Interstitial cystitis (IC), also known as bladder pain syndrome, is a chronic condition characterized by pelvic pain perceived to be related to the bladder along with urinary symptoms. The cause is multifactorial and likely includes alterations in bladder permeability and neurogenic inflammation. Diagnosis involves ruling out other causes through history, exam, cystoscopy, and urine testing. Treatment is individualized and may include conservative measures, oral medications like amitriptyline, intravesical therapies, minimally invasive procedures, and rarely surgery. Management aims to control symptoms and improve quality of life through a stepwise approach utilizing various options.

1. Interstitial
Cystitis
By: Ferid Ousman (Urology Resident, PGY-IV)
Moderator: Dr Seid Mohammed (Asst. prof. of Urology)

2. Table of Contents
05
Introduction
o Historical background
o Definition
o Epidemiology
Pathogenesis
o Etiology
o Pathology
Treatment
o Conservative
o Pharmacological
o Surgical
References
Diagnosis
o Mandatory
o Optional
04
06
01
02
Clinical presentation
03

3. Introduction
01

4. What is Interstitial Cystitis ???
o Chronic, potentially debilitating condition characterized by pain perceived to
be related to the bladder in conjunction with LUTs
o Aka bladder pain syndrome (BPS)
o Challenge to diagnose and treat
o Confused with other GU or GYN disorders
o Associated with depression and lower quality of life

5. Historical Background
o The term “IC" first came into use in 1878 (S. Gross)
o “a condition of chronic bladder inflammation of unknown etiology.”
o G. Hunner (1918):- “a peculiar form of bladder ulceration- Hunner ulcer.”
o JR Hand (1949): “small, discrete, submucosal hemorrhages' and ‘dot like bleeding points”
o JP Bourque (1951)- “painful bladder”, also referred to as PBD
o Walsh: 1978 in Campbell’s Urology coined the term “Glomerulations”
o NIDDK/NIH (1987)- formed a consensus definition of IC
o ICS (2002)- Used the term “Painful Bladder Syndrome”
o ESSIC (2006)- Changed the name to “Bladder Pain Syndrome”
o 2009- “Hypersensetive Bladder Syndrome” was the term used by JUA.
o 2011 AUA guideline used the term IC/BPS.

6. Definition
o ESSIC( 2007) - BPS recommended as preferred term
 “chronic pelvic pain, pressure, or discomfort perceived to be related to bladder accompanied
by at least 1 other urinary sxs such as persistent urge to void or frequency, in the absence of
infection or other pathology.”
o The International Continence Society (ICS)
 PBS- “ the complaint of suprapubic pain related to bladder filling, accompanied by other
symptoms such as frequency, in the absence of UTI or other obvious pathology”
 “ IC is a specific diagnosis and requires confirmation by typical cystoscopic and histological
features."
o 2008 consensus definition from SUFU, adapted by AUA
 “an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary
bladder, associated with LUTS of more than 6 weeks duration, in the absence of infection or
other identifiable causes.”

7. Epidemiology
o Prevalence is highly variable and likely underestimated
o Depends on definition and diagnostic criteria
o Current studies estimation
 RICE study: 2.7-6.5% of women and 1.9-4.2% of men in US
 Europe: prevalence of 18 cases per 100,000 women
 only 3-4 cases per 100,000 women are reported in Japan
o Highest prevalence in women (5:1)
o Median age is 40 years
o Uncommon in children
o White >> others (9:1)

8. Etiology
02

9. Etiology
o Little is known about etiology and pathogenesis of IC/BPS.
o The cause is likely multifactorial.
o Proposed etiologies (Theories):
 Altered bladder mucosal permeability
(deficiency of GAG layer)
 Mast cell activation
 Neurogenic hypersensitivity or inflammation
 Pelvic floor muscle dysfunction
 Immunological/Autoimmune Disorder
 Infection with a poorly characterized agent
 Production of a toxic substance in the urine
 Genetic Predisposition

10. Clinical presentation
 History
o Variable presentation
o Pain related to bladder filling is the hallmark sxs
o Urgency/frequency is very common, but not universal
o Symptoms may exacerbate gradually
o Tend to occur in cycles or flares.
 Physical Examination
o Usually non-revealing
o Variable tenderness of abd wall, hip girdle, pelvic floor
o tenderness or tightness of the pelvic floor muscles
o In males, scrotal and penile tenderness may be present

11. Diagnosis
03

12. Evaluation
o Current diagnostic strategies are primarily based on its definition.
o High clinical index of suspicion is a key to Dx:
o It remains diagnosis of exclusion.
o The main GOAL is to exclude other cause of the Sxs.
 Most challenging aspect
 Failure to diagnose others is one of the reason for therapeutic failure.
 Excluding malignancy is a main priority during evaluation

13. Basic Evaluation
 History
 Duration of Sxs
 Location, character, and severity
 Associated conditions
 Focused P/E
 Abdominal/Pelvic: masses, bladder distension, tenderness,
and hernias
 Pelvic floor muscles: sites of tenderness and trigger points
 Neurological exam to r/o occult neurologic problem

14. Basic assessment…
 Symptoms Score:
o O’Leary sant Symptom & Problem index
o PUF score
 Voiding diary:
 Daytime Frequency ranges from 17-25.
 Average voided volume of 85-175 ml
 Post-void residual: optional
 Lab Test:
 Urinalysis
 Urine culture (including culture for TB)
 may be indicated even in pts with a -ve UA
 Urine cytology : Optional

15. Cystoscopy
 Office Cystoscopy
o May be done as part of initial evaluation or after failed Rx
o Purposes:
 identify HL
 r/o bladder Ca/ CIS or other conditions causing sxs.
 assess functional bladder capacity
o May be considered optional in a young pts and no RF for
bladder Ca or other pelvic conditions
o Biopsy any suspicious lesions and HLs.

16. Cystoscopy …
 Cystoscopy with Hydrodistension (CHD)
o Optional
o Has both diagnostic and therapeutic value
o Procedure:
 Under GA or RA
 gravity filling of bladder at 70‒80 cmH20 for 1-2 minutes
 Bladder is drained and refilled
o Findings:
 Terminal hematuria upon draining the infusion fluid
 Glomerulations and/or HL
 Assess bladder capacity (Anesthetic BC)

17.  “Anesthetic bladder challenge”
o Optional
o Resolution of the pain after IV local anesthesia can be both diagnostic and therapeutic
o suggests that the pain is bladder origin.
o Nonspecific
 Potassium sensitivity test (PST)
o Detects abnormal bladder epithelium permeability by provoking pain and urinary urgency.
o PST +ve :- KCl pain/urgency rated as ≥ 2 as compared to water
o results are nonspecific for IC/BPS,
o It is a costly and painful test
o Not recommended in routine evaluation

18.  Urodynamic evaluation
o NOT-RECOMMENDED in routine evaluation
o Complex cases may benefit from studies
o To exclude other functional bladder pathologies.
o IC/BPS:
o Normal det. contraction and compliance, Dec. capacity and
hypersensetivity
 USG/ Other Pelvic Imaging
o Optional
o Expected to be normal if IC/BPS is the only Dx
o Should be completed for pts:
o Hematuria
o Alternative clinical condition are questioned

19. Treatment
05

20. Overview…
o There is no universally effective treatment or mgt approach.
o No single treatment works well overtime for most patients
o Currently there is NO CURATIVE treatment for this condition
o The main GOAL of Rx is to maximize sxs control and QoL, while
avoiding AEs and Rx complications.
o Goals of therapy must be realistic and mutually agreed upon b/n the
physician and patient.

21. General principles…
o Initial mgt should focus on conservative strategies
o Stepwise fashion until some degree of sxic relief is obtained.
o Initial Rx type and level depend on symptom severity, disease phenotypes/subtypes, clinician
judgment, and pt. preference
o A combination of treatments may be appropriate for some patients
o Consider “drug holidays” to periodically assess drug effectiveness
o Ineffective Rx should be discontinued once a clinically meaningful interval has elapsed.
o Reconsider diagnosis if no impv’t after multiple txt approaches

22. Conservative Therapies
o Recommended as first-line treatment
o Significant improvement in 45‒50% of patients
I. Patient education:
II. Self-care practices/ Behavioral modification
o Fluid mgt
o Dietary modification
o Application of local heat or cold
o Avoidance of certain activities/exercises
o Bladder training with urge suppression
III. Stress management and psychological support

23. Multimodal Pain therapy
o No data available about the efficacy of different form of
pain txt
o Simple analgesia can be tried
o Opioids should be used with caution
o Other Options:
 Pharmacological therapy: (Oral and Intravesical)
 Complementary therapy (e.g., physical therapy)
o minimize dependence on pain medications.

24. Physical Therapies
o For IC/BPS patients with pelvic floor tenderness
1) Physiotherapy and Massage
 RECOMMENDED for pts with pelvic floor dysfunction
 Appropriately trained clinicians should be available
 Maneuvers are directed toward relaxation, elongation, stretching, and
massaging of tightened muscles
 Kegel exercises should be avoided
 Case series: impv’t of symptoms in 50‒62% of patients
2) Acupuncture: Optional in motivated pts
3) Trigger-point injection: Optional for pts with trigger-point pain

25. Oral Therapy
 Amitriptyline
o Ideal initial oral therapy
o Statistically significant amelioration of symptoms
o Recommendation: start with 10mg/d and titrate wkly by 10mg to ceiling of 50mg/d
o Tx concept: Anticholinergic, antihistaminic, Pain Relief, sedation,
 Pentosan Polysulfate (PPS)
o Synthetic polysaccharide, similar to GAG of bladder surface
o Only oral medication approved by FDA
o Clinical response may take 3-6 months to occur
o MOA: correct GAG layer defect, inhibit histamine release

26. Oral Therapy…
 Hydroxyzine/Cimetidine
o OPTION for pts with allergic phenotype
o Role: blockade of mast cell release of histamine
o Common side effects: sleepiness, headache, dry mouth
o Clinically significant improvement (23%) vs. the
placebo group(13%)
 Gabapentin
o OPTION in pts with neuropathic pain (FDA approved)
o Analgesic, anxiolytic
o MoA: Inhibits neural up-regulation & neurogenic inflammation
o Advise: careful dose titration to balance sedative properties
o OPTION as a last resort in patients with inflammation
o patients refractory to other Treatment
o potential for serious side effects
o Close patient monitoring, including blood pressure, Cr and
CyA levels
 Cyclosporine A (CyA)

27. Intravesical Therapy
 Dimethyl sulfoxide- DMSO
o basis of intravesical therapy
o Mechanism of action
 desensitize nociceptive pathways in the LUT
 Muscle relaxation and anti-inflammatory
o At least 6-8 wk course recommended
o Often given as part of “Intravesical cocktail”
 Heparin
o Mucopolysaccharide
o May mimic activity of bladder mucous GAG
o Beneficial anti-adherence action
o Anti-inflammatory and surface protective action
o Sodium channel blocking anesthetic
o Usually used with other meds in cocktail solution
o Rapid action, so it helps for sxs flares or maintenance therapy
o Also has anti-inflammatory and antimicrobial properties
 Lidocaine
 Others IVT
o Intravesical PPS
o Hyaluronic acid
o Clorpactin
o Silver nitrate

28. Minimally Invasive Therapy
 Bladder Hydrodistension
o reserved for pts who have failed other Rx
o Short term efficacy up to 60%
 More effective in pts with HLs and small capacity bladder
o The technique has not been standardized
o Short-duration, Low-pressure is recommended
o Possible MOA:
 disruption of afferent nerves ending, anti inflammatory, or decreased nerve
growth factor
o Post-procedure sxs flare is common

29. MIT…
 Surgery for Hunner ulcer
o Endoscopic treatment is recommended for pts with HLs
 Fulguration
 Cautery
 Laser
 Submucosal injections of triamcinolone acetonide
o 70% of pts showed impv’t with an average duration of 7-12 mo
o Recommendation to prevent bladder or bowel perforation
 low bladder filling volume
 low-power setting (10‒15 W),
 firing during 1‒3 seconds in constant motion until the ulcer is blanched
o Majority of pts require repeat fulguration

30.  Intradetrusor botulinum toxin A
o Option for patients refractory to other treatments
o Not approved by the FDA
o May alleviate symptoms
o MOA: modulate sensory neurotransmission
o The duration and strength of response seem to be maintained with
repeat injections
o Pts must be counselled on potential side effects
 possibility of urinary retention and need to catheterize
MIT…

31. MIT…
 Neuromodulation
o For pts refractory to multiple treatment options
o is primarily achieved via sacral nerve stimulation (SNS)
 Pudendal nerve stimulations
 posterior tibial nerve stimulations
o not FDA approved
o Costly and not widely available at all centers.
o In one study,
 94% of patients reported imp’t in BC, frequency, pain, and
ICSI/ICPI score

32. Invasive Surgery
o Absolute last resort for ds refractory to ALL other treatment options.
o reported to be beneficial in improving pain, urinary sxs, and QoL
 But Pain relief is not guaranteed, even if the bladder is removed
 Those with HLs and diminished max. ABC, were more likely to have
improvement postoperatively
o Options:
o Substitution cystoplasty
 contracted bladder and
 frequency as the main problem, when pain is not significant
o Urinary diversion +/- cystectomy
 pts whose QoL is more or less destroyed

33.  Treatments that Should Not be Offered
o Long-term oral ABT administration
o Intravesical instillation of BCG
o High-pressure, long-duration hydrodistension
o Systemic (oral) long-term glucocorticoid
 Emerging therapies
o HBO ??
o PDE-5 Inhibitor ???
o Monoclonal antibodies against TNF ??
o Cannabinoids ??

34. References