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CUA: Interstitial Cystitis (2016): Difference between revisions

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== Background ==
== 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 ==
== Epidemiology ==
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* Can affect both sexes, but vast majority (90%) are female
* 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)
* 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 ==
== Diagnosis and Evaluation ==


=== UrologySchool.com Summary ===
=== UrologySchool.com Summary ===
* '''Mandatory (1):'''
* '''<span style="color:#ff0000">Mandatory (1):'''
*# '''History and Physical Exam'''
*# '''<span style="color:#ff0000">History and Physical Exam'''
* '''Recommended (4):'''
* '''<span style="color:#ff0000">Recommended (4):'''
*# '''Urinalysis/culture'''
*# '''<span style="color:#ff0000">Urinalysis/culture'''
*# '''Symptom scores'''
*# '''<span style="color:#ff0000">Symptom scores'''
*# '''Frequency volume chart'''
*# '''<span style="color:#ff0000">Frequency volume chart'''
*# '''Cystoscopy'''
*# '''<span style="color:#ff0000">Cystoscopy'''
* '''Optional (5):'''
* '''<span style="color:#ff0000">Optional (5):'''
*# PVR
*# <span style="color:#ff0000">'''PVR'''
*# Urine cytology
*# <span style="color:#ff0000">'''Urine cytology'''
*# Imaging
*# <span style="color:#ff0000">'''Imaging'''
*# Intravesical anesthetic challenge
*# <span style="color:#ff0000">'''Intravesical anesthetic challenge'''
*# Hydrodistension
*# <span style="color:#ff0000">'''Hydrodistension'''
* '''Not recommended: potassium sensitivity test, bladder biopsy, urodynamics'''
* '''Not recommended: potassium sensitivity test, bladder biopsy, urodynamics'''


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===== History =====
===== History =====
* '''Characteristic presentation includes a combination of pain, frequency, nocturia, and urgency'''
* '''<span style="color:#ff0000">Signs and Symptoms'''
** '''Pelvic pain is the main descriptor of IC/BPS'''
**'''<span style="color:#ff0000">Characteristic presentation includes a combination of pain, frequency, nocturia, and urgency'''
*** '''Pain that occurs only during voiding is not consistent with IC/BPS'''
*** '''<span style="color:#ff0000">Pelvic pain is the main descriptor of 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).'''
**** '''Pain that occurs only during voiding is not consistent with IC/BPS'''
*** 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
***** Vulvar disorders, which cause pain when urine makes contact with the vulva, should instead be considered
** '''Frequency is the most common presenting symptom i.e. patients seek medical attention for frequency, not the pain'''
**** 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
* '''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
*** '''Frequency is the most common presenting symptom i.e. patients seek medical attention for frequency, not the pain'''
** '''Symptoms of IC/BPS are generally worse a few days prior to menses, in contrast to endometriosis, which is worse during menses'''
** '''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 =====
===== Physical Exam =====
* '''Abdominal and pelvic exam''', with particular focus on looking for masses, bladder distension, hernias, and tenderness.
* '''<span style="color:#ff0000">Abdominal and pelvic exam</span>''', 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'''.
** '''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.
*** 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'''
* '''<span style="color:#ff0000">Digital rectal examination in males is essential</span>'''
* '''A musculoskeletal and focused neurological exam may also be contributory'''.
* '''<span style="color:#ff0000">A musculoskeletal and focused neurological exam may also be contributory</span>'''.
** 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.
** 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 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.
** 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
* '''<span style="color:#ff0000">Palpation of the levator muscles</span>''' 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'''.
** '''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.
** 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'''
 
** If signs of UTI are identified on urinalysis (e.g. positive for leukocytes), a culture and sensitivity is required.
==== Labs ====
*** '''If sterile pyuria persists''', '''consider testing for Chlamydia trachomatis, Mycoplasma, Ureaplasma, Corynebacterium species, Candida species, and Mycoplasma tuberculosis.'''
#'''<span style="color:#ff0000">Urinalysis +/- culture'''
** '''Absence of leukocytes does not rule out IC/BPS'''
#* 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.'''
** '''Useful to establish baseline symptom severity and to track response to therapeutic intervention'''
#* '''Absence of leukocytes does not rule out IC/BPS'''
** Options include:
 
**# Interstitial Cystitis Symptom Index (ICSI)
==== Other ====
**# Bladder Pain/IC Symptom Score (BPIC-SS)
#'''Symptom scores'''
**# Pain, Urgency, Frequency (PUF)
#* '''Useful to establish baseline symptom severity and to track response to therapeutic intervention'''
* '''Frequency/volume chart'''
#* Options include:
** To differentiate polyuria from the classic small voided volumes expected with IC/BPS.
#*# Interstitial Cystitis Symptom Index (ICSI)
* '''Cystoscopy'''
#*# Bladder Pain/IC Symptom Score (BPIC-SS)
** Expected to be normal
#*# Pain, Urgency, Frequency (PUF)
** Used to:
# '''Frequency/volume chart'''
**# Rule out bladder cancer/carcinoma in situ
#* To differentiate polyuria from the classic small voided volumes expected with IC/BPS.
**# Identify Hunner’s lesions that reflect severe disease, or even different disease (information that may impact treatment decisions)
# '''Cystoscopy'''
**# Determine effect on pelvic pain during bladder filling and emptying
#* Expected to be normal
**# Objectively evaluate “functional” bladder capacity
#* Used to:
**# Facilitate appropriate pelvic examination
#*# Rule out bladder cancer/carcinoma in situ
**# Reassure the patient
#*# 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): ===
=== Optional (5): ===
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=== First-line: conservative (5): ===
=== 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'''.
#* '''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'''
# '''<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.
#* 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'''
#* '''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):'''
 
*# '''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 ===
=== 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):'''
* '''<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
*#* 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)'''
*# '''<span style="color:#ff0000">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
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#* TUR in patients with Hunner’s ulcers
#* TUR in patients with Hunner’s ulcers
#* Hydrodistention, botox, sacral neuromodulation in patients with or without Hunner’s
#* 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.]
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