AUA: Interstitial Cystitis & Bladder Pain Syndrome (2022)

See Original Guidelines

Definition

• Definition of Interstitial Cystitis/Bladder Pain Syndrome (5):
  1. Unpleasant sensation (pain, pressure, discomfort)
  2. Perceived to be related to the urinary bladder
  3. Associated with lower urinary tract symptoms
  4. Of >6 weeks duration
  5. In the absence of infection or other identifiable causes

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:
  1. 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.
  2. 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%.
  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

• Diagnosis can be challenging
  • Patients present with a wide spectrum of symptoms, physical exam findings, and clinical test responses.

UrologySchool.com Summary

• Mandatory
  • History and Physical Exam
    • Including baseline voiding symptoms and pain levels
  • Labs (1)
    1. Urinalysis +/- culture
  • Other (1)
    • Evaluate for incomplete bladder emptying to rule out occult retention
• Optional (2)
  1. Cystoscopy
     • Should be performed if Hunner lesions are suspected
       • Reasonable to offer cystoscopy to IC/BPS patients over the age of 50
  2. Urodynamics

Mandatory

History and Physical Exam

History

• Signs and Symptoms
  • Pain (including sensations of pressure and discomfort)
    • Hallmark symptom of IC/BPS
    • Characterize location, severity, and type of pain
      • Location of pain
        • IC/BPS patients typically report (2):
          1. Suprapubic pain (or pressure, discomfort) related to bladder filling
          2. 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
      • Type of pain
        • Characteristics of pain related to IC/BPS (2)
          1. Pain is worsened with bladder filling (“painful bladder filling”) and/or
          2. 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
  • Storage lower urinary tract symptoms
    • 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
  • Other symptoms
    • Dyspareunia
    • Dysuria
    • Ejaculatory pain in men
    • 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
• Past medical history
  • Common other unexplained medical conditions that coexist with IC/BPS (6):
    1. Fibromyalgia
    2. Irritable bowel syndrome
    3. Chronic fatigue syndrome
    4. Sjogren's syndrome
    5. Chronic headaches
    6. 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

• Indications (2)
  1. Excluding conditions that may mimic IC/BPS (bladder cancer, bladder stones, urethral diverticula, and intravesical foreign bodies)
  2. Identification of a Hunner lesions
     • 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.
• Indications (3)
  1. Suspicion of outlet obstruction in either sex
  2. Possibility of poor detrusor contractility
  3. 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

1. Bacterial cystitis
2. Urinary calculi
3. Vaginitis
4. Carcinoma in situ of the bladder
5. Chronic bacterial prostatitis
6. 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/CPPSis in doubt, or do not respond to conventional treatments of CP/CPPS

Reviewed up to, including, statement 7

Management

General Principles

• Treatment decisions should be made after shared decision-making, with the patient informed of the risks, potential benefits, and alternatives
• Essential to set reasonable expectations
  • While most patients are able to achieve an acceptable QoL, very few go into complete remission.
• Efficacy of treatment should be periodically reassessed, and ineffective treatments should be stopped
  • Most treatments may benefit a subset of patients
  • No treatment reliably benefits most or all patients
• Multimodal pain management approaches (e.g., pharmacological, stress management, manual therapy if available) should be initiated.
  • Pain management should be continually assessed for effectiveness because of its importance to quality of life.
  • If pain management is inadequate, then consideration should be given to a multidisciplinary approach and the patient referred appropriately
• If no improvement occurs after multiple treatment approaches, the IC/BPS diagnosis should be reconsidered.

Options

1. Behavioral/nonpharmacologic
2. Oral medicines
3. Bladder instillations
4. Procedures
5. Major surgery

Treatment Approach

• Treatment approach should be tailored to the specific symptoms of each patient in order to optimize QoL
  • 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).
      • Patients with Hunner lesions should be treated differently from those without Hunner lesions.
    • Others have pelvic-floor phenotype (e.g., pelvic floor tenderness on exam). Women with this feature respond better to pelvic floor manual physical therapy (Statement 12).
    • A third group have 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.
  • To optimally treat patients with a more complex presentation and/or when standard treatment approaches are ineffective, urologists may need to 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, this update no longer divides treatments into first-line through sixth-line tiers

Behavioral/nonpharmacologic

• Education, self-care and behavioral modification are essential to any treatment plan
• Physical therapy should be offered for patients with pelvic floor tenderness if appropriately trained clinicians are available

Behavioral/Non-pharmacologic Treatments

• Patient Education
  • Patients should be educated on normal bladder function and what is known and not known about IC/BPS, the benefits versus risks/burdens of the available treatment alternatives
  • Patients should be made aware that it 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.
  • 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.
  • Patients should be counseled 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.
  • Patients should be informed that, given the chronic nature of IC/BPS, the typical course involves symptom exacerbations and remissions.
• Self-care practices and behavioral modifications that can improve symptoms should be discussed and implemented as feasible.
• Patients should be encouraged to implement stress management practices to improve coping techniques and manage stress-induced symptom exacerbations.
• Appropriate manual physical therapy techniques (e.g., maneuvers that resolve pelvic, abdominal and/or hip muscular trigger points, lengthen muscle contractures, and release painful scars and other connective tissue restrictions), if appropriately trained clinicians are available, should be offered to patients who present with pelvic floor tenderness. Pelvic floor strengthening exercises (e.g., Kegel exercises) should be avoided.

Oral Medications  

• Clinicians may prescribe pharmacologic pain management agents (e.g., urinary analgesics, acetaminophen, NSAIDs, opioid/non-opioid medications) after counseling patients on the risks and benefits. Pharmacological pain management principles for IC/BPS should be similar to those for management of other chronic pain conditions.
• Amitriptyline, cimetidine, hydroxyzine, or pentosan polysulfate may be administered as oral medications (listed in alphabetical order; no hierarchy is implied)
• Clinicians should counsel patients who are considering pentosan polysulfate about the potential risk for macular damage and vision-related injuries.
• Oral cyclosporine A may be offered particularly for patients with Hunner lesions refractory to fulguration and/or triamcinolone.

Intravesical Instillations

• DMSO, heparin, and/or lidocaine may be administered as intravesical treatments (listed in alphabetical order; no hierarchy is implied).

Procedures

• Cystoscopy under anesthesia with short-duration, low-pressure hydrodistension
  • May be undertaken as a treatment option.
• If Hunner lesions are present, then fulguration (with laser or electrocautery) and/or injection of triamcinolone should be performed.
• Intradetrusor onabotulinumtoxin A
  • May be administered if other treatments have not provided adequate improvement in symptoms and quality of life.
  • Patients must be willing to accept the possibility that post-treatment intermittent self-catheterization may be necessary.
• Neuromodulation
  • A trial of neuromodulation may be performed if other treatments have not provided adequate symptom control and quality of life improvement.
  • If a trial of nerve stimulation is successful, then a permanent neurostimulation device may be implanted.

Major Surgery

• Substitution cystoplasty, urinary diversion with or without cystectomy
• Indications
  1. May be undertaken in carefully selected patients with bladder-centric symptoms
  2. End-stage small fibrotic bladder (rare instance), for whom all other therapies have failed to provide adequate symptom control and quality of life improvement.

Treatments that Should Not be Offered

1. Long-term oral antibiotic administration
2. Intravesical instillation of bacillus Calmette-Guerin
3. High-pressure, long-duration hydrodistension
4. Systemic (oral) long-term glucocorticoid administration

References

• Clemens, J. Quentin, et al. "Diagnosis and treatment of interstitial cystitis/bladder pain syndrome." Journal of Urology 208.1 (2022): 34-42.