CUA: Interstitial Cystitis (2016): Difference between revisions

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== Diagnosis and Evaluation ==
== Diagnosis and Evaluation ==


* '''UrologySchool.com Summary'''
=== UrologySchool.com Summary ===
** '''Mandatory (1):'''
**# '''History and Physical Exam'''
** '''Recommended (4):'''
**# '''Urinalysis/culture'''
**# '''Symptom scores'''
**# '''Frequency volume chart'''
**# '''Cystoscopy'''
** '''Optional (5):'''
**# PVR
**# Urine cytology
**# Imaging
**# Intravesical anesthetic challenge
**# Hydrodistension
** '''Not recommended: potassium sensitivity test, bladder biopsy, urodynamics'''
 
* '''Mandatory (1):'''
* '''Mandatory (1):'''
** '''History and Physical Exam'''
*# '''History and Physical Exam'''
*** '''History'''
**** '''Characteristic presentation includes a combination of pain, frequency, nocturia, and urgency'''
***** '''Pelvic pain is the main descriptor of IC/BPS'''
****** '''Pain that occurs only during voiding is not consistent with IC/BPS'''
******* Vulvar disorders, which cause pain when urine makes contact with the vulva, should instead be considered '''(see Table 1 from Original Guideline for differential diagnosis).'''
****** In early or milder IC/BPS, patients may not describe frank pain, but rather describe sensations of “pressure,” “burning,” “sharp,” or “uncomfortable sensation of having to urinate.” Typically, this sensation is felt in the supra-pubic area, but it can be referred to areas located in the pelvis, including the urethra, vagina, labia, inguinal area, perineum, and/or lower abdomen or back
***** '''Frequency is the most common presenting symptom i.e. patients seek medical attention for frequency, not the pain'''
**** '''Patients may describe periods of worsening symptoms, which may be triggered''' by stress, intercourse, menses, or consumption of coffee, alcohol, citrus fruits, tomatoes, carbonated beverages, and spicy foods
***** '''Symptoms of IC/BPS are generally worse a few days prior to menses, in contrast to endometriosis, which is worse during menses'''
*** '''Physical exam'''
**** '''Abdominal and pelvic exam''', with particular focus on looking for masses, bladder distension, hernias, and tenderness.
***** '''The female pelvic exam should screen for vulvodynia, vaginitis, atrophic changes, prolapse, cervical pathology, and adnexal masses or tenderness'''.
****** Point tenderness, a mass, and expression of pus on palpation of the urethra are classic signs of a urethral diverticulum.
**** '''Digital rectal examination in males is essential'''
**** '''A musculoskeletal and focused neurological exam may also be contributory'''.
***** Although there is no physical finding specific to patients with IC/BPS, suprapubic tenderness and bladder neck point tenderness, in both males and females, is very often noted.
***** In males, tenderness may be elicited by palpating the perineal area between the scrotum and anus
***** In females, palpating the anterior vaginal wall along the course of the urethra up to the bladder neck may elicit pain.
**** '''Palpation of the levator muscles''' in both sexes, looking for tenderness, spasm/tight bands, and/or trigger points, is important for both diagnosis and treatment recommendations
***** '''Pelvic floor or rectal spasms may respond well to pelvic floor physiotherapy'''.
***** Hypo or hypersensitivity of the perineum, in combination with a weak or absent anal reflex, may suggest pudendal nerve entrapment.
* '''Recommended (4):'''
* '''Recommended (4):'''
** '''Urinalysis +/- culture'''
*# '''Urinalysis/culture'''
*** If signs of UTI are identified on urinalysis (e.g. positive for leukocytes), a culture and sensitivity is required.
*# '''Symptom scores'''
**** '''If sterile pyuria persists''', '''consider testing for Chlamydia trachomatis, Mycoplasma, Ureaplasma, Corynebacterium species, Candida species, and Mycoplasma tuberculosis.'''
*# '''Frequency volume chart'''
*** '''Absence of leukocytes does not rule out IC/BPS'''
*# '''Cystoscopy'''
** '''Symptom scores'''
* '''Optional (5):'''
*** '''Useful to establish baseline symptom severity and to track response to therapeutic intervention'''
*# PVR
*** Options include:
*# Urine cytology
***# Interstitial Cystitis Symptom Index (ICSI)
*# Imaging
***# Bladder Pain/IC Symptom Score (BPIC-SS)
*# Intravesical anesthetic challenge
***# Pain, Urgency, Frequency (PUF)
*# Hydrodistension
** '''Frequency/volume chart'''
* '''Not recommended: potassium sensitivity test, bladder biopsy, urodynamics'''
*** To differentiate polyuria from the classic small voided volumes expected with IC/BPS.
 
** '''Cystoscopy'''
=== Mandatory (1): ===
*** Expected to be normal
* '''History and Physical Exam'''
*** Used to:
** '''History'''
***# Rule out bladder cancer/carcinoma in situ
*** '''Characteristic presentation includes a combination of pain, frequency, nocturia, and urgency'''
***# Identify Hunner’s lesions that reflect severe disease, or even different disease (information that may impact treatment decisions)
**** '''Pelvic pain is the main descriptor of IC/BPS'''
***# Determine effect on pelvic pain during bladder filling and emptying
***** '''Pain that occurs only during voiding is not consistent with IC/BPS'''
***# Objectively evaluate “functional” bladder capacity
****** Vulvar disorders, which cause pain when urine makes contact with the vulva, should instead be considered '''(see Table 1 from Original Guideline for differential diagnosis).'''
***# Facilitate appropriate pelvic examination
***** In early or milder IC/BPS, patients may not describe frank pain, but rather describe sensations of “pressure,” “burning,” “sharp,” or “uncomfortable sensation of having to urinate.” Typically, this sensation is felt in the supra-pubic area, but it can be referred to areas located in the pelvis, including the urethra, vagina, labia, inguinal area, perineum, and/or lower abdomen or back
***# Reassure the patient
**** '''Frequency is the most common presenting symptom i.e. patients seek medical attention for frequency, not the pain'''
*** '''Patients may describe periods of worsening symptoms, which may be triggered''' by stress, intercourse, menses, or consumption of coffee, alcohol, citrus fruits, tomatoes, carbonated beverages, and spicy foods
**** '''Symptoms of IC/BPS are generally worse a few days prior to menses, in contrast to endometriosis, which is worse during menses'''
** '''Physical exam'''
*** '''Abdominal and pelvic exam''', with particular focus on looking for masses, bladder distension, hernias, and tenderness.
**** '''The female pelvic exam should screen for vulvodynia, vaginitis, atrophic changes, prolapse, cervical pathology, and adnexal masses or tenderness'''.
***** Point tenderness, a mass, and expression of pus on palpation of the urethra are classic signs of a urethral diverticulum.
*** '''Digital rectal examination in males is essential'''
*** '''A musculoskeletal and focused neurological exam may also be contributory'''.
**** Although there is no physical finding specific to patients with IC/BPS, suprapubic tenderness and bladder neck point tenderness, in both males and females, is very often noted.
**** In males, tenderness may be elicited by palpating the perineal area between the scrotum and anus
**** In females, palpating the anterior vaginal wall along the course of the urethra up to the bladder neck may elicit pain.
*** '''Palpation of the levator muscles''' in both sexes, looking for tenderness, spasm/tight bands, and/or trigger points, is important for both diagnosis and treatment recommendations
**** '''Pelvic floor or rectal spasms may respond well to pelvic floor physiotherapy'''.
**** Hypo or hypersensitivity of the perineum, in combination with a weak or absent anal reflex, may suggest pudendal nerve entrapment.
 
=== Recommended (4): ===
* '''Urinalysis +/- culture'''
** If signs of UTI are identified on urinalysis (e.g. positive for leukocytes), a culture and sensitivity is required.
*** '''If sterile pyuria persists''', '''consider testing for Chlamydia trachomatis, Mycoplasma, Ureaplasma, Corynebacterium species, Candida species, and Mycoplasma tuberculosis.'''
** '''Absence of leukocytes does not rule out IC/BPS'''
* '''Symptom scores'''
** '''Useful to establish baseline symptom severity and to track response to therapeutic intervention'''
** Options include:
**# Interstitial Cystitis Symptom Index (ICSI)
**# Bladder Pain/IC Symptom Score (BPIC-SS)
**# Pain, Urgency, Frequency (PUF)
* '''Frequency/volume chart'''
** To differentiate polyuria from the classic small voided volumes expected with IC/BPS.
* '''Cystoscopy'''
** Expected to be normal
** Used to:
**# Rule out bladder cancer/carcinoma in situ
**# Identify Hunner’s lesions that reflect severe disease, or even different disease (information that may impact treatment decisions)
**# Determine effect on pelvic pain during bladder filling and emptying
**# Objectively evaluate “functional” bladder capacity
**# Facilitate appropriate pelvic examination
**# Reassure the patient
 
=== Optional (5): ===
* '''Post-void residual'''
** '''Recommended with a history of poor emptying and/or palpable bladder'''
* '''Urine cytology'''
** '''Indicated if microscopic hematuria is present or if there are other risk factors for urothelial carcinoma'''
* '''Imaging'''
** '''Abdominal or pelvic ultrasonography, or other imaging modalities, may be useful when alternative clinical conditions are questioned, but are expected to be normal if IC/BPS is the only diagnosis.'''
* '''Intravesical anesthetic challenge'''
** '''An anesthetic challenge test, such as an alkalized lidocaine test, instills 10‒20 mL of an anesthetic mixture into an empty bladder. This fluid is held for 10‒15 minutes and then drained by catheter.'''
** '''This test can be performed after cystoscopy and can provide both relief to the patient, as well as diagnostic information and guide future therapy.'''
* '''Hydrodistension (HD)'''
** '''Performed under general or regional anesthetic'''
** '''Bladder is filled with NS by gravity drainage at a pressure of 80 cm H2O to its maximum anesthetic capacity (determined whereby the inflow backs up in the drip chamber or leakage occurs per urethra despite compression against the cystoscope) and distension is maintained for 2 to no more than 10 minutes; the bladder is drained at the end and capacity is measured'''
** '''HD under general anesthetic allows for stratification of patients into those with ulcers and glomerulations from those with no obvious mucosal abnormalities'''
** '''As the literature is conflicting regarding its utility, HD for diagnostic purposes may be appropriate in certain situations such as:'''
*** '''Patient is unable to tolerate cystoscopy under local anesthetic and is having a general anesthetic'''
*** '''When a patient has failed other treatment options and HD to assess disease severity may contribute information to the diagnosis'''
*** '''Assessing a patient for clinical trial eligibility'''


* '''Optional''' '''(5):'''
=== Not recommended (3): ===
** '''Post-void residual'''
# Potassium chloride sensitivity test
*** '''Recommended with a history of poor emptying and/or palpable bladder'''
#* Based on the assumption that a “dysfunctional epithelium” (glycosaminoglycan [GAG] layer) allows potassium ions to cross the abnormally permeable urothelium, depolarize nerves and muscles, and results in pain.
** '''Urine cytology'''
#* Sensitivity/specificity of the test are poor, adding no information over history and cystoscopy.
*** '''Indicated if microscopic hematuria is present or if there are other risk factors for urothelial carcinoma'''
# Bladder biopsy
** '''Imaging'''
#* There are no specific features found on bladder biopsy to confirm a diagnosis of IC/BPS.
*** '''Abdominal or pelvic ultrasonography, or other imaging modalities, may be useful when alternative clinical conditions are questioned, but are expected to be normal if IC/BPS is the only diagnosis.'''
# Urodynamics
** '''Intravesical anesthetic challenge'''
*** '''An anesthetic challenge test, such as an alkalized lidocaine test, instills 10‒20 mL of an anesthetic mixture into an empty bladder. This fluid is held for 10‒15 minutes and then drained by catheter.'''
*** '''This test can be performed after cystoscopy and can provide both relief to the patient, as well as diagnostic information and guide future therapy.'''
** '''Hydrodistension (HD)'''
*** '''Performed under general or regional anesthetic'''
*** '''Bladder is filled with NS by gravity drainage at a pressure of 80 cm H2O to its maximum anesthetic capacity (determined whereby the inflow backs up in the drip chamber or leakage occurs per urethra despite compression against the cystoscope) and distension is maintained for 2 to no more than 10 minutes; the bladder is drained at the end and capacity is measured'''
*** '''HD under general anesthetic allows for stratification of patients into those with ulcers and glomerulations from those with no obvious mucosal abnormalities'''
*** '''As the literature is conflicting regarding its utility, HD for diagnostic purposes may be appropriate in certain situations such as:'''
**** '''Patient is unable to tolerate cystoscopy under local anesthetic and is having a general anesthetic'''
**** '''When a patient has failed other treatment options and HD to assess disease severity may contribute information to the diagnosis'''
**** '''Assessing a patient for clinical trial eligibility'''
* '''Not recommended (3)''':
*# Potassium chloride sensitivity test
*#* Based on the assumption that a “dysfunctional epithelium” (glycosaminoglycan [GAG] layer) allows potassium ions to cross the abnormally permeable urothelium, depolarize nerves and muscles, and results in pain.
*#* Sensitivity/specificity of the test are poor, adding no information over history and cystoscopy.
*# Bladder biopsy
*#* There are no specific features found on bladder biopsy to confirm a diagnosis of IC/BPS.
*# Urodynamics


== Management ==
== Management ==


* '''First-line: conservative (5):'''
=== First-line: conservative (5): ===
*# '''Patient education'''
# '''Patient education'''
*# '''Dietary modifications'''
# '''Dietary modifications'''
*#* '''Common food triggers include''' '''coffee, tea, citrus fruits, carbonated and alcoholic beverages, bananas, tomatoes, spicy foods, artificial sweeteners, vitamin C, and wheat products'''.
#* '''Common food triggers include''' '''coffee, tea, citrus fruits, carbonated and alcoholic beverages, bananas, tomatoes, spicy foods, artificial sweeteners, vitamin C, and wheat products'''.
*#* Dietary modifications, such as a steady intake of water to dilute urine and reduce constipation, and an elimination diet trial have been advocated. No standardized protocol exists, but common practice is to instruct patients to avoid all foods on the list for a period varying from 1 week to 3 months and then methodically re-introduce one item at a time, with a waiting period of 3 days to identify potential offenders.
#* Dietary modifications, such as a steady intake of water to dilute urine and reduce constipation, and an elimination diet trial have been advocated. No standardized protocol exists, but common practice is to instruct patients to avoid all foods on the list for a period varying from 1 week to 3 months and then methodically re-introduce one item at a time, with a waiting period of 3 days to identify potential offenders.
*#* Only one placebo-controlled, RCT on the effect of diet in IC/BPS has been published, which failed to report any significant association.
#* Only one placebo-controlled, RCT on the effect of diet in IC/BPS has been published, which failed to report any significant association.
*# '''Bladder retraining'''
# '''Bladder retraining'''
*#* The goal is to reduce voiding frequency, potentially increase bladder capacity, and reduce the need to void in response to urgency or pain. Options include timed voiding and urge suppression.
#* The goal is to reduce voiding frequency, potentially increase bladder capacity, and reduce the need to void in response to urgency or pain. Options include timed voiding and urge suppression.
*# '''Stress management and psychological support (select patients)''' in patients with stress or psychological dysfunction
# '''Stress management and psychological support (select patients)''' in patients with stress or psychological dysfunction
*# '''Physical therapy techniques (select patients)'''
# '''Physical therapy techniques (select patients)'''
*#* '''Pelvic floor physiotherapy can be recommended for patients identified with pelvic floor dysfunction'''
#* '''Pelvic floor physiotherapy can be recommended for patients identified with pelvic floor dysfunction'''
*#* '''Massage techniques, acupuncture, and trigger point injections are options for patients with pelvic floor tenderness.'''
#* '''Massage techniques, acupuncture, and trigger point injections are options for patients with pelvic floor tenderness.'''


* '''Second-line: medications (oral, intravesical)'''
=== Second-line: medications (oral, intravesical) ===
** '''Oral (7):'''
* '''Oral (7):'''
**# '''Amitriptyline''' 25–75 mg po qhs
*# '''Amitriptyline''' 25–75 mg po qhs
**# '''Cimetidine''' 400 mg po bid
*# '''Cimetidine''' 400 mg po bid
**# '''Hydroxyzine''' 10–50 mg po qhs (perhaps in patients with an allergy history)
*# '''Hydroxyzine''' 10–50 mg po qhs (perhaps in patients with an allergy history)
**# '''Pentosan polysulfate''' 100 mg po tid '''(PPS, Elmiron)'''
*# '''Pentosan polysulfate''' 100 mg po tid '''(PPS, Elmiron)'''
**#* '''Expected benefits are predicted to be marginal'''
*#* '''Expected benefits are predicted to be marginal'''
**#* Common side effects included: diarrhea (25%); headache (18.2%); nausea (15%); pelvic pain (13%); abdominal pain (13%); and alopecia (5%).
*#* Common side effects included: diarrhea (25%); headache (18.2%); nausea (15%); pelvic pain (13%); abdominal pain (13%); and alopecia (5%).
**# '''Gabapentinoids'''
*# '''Gabapentinoids'''
**#* Option in patients with neuropathic pain
*#* Option in patients with neuropathic pain
**# '''Quercetin'''
*# '''Quercetin'''
**# '''Cyclosporine A'''
*# '''Cyclosporine A'''
**#* Close patient monitoring, including blood pressure, Cr and CyA levels are necessary. '''Due to the potential for serious side effects, should be reserved for severe patients with inflammation refractory to other treatment options.'''
*#* Close patient monitoring, including blood pressure, Cr and CyA levels are necessary. '''Due to the potential for serious side effects, should be reserved for severe patients with inflammation refractory to other treatment options.'''
** '''Intravesical'''
* '''Intravesical'''
*** '''Recommended (3): DMSO, heparin, lidocaine'''
** '''Recommended (3): DMSO, heparin, lidocaine'''
***# '''Dimethylsulfoxide (DMSO)'''
**# '''Dimethylsulfoxide (DMSO)'''
***#* '''MOA: organic solvent with anti-inflammatory and analgesic properties'''
**#* '''MOA: organic solvent with anti-inflammatory and analgesic properties'''
***#* Administered as a 50 mL solution of 50% DMSO with a dwell time of 30‒60 minutes, once weekly for 6 weeks. Monthly maintenance doses may be considered.
**#* Administered as a 50 mL solution of 50% DMSO with a dwell time of 30‒60 minutes, once weekly for 6 weeks. Monthly maintenance doses may be considered.
***#* Overall, favourable safety profile. Typical side effects include halitosis (garlic-like breath, as it is eliminated through the lungs) and potential flare-up after the first instillation, which usually improves after the second one.
**#* Overall, favourable safety profile. Typical side effects include halitosis (garlic-like breath, as it is eliminated through the lungs) and potential flare-up after the first instillation, which usually improves after the second one.
***#* Theoretically may cause dissolution of collagen that could '''potentially cause bladder fibrosis if used on a long-term basis.'''
**#* Theoretically may cause dissolution of collagen that could '''potentially cause bladder fibrosis if used on a long-term basis.'''
***# '''Heparin (alone or in combination)'''
**# '''Heparin (alone or in combination)'''
***#* '''MOA: GAG analogue'''
**#* '''MOA: GAG analogue'''
***#* May be instilled intravesically with '''virtually no systemic absorption'''
**#* May be instilled intravesically with '''virtually no systemic absorption'''
***#* '''DMSO combined with heparin better than DMSO alone''' (further reduces and defers relapses)
**#* '''DMSO combined with heparin better than DMSO alone''' (further reduces and defers relapses)
***# '''Lidocaine'''
**# '''Lidocaine'''
***#* '''MOA: local anesthetic'''
**#* '''MOA: local anesthetic'''
***#* Instillation on a daily or weekly basis of alkalinized lidocaine
**#* Instillation on a daily or weekly basis of alkalinized lidocaine
***#* '''Option for short-term relief IC/BPS symptoms''', primarily bladder pain
**#* '''Option for short-term relief IC/BPS symptoms''', primarily bladder pain
*** '''Options (hyaluronic acid, chondroitin sulfate, pentosan polysulfate, oxybutynin)''':
** '''Options (hyaluronic acid, chondroitin sulfate, pentosan polysulfate, oxybutynin)''':
***# '''Hyaluronic acid'''
**# '''Hyaluronic acid'''
***#* MOA: May help replenish the GAG layer of the bladder.
**#* MOA: May help replenish the GAG layer of the bladder.
***#* Efficacy unknown; 3 negative trials have been completed without published results
**#* Efficacy unknown; 3 negative trials have been completed without published results
***# '''Chondroitin sulfate'''
**# '''Chondroitin sulfate'''
***#* MOA: May help replenish the GAG layer of the bladder.
**#* MOA: May help replenish the GAG layer of the bladder.
***#* Should not be used as monotherapy, but may be considered as part of multimodal therapy for IC/BPS.
**#* Should not be used as monotherapy, but may be considered as part of multimodal therapy for IC/BPS.
***# '''Pentosan polysulfate (PPS, Elmiron)'''
**# '''Pentosan polysulfate (PPS, Elmiron)'''
***#* MOA: a weak analogue of heparin, may replenish the deficient GAG layer
**#* MOA: a weak analogue of heparin, may replenish the deficient GAG layer
***#* '''Intravesical PPS may be more effective than oral''' since only 1‒3% of oral PPS reaches the bladder.
**#* '''Intravesical PPS may be more effective than oral''' since only 1‒3% of oral PPS reaches the bladder.
***#* '''May be used alone or in combination with oral PPS'''
**#* '''May be used alone or in combination with oral PPS'''
***# '''Oxybutynin'''
**# '''Oxybutynin'''
*** '''Not recommended (resiniferatoxin, BCG):'''
** '''Not recommended (resiniferatoxin, BCG):'''
***# Resiniferatoxin (RTX)
**# Resiniferatoxin (RTX)
***#* A potent analogue of the chili pepper extract capsaicin; a neurotoxin that desensitizes C-fiber afferent neurons that transmit pain and, thus, could alleviate pain in IC/BPS.
**#* A potent analogue of the chili pepper extract capsaicin; a neurotoxin that desensitizes C-fiber afferent neurons that transmit pain and, thus, could alleviate pain in IC/BPS.
***#* Based on conflicting Level 2 evidence and the adverse side effect profile, RTX is not recommended
**#* Based on conflicting Level 2 evidence and the adverse side effect profile, RTX is not recommended
***# Bacillus Calmette-Guerin (BCG)
**# Bacillus Calmette-Guerin (BCG)


* '''Third-line: minimally invasive surgical procedures'''
=== Third-line: minimally invasive surgical procedures ===
** '''Treatment is recommended for patients with identified Hunner’s lesions'''
* '''Treatment is recommended for patients with identified Hunner’s lesions'''
*** Hunner’s lesions can be treated by:
** Hunner’s lesions can be treated by:
***# Transurethral resection
**# Transurethral resection
***# Fulguration with a Bugbee electrode
**# Fulguration with a Bugbee electrode
***# Transurethral coagulation using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser
**# Transurethral coagulation using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser
** '''Options in patients with or without Hunner’s lesions (3):'''
* '''Options in patients with or without Hunner’s lesions (3):'''
**# '''Hydrodistension (HD)'''
*# '''Hydrodistension (HD)'''
**# '''Botulinum toxin A (BTX-A)'''
*# '''Botulinum toxin A (BTX-A)'''
**#* Costly, may not be widely available
*#* Costly, may not be widely available
**#* Repeat injections are safe
*#* Repeat injections are safe
**#* Must describe potential side effects, particularly risk of urinary retention and need to catheterize
*#* Must describe potential side effects, particularly risk of urinary retention and need to catheterize
**# '''Sacral neuromodulation (SNM)'''
*# '''Sacral neuromodulation (SNM)'''
**#* Costly, may not be widely available
*#* Costly, may not be widely available
**#* Must describe potential side effects, particularly the need for future surgical revisions
*#* Must describe potential side effects, particularly the need for future surgical revisions


* '''Fourth-line: Radical surgery'''
=== Fourth-line: Radical surgery ===
** '''Last resort''' due to the invasiveness of surgery (substitution cystoplasty or urinary diversion ± cystectomy), the benign nature of IC/BPS, and multiple other treatment options available
* '''Last resort''' due to the invasiveness of surgery (substitution cystoplasty or urinary diversion ± cystectomy), the benign nature of IC/BPS, and multiple other treatment options available


* '''Emerging therapies'''
=== Emerging therapies ===
** Investigational treatments include:
* Investigational treatments include:
*** Hyperbaric oxygen
** Hyperbaric oxygen
*** Sildenafil
** Sildenafil
*** Monoclonal antibodies
** Monoclonal antibodies
*** Cannabinoids
** Cannabinoids
*** Intravesical liposomes.
** Intravesical liposomes.


== Questions ==
== Questions ==

Revision as of 10:11, 16 March 2024


See Original Guideline

Background

  • Definition of interstitial cystitis (IC)/bladder pain syndrome (BPS):
    1. An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the bladder
    2. Associated with lower urinary tract symptoms
    3. For > 6 weeks duration
    4. In the absence of infection or other identifiable causes

Epidemiology

  • Can affect both sexes, but vast majority (90%) are female
  • 2.7-6.5% of US females have symptoms consistent with a diagnosis of IC/BPS (wide variation in reported incidence and prevalence depending on the criteria used for diagnosis)

Diagnosis and Evaluation

UrologySchool.com Summary

  • Mandatory (1):
    1. History and Physical Exam
  • Recommended (4):
    1. Urinalysis/culture
    2. Symptom scores
    3. Frequency volume chart
    4. Cystoscopy
  • Optional (5):
    1. PVR
    2. Urine cytology
    3. Imaging
    4. Intravesical anesthetic challenge
    5. Hydrodistension
  • Not recommended: potassium sensitivity test, bladder biopsy, urodynamics

Mandatory (1):

  • History and Physical Exam
    • History
      • Characteristic presentation includes a combination of pain, frequency, nocturia, and urgency
        • Pelvic pain is the main descriptor of IC/BPS
          • Pain that occurs only during voiding is not consistent with IC/BPS
            • Vulvar disorders, which cause pain when urine makes contact with the vulva, should instead be considered (see Table 1 from Original Guideline for differential diagnosis).
          • In early or milder IC/BPS, patients may not describe frank pain, but rather describe sensations of “pressure,” “burning,” “sharp,” or “uncomfortable sensation of having to urinate.” Typically, this sensation is felt in the supra-pubic area, but it can be referred to areas located in the pelvis, including the urethra, vagina, labia, inguinal area, perineum, and/or lower abdomen or back
        • Frequency is the most common presenting symptom i.e. patients seek medical attention for frequency, not the pain
      • Patients may describe periods of worsening symptoms, which may be triggered by stress, intercourse, menses, or consumption of coffee, alcohol, citrus fruits, tomatoes, carbonated beverages, and spicy foods
        • Symptoms of IC/BPS are generally worse a few days prior to menses, in contrast to endometriosis, which is worse during menses
    • Physical exam
      • Abdominal and pelvic exam, with particular focus on looking for masses, bladder distension, hernias, and tenderness.
        • The female pelvic exam should screen for vulvodynia, vaginitis, atrophic changes, prolapse, cervical pathology, and adnexal masses or tenderness.
          • Point tenderness, a mass, and expression of pus on palpation of the urethra are classic signs of a urethral diverticulum.
      • Digital rectal examination in males is essential
      • A musculoskeletal and focused neurological exam may also be contributory.
        • Although there is no physical finding specific to patients with IC/BPS, suprapubic tenderness and bladder neck point tenderness, in both males and females, is very often noted.
        • In males, tenderness may be elicited by palpating the perineal area between the scrotum and anus
        • In females, palpating the anterior vaginal wall along the course of the urethra up to the bladder neck may elicit pain.
      • Palpation of the levator muscles in both sexes, looking for tenderness, spasm/tight bands, and/or trigger points, is important for both diagnosis and treatment recommendations
        • Pelvic floor or rectal spasms may respond well to pelvic floor physiotherapy.
        • Hypo or hypersensitivity of the perineum, in combination with a weak or absent anal reflex, may suggest pudendal nerve entrapment.

Recommended (4):

  • Urinalysis +/- culture
    • If signs of UTI are identified on urinalysis (e.g. positive for leukocytes), a culture and sensitivity is required.
      • If sterile pyuria persists, consider testing for Chlamydia trachomatis, Mycoplasma, Ureaplasma, Corynebacterium species, Candida species, and Mycoplasma tuberculosis.
    • Absence of leukocytes does not rule out IC/BPS
  • Symptom scores
    • Useful to establish baseline symptom severity and to track response to therapeutic intervention
    • Options include:
      1. Interstitial Cystitis Symptom Index (ICSI)
      2. Bladder Pain/IC Symptom Score (BPIC-SS)
      3. Pain, Urgency, Frequency (PUF)
  • Frequency/volume chart
    • To differentiate polyuria from the classic small voided volumes expected with IC/BPS.
  • Cystoscopy
    • Expected to be normal
    • Used to:
      1. Rule out bladder cancer/carcinoma in situ
      2. Identify Hunner’s lesions that reflect severe disease, or even different disease (information that may impact treatment decisions)
      3. Determine effect on pelvic pain during bladder filling and emptying
      4. Objectively evaluate “functional” bladder capacity
      5. Facilitate appropriate pelvic examination
      6. Reassure the patient

Optional (5):

  • Post-void residual
    • Recommended with a history of poor emptying and/or palpable bladder
  • Urine cytology
    • Indicated if microscopic hematuria is present or if there are other risk factors for urothelial carcinoma
  • Imaging
    • Abdominal or pelvic ultrasonography, or other imaging modalities, may be useful when alternative clinical conditions are questioned, but are expected to be normal if IC/BPS is the only diagnosis.
  • Intravesical anesthetic challenge
    • An anesthetic challenge test, such as an alkalized lidocaine test, instills 10‒20 mL of an anesthetic mixture into an empty bladder. This fluid is held for 10‒15 minutes and then drained by catheter.
    • This test can be performed after cystoscopy and can provide both relief to the patient, as well as diagnostic information and guide future therapy.
  • Hydrodistension (HD)
    • Performed under general or regional anesthetic
    • Bladder is filled with NS by gravity drainage at a pressure of 80 cm H2O to its maximum anesthetic capacity (determined whereby the inflow backs up in the drip chamber or leakage occurs per urethra despite compression against the cystoscope) and distension is maintained for 2 to no more than 10 minutes; the bladder is drained at the end and capacity is measured
    • HD under general anesthetic allows for stratification of patients into those with ulcers and glomerulations from those with no obvious mucosal abnormalities
    • As the literature is conflicting regarding its utility, HD for diagnostic purposes may be appropriate in certain situations such as:
      • Patient is unable to tolerate cystoscopy under local anesthetic and is having a general anesthetic
      • When a patient has failed other treatment options and HD to assess disease severity may contribute information to the diagnosis
      • Assessing a patient for clinical trial eligibility

Not recommended (3):

  1. Potassium chloride sensitivity test
    • Based on the assumption that a “dysfunctional epithelium” (glycosaminoglycan [GAG] layer) allows potassium ions to cross the abnormally permeable urothelium, depolarize nerves and muscles, and results in pain.
    • Sensitivity/specificity of the test are poor, adding no information over history and cystoscopy.
  2. Bladder biopsy
    • There are no specific features found on bladder biopsy to confirm a diagnosis of IC/BPS.
  3. Urodynamics

Management

First-line: conservative (5):

  1. Patient education
  2. Dietary modifications
    • Common food triggers include coffee, tea, citrus fruits, carbonated and alcoholic beverages, bananas, tomatoes, spicy foods, artificial sweeteners, vitamin C, and wheat products.
    • Dietary modifications, such as a steady intake of water to dilute urine and reduce constipation, and an elimination diet trial have been advocated. No standardized protocol exists, but common practice is to instruct patients to avoid all foods on the list for a period varying from 1 week to 3 months and then methodically re-introduce one item at a time, with a waiting period of 3 days to identify potential offenders.
    • Only one placebo-controlled, RCT on the effect of diet in IC/BPS has been published, which failed to report any significant association.
  3. Bladder retraining
    • The goal is to reduce voiding frequency, potentially increase bladder capacity, and reduce the need to void in response to urgency or pain. Options include timed voiding and urge suppression.
  4. Stress management and psychological support (select patients) in patients with stress or psychological dysfunction
  5. Physical therapy techniques (select patients)
    • Pelvic floor physiotherapy can be recommended for patients identified with pelvic floor dysfunction
    • Massage techniques, acupuncture, and trigger point injections are options for patients with pelvic floor tenderness.

Second-line: medications (oral, intravesical)

  • Oral (7):
    1. Amitriptyline 25–75 mg po qhs
    2. Cimetidine 400 mg po bid
    3. Hydroxyzine 10–50 mg po qhs (perhaps in patients with an allergy history)
    4. Pentosan polysulfate 100 mg po tid (PPS, Elmiron)
      • Expected benefits are predicted to be marginal
      • Common side effects included: diarrhea (25%); headache (18.2%); nausea (15%); pelvic pain (13%); abdominal pain (13%); and alopecia (5%).
    5. Gabapentinoids
      • Option in patients with neuropathic pain
    6. Quercetin
    7. Cyclosporine A
      • Close patient monitoring, including blood pressure, Cr and CyA levels are necessary. Due to the potential for serious side effects, should be reserved for severe patients with inflammation refractory to other treatment options.
  • Intravesical
    • Recommended (3): DMSO, heparin, lidocaine
      1. Dimethylsulfoxide (DMSO)
        • MOA: organic solvent with anti-inflammatory and analgesic properties
        • Administered as a 50 mL solution of 50% DMSO with a dwell time of 30‒60 minutes, once weekly for 6 weeks. Monthly maintenance doses may be considered.
        • Overall, favourable safety profile. Typical side effects include halitosis (garlic-like breath, as it is eliminated through the lungs) and potential flare-up after the first instillation, which usually improves after the second one.
        • Theoretically may cause dissolution of collagen that could potentially cause bladder fibrosis if used on a long-term basis.
      2. Heparin (alone or in combination)
        • MOA: GAG analogue
        • May be instilled intravesically with virtually no systemic absorption
        • DMSO combined with heparin better than DMSO alone (further reduces and defers relapses)
      3. Lidocaine
        • MOA: local anesthetic
        • Instillation on a daily or weekly basis of alkalinized lidocaine
        • Option for short-term relief IC/BPS symptoms, primarily bladder pain
    • Options (hyaluronic acid, chondroitin sulfate, pentosan polysulfate, oxybutynin):
      1. Hyaluronic acid
        • MOA: May help replenish the GAG layer of the bladder.
        • Efficacy unknown; 3 negative trials have been completed without published results
      2. Chondroitin sulfate
        • MOA: May help replenish the GAG layer of the bladder.
        • Should not be used as monotherapy, but may be considered as part of multimodal therapy for IC/BPS.
      3. Pentosan polysulfate (PPS, Elmiron)
        • MOA: a weak analogue of heparin, may replenish the deficient GAG layer
        • Intravesical PPS may be more effective than oral since only 1‒3% of oral PPS reaches the bladder.
        • May be used alone or in combination with oral PPS
      4. Oxybutynin
    • Not recommended (resiniferatoxin, BCG):
      1. Resiniferatoxin (RTX)
        • A potent analogue of the chili pepper extract capsaicin; a neurotoxin that desensitizes C-fiber afferent neurons that transmit pain and, thus, could alleviate pain in IC/BPS.
        • Based on conflicting Level 2 evidence and the adverse side effect profile, RTX is not recommended
      2. Bacillus Calmette-Guerin (BCG)

Third-line: minimally invasive surgical procedures

  • Treatment is recommended for patients with identified Hunner’s lesions
    • Hunner’s lesions can be treated by:
      1. Transurethral resection
      2. Fulguration with a Bugbee electrode
      3. Transurethral coagulation using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser
  • Options in patients with or without Hunner’s lesions (3):
    1. Hydrodistension (HD)
    2. Botulinum toxin A (BTX-A)
      • Costly, may not be widely available
      • Repeat injections are safe
      • Must describe potential side effects, particularly risk of urinary retention and need to catheterize
    3. Sacral neuromodulation (SNM)
      • Costly, may not be widely available
      • Must describe potential side effects, particularly the need for future surgical revisions

Fourth-line: Radical surgery

  • Last resort due to the invasiveness of surgery (substitution cystoplasty or urinary diversion ± cystectomy), the benign nature of IC/BPS, and multiple other treatment options available

Emerging therapies

  • Investigational treatments include:
    • Hyperbaric oxygen
    • Sildenafil
    • Monoclonal antibodies
    • Cannabinoids
    • Intravesical liposomes.

Questions

  1. What is the definition of interstitial cystitis?
  2. As per the CUA guidelines, what are the mandatory investigations in a patient being referred for suspected interstitial cystitis? What are the recommended investigations? What are the optional investigations? What investigations are not recommended?
  3. What is the most common presenting symptom in a patient with interstitial cystitis?
  4. What is the differential diagnosis of a patient presenting with symptoms suggestive of interstitial cystitis?
  5. What are the first-line treatment options for interstitial cystitis?
  6. What are recommended second-line oral treatment options for interstitial cystitis? Intravesical options?
  7. What are minimally invasive surgical procedures for patients with interstitial cystitis?

Answers

  1. What is the definition of interstitial cystitis?
    • An unpleasant sensation perceived to be from the bladder
    • Associated with lower urinary tract symptoms
    • For >6 weeks duration
    • In the absence of infection or other identifiable causes
  2. As per the CUA guidelines, what are the mandatory investigations in a patient being referred for suspected interstitial cystitis? What are the recommended investigations? What are the optional investigations? What investigations are not recommended?
    • Mandatory: history and physical
    • Recommended: urinalysis/culture, symptoms scores, frequency volume chart, cystoscopy
    • Optional: PVR, US, cytology, intravesical anesthetic schedule, hydrodistention
    • Not recommended: UDS, bladder biopsy, potassium sensitivity
  3. What is the most common presenting symptom in a patient with interstitial cystitis?
    • Urinary frequency
  4. What is the differential diagnosis of a patient presenting with symptoms suggestive of interstitial cystitis?
    1. Endometriosis
    2. Non-infectious cystitis
    3. Vulvar disorders
    4. OAB
    5. Pudendal nerve entrapment
    6. Prosate-related pain
    7. Pelvic floor disorders
  5. What are the first-line treatment options for interstitial cystitis?
    1. Patient education
    2. Dietary modification
    3. Bladder retraining
    4. Stress management
    5. Pelvic floor physiotherapy
  6. What are recommended second-line oral treatment options for interstitial cystitis? Intravesical options?
    • Oral:
      1. Amitriptyline
      2. Cimetidine
      3. Hydroxyzine
      4. Pentosan polysulfate
      5. Gabapentinoids
      6. Quercetin
      7. Cyclosporin A
    • Intravesical:
      • Recommended: DMSO, heparin, lidocaine
      • Options: hyaluronic acid, chondroitin sulfate, pentosan polysulfate, oxybutynin
  7. What are minimally invasive surgical procedures for patients with interstitial cystitis?
    • TUR in patients with Hunner’s ulcers
    • Hydrodistention, botox, sacral neuromodulation in patients with or without Hunner’s
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