’s lesions. Hunner’s lesions are
described as a circumscript, reddened mucosal area with
small vessels radiating towards a central scar, with a fibrin
deposit or coagulum attached to this area. This site ruptures
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Specific disease
associated
with pelvic pain
Pelvic pain
syndrome
Organ specific
symptoms present
yes
Pelvic
Neurology Sexology
floor
with increasing bladder distension, with petechial oozing of
blood from the lesion and the mucosal margins in a waterfall
manner. The presence of Hunner’s lesions has been
associated with more severe symptoms and smaller bladder
capacity, and their identification may help to direct treatment
strategies [20,21]. The ICS chronic pelvic pain working group
recommends cystoscopy to identify Hunner’s lesions as
effective treatment is available [22].
Hydrodistension
Hydrodistension is described as a prerequisite by the ESSIC
guideline in order to subtype patients with BPS according to
the ESSIC criteria (Table 4). Based on panel consensus, it was
felt that positive cystoscopic signs of BPS were glomerulations
(i.e. grades II–III) or Hunner’s lesions or both. Cystoscopic
findings are classified by the ESSIC group as: grade 0, normal
mucosa; grade I, petechiae in at least two quadrants; grade II,
large submucosal bleeding (ecchymosis); grade III, diffuse
 Bladder pain syndrome

Fig. 1 Continued.

IC/BPS
An unpleasant sensation (pain, pressure, discomfort) perceived to be related to
the urinary bladder, associated with lower urinary tract symptoms of more than six
week duration, in the absence of infection or other identifiable causes

RESEARCH TRIALS
BASIC ASSESSMENT Confirmed or FIRST-LINE TREATMENTS Patient enrollment as
– History – Urinalysis, culture Uncomplicated IC/BPS – General Relaxation/Stress Management appropriate at any point in
treatment process
– Frequency/Volume Chart – Cytology if smoking hx – Pain Management
– Post-void residual – Symtom questionnaire – Patient Education
– Physical examination – Pain evaluation – Self-care/Behavioral Modification

Signs/Symptoms of SECOND-LINE TREATMENTS

Dx Urinary Tract Infection
Complicated IC/BPS – Appropriate manual physical therapy techniques
– Oral: amitriptyline, cimetidine, hydroxyzine, PPS
– Intravesical: DMSO, Heparin, Lidocaine

– Pain Management
– Incontinence/OAB
TREAT & REASSESS
– GI signs/symptoms
Microscopic/gross
hematuria/sterile pyuria
THIRD-LINE TREATMENTS
– Gynecologic signs/symptoms – Cystoscopy under anesthesia w/ hydrodistention

CLINICAL MANAGEMENT PRINCIPLES – Pain Management

– Tx of Hunner’s lesions if found
– Treatments are ordered from most to least conservative;
surgical treatment is appropriate only after other treatment
CONSIDER: options have been found to be ineffective (except for
treatment of Hunner’s lesions if detected )
– Urine cytology FOURTH-LINE TREATMENTS
– Imaging – Initial treatment level depends on symptom severity, – Intradetrusor botulinum toxin A
– Cystoscopy clinician judgment, and patient preferences
– Neuromodulation
– Urodynamics – Multiple, simultaneous treatments may be
considered if in best interests of patient – Pain Management
– Laparoscopy
– Ineffective treatments should be stopped
– Specialist referral (urologic or
non-urologic as appropriate) – Pain management should be considered throughout course of therapy
with goal of maximizing function and minimizing pain and side effects
FIFTH-LINE TREATMENTS
– Diagnosis should be reconsidered if no improvement – Cyclosporine A
within clinically-meaningful time-frame
– Pain Management

SIXTH-LINE TREATMENTS
The evidence supporting the use of Neuromodulation, Cyclosporine A, and BTX for IC/BPS is limited by many factors – Diversion w/ or w/out cystectomy
including study quality, small sample sizes, and lack of durable follow up. None of these therapies have beeen approved
by the U.S. Food and Drug Administration for this indication. The panel belives that none of these interventions can – Pain Management
be recommended for generalized use for this disorder, but rather should be limited to practitioners with experience
managing this syndrome and willingness to provide long term care of these patients post intervention. – Substitution cystoplasty
Note: For patients with end-stage structurally small bladders, diversion
Copyright © 2014 American Urological Association Education and Research, Inc. is indicated at any time clinician and patient believe appropriate.

AUA guideline management algorithm [5]

global mucosal bleeding; grade IV, mucosal disruption, with Bladder Biopsy
or without bleeding/oedema.
Results of bladder biopsy form a key component of the
The EAU guidelines give a grade A recommendation to ESSIC classification system and are recommended by
subtyping patients with BPS according to the ESSIC ESSIC guidelines to confirm the diagnosis and for the
criteria, which require hydrodistension and biopsy. The purpose of phenotyping patients. It is recommended that
East Asian guidelines support this recommendation, but a total of three biopsies be taken from each lateral wall
highlight recent evidence showing that the presence of and dome, as well as a separate biopsy from any other
glomerulations does not correlate with symptoms and abnormal lesions. Positive findings on biopsy were
should not be included in the diagnosis or phenotyping of considered to be inflammatory infiltrates, granulation
BPS [23]. Consequently, the AUA, ICI and CUA guidelines tissue, detrusor mastocytosis, or intrafascicular fibrosis.
suggest hydrodistension is optional as a diagnostic test The EAU guideline states that biopsies are helpful in
because of conflicting evidence regarding its utility, but establishing or supporting the clinical diagnosis of both
may be appropriate in specific cases. The RCOG guideline classic and non-lesion types of the disease; however, other
does not recommend hydrodistension. guidelines state that none of these features are diagnostic

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Fig. 1 Continued.

PATIENT SELECTION
patient with chronic pelvic pain, pressure or discomfort
perceived to be related to the urinary bladder
accompanied by at least one other urinary symptom
such as persistent urge to void or frequency

EXCLUSION OF CONFUSABLE DISEASES

medical history, physical examination, urinanalysis, urine
cultures, PSA in males >40 yrs, uroflowmetry, post-void
residual urine volume by ultrasound scanning,
cystoscopy and biopsy

CLASSIFICATION OF BPS
cystoscopy with hydrodistension1 and biopsy if indicated

symbol 1: cystoscopy findings symbol 2: biopsy findings

X: not done X: not done

1: normal A: normal
2: glomerulations grade II or B: inconclusive
III C: inflammatory infiltrates,
3: Hunner’s lesion (with or granulation tissue, detrusor
without glomerulations) mastocytosis or intra-
fascicular fibrosis
1 in the same session as the cystoscopy above if possible
ESSIC guideline diagnostic algorithm [6,7]

and so the AUA guideline states that bladder biopsy is
only indicated to exclude other pathologies if a lesion of
uncertain nature is present, but should not form part of
the routine diagnostic process. Similarly, the East Asian
guidelines suggest bladder biopsy is optional, and it is not
recommended by RCOG and CUA guidelines (grade C,
level of evidence 3) for the diagnosis of BPS.
Pelvic Imaging
The role of pelvic imaging is only specifically mentioned in
the East Asian and CUA guidelines as an optional test when
alternative clinical conditions are suspected; however, all
guidelines state that other conditions that could cause pelvic
pain must be excluded in order to diagnose BPS, therefore,
pelvic imaging should be performed to exclude other
conditions if clinically suspected.
Urodynamics
There is agreement among guidelines that urodynamics
should not be recommended as part of the standard
diagnostic investigation of BPS. It is considered an optional
test that should only be performed for patients with a
complicated history that suggests the possibility of alternative
diagnoses (e.g. voiding dysfunction, BOO, overactive bladder
and stress urinary incontinence).
Potassium Sensitivity Test
The intravesical instillation of potassium chloride as a
diagnostic test for BPS is controversial and not widely
performed [24]. It was thought that abnormal epithelial
(GAG layer) permeability allowed potassium ions to cross the
epithelium, resulting in pain; however, potassium chloride has
been shown to have poor sensitivity and specificity for
diagnosing IC, and does not conclusively predict successful
response to epithelial-directed therapies, such as pentosan
polysulphate [25,26], therefore, the ICI does not consider it a
valid diagnostic test for IC and so recommends against its use
(grade A, level of evidence 1). It is considered an optional test
by the ESSIC and East Asian guidelines, but in view of the
discomfort caused by the test and the lack of proven
diagnostic or predictive utility, it is not recommended by the
RCOG and CUA guidelines (grade C, level of evidence 3).
Intravesical Local Anaesthetic Challenge Test
The intravesical instillation of local anaesthetic as a
diagnostic test to determine whether pelvic pain is

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 Bladder pain syndrome

Fig. 1 Continued.

BLADDER PAIN SYNDROME

Pain, pressure or discomfort perceived “Complicated” BPS:

SYMPTOMS to be related to the bladder with at • Incontinence
least one other urinary symptom (e.g. • Urinary infection
frequency, nocturia) • Haematuria
• Gynaecologic signs/symptoms

History
BASIC • Bladder diary or frequency/volume Consider:
ASSESSMENT chart • Urine cytology
• Focused physical examination • Further imaging
• Urinalysis, culture • Endoscopy
• Urodynamics
• Laparoscopy
URINARY INFECTION

Test and reassess

“Uncomplicated BPS” Normal Abnormal

1ST LINE RX
Conservative Therapy
Stress reduction (B)
Patient education (B)
Dietary manipulation (B
Nonprescription analgesics
Pelvic floor relaxation
Pelvic floor physical therapy (A)
Consult if associated disease

TREAT AS INDICATED

BPS REQUIRING MORE ACTIVE INTERVENTION

Consider oral and or intravesical therapies; (B)

2ND LINE
Consider physical therapy; (A)
TREATMENT
Consider cystoscopy with hydrodistention under anaesthesia and treatment of any
Hunner lesion (B)
(no hierarchy implied)

3RD LINE Consider, in not done previously:

TREATMENT Cystoscopy under anaesthesia with bladder hydrodistension fulguration, resection or
steroid injection of Hunner lesion (B)

Sacral Nerve stimulation (B)

4TH LINE
Intra-detrusor botulinum toxin (B)
TREATMENT
Cyclosporine A (C)
Consider new treatment trials
(no hierarchy implied)

Consider: Improved with acceptable

5TH LINE
Diversion with or without cystectomy (C) quality of life:
TREATMENT
Substitution cystoplasty Follow and support

Note: The only FDA approved therapies are DMSO and pentosan polysulfate.
Consider CONTINENCE PRODUCTS for temporary support during treatment.

• Pain management is a primary consideration at every step of the algorithm

• Patient enrollment in appropriate research trial is a reasonable option at any point

• Evidence supportingSNS, cyclosporine A, and botulinum toxin for BPS remains limited. These interventions are appropriate only for practitioners with
experience in treating BPS and who are willing to provide long-term care post-intervention

ICI guideline management algorithm [8]

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Malde et al.

Fig. 1 Continued.

Hypersensitive bladder symptoms

Basic evaluation

Hypersensitive bladder (HSB)

Conservative or medical treatment

Other diseases
Not improved Cystoscopy (+Hydrodistension)

Treatment
IC (Hunner or non-Hunner) or non-IC HSB

Hydrodistension, fulguration of Hunner lesion

Not improved

Repeated or combined treatment with instillation, injection, and electrostimulation,

or cystectomy

East Asian guideline management algorithm [10]. Basic evaluation consists of the mandatory and
recommended or optional tests outlined in Table 3.

originating from the bladder has been evaluated [27].
The CUA guideline suggests this as an optional test for
those cases in which there is uncertainty as to whether
pain is originating from the bladder (grade C, level of
evidence 3). This diagnostic test is not mentioned in the
other guidelines.
Treatment
The principles of management of patients with BPS are to
improve quality of life and encourage realistic patient
expectations. The optimal management should involve
multimodal behavioural, physical and psychological
techniques, and management should proceed in a step-
wise manner, starting with the most conservative. The
different grades of recommendation for all treatment
options are shown in Table 5, and Fig. 1 shows the
different management algorithms from the different
guidelines.
Conservative Therapies
All guidelines recommend patient education regarding normal
bladder function, the chronic nature of BPS, and promoting
realistic expectations for management. Behavioural
modification strategies such as timed voiding, fluid
modification and bladder training are also recommended.
Dietary factors (e.g. acidic beverages, spicy foods, alcohol)
have been reported to exacerbate symptoms in up to 90% of
patients with BPS and so personalized dietary manipulation
should be part of the treatment strategy for these patients.
Physiotherapy is also recommended, especially for patients
with pelvic floor dysfunction, and phenotype-directed
multimodal management approaches (including stress
management and psychotherapy) are suggested as first-line
management options. The EAU and CUA guidelines highlight
the UPOINT classification system for phenotyping patients
with bladder or pelvic pain (Fig. 2). Acupuncture is
recommended by the East Asian, RCOG and CUA guidelines
as a non-invasive option for motivated patients, and trigger-
point injections with local anaesthetic are given a grade D
recommendation by the CUA guideline panel as an option
for patients with pelvic floor trigger-point pain.
Oral Therapies
Oral medications are considered second-line therapies.
There is variation in the oral therapies that are
recommended and the grades of recommendation assigned
by the different guidelines. Amitriptyline is recommended
by most guidelines with a grade A or B recommendation.
The RCOG guideline is the only one that does not
recommend oral pentosan polysulphate, based on the
results of a recent placebo-controlled trial that failed to

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 Bladder pain syndrome

Fig. 1 Continued.

Initial assessment If urinary tract infection: treat and reassess

• History: assess urinary
symptoms, pain, QoL
• Urine dipstick +/– MSU Consider other causes:
• Physical examination Malignancy, infection, overactive bladder, bladder
• Frequency/volume charts calculi, bladder outlet obstruction, prolapse,
endometriosis, radiation/drug-related cystitis

First-line treatments:
• Conservative: analgesia, stress relief, dietary modification, exercise, physical therapy, support groups
• If treatment fails – refer to secondary care

Second-line treatments:
• Oral amitriptyline, cimetidine
• If treatment fails – refer to an MDT, pain team +/– clinical psychologist

Third-line treatments:
• Intravesical DMSO, heparin, botulinum toxin A, lidocaine, chondroitin sulfate, hyaluronic acid

Fourth-line treatments:
• Neuromodulation – posterior tibial nerve or sacral nerve stimulation
• Oral cyclosporin A

Fifth-line treatments:
• Cystoscopy and hydrodistension
• If Hunner lesions are noted or if major surgery is considered – refer to a tertiary centre

Treatments that are not recommended: Long-term antibiotics, intravesical resiniferatoxin, intravesical BCG,
intravesical PPS, high-pressure long-duration hydrodistension and long-term oral glucocorticoids.

RCOG/BSUG guideline management algorithm [11]

show any difference between the treatment and control
groups [28]. The RCOG guideline also does not
recommend the use of hydroxyzine, based on a
randomized controlled trial showing no significant benefit
[29].
Intravesical Therapies
Intravesical instillations of anti-inflammatories, analgesics, or
agents that replenish the defective GAG layer in BPS have
been studied. Instillation of lidocaine/sodium bicarbonate and
pentosan polysulphate have both been given a grade A
recommendation by the EAU. Intravesical BCG is
unanimously not recommended. The CUA guideline
recommends intravesical alkalinized lignocaine for acute flare
symptoms (grade B, level of evidence 2), and this is also
recommended by the EAU for short-term improvement in
symptoms (grade A, level of evidence 1).
Cystoscopic Techniques
Bladder hydrodistension and transurethral fulguration of
Hunner’s lesions are discussed as third-line options for the
treatment of BPS after failure of the second-line therapies
described above. The technique of therapeutic
hydrodistension has not been standardized, but the ESSIC
group recommend maintaining distension at maximum
capacity for 3 min, with the irrigation fluid at a height of
80 cm above the pubic symphysis. This so-called low-
pressure, short-duration hydrodistension is one of the
commonest treatments used for BPS [30], but the evidence
base for its therapeutic role is limited. Although the majority

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Malde et al.

Fig. 1 Continued.

IC/BPS

All patients:
1. Patient education
2. Dietary modifications
3. Sexual counselling

Further treatment options selected based on:

Symptom phenotype
Degree of quality of life impairment
Patient preference
Availability/access
Adverse event profile

SYMPTOM PHENOTYPES

Organ-specific*
Urinary* Infectious Neurologic/systemic Tenderness
Psychosocial
Non-Hunner’s Hunner’s Antimicrobials
Bladder training Gabapentanoids Pelvic floor
Stress management
Anticholinergics Amitriptyline CyA Hydroxyzine physiotherapy,
and
Intravesical Cimetidine Endoscopic Cimetidine massage,
psychological support
agents (Heparin, Hydroxyzine (Fulguration, Sacral neuromodulation acupuncture,
DMSO, HA, CS, PPS laser, resection, trigger point
PPS, oxybutynin) Quercetin steroid injection) injections
Hydrodistension Intravesical agents Novel therapies
Botulinum toxin A (DMSO, Hep, HA (hyperbaric oxygen)
Sacral neuromodulation CS, alkalinized Radical surgery
Radical surgery lidocaine, PPS
Hydrodistension
Botulinum Toxin A
Radical surgery)
*Almost all patients will have these phenotypes.

CUA guideline management algorithm [12]

of guidelines give a grade C or D recommendation as an
option for its use, the EAU guidelines do not recommend
bladder distension as a treatment for BPS because of lack of
evidence.
Transurethral fulguration, resection, or laser coagulation of
Hunner’s lesions, if present, have been reported to provide
good temporary relief of symptoms in several case series. The
procedure is therefore recommended by all guidelines for
patients with Hunner’s lesions (BPS type 3C) only.
Other Treatments
Fourth-line treatments include intravesical botulinum toxin A
(BTX-A) or sacral neuromodulation. Evidence for BTX-A is
predominantly from observational studies, although two small
randomized controlled trials have reported conflicting results
[31,32]. Based on an updated literature review, including
trials combining BTX-A with hydrodistension and trials using
the 100-U dose, the AUA guideline now recommends BTX-A
as a fourth-line option after failure of other treatments. The
EAU guideline gives a grade A recommendation to the use of
BTX-A in combination with hydrodistension, as opposed to
BTX-A alone (grade C), and all other guidelines recommend
it as an option after failure of other therapies in patients who
are well counselled about the risks (such as need for clean
intermittent self-catheterization).
Sacral neuromodulation can also be offered as a fourth-line
treatment, and the EAU recommend this is offered before
radical surgery (grade B). Evidence of efficacy is
predominantly from observational studies, but all guidelines
recommend sacral neuromodulation as an option for patients
who have failed other treatments.

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 Bladder pain syndrome

Fig. 2 The UPOINT system for phenotyping patients with chronic pelvic pain.

Phenotyping Assessment

Urology Urinary flow, micturition diary, cystoscopy, ultrasound, uroflowmetry,

Psychology Anxiety about pain, depression and loss of function, history of negative sexual experiences

Ask for gynaecological, gastro-intestinal, ano-rectal, sexological complaints

Organ specific
Gynaecological examination, rectal examination

Infection Semen culture and urine culture, vaginal swab, stool culture

Ask for neurological complaints (sensory loss, dysaesthesia).

Neurological
Neurological testing during physical examination: sensory problems, sacral reflexes and muscular function.

Tender muscle Palpation of the pelvic floor muscles, the abdominal muscles and the gluteal muscles

Oral cyclosporin A has been studied in a number of small
observational studies, and one randomized controlled trial,
all reporting sustained efficacy, especially in patients with
Hunner’s lesions; however, it requires close patient
monitoring, including blood pressure and serum drug
concentration monitoring, and has the potential for
serious adverse events (e.g. nephrotoxicity,
immunosuppression). It is therefore recommended as an
option in the AUA, East Asian, RCOG and CUA
guidelines for clinicians experienced in its use, but is
recommended as a last resort for patients with
inflammation and severe refractory symptoms in the CUA
guideline.
Major Surgery
Radical surgery with substation cystoplasty (with supra- or
sub-trigonal cystectomy) or urinary diversion (with or
without cystectomy) is described as an option of last resort
by all guidelines. The evidence is based on single-centre
case series and good outcomes have been reported in well
selected patients (those with identified bladder disease such
as small bladder capacity or Hunner’s lesions) [33].
Patients should be adequately counselled that pain relief is
not guaranteed, and that pain may persist even if the
bladder is removed. This is especially true for patients with
non-ulcer BPS, or a preserved trigone (supratrigonal
cystectomy) [33,34]. In those undergoing urinary diversion
alone, the rate of subsequent cystectomy for ongoing
symptoms has been reported to be as high as 50% [35]. It
is therefore recommended that radical surgery only be
undertaken by experienced and BPS-knowledgeable surgeons
(EAU grade A).
Future Research
There is still a lack of understanding of the underlying
pathophysiological mechanisms and aetiological factors
responsible for BPS, and no accurate diagnostic tests exist.
Furthermore, the wide range of treatments studied
highlights the lack of fully effective therapies for this
condition. In response to this, the Multidisciplinary
Approach to the Study of Chronic Pelvic Pain (MAPP)
research network was formed with the aim of improving
our understanding of urological chronic pelvic pain
syndrome, through basic science, translational and clinical
research [36]. Further insights from these studies are likely
to improve significantly our understanding of this
condition, and will pave the way for novel diagnostics and
therapies in the future.
Conclusion
There are multiple national and international guidelines for the
diagnosis and management of BPS, and the present review has
highlighted the differences in nomenclature, definitions and
recommended diagnostic tests among guidelines. There is a
need for standardization to aid diagnosis of this condition and
improve the comparability of future research trials in this area.
The term BPS is increasingly recommended, with IC being
reserved for those who have Hunner’s lesions. The diagnosis

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Malde et al.
can be made clinically without the need for invasive
investigation, but cystoscopy should be considered to exclude
other conditions that could mimic BPS. Hydrodistension also
allows subtyping of patients with BPS, and may help
individualize treatment strategies.
Multiple treatment options exist, and all guidelines
recommend a step-wise approach, starting with the most
conservative. There is a focus on the importance of
phenotype-directed multimodal therapy in the majority of
guidelines. Overall, the evidence base for the majority of
therapies is mixed, and large randomized trials are required
to improve the quality of future guideline recommendations.
Conflict of Interest
None declared.
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Correspondence: Sachin Malde, Department of Urology,
Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
e-mail: Sachmalde@gmail.com
Bladder pain syndrome
Abbreviations: BPS, bladder pain syndrome; BSUG, British
Society of Urogynaecology; BTX-A, botulinum toxin A; CUA,
Canadian Urological Association; EAU, European Association
of Urology; ESSIC, International Society for the Study of BPS;
HSB, hypersensitive bladder syndrome; IASP, International
Association for the Study of Pain; ICI, International
Consultation on Incontinence; IC, interstitial cystitis; ICSI/
ICPI, Interstitial Cystitis Symptom and Problem Index; PBS,
painful bladder syndrome; RCOG, Royal College of
Obstetricians and Gynaecologists.
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