Interstitial Cystitis

What is IC? WHEN TO SUSPECT IC

 Clinical syndrome Pain, Frequency/Nocturia and Urgency
 AKA painful bladder syndrome AND
 “Unpleasant sensation perceived to be related to Physical exam excludes Vaginitis, Urethral or Vulvar
the urinary bladder and associated with lower lesion or Infection
urinary tract symptoms of 6+ weeks duration, in AND
the absence of infection or other identifiable UA is negative for Hematuria
causes.” AND
Urine culture during symptoms is Negative
Epidemiology AND
 500,000 – 1,000,000 cases estimated in U.S. No Hx of Neurological problem, Pelvic trauma,
 ICSI from 1990 to 2002: 1.2 to 450 per 100,000 Malignancy of recent Pelvic Surgery
 Proposed pain and urgency/frequency symptom
scale (PUF) has been used to identify patients with Signs & Symptoms
IC  PAIN: suprapubic or pelvic
o Prevalence may be as high as 1 in 45  Bladder pain that worsens with bladder filling and
women is alleviated with voiding
o http://www.lasvegasurogynecology.com/  Dysuria
PUF.pdf  Urinary frequency & urgency
 Almost exclusively in women; 40% report  Nocturia: mild to severe (1 to >12 times per night)
symptoms worsen pre-menstrually, specifically  Spasm of the rectum and levator ani muscles
around time of ovulation  Anterior vaginal wall, suprapubic region, and
pelvic floor muscle tenderness on pelvic
Interstitial Cystitis Symptoms Index (ICSI) examination
During the past month:  Women
 How often have you felt the strong need to urinate o Dyspareunia
with little or no warning? o Female sexual dysfunction
 Have you had to urinate less than 2 hours after  Men
you finished urinating? o Pain at the tip of the penis, the groin, or
 How often did you most typically get up at night to the testes
urinate? o Ejaculation often produces pain owing to
 Have you experienced pain or burning in your severe spasm of the pelvic floor
bladder? o Prostate, bladder, testes, and epididymis
Etiology tenderness
 Unknown, multifactorial O/E
 Deficiency in the glycosaminoglycan (GAG) layer -  Perform pelvic examination to help exclude
Toxic substances gynecologic disease
 Autoimmune disorder  Measure the patient's temperature . Fever
 Infection - History of UTIs suggests infection rather than IC
 Toxic substance in urine  Examine the abdomen for masses, hernias, and
 Neurogenic hypersensitivity or inflammation other abnormalities suggesting alternate
 Pelvic floor muscle dysfunction/dysfunctional diagnoses
voiding
Patient History Chronic abacterial prostatitis
 Questionnaires  Similar presentation as IC/BPS except that the
 Risk factors: consumption of caffeinated and patient is male.
alcoholic drinks, anorectal disease, IBS  Initially treat with alpha blocker and quinolone for
 Associated conditions: depression, sexual 6 weeks
dysfunction/abuse, emotional/physical abuse or  If patients does not improve think and treat as
neglect, constipation, chronic pain or IC/BPS
inflammatory conditions

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Diagnosis
1. Cystoscopy: Findings: glomerulations, mucosal
ulcers (Hunner’s lesions), petechial hemorrhage
2. Parson’s test
3. Urodynamics: Poorly compliant bladder
4. Urinary biomarkers: Nitric oxide
5. Bladder biopsy: Controversial
Problems in diagnosing IC
 The diagnosis of PBS/IC is clinical and based on
symptomatology
 PBS/IC is a diagnosis of exclusion.
 There is no evidence to qualify or quantify the
symptoms to include or exclude patients from the
diagnosis of PBS/IC.
Cystoscopy
Typical appearance of glomerulations after bladder
distention in a patient with nonulcerative interstitial cystitis.
Typical appearance of Hunner's ulcer in a patient with
interstitial cystitis before bladder distention.
Dr Prashant Bansal
Interstitial Cystitis
 "Classic" disease. "Hunner's ulcers“ about 5% of
all patients have this type of disease.
 Non-classical" disease. Patients with this
condition have many symptoms, but examination
of the bladder surface shows no obvious
inflammation. Most patients with IC/PBS have
non-classical disease
Copenhagen Cystoscopic classification of bladder
mucosa
 Grade 0= normal mucosa
 Grade I = petechiae in at least two quadrants
 Grade II = large submucosal bleeding (ecchymosis)
 Grade III = diffuse global mucosal bleeding
 Grade IV = mucosal disruption, with or without
bleeding/oedema
Can bladder be normal on cystoscopy in IC/BPS?
 yes
Can bladder with normal capacity under anaesthesia
have IC/BPS?
 Yes
PST /Potassium sensitivity test/ Parsons test
 Saline vs KCl infusion : 500 cc
 Positive test may indicate increased permeability
and/or increased neural activity.
 Easy to perform – office procedure
 0.4 m –sensory n. irritate
 Problems
o not recommended as diagnostic tool –
inflammatory diseases like radiation and
bacterial cystitis, malignancy have positive
test.
o Low sensitivity (69.5%) low specificity
(50%, positive, chronic prostatitis,
gynecologic pain)
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Basic urodynamic abnormalities

 Sensory urgency
 Intolerance to increments of bladder volume
 Decrease in bladder compliance <30ml/cm water
 Smaller maximal capacity under anesthesia

Overlapping Sx of PBS with OAB

Bladder biopsy
 Confirm diagnosis and for DDx
 Pathologic findings are not well described and
classified
 Fibrosis – prognostic value
 Research purposes
 Problems:
o Costs and complications
o No pathognomonic findings
Clinical markers
Antiproliferative factor (APF)
 Unique protein found only in urine of IC patients
 APF is expressed solely in the bladder epithelium
of IC patients with no expression evident in
normal human bladder epithelial cells.
 Implications
o APF may cause the epithelial thinning or
ulceration seen in IC
o Urine APF may be useful as a diagnostic
biomarker for IC, and as a disease
parameter for treatment studies
o Agents that inhibit APF production or
activity may potentially be useful for the
treatment of IC

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Clinical Guidelines

 AUA
o Created flowchart of suggested order of treatment
o Progress 1st line through 6th line as needed
 JUA
o Created clinical practice guidelines
o Level A evidence: highly recommended
o Level B evidence: recommended
o Level C evidence: no clear recommendation possible
o Level D evidence not recommended
 Conservative treatments first
 Avoid surgery if possible
 Exception is fulguration of Hunner’s lesions, must be done first
 Multiple simultaneous treatments often best. Pain management should be priority

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Staged Treatment Weiss JM, 2001

1st Line - Conservative  Manual release of myofascial trigger points via
 Education internal palpation, compression, and lateral
 Self care stretching
 Stress management  HEP: biofeedback, Kegel exercises, external pelvic
2nd Line - Pain management muscle stretches and strengthening, and stress
 Oral treatments reduction
3rd Line  70% had moderate to marked improvement
 Intravesical treatments FitzGerald et al., 2009; FitzGerald et al., 2012
 Cystoscopy + Low pressure HD  Soft tissue mobilization of all trigger points found
 Hunner’s Fulguration in pelvic floor, anteriorly from knees to costal
 Cocktails cartilages, and posteriorly from T10 to popliteal
4th line crease
 BOTOX A  Manual stretching, scar mobilization, and
 SNS myofascial release
5th line  Individualized HEP of stretching and exercises
 Cyclosporine A  Explicitly told participants to avoid Kegels until
6th line trigger points resolved
 Surgery  59% reported moderate or marked symptom
improvement
1st line treatments: conservative Oral pain management
 Patient education about IC and treatment options  Amitriptyline (B), Cimetidine (C), Hydroxyzine (C) :
 Behavioral modifications (B) inhibit histamine receptors to decrease pain signal
o Timed voiding transmission
o Controlled fluid intake  Pentosan polysulfate (B)
o Stress reduction o Repairs damaged GAG layer of bladder
o Avoidance of triggers mucosa.
o Dietary changes: avoid acidic foods, o Takes 3-6 months to see effects
coffee, tea, soda, spicy foods, artificial o Only effective in approximately 25% of
sweetener, and alcohol. 4 C’s: carbonated, patients
caffeine, citrus, high concentration of Oral triple drug therapy
vitamin C  Amitriptyline 25 mg HS + Hydroxyzine 25 mg HS +
nd Gabapantin 100 mg HS
2 line treatments
Physical Therapy (C)  All patients take this treatment for 3 months
 Biofeedback  Depending on response dose can be adjusted
 Soft tissue mobilization  Pentosan given in only few patients OD/BD/TDS.
 Stretching No effect (vs placebo)at the currently established
 Pelvic floor muscle training? dose or at a third of the daily dose.
o AUA says avoid
o JUA says nothing
o Research mixed

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3rd line treatment
Cystoscopy with short duration, low pressure
hydrodistension (B).
 Most common treatment, 50% efficacy, effects
last about 6 months.
 Inflate bladder with saline to 80 cm H2O or 800 -
1000 mL, maintain pressure for a few minutes
then drain bladder.
HYDRODISTENSION (With diagnostic Cystoscopy)
 Always under anesthesia (SA preferred)
 16 ch foleys inserted 1st to check urethra and PVR
 Reservoir height 80 cms
 Bladder distended, drained and distended again
for 3 minutes (double distension)
 Do not increase Reservoir height to dilate the
bladder
 Filled till 750- 800 ml maximum
 Fulgurate Hunner’s lesion if present
 Foley catheter kept for 3-4 hours
 Controversial treatment
 Gives initial relief in almost all the patients
 Repeat only if effective for around a year
Hunners lesion
 Coagulation with cautery
 Coagulation with laser
 Triamcinolone injection at the base of ulcer
Dr Prashant Bansal
Interstitial Cystitis
Intravesical treatments
 Used when patients fail oral therapy
 Rescue therapy in flare up
1. Dimethyl sulfoxide (B): anti-inflammatory,
analgesic, and muscle relaxant
2. Heparin (C): functions as GAG layer for bladder
3. Lidocaine (C): analgesic
4. Intravesical Tacrolimus
Bladder cocktails
1. Parsons "Therapeutic Solution
2. Robert Moldwin Anesthetic Solution
3. Kristene Whitmore
4. Nagendra Mishra
5. DMSO cocktail – Philip Hanno
Parsons (UCSD) "Therapeutic Solution
 40,000 U heparin
 8 mL 1% lidocaine or 2% lidocaine
 3 mL 8.4% sodium bicarbonate
 Administration:
 May be given up to twice daily.can be taught to
self-administer.
 Should be held in the bladder for 15-30 minutes
 It is the sodium bicarbonate that allows the
solution to give instant relief.
Dr. Robert Moldwin Anesthetic Solution
 1:1 mixture of 0.5% Marcaine® and 2% lidocaine
jelly (about 30-40 cc total)
 40 mg triamcinolone
 10-20,000 IU heparin sulfate
 80 mg gentamycin (3)
 Administration:
 hold the solution for about 30 minutes, then void.
 relief of pain within 5-10 minutes.
 Patients may experience “rebound” pain once the
solution has worn off (within 3-5 hours).
 administer the cocktail on a weekly basis for 8-12
weeks.
 Then, the duration between instillations is
increased to q 2 weeks to q 3 weeks, etc.,
ultimately with the goal of discontinuance.
Dr. Kristene Whitmore
 Marcaine 0.5% (20cc)
 Heparin 10,000 units (10cc)
 Hydrocortisone 100mg (5cc of normal saline)
 Sodium Bicarbonate 48 meq (40cc)
 Administration:
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 1 x week. Should be held in the bladder for about

30 minutes.

Marcaine with steroid cocktail – Nagendra Mishra

 Bupivacaine 40 ml 0.5 %
 Heparin sulphate 25,000 IU
 Dexamethasone 2 cc
 Heparin sulphate 10,000 IU
 Sodium bicarbonate 20 ml
 Administration:
 Should be held in the bladder for 20 minutes.
 Administered every 2 wks for a total of 6
treatments and then as needed.

DMSO cocktail – Philip Hanno

 DMSO (Rimso 50) 50 cc
 Sodium bicarbonate 44 meq (one ampule)
 Kenalog 10 mg
 Heparin sulphate 20,000 IU
 Administration:
 should be held in the bladder for 20 minutes
 administered 1 x a week for 6 weeks. May be
followed by monthly maintenance

Pentosan polysulfate cocktail - Jurjen J. Bade

 Pentosan polysulfate sodium 300mg
 Lidocaine 2% 10cc
 Sodium bicarbonate - 10cc
 NaCl 0.9% to reach a total volume of 60cc.
 Administration:
 Initially weekly. After 6-8 weeks should be
tapered: every 2 weeks, then every 3 weeks etc.

Intravesical Tacrolimus
 Formulation being developed
 Administered in 14 patients of severe disease
 7 improved

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4th line treatment: neurostimulation (C) 5th line treatments

Cyclosporine A (C)
 Anti-inflammatory and immunosuppressive
 More effective for patients with Hunner’s lesions
(85% vs. 30% effective)
Intradetrusor botox injection (C)
 Risk of requiring intermittent catheterization after
treatment
 Up to 4 injections, separated by 6 months
effective for symptom and pain relief as well as
increasing bladder capacity
 Not as effective for patients with Hunner’s lesions
Bilateral S3 nerve stimulators.
 Significant decrease in frequency and nocturia .
 Significant improvement in Urinary Distress
Inventory short form scores, showing patient
satisfaction .
 Decrease in episodes of fecal incontinence.
TENS for pain relief.
 External low back or supra-pubic placement.
 Internal placement of device in vagina .
Botox and Interstim
 No improvement with Botox
 No experience with interstim
 Removed from protocol
Botox
 I have not found it useful in patients
 The effect lasts till the effect of HD
 Most of the patients subjected to surgery have
undergone botox injection
Interstim
 No experience
 Only recommended if all the therapies fail

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6th line treatment: surgery (C)
Cystoplasty
 Part/all of bladder removed and replaced by
section of bowel to function as new bladder
 Uncommon
Urinary diversion with/without cystectomy
 Section of bowel becomes conduit for ureters,
stoma created in abdomen, allows urine to drain
continually into external collection bag
 Section of bowel becomes conduit for ureters,
drains into another section of bowel that has
become internal pouch that must be emptied
through intermittent self-catheterization
 Rarely performed because many patients will still
experience some symptoms, mainly pain, after
surgery
Surgery
 Last resort in patient with severe disease
 Ileocystoplasty in 7 cases
 6 excellent result
Substitution cystoplasty
 Remove trigone or not
 Patients likely to fail
o Pain in urethra
o Large capacity bladder
o Without hunners lesion
Urinary diversion
 With or without cystectomy
 Relieves frequency and nocturia and may relieve
pain
 Pain relief not guaranteed and pain can persist in
non ulcer disease
 74 % patients reported pain free for a median
period of 66 months
Augmentation/Relaxing Cystoplasty
 Patch cystoplasty in normal capacity bladder
 Hypothesis is to reduce detrusor stretch
 7 patients done
 Excellent results in six patients
 Seventh patient had complications
 Comparatively simple surgery
Dr Prashant Bansal
Interstitial Cystitis
Treatment in pregnancy
 PPS ,amitriptytine and intravesical heparin
 Pregnancy has a positive effect on the disease….
Clinically I have seen patients symptoms getting
ameliorated after pregnancy…
 This makes pregnancy more desirable in a young
married female with BPS with BPS who has not
completed her family yet….
Treatment not to be offered
 Long term antibiotics
 Long term steroids
 Intravesical BCG
 Long duration high pressure hydrodistension
Example of Treatment Protocol
 Dietary restrictions
 Fluid restriction to 64 oz per day, 16 oz per meal
and 8 oz between each meal
 Timed voiding every 2-3 hours
 Kegels: 15 contractions 2x per day
 Pharmacology: macrodantin (anti-inflammatory),
hydroxyzine (anti-inflammatory), Urised (anti-
spasmodic)
 Continued pentosan polysulfate if patient had
been on it at least 6 months prior
 Hydrodistension
 3x in one session, 2 weeks after treatment
initiated
 All participants did not have Hunner’s lesions
 Saw statistically signficant improvement in quality
of life measured on O’Leary-Sant IC Symptom
Index
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