bladder pain syndrome is highly prevalent. it is a diagnosis of exclusion. the biggest hurdle in management is diagnosis. more often than not patients suffering with BPS move from pillar to post, from a clinician to another, often getting urethral dilatations, receiving NSAIDS and even antipsychotics (having been labelled as 'psychiatric' patient). once diagnosis is made, treatment is multipronged and based on phenotype - the concept is called UPOINT. interstitial cystitis is a small but significant minority (moreover ulcerative type) of BPS. Gabapentin, amitriptyline and pentosan polysulfate are cornerstone pharmacotherapeutic agents for IC/BPS

1. Interstitial cystitis –
bladder pain syndrome
​Dr Mayank Mohan Agarwal
​MS, MRCS(Ed), ​DNB, MCh (PGI, Chd)
​VMMF and IAUA Fellowships Uro-Oncology, Pelvic Floor Reconstruction
(MSKCC, NY; UCLA, LA; WFUBMC, NC)​
Formerly Associate Professor of Urology, PGIMER, Chandigarh (India)
Formerly Consultant & Head of Urology, NMC specialty hospital, Abu Dhabi (UAE)
Consultant and Head of Urology
Aster Ramesh Cardiac and Multispecialty Hospitals
Guntur (AP), India

2. INTRODUCTION
• Bourque (1951): Aunt Minnie description of IC
“We have all met........patients who suffer chronically
from their bladder; .......distressed.......constantly, having
to urinate often, .......day and night, and suffering pains
every time they void. .......these miserable patients are
unhappy, ........finally influence their general state of
health physically ......and mentally ......”

3. SUMMARY
• ETIOLOGY
• PRESENTATION
• WORKUP
• MANAGEMENT

4. Definition
• IC / BPS
o Chronic (>6-12wk) symptoms of pain emanate from
the bladder and/or pelvis
o Urinary urgency (for pain) and/or frequency
o In the absence of another identified cause
– Clinical diagnosis ‘of exclusion’
• IC
o The above with
o “typical cystoscopic and histological features,”

5. Classification
• European society for study of IC classification: 2008

6. Classification
• European society for study of IC classification: 2008

7. Classification
• European society for study of IC classification: 2008

8. Epidemiology
• Prevalence 10%
• Strict criteria –
– USA 60/100,000
– Europe 20/100,000
– Japan 3/100,000
• Mostly women (90%)
• Median age 40y (children to old age)

9. ETIOPATHOGENESIS

10. Pelvic floor
dysfunction
INSULT
autoimmune
infection
Neurogenic
inflammn
Trauma /
overdistensn
Damage to
epithelium
Leakage into
interstitium
Immuno-
stimulation
C-fibre
activation
Mast cell
activation
NON-NOCICEPTION
PROGRESSIVE
BLADDER INJURY
APF REPAIR<<DAMAGE

11. PRESENTATION
• Recurrent pelvic pain or discomfort (pressure, burning,
throbbing, etc.)
• at least 4-6 weeks’ duration
• Increases with bladder filling and /or decreases with
micturition in the absence of definable pathology
• associated with urinary frequency and/ or urgency

12. PRESENTATION
• Recurrent pelvic pain or discomfort (pressure, burning,
throbbing, etc.)
• at least 4-6 weeks’ duration
• Increases with bladder filling and /or decreases with
micturition in the absence of definable pathology
• associated with urinary frequency and/ or urgency

13. • Incontinence very uncommon
• Other symptoms – dyspareunia, pelvic pain
• Part of CPPS
• Other associations –
– Allergies
– Irritable bowel syndrome
– Fibromyalgia
– SLE
– Anxiety / depression
PRESENTATION
CPPSU-CPPSBPSIC

14. Workup
• No consensus on minimum and optimal workup
• No shortcut to detailed History & examination
that’s where is remains underdiagnosed and mistreated
• Diagnosis of exclusion –
what all to exclude
• Tools –
– Questionnaires
– Urine-analysis
– Imaging
– Urodynamics
– Cystoscopy
Mycobacterial infections
CIS
Endometriosis
Other inflammatory conditions

15. Questionnaires
• NOT FOR DIAGNOSIS
• For objectively assessing severity and effect of therapy
– University of Wisconsin IC scale
– O’Leary-Sant IC symptom index
– Pelvic pain and urgency/frequency scale (PUF)
– Genitourinary pain index (GUPI)
• Research tools
• Clinical practice –
(bio)feedback
Questions related to bladder, pelvic
pain and sex

16. Urine-analysis
• ALWAYS –
– microscopy and bacterial culture
• PREFERABLE – (MUST if sterile pyuria, µ-hematuria)
– Urine cytology for malignant cells
(x 3 days) NOT first morning sample
– Urine for AFB µ-s & c/s or PCR (genexpert, LPA)
(x 3-5 days) MUST be first morning (or
overnight collection)
• INVESTIGATIONAL
– Nanobacteria culture
– Antiproliferative factor

17. Imaging
Ultrasonography
• Extension of clinical examination
• Readily available
• Surprises not uncommon
CT / MRI rarely needed

18. Urodynamics
• Not routinely indicated in ‘pure’ BPS symptoms
• Possible indications –
– U/UUI predominant presentation
• DO (~15% coexist)
• Compliance (generally normal in IC)
– Voiding phase dysfunction (VUDS):
• DUA not uncommon
– Doubtful history especially when refractory to
medication

19. •55 F
•Severe perineal pain A/W voiding X 3 years
•Lump like feeling in perineum
•Hysterectomy 1 yr back
PAIN

20. •55 F
•Severe perineal pain A/W voiding X 3 years
•Lump like feeling in perineum
•Hysterectomy 1 yr back
PAIN

21. 55F, LUTS X 1 year - straining, urgency for
suprapubic pain on full bladder, frequency of
urine. recurrent UTI like symptoms. hematuria
and severe pelvic pain on postponing urination.
O/E pelvic floor tone increased, no tender
pointsCT / urine cytology / urine culture - WNL.
partial benefit with gabapentin and tizanidine.

22. 55F, LUTS X 1 year - straining, urgency for
suprapubic pain on full bladder, frequency of
urine. recurrent UTI like symptoms. hematuria
and severe pelvic pain on postponing urination.
O/E pelvic floor tone increased, no tender
pointsCT / urine cytology / urine culture - WNL.
partial benefit with gabapentin and tizanidine.
55 F, LUTS X 1 year - straining, urgency for
suprapubic pain on full bladder, frequency of
urine. recurrent UTI like symptoms. hematuria
and severe pelvic pain on postponing urination.
O/E pelvic floor tone increased, no tender
pointsCT / urine cytology / urine culture - WNL.
partial benefit with gabapentin and tizanidine.

23. 55 F, LUTS X 1 year - straining, urgency for
suprapubic pain on full bladder, frequency of
urine. recurrent UTI like symptoms. hematuria
and severe pelvic pain on postponing urination.
O/E pelvic floor tone increased, no tender
pointsCT / urine cytology / urine culture - WNL.
partial benefit with gabapentin and tizanidine.

24. 55 F, LUTS X 1 year - straining, urgency for
suprapubic pain on full bladder, frequency of
urine. recurrent UTI like symptoms. hematuria
and severe pelvic pain on postponing urination.
O/E pelvic floor tone increased, no tender
pointsCT / urine cytology / urine culture - WNL.
partial benefit with gabapentin and tizanidine.

25. CYSTOSCOPY
• Micropyuria
• Microhematuria
• Severe symptoms – particularly small fixed capacity on
bladder diary and scalding pain
• Chronic smoker – male more than 40
• Failure of initial therapy

26. CYSTOSCOPY
Glomerulations
Hunner’s ulcer / scar
YES NO
Biopsy
Hydrodistension
Fulguration
Re-distension
YES NO
Conclude
ALWAYS - ALWAYS UNDER ANESTHESIA

27. • Therapeutic distension
– 80-100 cmH2O for ~ 8 mins
• UNDER VISION
• Initial efficacy ~60%
Capacity excellent fair
<600ml 26% 29%
>600ml 12% 43%
• Short lasting <3m
• Non-ulcer IC, number of glomerulations ≠ symptoms
Badenoch 1971; Hamer 1992; Hanno & Wein 1991

28. Dietary modification
Long list of ‘what to avoid’ by IC foundation
• Irritants – tea, coffee, cola, tobacco, chocolate, spicy
• High potassium content – fruits, dry fruits, juices
• Organic – preservative, ‘sugar-free’
Often prohibitive
Avoid what you can not tolerate

29. Pelvic floor
dysfunction
INSULT
autoimmune
infection
Neurogenic
inflammn
Trauma /
overdistensn
Damage to
epithelium
Leakage into
interstitium
Immuno-
stimulation
C-fibre
activation
Mast cell
activation
NON-NOCICEPTION
PROGRESSIVE
BLADDER INJURY
APF REPAIR<<DAMAGE

30. Pelvic floor
dysfunction
INSULT
autoimmune
infection
Neurogenic
inflammn
Trauma /
overdistensn
Damage to
epithelium
Leakage into
interstitium
Immuno-
stimulation
C-fibre
activation
Mast cell
activation
NON-NOCICEPTION
PROGRESSIVE
BLADDER INJURY
APF REPAIR<<DAMAGE
PENTOSAN
POLYSULFATE
AMITRIPTYLINE
GABAPENTIN
HYDROXYZINE
MONTELEUKAST
CYCLOSPORINE
AZATHIOPRINE

31. UPOINT (CPPS ≡ BPS/IC)
• URINARY
• PSYCHOLOGICAL
• ORGAN SPECIFIC
• INFECTION
• NEUROLOGICAL
• TENDERNESS
Nickel et al. phenotype directed management of IC/BPS. Urology 2014; 84: 175

32. Management
Behavioral
modification
Fluid and diet
modification
Stress
management
EDUCATION
PFMT,
relaxation
biofeedback
Thiel’s massage
Trigger point
release
Gabapentin
PPS
Hydroxyzine
Montelukast
Amitriptyline
Nortriptyline
Cyclosporine
Tacrolimus
Azathioprine
Oral
medications
Invasive
treatment
Intravesical
DMSO
PPS
cocktail
Botox
Interstim

33. Management
Behavioral
modification
Fluid and diet
modification
Stress
management
EDUCATION
PFMT,
relaxation
biofeedback
Thiel’s massage
Trigger point
release
Gabapentin
PPS
Hydroxyzine
Montelukast
Amitriptyline
Nortriptyline
Cyclosporine
Tacrolimus
Azathioprine
Oral
medications
Invasive
treatment
Intravesical
DMSO
PPS
cocktail
Botox
Interstim

34. PPS: is it effective?
• Better than placebo
– Pain – 16.6%
– Urgency – 13%
– Frequency – 16.6%
– Nocturia – nil
• Better than ‘nothing’ –
– 34% vs 18%
Hwang et al. Efficacy of PPS in IC. Urology 1997 Sant et al. Pilot trial of oral PPS and hydroxyzine. J urol 2003

35. PPS: is it effective?
• Better than placebo
– Pain – 16.6%
– Urgency – 13%
– Frequency – 16.6%
– Nocturia – nil
• Recent evidence contradictory
Hwang et al. Efficacy of PPS in IC. Urology 1997 Nickel et al. PPS in IC/BPS: Insights from RCT. J urol 2015

36. PPS: what’s the correct dose
• RCT – 3 groups 300 – 600 – 900mg /d
• No placebo group?
• Percentage of patients with 50–100% improvement on
PORIS (Patient’s Overall Rating of Symptom Index)
• 300mg/d
0
10
20
30
40
50
60
4wk 8wk 12wk 16wk 24wk 32wk
300 mg/day 600 mg/day 900 mg/day
Nickel et al. RCT dose ranging PPS for IC. Urology 2005.

37. PPS: early or late?
• Retrospective secondary analysis of the RCT (n = 128)
• Dose 300mg/d x 32 weeks
• Better if started within 6 months of diagnosis
Nickel et al. timing of initiation of PPS after IC diagnosis: effect on symptom improvement. Urology 2008

38. PPS in combination
• Oral PPS 200mg bid
• intravesical PPS 200mg / 30 min
0
20
40
60
80
100
treatment placebo
Davis et al. oral + intravesical PPS: RCT. J urol 2008

39. • Oral PPS 300mg/d
• Subcutaneous heparin
PPS in combination
0
5
10
15
20
25
30
responders at 3m responders at 6m
PPS + heparin PPS
Ophoven et al. PPS + heparin for IC. Urology 2005

40. Strategy for management
Initiate with
• Behavioral modification
• Diet modification
• First line Medications –
– Gabapentin
– ± amitriptyline
– ± hydroxyzine or montelukast
• If cystoscopically confirmed IC  initiate on PPS

41. Minimize Antibiotic use
Hospital and surgical hygiene