Editing AUA: Interstitial Cystitis & Bladder Pain Syndrome (2022)



'''See [https://pubmed.ncbi.nlm.nih.gov/35536143/ Original Guidelines]'''

'''See [https://www.auanet.org/documents/Guidelines/PDF/ICBPS%20Guideline/Interstitial%20Cystitis%20JU%20Summary%20Algorithm.pdf AUA IC/BPS Diagnosis and Treatment Algorithm]'''

== Definition ==

* '''<span style="color:#ff0000">Definition of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) (5):'''
*# '''<span style="color:#ff0000">Unpleasant sensation (pain, pressure, discomfort)'''
*# '''<span style="color:#ff0000">Perceived to be related to the urinary bladder'''
*# '''<span style="color:#ff0000">Associated with lower urinary tract symptoms''' 
*#'''<span style="color:#ff0000">Of >6 weeks duration'''
*# '''<span style="color:#ff0000">In the absence of infection or other identifiable causes'''
*'''Originally considered to be a bladder disease, has now been recognized as a chronic pain syndrome'''

== Epidemiology ==

* '''Most commonly diagnosed age > 40'''
**Diagnosis may be delayed
*May be greatly under-diagnosed in males
*Difficult to define prevalence since there is no objective marker to establish the presence of IC/BPS
* Population-based prevalence studies of IC/BPS have used 3 methods:
*# Surveys 
*#*Ask participants if they have ever been diagnosed with the condition (self-report studies)
*#** In NHANES III, the self-reported prevalence was 470 per 100,000 population, including 60 per 100,000 men and 850 per 100,000 women.
*# Questionnaires/Symptom Assessments
*#*Identify the presence of symptoms that are suggestive of IC/BPS
*#** In the US Nurses Health Study (NHS), questions about IC/BPS symptoms were included and the prevalence of IC/BPS symptoms was 2.3%.
*# Administrative billing data 
*#*Identify the number of individuals in a population who have been diagnosed with IC/BPS (clinician diagnosis).
*#** Using administrative billing data from the Kaiser Permanente Northwest managed care population in the Portland, Oregon metropolitan area, the prevalence of the diagnosis was found to be 197 per 100,000 women and 41 per 100,000 men.

== Pathophysiology ==

* Limited understanding of IC/BPS pathophysiology

== Natural History ==

* '''Psychosocial functioning and QoL consequences of IC/BPS:'''
** '''Damaging work life, psychological well-being, personal relationships and general health'''
** '''Worse QoL'''
** '''Higher rates of depression'''
** '''Significantly more pain, sleep dysfunction, catastrophizing, depression, anxiety, stress, social functioning difficulties and sexual dysfunction'''
* The impact of IC/BPS on QoL is as severe as that of rheumatoid arthritis and end-stage renal disease.

== Diagnosis and Evaluation ==

*IC/BPS is a heterogeneous clinical syndrome.
** Some IC/BPS patients have
*** Bladder-centric phenotypes (e.g., Hunner lesions, small bladder capacity, pain improved with intravesical local anesthetics).
*** Pelvic-floor phenotype (e.g., pelvic floor tenderness on exam).
**** Females with this feature respond better to pelvic floor manual physical therapy.
*** Systematic or widespread symptoms characterized by the presence of “widespread pain” (significant non-urologic pain outside the pelvis), COPC (e.g., fibromyalgia, IBS), widespread psychosocial difficulties (e.g., anxiety, depression, higher levels of current and lifetime stress, early life and adult traumatic events, negative affect, poor illness coping), or poly-symptomatic, poly-syndromic(PSPS) presentation with widespread somatic symptoms across multiple organ systems.
*'''Diagnosis can be challenging'''
**Patients present with a wide spectrum of symptoms, physical exam findings, and clinical test responses.

=== UrologySchool.com Summary ===

* '''<span style="color:#ff0000">Mandatory'''
** '''<span style="color:#ff0000">History and Physical Exam'''
*** Including baseline voiding symptoms and pain levels
** '''<span style="color:#ff0000">Labs (1)'''
**# '''<span style="color:#ff0000">Urinalysis +/- culture'''
**'''<span style="color:#ff0000">Other (1)'''
***'''Evaluate for incomplete bladder emptying to rule out occult retention'''
* '''<span style="color:#ff0000">Optional (2)'''
*# '''<span style="color:#ff0000">Cystoscopy'''
*#*'''<span style="color:#ff0000">Should be performed if Hunner lesions are suspected'''
*#**'''Reasonable to offer cystoscopy to IC/BPS patients over the age of 50'''
*# '''<span style="color:#ff0000">Urodynamics'''

=== Mandatory ===

==== History and Physical Exam ====

===== History =====
* '''<span style="color:#ff0000">Signs and Symptoms'''
** '''<span style="color:#ff0000">Pain (including sensations of pressure and discomfort)''' 
***'''<span style="color:#ff0000">Hallmark symptom of IC/BPS'''
*** '''<span style="color:#ff0000">Characterize location, severity, and type of pain''' 
****'''<span style="color:#ff0000">Location of pain'''
*****'''IC/BPS patients typically report (2):''' 
*****#'''Suprapubic pain (or pressure, discomfort) related to bladder filling''' 
*****#'''Pain throughout the pelvis, including the urethra, vulva, vagina, rectum, as well in extragenital locations such as the lower abdomen and back'''
*****#* Males with IC/BPS are 
*****#**Less likely to report perineal pain as their most bothersome symptom
*****#**More likely to have suprapubic tenderness
**** '''<span style="color:#ff0000">Type of pain''' 
*****'''<span style="color:#ff0000">Characteristics of pain related to IC/BPS (2)'''
*****#'''<span style="color:#ff0000">Pain is worsened with bladder filling (“painful bladder filling”) and/or''' 
*****#'''<span style="color:#ff0000">Strong urge to urinate was due to pain, pressure, or discomfort (“painful urgency”)'''
*****Many patients use other words to describe symptoms, especially “pressure” and may actually deny pain
** '''<span style="color:#ff0000">Storage lower urinary tract symptoms'''
***'''<span style="color:#ff0000">Patients may also present with marked urinary urgency and frequency'''
****Typically IC/BPS patients void to avoid or to relieve pain; OAB patients, however, void to avoid incontinence.
***'''Characterize number of voids per day and sensation of constant urge to void'''
** '''<span style="color:#ff0000">Other symptoms'''
***'''<span style="color:#ff0000">Dyspareunia'''
***'''<span style="color:#ff0000">Dysuria'''
***'''<span style="color:#ff0000">Ejaculatory pain in men'''
***'''<span style="color:#ff0000">Relationship of pain to menstruation in women should be noted'''
**'''Symptom duration'''
*** '''IC is a chronic disorder and symptoms should be present for at least 6 weeks with documented negative urine cultures for infection'''
*** Initially it is not uncommon for patients to report a single symptom such as dysuria, frequency, or pain, with subsequent progression to multiple symptoms
** '''Symptom flares'''
***Symptoms may suddenly intensify for several hours, days, or weeks
***Not uncommon.
** '''Baseline voiding symptoms and pain levels should be obtained in order to measure subsequent treatment effects.'''
***Validated questionnaires such as the GUPI or the ICSI are useful to gather comprehensive symptom information, including symptoms in addition to those of pain or discomfort
* '''<span style="color:#ff0000">Past medical history'''
** '''<span style="color:#ff0000">Common other unexplained medical conditions that coexist with IC/BPS (6):'''
**#'''<span style="color:#ff0000">Fibromyalgia'''
**#'''<span style="color:#ff0000">Irritable bowel syndrome'''
**#'''<span style="color:#ff0000">Chronic fatigue syndrome'''
**#'''<span style="color:#ff0000">Sjogren's syndrome'''
**#'''<span style="color:#ff0000">Chronic headaches'''
**#'''<span style="color:#ff0000">Vulvodynia'''
** '''Patients with IC/BPS frequently exhibit mental health disorders such as depression and anxiety'''
* '''Past surgical history'''
** High rate of prior pelvic surgery (especially hysterectomy) and levator ani pain in women with IC/BPS, suggesting that trauma or other local factors may contribute to symptoms
*** The high incidence of other procedures such as hysterectomy or laparoscopy may be the result of a missed diagnosis and does not necessarily indicate that the surgical procedure itself is a contributing factor to symptoms

===== Physical Exam =====
* '''Abdomen'''
** '''Suprapubic tenderness is common'''
** Presence of hernias
* '''Pelvis'''
** Palpation of the external genitalia, bladder base in females, and urethra in both sexes.
** Pelvic floor muscles should be palpated in both sexes for locations of tenderness and trigger points.
** Pelvic support for the bladder, urethra, vagina, and rectum should be documented.
** Focused evaluation to rule out vaginitis, urethritis, tender prostate, urethral diverticulum, or other potential sources of pain or infection is important.
* '''Brief neurological exam'''
** Rule out an occult neurologic problem

==== Labs ====

===== Urinalysis +/- culture =====

* '''Even if negative urinalysis, urine culture may be indicated to detect lower levels of bacteria that are clinically significant but not readily identifiable with a dipstick or on microscopic exam'''

=== Optional ===

* '''Cystoscopy and/or urodynamics should be considered when the diagnosis is in doubt; these tests are not necessary for making the diagnosis in uncomplicated presentations.'''

==== Cystoscopy ====

* '''<span style="color:#ff0000">Indications (2)'''
*# '''<span style="color:#ff0000">Excluding conditions that may mimic IC/BPS (bladder cancer, bladder stones, urethral diverticula, and intravesical foreign bodies)'''
*# '''<span style="color:#ff0000">Identification of a Hunner lesions</span>'''
*#* '''Hunner lesions'''
*#** '''Common in IC/BPS patients of age over 50 years.'''
*#***'''Reasonable to offer cystoscopy to IC/BPS patients over the age of 50'''
*#** '''Identification of Hunner lesions can allow for more directed effective therapies'''
*#***IC/BPS with Hunner lesions represents a different phenotype than IC/BPS without Hunner lesions
*#****Hunner lesions patients are older, have greater urinary frequency and nocturia, higher ICSI scores, and lower bladder capacity
*#***Early diagnosis by cystoscopy is justified in patients suspected to have Hunner lesions, without requiring them to fail other behavioral or medical treatments before recommending cystoscopy. 
*#***If Hunner lesions are found on cystoscopy, triamcinolone injection and/or fulguration can be performed; and for those who fail triamcinolone and/or fulguration, oral Cyclosporine A (CyA)and/or other multi-modal therapies may be offered
*#**May be present in both males and females.
*#**The only consistent cystoscopic finding that leads to a diagnosis of IC/BPS, though there are no agreed-upon cystoscopic findings diagnostic for IC/BPS
*#** May be identified in an acute phase (as an inflamed, friable, denuded area) or a more chronic phase (blanched, nonbleeding area)
*#***Classically, the lesions are inflamed and friable and have a stellate appearance with blood vessels radiating from the center with or without a coagulum. Alternatively, they may be blanched in appearance without inflammation or bleeding or may have a red waterfall bleeding appearance with bladder distention.
*#***Look for and map out the locations of Hunner lesions during the early phase of cystoscopy since the lesions may begin to bleed during bladder filling and may be obscured later.
*Although most IC/BPS patients may tolerate office flexible cystoscopy, some may prefer to have cystoscopy performed under anesthesia. 

==== Cystoscopy with hydrodistension under anesthesia ====
* Hydrodistension (less than 80 cm H2O, less than 5 minutes) is not necessary for routine clinical use to establish a diagnosis of IC/BPS diagnosis.
** Most Hunner lesions can be diagnosed with office cystoscopy under local anesthesia without hydrodistention.
**If hydrodistension is performed to determine whether Hunner lesions are present or as a treatment, then the technique should be specified and the bladder capacity determined.
***Useful for the clinician and patient to understand when bladder capacity is severely reduced (a low capacity due to fibrosis).
*'''The finding of glomerulations on hydrodistention is variable and not consistent with clinical presentation'''
** '''Glomerulations'''
***'''Pinpoint petechial hemorrhages'''
***'''May be detected on cystoscopy but these lesions are non-diagnostic and non-specific for IC/BPS'''
****Commonly seen in other conditions which may co-exist with or be misdiagnosed as IC/BPS such as chronic undifferentiated pelvic pain or endometriosis.
****May also be present in asymptomatic patients undergoing cystoscopy for other conditions
****May be seen in patients who have undergone radiation therapy, in the presence of active bladder carcinoma, associated with chemotherapeutic or toxic drug exposure, and in patients with defunctionalized bladders, and in patients without any urologic symptoms.
***Diffuse glomerulations are commonly seen in males with IC/BPS

==== Bladder Biopsy ====

* '''Not part of the routine diagnostic process'''
* '''May be indicated to exclude other pathologies if a lesion of uncertain nature is present'''
* Presents a risk of perforation

==== Urodynamics ====

* No agreed-upon urodynamic criteria diagnostic for IC/BPS
* '''Pain with filling (hypersensitivity) is consistent with IC/BPS.'''
* '''Not recommended for routine clinical use to establish an IC/BPS diagnosis.'''
* '''<span style="color:#ff0000">Indications (3)'''
*# '''<span style="color:#ff0000">Suspicion of outlet obstruction in either sex'''
*# '''<span style="color:#ff0000">Possibility of poor detrusor contractility'''
*# '''<span style="color:#ff0000">Other conditions that could explain why patients are initially refractory to first-line therapy'''

=== Not recommended ===

* Potassium sensitivity test
** Might help to identify the patients who are most likely to respond to urothelium-restoring treatments
** Risk/benefit ratio was too high for routine clinical use

=== Differential Diagnosis ===

# '''<span style="color:#ff0000">Bacterial cystitis'''
# '''<span style="color:#ff0000">Urinary calculi'''
# '''<span style="color:#ff0000">Vaginitis'''
# '''<span style="color:#ff0000">Carcinoma in situ of the bladder'''
# '''<span style="color:#ff0000">Chronic bacterial prostatitis'''
#'''<span style="color:#ff0000">Chronic prostatitis/chronic pelvic pain syndrome'''

==== Chronic Prostatitis/Chronic Pelvic Pain Syndrome ====

* Also known as NIH Type III prostatitis
* Diagnosis and Evaluation
**History and Physical Exam
***History
****Signs and Symptoms
*****Pain in the perineum, suprapubic region, testicles or tip of the penis.
****** Pain is often exacerbated by urination or ejaculation
******Pain is the primary defining characteristic of CP/CPPS
***** Voiding symptoms such as sense of incomplete bladder emptying and urinary frequency are also commonly reported
* Overlap between IC/BPS and CP/CPPS
** In general, diagnosis of IC/BPS should be strongly considered in men whose pain is perceived to be related to the bladder, or they have symptoms of “painful bladder filling” and/or “painful urgency”
**There should be high vigilance to look for Hunner lesions in men who present with chronic pelvic pain that is worse with bladder filling, associated with urinary frequency and strong urge to urinate, and in whom the diagnosis of CP/CPPS is in doubt, or do not respond to conventional treatments of CP/CPPS
== Management ==

=== <span style="color:#800080">UrologySchool.com Summary ===

* '''<span style="color:#ff0000">Recommended (3):'''
*# '''<span style="color:#ff0000">Patient education, self-care, and behavioral modifications'''
*# '''<span style="color:#ff0000">Physical therapy, if pelvic floor tenderness present'''
*# '''<span style="color:#ff0000">Treatment of Hunner lesions (triamcinolone injection and/or fulguration), if present'''
*#* '''<span style="color:#ff0000">Patients with Hunner lesions should be treated        differently from those without Hunner lesions.'''
* '''<span style="color:#ff0000">Optional'''
** '''<span style="color:#ff0000">Oral medications (5):'''
**# '''<span style="color:#ff0000">Amitriptyline'''
**# '''<span style="color:#ff0000">Cimetidine'''
**# '''<span style="color:#ff0000">Hydroxyzine''' 
**# '''<span style="color:#ff0000">Pentosan polysulfate'''
**# '''<span style="color:#ff0000">Cyclosporine A, if patient with Hunner lesions refractory to fulguration and/or triamcinolone.'''
** '''<span style="color:#ff0000">Intravesical instillations (3):'''
**# '''<span style="color:#ff0000">DMSO'''
**# '''<span style="color:#ff0000">Heparin'''
**# '''<span style="color:#ff0000">Lidocaine'''
** '''<span style="color:#ff0000">Procedures (3):'''
**# '''<span style="color:#ff0000">Cystoscopy under anesthesia with short-duration, low-pressure hydrodistension'''
**# '''<span style="color:#ff0000">Intradetrusor onabotulinumtoxin A, if other treatments have not provided adequate improvement in symptoms and quality of life'''
**# '''<span style="color:#ff0000">Neuromodulation, if other treatments have not provided adequate improvement in symptoms and quality of life'''
** '''<span style="color:#ff0000">Major surgery (2):'''
**# '''<span style="color:#ff0000">Substitution cystoplasty'''
**# '''<span style="color:#ff0000">Urinary diversion with or without cystectomy'''

=== General Principles ===
* '''Essential to set reasonable expectations'''
** While most patients are able to achieve an acceptable quality of life, very few go into complete remission.
*** Focus of pain management is to minimize discomfort and maximize the patient's ability to function in daily life
**** 100% pain relief is often not achievable
* '''Treatment approach should be tailored to the specific symptoms of each patient in order to optimize quality of life'''
** To optimally treat patients with a more complex presentation and/or when standard treatment approaches are ineffective, may need a multidisciplinary approach and partner with other clinicians such as primary care providers, nurse practitioners, registered dietitians, physical therapists, pain specialists, gastroenterologists, and/or gynecologists.
* '''Initial treatment should be nonsurgical (except in patients with Hunner lesions)'''
** '''In contrast to the prior versions of this guideline, treatments no longer divided into first-line through sixth-line tiers'''
* '''Efficacy of treatment should be periodically reassessed, and ineffective treatments should be stopped'''
** Pain management should be continually assessed for effectiveness because of its importance to quality of life.
** Most treatments may benefit a subset of patients
** No treatment reliably benefits most or all patients
* '''If no improvement occurs after multiple treatment approaches, the IC/BPS diagnosis should be reconsidered.'''

=== Behavioral/nonpharmacologic ===
* '''<span style="color:#ff0000">Patient education, self-care practices, and behavioral modification are essential to any treatment plan'''

==== Patient Education ====
*Patients should be counseled
**On normal bladder function and what is known and not known about IC/BPS, the benefits versus risks/burdens of the available treatment alternatives
**That IC/BPS is typically a chronic disorder requiring continual and dynamic management and of that no single treatment has been found to be effective for a majority of patients.
**That adequate symptom control is achievable but may require trials of multiple therapeutic options (including combination therapy) to identify the regimen that is effective for that patient.
**That identifying an effective pain relief regimen may require multiple trials of different medications in order to identify the medication(s) that produce optimal effects for that particular patient.
**That, given the chronic nature of IC/BPS, the typical course involves symptom exacerbations and remissions.

==== Self-care practices ====
*Suggesting that patients become aware of and avoid specific behaviors which, reproducibly for a particular patient, worsen symptoms, is appropriate and can provide some sense of control in a disease process
**Controllable behaviors or conditions that in some patients may worsen symptoms include
***Certain types of exercise (e.g., pelvic floor muscle exercises
***Sexual intercourse
***Wearing of tightfitting clothing
***Presence of constipation

==== Behavioral modifications ====
*Strategies may include:
**Altering the concentration and/or volume of urine, either by fluid restriction or additional hydration
**Application of local heat or cold over the bladder or perineum
**Avoidance of certain foods known to be common bladder irritants for IC/BPS patients such as coffee or citrus products; use of an elimination diet to determine which foods or fluids may contribute to symptoms
**Over-the-counter products (e.g., nutraceuticals, calcium glycerophosphates, phenazopyridine)
**Techniques applied to trigger points and areas of hypersensitivity (e.g., application of heat or cold)
**Strategies to manage IC/BPS flare-ups (e.g. meditation, imagery)
**Pelvic floor muscle relaxation
**Bladder training with urge suppression
**Other 

==== Stress management ====

* '''Patients should be encouraged to implement stress management practices to improve coping techniques and manage stress-induced symptom exacerbations.'''
** Psychological stress is associated with heightened pain sensitivity in general
* Interventions aimed at general relaxation have proven helpful in most other forms of chronic pain and can be recommended to IC/BPS patients.

==== Physical therapy techniques, for patients who present with pelvic floor tenderness ====

* Many patients with IC/BPS exhibit tenderness and/or banding of the pelvic floor musculature, along with other soft tissue abnormalities. When such soft tissue abnormalities are present, manual physical therapy can provide symptom relief
* Appropriate manual physical therapy techniques include maneuvers that 
** Resolve pelvic, abdominal and/or hip muscular trigger points
** Lengthen muscle contractures
** Release painful scars and other connective tissue restrictions
* '''Appropriate physical therapy expertise and experience is not available in all communities.''' 
** '''In the absence of appropriate expertise,''' '''routine forms of pelvic physical therapy that are primarily aimed at strengthening of the pelvic floor are not recommended'''

=== Oral Medications ===

* '''Pharmacologic pain management agents (e.g., urinary analgesics, acetaminophen, NSAIDs, opioid/non-opioid medications) may be prescribed after counseling patients on the risks and benefits.''' 
** Pain management should be an integral part of the treatment approach and should be assessed at each clinical encounter for effectiveness
** Finding the medication or combination of medications that provide effective pain control requires a 'trial and error' method of prescribing.
*** Currently, there is no method to predict which drug is most likely to alleviate pain in a given IC/BPS patient
*** '''Multimodal pain management approaches (e.g., pharmacological, stress management, manual therapy if available) is likely to be the most effective and should be initiated.'''
*** A multimodal approach in which pharmacologic agents are combined with other therapies 
*** Effective treatment of symptom flares may require a pain treatment protocol with some flexibility to manage flare related breakthrough pain
* '''Pharmacological pain management principles for IC/BPS should be similar to those for management of other chronic pain conditions.'''
** Non-opioids alternatives to manage pain should be used preferentially.
*** Due to the global opioid crisis, the judicious use of chronic opioids is advised and only after informed decision-making with the patients and with periodic follow-ups to assess efficacy, adverse side effects, compliance, and potential of abuse or misuse.

==== Options (5): ====

# '''<span style="color:#ff0000">Amitriptyline'''
# '''<span style="color:#ff0000">Cimetidine'''
# '''<span style="color:#ff0000">Hydroxyzine'''
# '''<span style="color:#ff0000">Pentosan polysulfate'''
# '''<span style="color:#ff0000">Cyclosporine A, if patient with Hunner lesions refractory to fulguration and/or triamcinolone.'''
Listed in alphabetical order; no hierarchy is implied

* See [https://www.uspharmacist.com/CMSImagesContent/2016/9/USP1609-Interstitial-T2.gif Table] for dosing regimens

===== Amitriptyline =====

* Adverse events
** Common (up to 80% of patients), though generally not serious
*** Medication side effects were the major reason for withdrawal from the studies
** Sedation, drowsiness, nausea
* Dosing
** Begin at low doses (e.g., 10 mg), titrate gradually to 75-100 mg if tolerated

===== Cimetidine =====

* Adverse events
** Neither common nor significant

===== Hydroxyzine =====

* Adverse events
** Common (up to 80% of patients), though generally not serious
** Sedation, weakness

===== Pentosanpolysulfate (PPS) =====
* '''<span style="color:#ff0000">The only FDA-approved oral agent for the treatment of IC/BPS'''
* Efficacy
** Some evidence that PPS has lower efficacy in patients with Hunner lesions.
* '''Adverse events'''
** '''Macular damage and vision-related injuries''' 
*** Counsel patients who are considering PPS about the potential risk for macular damage and vision-related injuries.
**** Symptoms of retinal pigmentary maculopathy associated with PPS use (3)
***** Difficulty reading
***** Slow adjustment to low or reduced light environments
***** Blurred vision
*** Given these concerns, the FDA approved a new warning label for PPS in June 2020 which states that:
**** A detailed ophthalmologic history should be obtained in all patients prior to starting treatment with PPS.
**** For patients with preexisting ophthalmologic conditions, a comprehensive baseline retinal examination is recommended prior to starting therapy.
**** In addition, a retinal examination is suggested for all patients within six months of initiating treatment and periodically while continuing treatment. If pigmentary changes in the retina develop, then risks and benefits of continuing treatment should be reevaluated, since these changes may be irreversible.
** Gross hematuria

===== Oral cyclosporine A     =====

* '''<span style="color:#ff0000">Indications'''
** '''<span style="color:#ff0000">May be offered particularly for patients with Hunner lesions refractory to fulguration and/or triamcinolone.'''
* '''<span style="color:#ff0000">Adverse events'''
** '''<span style="color:#ff0000">Potentially serious'''
*** '''A monitoring protocol should also take into account the risks of hepatotoxicity, hyperuricemia, hypomagnesemia, hematologic abnormalities and malignancies, especially skin cancer and lymphomas'''
** '''Hypertension'''
** '''Gingival hyperplasia'''
** '''Facial hair growth'''
** '''Nephrotoxicity (increased serum creatinine)'''
** '''Alopecia'''
** '''Cutaneous lymphoma'''
** '''Mouth ulcers'''
** '''Acute gout'''
** '''Immunosuppression'''

=== Intravesical Instillations ===

==== Options (3): ====

# '''<span style="color:#ff0000">DMSO'''
# '''<span style="color:#ff0000">Heparin'''
# '''<span style="color:#ff0000">Lidocaine'''

Listed in alphabetical order; no hierarchy is implied

===== DMSO =====
* Administration
** Limit instillation dwell time to 15-20 minutes
** Often administered as a part of a "cocktail" that may include heparin, sodium       bicarbonate, a local steroid, and/or a lidocaine preparation
* Adverse events
** Rapidly absorbed into the bladder wall
*** if a "cocktail" preparation is administered, be aware that DMSO potentially enhances absorption of other substances, creating the        possibility for toxicity from drugs such as lidocaine.
** Longer periods of holding are associated with significant pain.

===== Heparin =====
* Adverse events
** Infrequent and minor

===== Lidocaine =====
* Efficacy
** Relief is usually short-term (i.e. less than two weeks)
* Administration
** Procedure can be associated with pain
** Heparin or PPS may be added to lidocaine alone.
* Adverse events
** Typically not serious
** Dysuria, urethral irritation, bladder pain

=== Procedures ===

==== Cystoscopy under anesthesia with short-duration (<10 minutes), low-pressure (60-80 cm H20) hydrodistension ====

* ''' <span style="color:#ff0000">May be undertaken as a treatment option'''

* Goals (3)
** Before distension, inspect the bladder for other potential symptom causes (e.g., stones, tumors) and for Hunner lesions.
*** If Hunner lesions are identified, fulguration (with laser or electrocautery) and/or injection of triamcinolone should be performed under anesthesia
**** Patients should be counseled that periodic retreatment is likely to be necessary when symptoms recur.
** If no bladder abnormalities or ulcers are found, then the distension may proceed and serve as a treatment.
*** Hunner lesions can be easier to identify after distention when cracking and mucosal bleeding become evident.
** Distension allows for disease "staging" by determining anatomic as opposed to functional bladder capacity and identifying the subset of patients who suffer reduced capacity as a result of fibrosis

==== Intradetrusor onabotulinumtoxin A ====

* '''<span style="color:#ff0000">Indications'''
** '''<span style="color:#ff0000">May be administered if other treatments have not provided adequate improvement in symptoms and quality of life.'''
* '''Adverse events'''
** '''Dysuria'''
** '''Need for abdominal straining to void'''
** '''Large post-void residuals (greater than 100 mL)'''
** '''Need for clean intermittent self-catheterization that persisted for 1-3 months and in some cases longer.'''
*** '''<span style="color:#ff0000">Patients must be willing to accept the possibility that post-treatment intermittent self-catheterization may be necessary.'''

==== Neuromodulation ====

* '''<span style="color:#ff0000">A trial of neuromodulation may be performed if other treatments have not provided adequate symptom control and quality of life improvement.'''
** Neuromodulation is not currently FDA-approved for IC/BPS treatment; however, many patients meet the frequency/urgency indication for which sacral neuromodulation is approved.
* '''If a trial of nerve stimulation is successful, then a permanent neurostimulation device may be implanted.'''

=== Major Surgery ===

* Should be performed only by surgeons with extensive experience in IC/BPS and dedication to long-term care for the patient

==== Indications (2) ====
# '''<span style="color:#ff0000">Carefully selected patients with bladder-centric symptoms'''
#* Symptoms from other sources (e.g., neuropathic pain, pelvic muscle dysfunction) will not improve with lower urinary tract reconstruction
#** Patient selection has by far the greatest influence on outcome
#*** Much more important to select the right patient than the type of operation (e.g., cystoplasty versus diversion; diversion with versus without cystectomy)
#**Patients who have reached the point of major surgery will have tried at least one local        anesthetic bladder instillation. If pain does not change while the anesthetic is in the bladder, then an extravesical source is likely.
#* Unless there is clear evidence of primary bladder pathology (e.g., small capacity under anesthesia, Hunner lesions), patients should have a multidisciplinary evaluation including assessment for neuropathic pain and psychological profile.
# '''<span style="color:#ff0000">End-stage small fibrotic bladder (rare instance), for whom all other therapies have failed to provide adequate symptom control and quality of life improvement.'''
#* '''<span style="color:#ff0000">Best known predictors of success (3)'''
#*# '''<span style="color:#ff0000">End-stage fibrotic bladder'''
#*# '''<span style="color:#ff0000">Small bladder capacity under anesthesia'''
#*# '''<span style="color:#ff0000">Presence of Hunner lesions'''
#* '''Features that indicate pain sources outside the bladder and a higher risk of failure:'''
#** '''Polysymptomatic or polysyndromic presentation (most important)'''
#*** '''Major surgery is not recommended in patients with Polysymptomatic or polysyndromic presentation'''
#** '''Large capacity under anesthesia'''
#** '''Absence of Hunner lesions,'''
#** '''Lack of relief with local anesthetic bladder instillations'''
#** '''Pelvic muscle tightness/tenderness'''
#** '''Genital hyperesthesia'''
#** '''Pain beyond the pelvis, such as the presence of widespread pain'''

==== Surgical Approach ====

===== Options =====
# '''<span style="color:#ff0000">Substitution cystoplasty'''
# '''<span style="color:#ff0000">Urinary diversion with or without cystectomy'''

===== Surgical Approach Selection =====
# Supratrigonal cystectomy and augmentation with ileum and/or cecum
#* Advantages
#*# Avoids need for an external appliance
#*# Many patients are able to void spontaneously
#*# Preserve the ureteric orifices, avoiding the risk of anastomotic stricture
#* Disadvantages
#*# Metabolic changes
#*# Risks of rupture and the possible need for intermittent catheterization
#*# Risks of persistent pain or recurrent ulcers in the trigone
# Supravesical urinary diversion
#* Advantages
#*# Resolves frequency and nocturia
#*# Eliminates contact of urine with the bladder and urethral mucosa.
#*# Avoids any need for intermittent catheterization per urethra
#* Disadvantages
#*# Metabolic changes
#* Leaving the bladder in situ is a matter of debate.
#** Length and risks of surgery are decreased, but some patients have persistent pain or other problems with the remaining bladder.

=== Treatments that Should Not be Offered ===

# '''<span style="color:#ff0000">Long-term oral antibiotic administration'''
# '''<span style="color:#ff0000">Intravesical instillation of bacillus Calmette-Guerin'''
# '''<span style="color:#ff0000">High-pressure, long-duration hydrodistension'''
# '''<span style="color:#ff0000">Systemic (oral) long-term glucocorticoid administration'''
# '''<span style="color:#ff0000">Pelvic floor strengthening exercises (e.g., Kegel exercises).'''
#* No evidence that physical therapy aimed at pelvic floor strengthening (such as Kegel exercises) can improve symptoms, and in fact this type of pelvic floor therapy may worsen the condition

== References ==

* [https://pubmed.ncbi.nlm.nih.gov/35536143/ Clemens, J. Quentin, et al. "Diagnosis and treatment of interstitial cystitis/bladder pain syndrome." ''Journal of Urology'' 208.1 (2022): 34-42.]