CUA: Interstitial Cystitis (2016): Difference between revisions

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== Background ==

* '''Definition of interstitial cystitis (IC)/bladder pain syndrome (BPS):'''

* '''Definition of interstitial cystitis (IC)/bladder pain syndrome (BPS):'''

*# '''An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the bladder'''

*# '''An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the bladder'''

*# '''Associated with lower urinary tract symptoms'''

*# '''Associated with lower urinary tract symptoms'''

*# '''For > 6 weeks duration'''

*# '''For > 6 weeks duration'''

*# '''In the absence of infection or other identifiable causes'''

*# '''In the absence of infection or other identifiable causes'''

== Epidemiology ==

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* 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)

== Differential Diagnoses[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065402/table/t1-cuaj-5-6-e136/ §] ==

# '''Endometriosis'''

# '''Non-infectious cystitis'''

# '''Vulvar disorders'''

# '''Overactive bladder'''

# '''Pudendal nerve entrapment'''

# '''Prostate-related pain'''

# '''Pelvic floor disorders'''

== Diagnosis and Evaluation ==

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*# '''Cystoscopy'''

* '''Optional (5):'''

*# PVR

*# '''PVR'''

*# Urine cytology

*# '''Urine cytology'''

*# Imaging

*# '''Imaging'''

*# Intravesical anesthetic challenge

*# '''Intravesical anesthetic challenge'''

*# Hydrodistension

*# '''Hydrodistension'''

* '''Not recommended: potassium sensitivity test, bladder biopsy, urodynamics'''

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*** '''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).'''~~

***** Vulvar disorders, which cause pain when urine makes contact with the vulva, should instead be considered

**** 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'''

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=== 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'''.

#* 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.

# '''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.

# '''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'''

#* '''Massage techniques, acupuncture, and trigger point injections are options for patients with pelvic floor tenderness.'''

=== Second-line: medications (oral, intravesical) ===

* '''Oral (7):~~'''~~

*# '''Amitriptyline''' 25–75 mg po qhs

==== Oral (7): ====

*# '''Cimetidine''' 400 mg po bid

# '''Amitriptyline''' 25–75 mg po qhs

*# '''Hydroxyzine''' 10–50 mg po qhs (perhaps in patients with an allergy history)

# '''Cimetidine''' 400 mg po bid

*# '''Pentosan polysulfate''' 100 mg po tid '''(PPS, Elmiron)'''

# '''Hydroxyzine''' 10–50 mg po qhs (perhaps in patients with an allergy history)

*#* '''Expected benefits are predicted to be marginal'''

# '''Pentosan polysulfate''' 100 mg po tid '''(PPS, Elmiron)'''

*#* Common side effects included: diarrhea (25%); headache (18.2%); nausea (15%); pelvic pain (13%); abdominal pain (13%); and alopecia (5%).

#* '''Expected benefits are predicted to be marginal'''

*# '''Gabapentinoids'''

#* Common side effects included: diarrhea (25%); headache (18.2%); nausea (15%); pelvic pain (13%); abdominal pain (13%); and alopecia (5%).

*#* Option in patients with neuropathic pain

# '''Gabapentinoids'''

*# '''Quercetin'''

#* Option in patients with neuropathic pain

*# '''Cyclosporine A'''

# '''Quercetin'''

*#* 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.'''

# '''Cyclosporine A'''

* '''Intravesical~~'''~~

#* 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.'''

** '''Recommended (3): DMSO, heparin, lidocaine'''

**# '''Dimethylsulfoxide (DMSO)'''

==== Intravesical ====

**#* '''MOA: organic solvent with anti-inflammatory and analgesic properties'''

* '''Recommended (3): DMSO, heparin, lidocaine'''

**#* 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.

*# '''Dimethylsulfoxide (DMSO)'''

**#* 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.

*#* '''MOA: organic solvent with anti-inflammatory and analgesic properties'''

**#* Theoretically may cause dissolution of collagen that could '''potentially cause bladder fibrosis if used on a long-term basis.'''

*#* 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.

**# '''Heparin (alone or in combination)'''

*#* 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.

**#* '''MOA: GAG analogue'''

*#* Theoretically may cause dissolution of collagen that could '''potentially cause bladder fibrosis if used on a long-term basis.'''

**#* May be instilled intravesically with '''virtually no systemic absorption'''

*# '''Heparin (alone or in combination)'''

**#* '''DMSO combined with heparin better than DMSO alone''' (further reduces and defers relapses)

*#* '''MOA: GAG analogue'''

**# '''Lidocaine'''

*#* May be instilled intravesically with '''virtually no systemic absorption'''

**#* '''MOA: local anesthetic'''

*#* '''DMSO combined with heparin better than DMSO alone''' (further reduces and defers relapses)

**#* Instillation on a daily or weekly basis of alkalinized lidocaine

*# '''Lidocaine'''

**#* '''Option for short-term relief IC/BPS symptoms''', primarily bladder pain

*#* '''MOA: local anesthetic'''

** '''Options (hyaluronic acid, chondroitin sulfate, pentosan polysulfate, oxybutynin)''':

*#* Instillation on a daily or weekly basis of alkalinized lidocaine

**# '''Hyaluronic acid'''

*#* '''Option for short-term relief IC/BPS symptoms''', primarily bladder pain

**#* MOA: May help replenish the GAG layer of the bladder.

* '''Options (hyaluronic acid, chondroitin sulfate, pentosan polysulfate, oxybutynin)''':

**#* Efficacy unknown; 3 negative trials have been completed without published results

*# '''Hyaluronic acid'''

**# '''Chondroitin sulfate'''

*#* 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

**#* Should not be used as monotherapy, but may be considered as part of multimodal therapy for IC/BPS.

*# '''Chondroitin sulfate'''

**# '''Pentosan polysulfate (PPS, Elmiron)'''

*#* MOA: May help replenish the GAG layer of the bladder.

**#* MOA: a weak analogue of heparin, may replenish the deficient GAG layer

*#* Should not be used as monotherapy, but may be considered as part of multimodal therapy for IC/BPS.

**#* '''Intravesical PPS may be more effective than oral''' since only 1‒3% of oral PPS reaches the bladder.

*# '''Pentosan polysulfate (PPS, Elmiron)'''

**#* '''May be used alone or in combination with oral PPS'''

*#* MOA: a weak analogue of heparin, may replenish the deficient GAG layer

**# '''Oxybutynin'''

*#* '''Intravesical PPS may be more effective than oral''' since only 1‒3% of oral PPS reaches the bladder.

** '''Not recommended (resiniferatoxin, BCG):'''

*#* '''May be used alone or in combination with oral PPS'''

**# Resiniferatoxin (RTX)

*# '''Oxybutynin'''

**#* 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.

* '''Not recommended (resiniferatoxin, BCG):'''

**#* Based on conflicting Level 2 evidence and the adverse side effect profile, RTX is not recommended

*# Resiniferatoxin (RTX)

**# Bacillus Calmette-Guerin (BCG)

*#* 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

*# 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:

** '''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

*#* Repeat injections are safe

*#* 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

*#* Must describe potential side effects, particularly the need for future surgical revisions

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#* TUR in patients with Hunner’s ulcers

#* Hydrodistention, botox, sacral neuromodulation in patients with or without Hunner’s

== References ==

* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065402/ Cox, Ashley, et al. "CUA guideline: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome." ''Canadian Urological Association Journal'' 10.5-6 (2016): E136.]

@@ Line 5: / Line 5: @@
 == Background ==
-* '''Definition of interstitial cystitis (IC)/bladder pain syndrome (BPS):'''
+* '''<span style="color:#ff0000">Definition of interstitial cystitis (IC)/bladder pain syndrome (BPS):'''
-*# '''An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the bladder'''
+*# '''<span style="color:#ff0000">An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the bladder'''
-*# '''Associated with lower urinary tract symptoms'''
+*# '''<span style="color:#ff0000">Associated with lower urinary tract symptoms'''
-*# '''For > 6 weeks duration'''
+*# '''<span style="color:#ff0000">For > 6 weeks duration'''
-*# '''In the absence of infection or other identifiable causes'''
+*# '''<span style="color:#ff0000">In the absence of infection or other identifiable causes'''
 == Epidemiology ==
@@ Line 15: / Line 15: @@
 * 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)
+== Differential Diagnoses[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065402/table/t1-cuaj-5-6-e136/ §] ==
+# '''<span style="color:#ff0000">Endometriosis'''
+# '''<span style="color:#ff0000">Non-infectious cystitis'''
+# '''<span style="color:#ff0000">Vulvar disorders'''
+# '''<span style="color:#ff0000">Overactive bladder'''
+# '''<span style="color:#ff0000">Pudendal nerve entrapment'''
+# '''<span style="color:#ff0000">Prostate-related pain'''
+# '''<span style="color:#ff0000">Pelvic floor disorders'''
 == Diagnosis and Evaluation ==
@@ Line 27: / Line 37: @@
 *# '''<span style="color:#ff0000">Cystoscopy'''
 * '''<span style="color:#ff0000">Optional (5):'''
-*# <span style="color:#ff0000">PVR
+*# <span style="color:#ff0000">'''PVR'''
-*# <span style="color:#ff0000">Urine cytology
+*# <span style="color:#ff0000">'''Urine cytology'''
-*# <span style="color:#ff0000">Imaging
+*# <span style="color:#ff0000">'''Imaging'''
-*# <span style="color:#ff0000">Intravesical anesthetic challenge
+*# <span style="color:#ff0000">'''Intravesical anesthetic challenge'''
-*# <span style="color:#ff0000">Hydrodistension
+*# <span style="color:#ff0000">'''Hydrodistension'''
 * '''Not recommended: potassium sensitivity test, bladder biopsy, urodynamics'''
@@ Line 43: / Line 53: @@
 *** '''<span style="color:#ff0000">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).'''
+***** Vulvar disorders, which cause pain when urine makes contact with the vulva, should instead be considered
 **** 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'''
@@ Line 119: / Line 129: @@
 === First-line: conservative (5): ===
-# '''Patient education'''
+# '''<span style="color:#ff0000">Patient education'''
-# '''Dietary modifications'''
+# '''<span style="color:#ff0000">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.
-# '''Bladder retraining'''
+# '''<span style="color:#ff0000">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.
-# '''Stress management and psychological support (select patients)''' in patients with stress or psychological dysfunction
+# '''<span style="color:#ff0000">Stress management and psychological support (select patients)''' in patients with stress or psychological dysfunction
-# '''Physical therapy techniques (select patients)'''
+# '''<span style="color:#ff0000">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):'''
-*# '''Amitriptyline''' 25–75 mg po qhs
+==== Oral (7): ====
-*# '''Cimetidine''' 400 mg po bid
+# '''<span style="color:#ff0000">Amitriptyline</span>''' 25–75 mg po qhs
-*# '''Hydroxyzine''' 10–50 mg po qhs (perhaps in patients with an allergy history)
+# '''<span style="color:#ff0000">Cimetidine</span>''' 400 mg po bid
-*# '''Pentosan polysulfate''' 100 mg po tid '''(PPS, Elmiron)'''
+# '''<span style="color:#ff0000">Hydroxyzine</span>''' 10–50 mg po qhs (perhaps in patients with an allergy history)
-*#* '''Expected benefits are predicted to be marginal'''
+# '''<span style="color:#ff0000">Pentosan polysulfate</span>''' 100 mg po tid '''(PPS, Elmiron)'''
-*#* Common side effects included: diarrhea (25%); headache (18.2%); nausea (15%); pelvic pain (13%); abdominal pain (13%); and alopecia (5%).
+#* '''Expected benefits are predicted to be marginal'''
-*# '''Gabapentinoids'''
+#* Common side effects included: diarrhea (25%); headache (18.2%); nausea (15%); pelvic pain (13%); abdominal pain (13%); and alopecia (5%).
-*#* Option in patients with neuropathic pain
+# '''Gabapentinoids'''
-*# '''Quercetin'''
+#* Option in patients with neuropathic pain
-*# '''Cyclosporine A'''
+# '''Quercetin'''
-*#* 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.'''
+# '''Cyclosporine A'''
-* '''Intravesical'''
+#* 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.'''
-** '''Recommended (3): DMSO, heparin, lidocaine'''
-**# '''Dimethylsulfoxide (DMSO)'''
+==== Intravesical ====
-**#* '''MOA: organic solvent with anti-inflammatory and analgesic properties'''
+* '''<span style="color:#ff0000">Recommended (3): DMSO, heparin, lidocaine'''
-**#* 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.
+*# '''<span style="color:#ff0000">Dimethylsulfoxide (DMSO)'''
-**#* 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.
+*#* '''<span style="color:#ff0000">MOA: organic solvent with anti-inflammatory and analgesic properties'''
-**#* Theoretically may cause dissolution of collagen that could '''potentially cause bladder fibrosis if used on a long-term basis.'''
+*#* 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.
-**# '''Heparin (alone or in combination)'''
+*#* 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.
-**#* '''MOA: GAG analogue'''
+*#* Theoretically may cause dissolution of collagen that could '''potentially cause bladder fibrosis if used on a long-term basis.'''
-**#* May be instilled intravesically with '''virtually no systemic absorption'''
+*# '''<span style="color:#ff0000">Heparin (alone or in combination)'''
-**#* '''DMSO combined with heparin better than DMSO alone''' (further reduces and defers relapses)
+*#* '''<span style="color:#ff0000">MOA: GAG analogue'''
-**# '''Lidocaine'''
+*#* May be instilled intravesically with '''virtually no systemic absorption'''
-**#* '''MOA: local anesthetic'''
+*#* '''DMSO combined with heparin better than DMSO alone''' (further reduces and defers relapses)
-**#* Instillation on a daily or weekly basis of alkalinized lidocaine
+*# '''<span style="color:#ff0000">Lidocaine'''
-**#* '''Option for short-term relief IC/BPS symptoms''', primarily bladder pain
+*#* '''<span style="color:#ff0000">MOA: local anesthetic'''
-** '''Options (hyaluronic acid, chondroitin sulfate, pentosan polysulfate, oxybutynin)''':
+*#* Instillation on a daily or weekly basis of alkalinized lidocaine
-**# '''Hyaluronic acid'''
+*#* '''Option for short-term relief IC/BPS symptoms''', primarily bladder pain
-**#* MOA: May help replenish the GAG layer of the bladder.
+* '''Options (hyaluronic acid, chondroitin sulfate, pentosan polysulfate, oxybutynin)''':
-**#* Efficacy unknown; 3 negative trials have been completed without published results
+*# '''Hyaluronic acid'''
-**# '''Chondroitin sulfate'''
+*#* 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
-**#* Should not be used as monotherapy, but may be considered as part of multimodal therapy for IC/BPS.
+*# '''Chondroitin sulfate'''
-**# '''Pentosan polysulfate (PPS, Elmiron)'''
+*#* MOA: May help replenish the GAG layer of the bladder.
-**#* MOA: a weak analogue of heparin, may replenish the deficient GAG layer
+*#* Should not be used as monotherapy, but may be considered as part of multimodal therapy for IC/BPS.
-**#* '''Intravesical PPS may be more effective than oral''' since only 1‒3% of oral PPS reaches the bladder.
+*# '''Pentosan polysulfate (PPS, Elmiron)'''
-**#* '''May be used alone or in combination with oral PPS'''
+*#* MOA: a weak analogue of heparin, may replenish the deficient GAG layer
-**# '''Oxybutynin'''
+*#* '''Intravesical PPS may be more effective than oral''' since only 1‒3% of oral PPS reaches the bladder.
-** '''Not recommended (resiniferatoxin, BCG):'''
+*#* '''May be used alone or in combination with oral PPS'''
-**# Resiniferatoxin (RTX)
+*# '''Oxybutynin'''
-**#* 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.
+* '''Not recommended (resiniferatoxin, BCG):'''
-**#* Based on conflicting Level 2 evidence and the adverse side effect profile, RTX is not recommended
+*# Resiniferatoxin (RTX)
-**# Bacillus Calmette-Guerin (BCG)
+*#* 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
+*# 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:
+** '''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):'''
+* '''<span style="color:#ff0000">Options in patients with or without Hunner’s lesions (3):'''
-*# '''Hydrodistension (HD)'''
+*# '''<span style="color:#ff0000">Hydrodistension (HD)'''
-*# '''Botulinum toxin A (BTX-A)'''
+*# '''<span style="color:#ff0000">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
-*# '''Sacral neuromodulation (SNM)'''
+*# '''<span style="color:#ff0000">Sacral neuromodulation (SNM)'''
 *#* Costly, may not be widely available
 *#* Must describe potential side effects, particularly the need for future surgical revisions
@@ Line 257: / Line 269: @@
 #* TUR in patients with Hunner’s ulcers
 #* Hydrodistention, botox, sacral neuromodulation in patients with or without Hunner’s
+== References ==
+* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065402/ Cox, Ashley, et al. "CUA guideline: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome." ''Canadian Urological Association Journal'' 10.5-6 (2016): E136.]