Interstitial Cystitis 

Updated: Nov 21, 2020
Author: Eric S Rovner, MD; Chief Editor: Edward David Kim, MD, FACS 

Overview

Practice Essentials

Interstitial cystitis is a clinical syndrome characterized by daytime and nighttime urinary frequency, urgency, and pelvic pain. Interstitial cystitis has no clear etiology or pathophysiology, and diagnostic criteria for the syndrome remain undefined. Despite considerable research, universally effective treatments do not exist; therapy usually consists of various supportive, behavioral, and pharmacologic measures. Surgical intervention is rarely indicated.[1]

The International Continence Society has coined the term painful bladder syndrome (suprapubic pain with bladder filling associated with increased daytime and nighttime frequency, in the absence of proven urinary infection or other obvious pathology) and reserves the diagnosis of interstitial cystitis for patients with characteristic cystoscopic and histologic features of the condition.[2]

An international consensus panel was able to generally agree on the following definition of interstitial cystitis/bladder pain syndrome (IC/BPS): unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder and associated with lower urinary tract symptoms of more than 6 weeks' duration, in the absence of infection or other identifiable causes. American Urological Association (AUA) guidelines published in 2011 and amended in 2014 use an evidence-based approach to provide a clinical framework for the diagnosis and management of this condition.[3] The Canadian Urological Association issued a guideline on diagnosis and treatment of IC/BPS in 2016.[4]

Despite years of intensive research, there are no specific clinical or urinary markers currently clinically available; no absolutely specific radiographic, laboratory, or serologic findings; and no biopsy patterns that are pathognomonic for interstitial cystitis. The syndrome remains a diagnosis of exclusion (see Presentation, DDx, and Workup.)

Intensive study has been done to attempt to identify biomarkers for IC/BPS. Some interesting studies have shown that bladder nitric oxide is an accurate marker for Hunner lesions, but these are not present in all patients, and the test requires specific equipment, which has limited its widespread clinical use.[5] Differences in levels of cytokines and chemokines, specifically CXCL-10, have shown some ability to differentiate patients with and without Hunner lesions.[6] Other studies of ulcerative IC/BPS have shown that numerous other cytokines and chemokines are up-regulated as well, heralding a possible urinary test to identify patients.[7]

Perhaps the most promising urinary biomarker for IC/BPS is antiproliferative factor (APF).[8] This small 8–amino-acid peptide has been associated with suppression of cell growth, increases in transcellular permeability, and lowering of levels of proteins that form intercellular junctional complexes. APF is synthesized and secreted by bladder epithelial cells from patients with IC/BPS and may play a key role in pathophysiology.[9] In vitro studies have shown that removal of APF from cell culture media restored cell proliferation and membrane integrity.[10] Studies have also suggested a role for APF in the therapeutic effect of hydrodistension in patients with IC/BPS, although further confirmatory studies are necessary.[11]

Treatment

The most important element in treating patients with interstitial cystitis is education and emotional support. Periodic exacerbations are managed as they occur because no long-term therapy has been shown to prevent or delay recurrent episodes. Therefore, the purpose of treatment is to palliate and alleviate symptoms.

Because no discrete pathognomonic pathologic criteria exist for assessing and monitoring disease severity, indications and goals for treatment are based on the degree of patient symptoms. Assessing patient response to treatment is also complicated because of the subjective nature of symptoms; the waxing and waning nature of symptoms without treatment; and the lack of objective serologic, physical, or histopathologic findings. Conservative measures and oral or intravesical treatments are considered first-line treatment. (See Treatment.)

Background

In 1887, Skene initially described a condition characterized by inflammation that destroyed the urinary bladder "mucous membrane partly or wholly and extended to the muscular parietes." Guy Hunner popularized the disease with the description of characteristic bladder wall ulcers in association with a symptom complex of chronic bladder inflammation.[12] The first comprehensive epidemiologic description of interstitial cystitis is credited to Hand, who in 1949 described the widespread, small, submucosal bladder hemorrhages and the significant variation in bladder capacity characteristic of the condition.

 

Pathophysiology

The pathophysiology of interstitial cystitis is poorly understood. The disorder may represent a number of as yet undefined, disparate pathologic conditions that ultimately present as the clinical syndrome of urinary frequency, urgency, and pelvic pain. Some research suggests that the following may all play a role in the disease pathophysiology[13] :

  • Pelvic floor dyfunction
  • Dysregulated immune or inflammatory signals
  • Neural hypersensitivity
  • Disruption of the proteoglycan/glycosaminoglycan (GAG) layer.

The transitional cell apical membrane of the bladder is coated with GAGs and proteoglycans. Disruption of this layer can lead to transmigration of urinary solutes across the mucosal surface, affecting nerves and muscles and potentially leading to pain. Thus, restoration of this layer remains a mainstay in treatment of IC/BPS.[14]

Up-regulation of histaminergic[15] and muscarinic neurotransmitter receptors has been shown to be present in patients with IC/BPS, which may contribute to the pain, urgency, and frequency that occurs in IC/BPS.[16, 17] Additionally, up-regulation of neural afferent pathways has been shown in IC/BPS,[18] as well as a central hyperresponsiveness in association with other conditions, including fibromyalgia, irritable bowel syndrome, and depression/anxiety disorders.[19]

Clinically, interstitial cystitis is often divided into 2 distinct subgroups based on findings at cystoscopy and bladder overdistention. These categories are the ulcerative (ie, classic) and nonulcerative (ie, Messing-Stamey) types. Such differences may have important implications for diagnosis and therapy. Evidence showing progression of ulcerative to nonulcerative disease, or vice versa, is lacking.[20] Clinical presentation is also variable, with nonulcerative patients presenting with a more diffuse pain syndrome and multiple systemic complaints. Ulcerative patients tend to have higher daytime and nighttime frequency and lower bladder capacity, indicating that it may be more of a condition of the bladder itself than the nonulcerative type.[21]

As such, the ulcerative subtype responds better to bladder-targeted therapies, including cauterization[22] and cystectomy.[23] Cystectomy has also led to significant improvements in quality of life in patients with severe ulcerative interstitial cystitis.[21] Fulguration may provide significant long-term benefit in patients with ulcerative disease if the ulcers involve less than 25% of the bladder. However, a significant subpopulation requires repeat treatment, and many of those patients progress to cystectomy.[24]

Ulcerative

The hallmark of classic interstitial cystitis is a diffusely reddened appearance to the bladder surface epithelium associated with 1 or more ulcerative patches surrounded by mucosal congestion (ie, Hunner ulcer) on the dome or lateral walls of the bladder upon cystoscopic examination. These ulcers may become apparent only after overdistention, because discrete areas of mucosal scarring rupture during the procedure. Overdistention in this type of interstitial cystitis results in fissures and cracks that bleed in the bladder epithelium.

In the United States, the ulcerative type is rare (< 10% of cases), and some authors consider this type to be more resistant to therapy. Biopsy findings show that the ulcerative lesion can be transmural, associated with marked inflammatory changes, granulation tissue, mast cell infiltration, and, in some cases, fibrosis. This classic form of interstitial cystitis can be associated with progressively smaller bladder capacity over time.

Nonulcerative

The nonulcerative type of interstitial cystitis is characterized by similar clinical symptoms (ie, frequency, urgency, pelvic pain), but the cystoscopic findings noted for the ulcerative lesion are absent. Instead, after overdistention, these patients demonstrate glomerulations that are discreet, tiny, raspberry-like lesions appearing on the dome and lateral walls of the bladder and tiny mucosal tears and submucosal hemorrhages. Bladder biopsy findings in these patients often are unremarkable, in contrast to those found in patients with classic interstitial cystitis.

Etiology

The etiology of interstitial cystitis remains unknown and is likely multifactorial.[25, 26, 27] Proposed etiologies include the following:

  • Pathogenic role of mast cells in the detrusor and/or mucosal layers of the bladder

  • Deficiency in the glycosaminoglycan layer on the luminal surface of the bladder, resulting in increased permeability of the underlying submucosal tissues to toxic substances in the urine[28]

  • Infection with a poorly characterized agent (eg, a slow-growing virus or an extremely fastidious bacterium)

  • Production of a toxic substance in the urine

  • Neurogenic hypersensitivity or inflammation mediated locally at the bladder or spinal cord level

  • Manifestation of pelvic floor muscle dysfunction or dysfunctional voiding

  • Autoimmune disorder

Although interstitial cystitis has not traditionally been considered a heritable condition, a 2005 study from the University of Maryland reported a higher occurrence of interstitial cystitis in monozygotic versus dizygotic twins, suggesting the disease has at least a partial genetic predisposition.[29]

Patients with interstitial cystitis are more likely to have undergone prior gynecologic surgery and/or to have a history of urinary tract infections and are 10-12 times more likely to report childhood bladder problems. In addition, interstitial cystitis is associated with the following chronic illnesses:

Other autoimmune conditions have also been shown to bear resemblance or be associated with IC/BPS. Sjögren syndrome and fibromyalgia syndrome show antibodies against urothelium, smooth muscle, and connective-tissue components of the urinary bladder. Indeed, the pathophysiology of those conditions is similar to that of IC/BPS.[30]

Psychiatric conditions associated with interstitial cystitis include anxiety disorder, depression, and adjustment reactions.

Epidemiology

Reports on the prevalence of interstitial cystitis conflict, depending on the country of origin and the criteria used for diagnosis. In addition, there is significant overlap with conditions such as urinary tract infection, pelvic pain syndromes, and overactive bladder.[31]

Current studies estimate that 2.7% to 6.5% of women in the United States have symptoms consistent with a diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS).[32] The broad range in prevalence depends on whether a high-sensitivity definition (6.53%) is used versus a highly specific definition (2.7%). Roughly translated, these numbers indicate that 3.3-7.9 million US women older than 18 years have symptoms of IC/BPS. Of those women, however, only 9.7% report being assigned a diagnosis of IC/BPS.[33]

In the United States, Curhan et al showed a prevalence of 60-70 cases per 100,000 women. The 2004 United States Nurses Health Study indicated a prevalence of 2.3%.[34] The estimated annual incidence rate of interstitial cystitis in the US is 2.6 cases per 100,000 women.

Reports from Europe indicate a prevalence of 18 cases per 100,000 women, whereas only 3-4 cases per 100,000 women are reported in Japan. The marked differences between these countries and the United States are likely due to differences in diagnostic criteria, varying from all-encompassing clinical criteria (eg, those from the National Institute of Diabetes & Digestive & Kidney Diseases [NIDDK] of the US National Institutes of Health) to very strict criteria based on a pathologic diagnosis. Epidemiological studies are difficult, given the wide variability in which patients are identified as research subjects. Some studies ask individuals to self-identify, while others survey physicians who may be unfamiliar with IC/BPS.[35]

Using a validated IC/BPS case definition, Berry et al discovered that only 50% of women who met criteria for IC/BPS had been evaluated by a urologist and only 10% carried the diagnosis, which strengthens the argument that this disease is largely underreported.[35]

Race-, sex-, and age-related differences in demographics

Of patients with interstitial cystitis, 94% are white and approximately 90% are female. Household size, marital status, number of male sexual partners, educational status, and parity were previously not statistically different between patients with interstitial cystitis and healthy controls. However, more recent data from the RAND interstitial cystitis cohort have shown that according to a standardized definition, women in that study were considerably more likely to be uninsured, less likely to be married, and had more children than others with the reported diagnosis of IC/BPS.[32]

Interstitial cystitis appears to be slightly more common in Jewish women.

The condition is also dramatically under-reported in men. There is significant overlap of symptoms of IC/BPS to symptoms of patients with chronic prostatitis/chronic pelvic pain syndrome. In fact, 17% of men were reported to have symptoms of both complexes. This supports the hypothesis that IC/BPS and chronic prostatitis/chronic pelvic pain syndrome share a common pathophysiology in men. However, many of these studies rely on the patient's self-reported symptoms, so estimates of incidence in men are likely higher than previously reported.[36]

Median age at presentation is 40 years. However, Close et al have shown that interstitial cystitis may occur in children. In their series, the median age of onset was 4.5 years, with a mean age of diagnosis of 8.2 years. The children had diffuse glomerulations and terminal hematuria. Of the 16 children in the study, 15 improved after bladder hydrodistention.[37]

Prognosis

Interstitial cystitis is a chronic condition that most often follows a variable course characterized by intermittent periods of exacerbations and remissions. However, rarely, patients experience chronic progression to a small-capacity bladder with resultant severe lower urinary tract symptoms and risk of upper tract deterioration.

Unfortunately, interstitial cystitis responds poorly to treatment in many cases. To date, no treatment has been shown to decrease disease progression; therefore, the purpose of treatment is to palliate and alleviate symptoms. In the rare cases that classic interstitial cystitis leads to bladder wall scarring that results in a contracted, small-capacity bladder, the patient may require augmentation cystoplasty or some form of urinary diversion.

Because of the chronic nature of interstitial cystitis and the significant effect on the patient's quality of life, the psychological impact of the condition can be enormous. Ongoing emotional support is essential.[38, 39] Again, using the RAND interstitial cystitis cohort and a bladder symptom impact scale (BSI), women with a higher BSI score were more likely to have worse general mental and physical health–related quality of life, have more severe depressive symptoms, and a lower perceived control over life in general. They were also found to have worse coping skills overall than women with lesser or no symptoms.[40]

An example of the impact of education and counseling on the treatment of the interstitial cystitis/bladder pain syndrome (IC/BPS) complex comes from 2 placebo-controlled trials that compared education plus placebo with placebo alone and amitriptyline alone. In those studies, patients receiving education achieved among the highest response rates.[41]

Patient Education

More information about interstitial cystitis and support information for patients can be obtained from the following associations:

Interstitial Cystitis Association

51 Monroe St. Suite 1402

Rockville, MD 20580

Phone: 1-800-help ICA

Email: ICAmail@ichelp.com

 

Urology Care Foundation

1000 Corporate Boulevard,

Linthicum, MD 21090

Phone: 410-689-3700 or 1-800-828-7866

Fax: 410-689-3998

Other information sources include the following:

  • HealthlinkUSA

  • Interstitial Cystitis Network: The Interstitial Cystitis Network is a large archive of information on the Web for interstitial cystitis, including patient materials, a research library, and physician referrals

  • The National Institutes of Health maintains a patient information site for Interstitial Cystitis

  • Urology Channel, which is a source of general health information about urologic subjects, has a review of interstitial cystitis

For patient education information, see Interstitial Cystitis.

 

Presentation

History

Because interstitial cystitis is a poorly defined entity of unknown etiology, the clinical presentation is often not uniform and the symptoms vary in severity and nature. The onset of symptoms is often, but not invariably, acute, and the patient is sometimes able to describe the moment at which symptoms began. Patients often associate the onset of symptoms with a specific urinary tract infection (UTI), catheterization, or bladder or pelvic surgery.

Symptoms of interstitial cystitis may include the following:

  • Urinary frequency, urgency, and pain
  • A sense of pressure, discomfort, or pain in the pelvis
  • A vague sense of incomplete bladder emptying
  • A constant sensation of needing to void, or a compulsion to void
  • Dyspareunia, sex-related distress, and decline in libido and orgasm frequency are also common

Interstitial cystitis is characterized by periods of exacerbation followed by variable periods of remission; some patients have completely asymptomatic periods interspersed with flares. Symptoms may vary daily or weekly or may be constant and unrelenting for months or years and then resolve spontaneously with or without therapy. Spontaneous remission occurs in as many as 50% of patients at a mean of 8 months. In females, symptoms may fluctuate relative to the ovulatory cycle. As with other autoimmune conditions, some pregnant women may experience periods of remission during the second and third trimester, further supporting an immune-mediated pathophysiology.

The most prevalent feature of interstitial cystitis is irritative lower urinary tract symptoms, including urinary frequency in association with varying degrees of pain. The exact number of micturitions, daytime or nighttime, is not important; however, according to the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) criteria, more than 8 micturitions per day is considered adequate for inclusion into clinical studies.[42] Daytime frequency in the absence of nocturia is not characteristic of interstitial cystitis. The absence of significant nocturia may suggest an alternative diagnosis (eg, sensory urgency). Urinary incontinence is quite rare. Patients with a primary complaint of incontinence may require further evaluation, including urodynamic studies.

Pain with bladder filling is a common finding that may be reproduced urodynamically or with cystography. Patients may report constant pelvic pain or pain related to a full bladder. Such pain is often relieved partially or wholly by voiding. Dysuria (pain with voiding) may be associated with interstitial cystitis; however, this is a distinct symptom that may imply another diagnosis and suggests that additional evaluation of the lower urinary tract and genital tract is indicated. Dyspareunia is common in as many as 50% of women.

Men with interstitial cystitis may report perineal, groin, penile, or scrotal pain. The diagnosis of prostadynia or nonbacterial prostatitis (chronic pelvic pain syndrome) should be entertained in these patients.

Patients with interstitial cystitis have a high incidence of associated conditions, including allergies, irritable bowel syndrome, fibromyalgia, and focal vulvitis. A substantial emotional and psychological overlay to the complaints, due to the duration and severity of symptoms, may or may not be present.

In a population-based sample of 3397 women with interstitial cystitis/bladder pain syndrome (IC/BPS), more than half reported poor sleep quality, sleep duration of 6 hours or less, or trouble sleeping due to symptoms. Short sleep duration was significantly associated with greater impairment in IC/BPS quality of life and poorer self-reported physical health. Poor sleep quality was significantly associated with greater quality of life impairment, poorer physical health, and increased sexual dysfunction. Nocturnal IC/BPS symptoms were significantly associated with greater IC/BPS impairment, poorer physical and mental health, and greater sexual dysfunction.[43]

Questionnaires

Validated questionnaires may serve as an aid in clinical diagnosis, as a means of tracking symptom response to therapy in clinical practice, or as an assessment of response to treatments in study populations. However, despite the usefulness of these metrics, interstitial cystitis remains a diagnosis of exclusion. The Wisconsin Interstitial Cystitis Scale was initially validated in a small population[44] and has subsequently been shown in larger studies to be valid and easy to implement.[45] It has also been shown to correlate well with other validated interstitial cystitis questionnaires.[46]

The Interstitial Cystitis Symptom Index and the Problem Index (O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index) are self-administered questionnaires that have been found to be valid and reliable and to serve as useful adjuncts to aid in diagnosis. They were not designed to be used as screening tools.[47] These indices have also been shown to be responsive to changes in interstitial cystitis symptoms[48] and may therefore be useful in measuring response to therapy in clinical and research settings.

The Pelvic Pain and Urgency/Frequency Patient Symptom Scale is a tool that can be used for screening, and it measures both urinary symptoms, such as pain and urgency, and symptoms related to sexual intercourse. It has 2 scales, one that measures symptoms and a second "bother score" that measures how troublesome these symptoms actually are to the patient. Parsons et al showed that this scale identified accurately 74% of patients with IC/BPS with scores of greater than 10 and 91% of patients with scores of 20 or greater. Additionally, it is easily filled out and has been used as a monitoring tool to assess treatment response.[49]

Physical Examination

Abdominal, pelvic, and directed neurologic examinations should be performed in all patients with voiding dysfunction. Nevertheless, the findings from these examinations are often unrevealing in patients with interstitial cystitis. Women with interstitial cystitis may express some discomfort with palpation over the urethra and bladder base. A correlation has been noted between urethral tenderness and the finding of a Hunner ulcer on cystoscopic examination.

Pain upon urethral palpation in the presence of an anterior vaginal wall mass may suggest urethral diverticulum, whereas cervical motion tenderness may suggest pelvic inflammatory disease. On examination with a speculum, any of the following findings suggest a diagnosis other than interstitial cystitis:

  • Prolapse
  • Masses
  • Evidence of vaginitis, herpes, vestibular adenitis, vulvovestibulitis, vulvodynia, or other pathology

Palpation for a full bladder and bimanual examination evaluating for adnexal masses should be part of the complete examination. Rectal examination should always be performed to evaluate for masses or tenderness and to assess rectal and pelvic floor (levator) muscle tone. Neurologic examination findings are usually unremarkable, but abnormalities of motor function, sensation, or reflexes may indicate spinal cord or nerve root dysfunction and should prompt further evaluation for other diagnoses.

Physical examination findings can help differentiate interstitial cystitis/bladder pain syndrome from provoked vestibulodynia disorder (PVD). To examine the vestibule (the tissue surrounding the urethral meatus, at the opening of the vagina), the clinician moves the labia minora to the side and lightly touches the tissue with a cotton swab. This maneuver is normally painless, but can elicit burning or cutting pain or pelvic pain in a woman with PVD.[50]

Pain on vestibular examination should prompt investigation of the cause of PVD (eg, testosterone deficiency, neurologic factors, pelvic muscle hypertonicity), as this will determine treatment. Testosterone deficiency is treated with cessation of oral contraceptives or, in menopausal women, application of estrogen/testosterone creams. Neuroproliferative PVD is treated with vulvar vestibulectomy. Hypertonicity of the pelvic floor muscles is treated in part with physical therapy.[50]

Male patients commonly have no abnormalities upon examination. In male patients with irritative lower urinary tract symptoms, bladder outlet obstruction and chronic nonbacterial prostatitis are important diagnostic considerations.

NIDDK criteria

Because no pathognomonic criteria exist for the diagnosis of interstitial cystitis, the modified National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) criteria for the inclusion of patients in interstitial cystitis basic and clinical research studies can be used. These criteria, initially developed in 1987, were originally intended not to define interstitial cystitis but to ensure that studies of the disease had relatively comparable patient populations. Nevertheless, the criteria became the de facto definition of the disease, although a significant number of patients with interstitial cystitis do not meet the criteria.[42]

The NIDDK criteria for interstitial cystitis include 2 sets of inclusion criteria and 1 of exclusion criteria. For the inclusion criteria, 1 of the cystoscopic findings and at least 1 subjective symptom must be present. All of the exclusion criteria must be absent.

Cystoscopic criteria include 1 of the following findings after distention under anesthesia for 1-2 minutes at 80-100 cm water (bladder must be distended up to 2 times before evaluation):

  • Glomerulations in at least 3 quadrants of the bladder and at least 10 glomerulations per quadrant
  • Classic Hunner ulcer
  • Glomerulations must not be along the path of the cystoscope

Subjective symptoms include the following:

  • Pain associated with the bladder
  • Urinary urgency

The presence of any of the following criteria is intended to exclude patients with other diseases that can cause bladder symptoms and patients with atypical characteristics:

  • Cystometric bladder capacity greater than 350 mL in a conscious patient with either gas or liquid filling
  • Absence of an intense urge to void when patient's bladder has been filled with 100 mL of gas or 150 mL water during cystometry at a fill rate of 30-100 mL/min
  • Demonstration of phasic involuntary bladder contractions on cystometry findings at a fill rate of 30-100 mL/min (note that although this is an exclusion criterion per the NIDDK, detrusor instability may be present in as many as 14% of patients with a clinical diagnosis of interstitial cystitis)
  • Duration of symptoms less than 9 months
  • Nocturia
  • Symptoms relieved by antimicrobials, urinary antiseptics, anticholinergics, or antispasmodics
  • Micturition frequency of less than 8 times daily
  • Diagnosis of bacterial prostatitis or cystitis within a 3-month period
  • Presence of ureteral or bladder calculi
  • Active genital herpes
  • Uterine, cervical, vaginal, or urethral cancer
  • Urethral diverticulum
  • Cyclophosphamide or other chemical cystitis
  • Tuberculous cystitis
  • Radiation cystitis
  • Benign or malignant bladder tumors
  • Vaginitis
  • Age younger than 18 years

It should be noted, however, that strict application of these criteria would have misdiagnosed more than 60% of patients who were diagnosed by researchers as definitely or likely having IC/BPS.[51]

 

DDx

Diagnostic Considerations

Diagnosing interstitial cystitis remains difficult even more than a century after it was described by Skene, in 1887. No pathognomonic findings exist with regard to patient history, physical examination findings, laboratory findings, or cystoscopy findings. The exclusion of other clinical entities remains the foremost goal of the workup and evaluation of patients thought to have this condition.

A careful, complete, and empathetic history and physical examination are critical. Cystoscopy is an adjunctive, although important, study. The classic Hunner ulcer in the setting of a small-capacity bladder (ie, assessed under anesthesia) is rarely seen to confirm the diagnosis with certainty. Until interstitial cystitis is defined completely or a definitive marker becomes universally available, the diagnosis remains one of exclusion.

The differential diagnosis of urinary frequency, urgency, and/or pain includes the following types of conditions:

  • Infectious or inflammatory
  • Gynecologic
  • Urologic
  • Neurologic

Infectious or inflammatory conditions to consider include the following:

  • Recurrent urinary tract infection (UTI)
  • Urethral diverticulum
  • Infected Bartholin gland or Skene gland
  • Vulvovestibulitis
  • Tuberculous/eosinophilic cystitis
  • Vaginitis (eg, bacterial, viral [eg, herpes])
  • Schistosomiasis

Gynecologic causes to consider include the following:

  • Pelvic malignancy or mass (eg, fibroid, endometrioma)
  • Endometriosis
  • Mittelschmerz
  • Pelvic inflammatory disease
  • Genital atrophy

Urologic causes to consider include the following:

  • Bladder cancer or carcinoma in situ (CIS)
  • Radiation cystitis
  • Overflow incontinence
  • Acontractile detrusor
  • Prostatodynia
  • Chronic pelvic pain syndrome
  • Bladder outlet obstruction (eg, urinary retention with overflow incontinence)
  • Large postvoid residual volume
  • Open bladder neck (eg, intrinsic sphincteric deficiency, urolithiasis, urethritis)

Neurologic causes to consider include the following:

  • Neurogenic detrusor overactivity
  • Parkinson disease
  • Lumbosacral disk disease
  • Spinal stenosis
  • Spinal tumor
  • Multiple sclerosis
  • Cerebrovascular accident

Other possible diagnoses to consider include the following:

  • Dysfunctional voiding
  • Vulvodynia
  • Pelvic floor myalgia
  • Degenerative joint disease
  • Hernia
  • Inflammatory bowel disease
  • Gastrointestinal neoplasm
  • Diverticulitis
  • Adhesions from prior surgery

Clinically, the practitioner is somewhat obligated to consider these potential alternative diagnoses prior to diagnosing interstitial cystitis. The implications of a diagnosis of interstitial cystitis are profound in that it is a chronic condition without universally effective therapy.

 

Workup

Approach Considerations

The diagnosis of interstitial cystitis is most often made when long-standing urinary frequency, urgency, and pelvic pain exist in the absence of a readily identifiable etiology, such as urinary tract infection (UTI). Urinalysis and urine culture are mandatory. A voiding diary is helpful in establishing baseline voiding frequency.

Cystoscopy is considered by some clinicians to be mandatory in order to diagnose interstitial cystitis However, this is somewhat controversial because of the lack of specific or pathognomonic findings (except perhaps the very rare finding of a Hunner ulcer).

Urodynamic evaluation is optional, and finding detrusor overactivity or pelvic floor dysfunction may suggest an alternative diagnosis.

Imaging the bladder

No known radiographic, ultrasonographic, or other imaging findings are specific for interstitial cystitis. Unless indicated to help exclude alternative diagnoses, radiographic studies have only a limited role in the evaluation of interstitial cystitis. Cross-sectional imaging, including magnetic resonance imaging (MRI), computed tomography (CT) scanning, and pelvic ultrasonography, may be performed when clinically indicated to evaluate for a suspected pelvic mass that is causing compression of the bladder or for an adjacent inflammatory process (eg, diverticulitis).

Patients with interstitial cystitis have pelvic floor hypertonicity on MRI, which manifests as shortened levator, increased posterior puborectalis angles, and decreased puborectal distances.[53]  

Cystography and voiding cystourethrography may be used to evaluate the bladder for other causes of irritative lower urinary tract symptoms, including the following:

  • Intravesical masses
  • Stones
  • Bladder diverticula
  • Urethral diverticula
  • Urethral stricture
  • Meatal stenosis
  • Findings suggestive of a neurogenic or nonneurogenic voiding dysfunction

Additional studies

Urethral and vaginal culture results should be obtained for pathologic organisms (eg, fungi and gonorrheal, chlamydial, and trichomonal species).

Various assays for stress protein genes, glycosaminoglycans, mast cell tryptase, Tamm-Horsfall protein autoantibodies, and others have been suggested by numerous investigators. However, these assays are currently used primarily for research purposes and do not have a defined role in the diagnosis of interstitial cystitis. Antiproliferative factor (APF) has shown promise in research assays as a biomarker for worsened disease and is currently being investigated as a clinical marker.[8, 9]

In men, expressed prostatic secretions yield no findings specific for interstitial cystitis. Nonetheless, localizing cultures and microscopic examination should be performed to exclude bacterial prostatitis.

Cystoscopy

Aside from a thorough history and physical examination, cystoscopy is described as the most important diagnostic tool for assessing a patient who may have interstitial cystitis. Cystoscopy, with bladder overdistention, is performed to help exclude other causes of symptoms suggestive of interstitial cystitis and to provide evidence for the diagnosis of interstitial cystitis. In addition, a biopsy of the bladder can be performed to evaluate for carcinoma in situ or other inflammatory conditions. Contraindications to cystoscopy and bladder distention include the following:

  • Anesthetic risk
  • History of prior rupture during distention
  • Pregnancy
  • Urinary tract infection

Cystoscopy is sometimes performed without anesthesia; however, bladder hypersensitivity with filling and pelvic pain may limit the examination considerably. Importantly, patients who can tolerate several hundred milliliters of fluid during bladder filling, with manipulation and examination, without general anesthesia probably do not have interstitial cystitis.

In general, cystoscopy is performed while the patient is under anesthesia in order to provide sufficient distention to examine for coexisting urethral and bladder pathology (eg, transitional cell carcinoma) and features of interstitial cystitis, such as Hunner ulcers and glomerulations. Bladder capacity values are also recorded.

Researchers from the University of Pittsburgh reported that ulcers of bladder mucosa and areas with angiogenesis can be easily detected by using a flexible cystoscope with a narrow-band imaging (NBI) system. In their study of 52 patients, Ueda et al identified conventional ulcers in 37 patients, matching the accuracy of conventional cystoscopy. Moreover, in an additional 13 cases, NBI identified abnormal areas without ulcers, which were later correlated with areas of petechial hemorrhage and glomerulation after hydrodistension. The authors suggest that this system is highly practical for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS), but it has yet to be widely adopted.[54]

Diagnostic hydrodistention

Diagnostic hydrodistention (ie, overdistention) is performed by placing the irrigation fluid at 60-80 cm water above the patient's bladder. Fluid is run into the bladder under gravity until it slows to a drip. Manual compression of the urethra around the cystoscope sheath should be performed as the bladder fills to help prevent the escape of fluid and to ascertain the true bladder capacity. Continuous intravesical observation of the bladder wall is necessary to note perforation and extravasation as the bladder is filled. A seemingly large bladder capacity or exceedingly prolonged filling time without deceleration of the filling rate may indicate bladder perforation.

Examination of the fully distended bladder should be unremarkable, except perhaps for some mild trabeculation. The diagnostic distention is typically held for 1-2 minutes, and then the bladder is drained. The amount of drainage (bladder capacity under anesthesia) and the color of the effluent are recorded. Characteristically, the last 50-100mL of effluent may be blood tinged (terminal pinking) in patients with interstitial cystitis. The bladder capacity may be reduced in patients with the ulcerative variety of interstitial cystitis, whereas the bladder capacity is normal or only slightly reduced in patients with the nonulcerative form of interstitial cystitis.

Reinspection of the bladder may reveal diffuse, pinpoint petechial hemorrhages within the bladder (ie, glomerulations). These lesions are small, hemorrhagic, and raspberry-like in appearance and are graded as mild, moderate, or severe, depending on their numbers. Glomerulations represent the most consistent finding on cystoscopy in patients with interstitial cystitis.

Typically, the glomerulations are present in at least 3 quadrants of the bladder, sparing the trigone. These glomerulations may appear in a checkerboard-like or lattice-like configuration or may appear as splotchy areas over a section of the bladder. Glomerulations noted only along the posterior wall suggest trauma from the cystoscope sheath and not necessarily any pathologic process, such as interstitial cystitis.

Glomerulations are not specific for interstitial cystitis, although some authors state that glomerulations are not present in healthy bladders. Others have speculated that the appearance of glomerulations may simply be a manifestation of chronic bladder underfilling due to hypersensitivity or sensory urgency rather than any specific primary pathologic process, such as interstitial cystitis. A systematic literature review by Wennevik et al found that glomerulations did not correlate with symptoms and were found in patients without IC/BPS.[55]

Glomerulations may also develop in various other bladder conditions, including the following:

  • Neoplasia
  • Infective cystitis
  • Radiation cystitis
  • Chemical cystitis
  • Defunctionalized bladder (ie, in patients on dialysis)
  • Chronically underfilled  bladder (eg, patients who have undergone urinary diversion).

Relief of urinary frequency, urgency, and pain has been reported, at least temporarily, in as many as 60% of patients following bladder overdistention. Some studies have additionally shown that this relief is durable for periods up to and exceeding 1 month.[56] However, many patients find that their symptoms are transiently exacerbated immediately following this procedure.

Bladder Biopsy

Some centers advocate limiting the use of cystoscopy and biopsy in the evaluation and workup of patients thought to have interstitial cystitis; however, such a biopsy may be helpful to help exclude other disorders. Biopsies are performed primarily to help rule out other varieties of cystitis or malignant or premalignant (eg, carcinoma in situ) lesions. They are also performed to evaluate for detrusor mastocytosis, which some authors have used in directing therapy (see discussion below). Postoperative catheter drainage should be instituted in patients who undergo deep biopsies to reduce the chance of perforation, extravasation, or both.

No pathognomonic histologic findings exist for interstitial cystitis, although some authors have found increased numbers of mast cells in the detrusor muscle or submucosa in affected individuals. The finding of mast cells may suggest a potential role for antihistamine compounds in the treatment of the condition. However, this finding neither confirms nor excludes the diagnosis.

An increased activation of the extrinsic apoptotic pathway in biopsy samples has also been shown and may ultimately lead to a better understanding of the disease, but, again, no diagnostic criteria can be associated with this finding.[57]

Potassium Sensitivity Test

Some authors have found that certain subgroups of patients with interstitial cystitis have increased urothelial permeability to certain intravesical constituents. This potential property is exploited in the potassium sensitivity test as a diagnostic test for interstitial cystitis.

For this test, 40 mL of potassium chloride solution (40 mEq KCl/100 mL water) are instilled into the bladder for 5 minutes.[49] In patients with interstitial cystitis or other conditions of the bladder that affect urothelial permeability, the patient experiences acute and severe pain with intravesical instillation of the potassium chloride solution, and a diagnosis is made with an increase of 2 or more points on a pain or urgency scale. Patients who do not have interstitial cystitis may experience little or no pain from the solution. In patients who do experience pain, a rescue solution of heparin and lidocaine is instilled upon completion of the study. Because of its lack of sensitivity and specificity, this test does not usually alter clinical decision-making and thus is generally not used.[3]

Urine Studies

Urinalysis results are usually normal. Microscopic hematuria and pyuria are present in some patients. Much research is being undertaken to identify urine markers expressed in patients with interstitial cystitis to develop a noninvasive laboratory test. By definition, urine culture results should be negative.

The absence of any abnormal urine cytology findings specifically suggests a diagnosis of interstitial cystitis. A voided or catheterized urine specimen demonstrating cytologic changes consistent with dysplasia, carcinoma in situ, or frank cancer should prompt immediate further urologic evaluation.

 

Urodynamic Studies

Urodynamic studies are not part of the routine evaluation for interstitial cystitis. Few urodynamic findings are consistent in patients with interstitial cystitis, and findings specific for the syndrome do not exist. On filling cystometry, most patients have increased sensation with a decreased volume at all filling intervals. Pain with bladder filling that reproduces the patients' interstitial cystitis symptoms is very supportive of a diagnosis of interstitial cystitis. Sphincter electromyography may show some increased activity caused by pain with bladder filling.

The prevalence of involuntary bladder contractions in patients with interstitial cystitis symptoms ranges from 0-14%; however, bladder contractions on filling cystometry studies are commonly cited as mitigating evidence against a diagnosis of interstitial cystitis, as per the NIDDK criteria. Volitional bladder contractions in patients with interstitial cystitis are quite similar to those in healthy persons.

Bladder compliance in patients with interstitial cystitis is usually normal. Postvoid residual volume should be minimal. Findings from pressure flow studies and free uroflow studies are usually unremarkable. True detrusor-sphincter dyssynergia excludes the diagnosis of interstitial cystitis.

 

Treatment

Approach Considerations

The difficulty in treating interstitial cystitis begins in the primary care office, where knowledge of the condition is suboptimal.[58] An integral part of therapy for interstitial cystitis is extensive patient education regarding the chronic nature of the disease and realistic assessments of the condition, prognosis, and potential responses to therapy. Ongoing reassurance and physical and emotional support are important as the diagnostic evaluation progresses and therapies are applied.

Only rarely will patients with interstitial cystitis have an immediate, complete, and durable response to any particular therapy. They must be counseled at length regarding the lack of universally effective therapies. Often, referral to one of the local interstitial cystitis support groups, especially a local chapter of the Interstitial Cystitis Association, can be helpful in providing a continuing network of support for the patient.

Ideally, in clinical practice, the treatment of interstitial cystitis should be initiated with the least invasive, least expensive, and most reversible therapy. In general, this consists of a program of dietary and fluid management, time and stress management, and behavioral modification. Thereafter, treatments are applied in a progressively more invasive step-wise fashion until some degree of symptomatic relief is obtained.[3]

The level of initial treatment may also be influenced by clinical judgment, taking into account the severity of presenting symptoms and patient-specific factors. At times, multiple simultaneous treatments may be used in select patients. In patients who have shown no response to multiple treatment modalities, reassessment for any underlying patient condition should be undertaken.[3]

Interventions may include the following:

  • Oral pharmacologic agents (eg, pentosan polysulfate sodium [Elmiron], antihistamines, tricyclic antidepressants, analgesics, anti-inflammatory agents)

  • Intravesical therapy (ie, medications intermittently instilled directly into the bladder via a catheter)

  • Surgical therapies

  • Electrical stimulation

  • Complementary therapies (eg, acupuncture, hypnosis, pelvic floor massage)

In a chronic, often poorly controlled condition such as interstitial cystitis, patients may seek alternative, holistic, or complementary therapies. These patients should be cautioned that such therapies, while potentially successful, often have not been validated scientifically. Desperate patients should be counseled to avoid potentially harmful, unproven therapies. However, one such complementary therapy, pelvic floor massage, has been shown to have some modest efficacy in a select group of patients in a well-done controlled trial.[59]

Following each intervention, the patient is reassessed for response. Unfortunately, therapies are often applied in a haphazard, "hit-or-miss" fashion, combining numerous different therapies before the patient's response to each therapy is truly assessed. This approach is sometimes partly driven by unrealistic patient demands and expectations regarding the success of various therapeutic interventions.

Again, patients must receive extensive counseling regarding the nature and prognosis of their condition and its response to therapy. This is critically important, and such counseling must be initiated prior to embarking on invasive interventions for which no proven overwhelming benefit may be achieved.

Behavioral Therapy

Biofeedback and pelvic floor rehabilitation, bladder training programs (ie, progressively increasing the voiding interval over the course of weeks to months), and other behavioral measures are excellent initial interventions and have been used by some authors with some success.[60, 61] The urinary frequency and urgency components seem to respond better to these interventions than the pelvic pain component.

Treatment decisions

Ultimately, the decision to abandon or augment behavioral therapy and to pursue other therapeutic options is made by the patient and physician when a general lack of progress occurs or when symptoms progress. Very few, if any, studies have looked at the minimal duration of time necessary to assess response to behavioral therapy in patients with interstitial cystitis. Furthermore, an optimal behavioral program has also not been defined.

Given the chronic nature of the condition and the possibility of spontaneous improvement or remission, progressively more invasive and expensive treatment should be initiated with caution. Generally, if tolerated by the patient, a trial of 3-6 months of behavioral therapy is warranted prior to proceeding to more invasive or expensive therapies.

Dietary Therapy

Various dietary measures have been examined as therapy for interstitial cystitis.[62] These dietary measures and the previously mentioned behavioral measures can be effective when used alone, but they can also be complementary to virtually all other interventions for interstitial cystitis. Some studies have reported that up to 90% of patients reported symptom exacerbations linked to food, beverage, and dietary supplements.[63]

Foods that have been implicated in aggravating symptoms of interstitial cystitis and, in the opinion of some authors, can precipitate symptomatic flares, include the following:

  • Coffee
  • Alcohol (beer, red wine, white wine, champagne)
  • Carbonated beverages
  • Monosodium glutamate (MSG)
  • Artificial sweeteners
  • Tomatoes
  • Vinegar
  • Citrus
  • Spicy foods
  • Chocolate
  • Cranberry juice
  • Particular fruits and vegetables

Avoiding these food items or substituting other food items is often advised. In a 2011 study, use of calcium glycerophosphate, sodium bicarbonate, or both before eating foods that triggered symptoms showed a trend toward improvement of symptoms.[64]

Patients may be instructed to fill out a food diary, recording the relationship between the consumption of various food and drink items and their interstitial cystitis symptoms. In this manner, items that provoke or exacerbate the interstitial cystitis symptom complex can be eliminated from the diet in a methodical fashion.

Common theories for dietary exacerbations include the hypothesis that the disrupted urothelial barrier is sensitive to metabolites of these foods. Alternative theories include the mechanism of "cross-talk," or the idea that stimuli from one organ can lead to changes in another organ by integrated sensory pathways. In other words, stimulation of the bowel by certain dietary substances can modulate pelvic pain in interstitial cystitis/bladder pain syndrome (IC/BPS).[65]

On the other hand, foods that have been identified as least bothersome to patients with IC/BPS include the following[65] :

  • Water
  • Milk
  • Bananas
  • Bluberries
  • Melon
  • Carrots
  • Broccoli
  • Mushrooms
  • Peas
  • Chicken
  • Eggs
  • Most meats
  • Rice
  • Popcorn

Oral Medication

Oral medications should be considered only after the aforementioned conservative measures have failed. With the exception of pentosan polysulfate sodium, the drugs listed in the Medication section are not specific for the treatment of interstitial cystitis; however, all of them have demonstrated some degree of efficacy in controlled or uncontrolled studies.

The duration of individual pharmacotherapy is variable. The clinical studies on pentosan polysulfate sodium seem to suggest that maximal effects are not observed until the patient has been on drug therapy for 5-6 months. Other medications are dispensed and their effects are reevaluated as per the expected pharmacokinetics. For example, steady-state serum levels of many tricyclic antidepressants are not attained until 6-8 weeks of stable dosing. Only at this time can the drug dose be safely and reasonably adjusted.

A study funded by the National Institutes of Health found that using pentosan polysulfate sodium alone or in combination with hydroxyzine was slightly beneficial, but this was not significant. The study compared placebo with oral pentosan polysulfate sodium, hydroxyzine, and a combination of both.[66]

In a randomized, double-blind, placebo-controlled study, amitriptyline was shown to provide statistically significant improvement in the O'Leary-Sant interstitial cystitis symptom index and problem index, pain, and urgency intensity. Common adverse effects of amitriptyline include dry mouth, weight gain, constipation, and sedation.[67]

In a 2010 intention-to-treat study by Foster et al, 271 women were randomized to behavioral therapy alone or therapy with amitriptyline dose escalation. No difference was found between the amitriptyline and placebo groups overall. However, subgroup analysis showed a mild improvement in symptoms in women on 50 mg of amitriptyline as compared with placebo.[68]

Cimetidine is a second-line therapy according to the AUA guidelines and is thought to demonstrate effectiveness via competitive inhibition of the H2 histamine receptor.[15]

Anticholinergic agents such as oxybutynin and tolterodine can be used to treat the urinary frequency component of interstitial cystitis; however, these agents can impair bladder emptying and thus may exacerbate pelvic pain. They should be used with caution in patients with interstitial cystitis, and the patient should be informed that these agents are not indicated specifically for the treatment of interstitial cystitis.

In a randomized, prospective, nonblinded study, cyclosporine (a calcineurin inhibitor) significantly reduced micturition frequency and demonstrated superior clinical response rates when compared with pentosan polysulfate sodium; however, treatment-related toxicity was higher in the cyclosporine arm.[69] Further, response rates in some studies were much lower after treatment with cyclosporine in patients without Hunner ulcers.[70] Cyclosporine is currently included in the American Urological Association (AUA) guidelines as a fifth-line treatment option.[3]

Studies of immune modulators not evaluated in the AUA guidelines can be found in primary literature. These include mycophenolate mofetil (MMF), tanezumab, and certolizumab pegol.

Data on MMF are sparse, and the response was poor in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS) in a well-done controlled trial.[71]

Tanezumab is a monoclonal antibody that inhibits nerve growth factor (NGF), thereby disrupting transmission of pain signals to the spinal cord and brain. It is pending FDA approval for treatment of chronic pain from moderate-to-severe osteoarthritis. As increased urinary and serum NGF has been found in IC/BPS patients, randomized trials have been performed, with initial results demonstrating reduction in daily pain scores and urgency episodes.[72] Pooled analyses from 3 small clinical trials of tanezumab in patients with urological chronic pelvic pain, including chronic prostatitis/chronic pelvic pain syndrome and IC/BPS, showed significant improvement in pain intensity for patients with symptoms suggesting the concomitant presence of nonurological-associated somatic syndromes, but not for those with pelvic pain symptoms only.[73]

Certolizumab pegol is a recombinant humanized anti–human tumor necrosis factor alpha neutralizing antibody that is approved for use in rheumatoid arthritis and other autoimmune disorders. In a randomized, double-blind, controlled trial, women with moderate to severe interstitial cystitis/bladder pain syndrome were more likely to experience significant improvement in symptoms with certolizumab pegol than with placebo therapy. By 18 weeks, patients in the certolizumab pegol arm showed significant reductions in Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), pain, and urgency.[74]

Treatment algorithm

The treatment of interstitial cystitis is complex and various algorithms have been developed. The AUA guidelines algorithm have suggested a stepwise, logical approach.[3]

The authors' algorithm for treatment is largely based on whether the patient has predominantly pelvic pain or urgency/frequency. In the authors' experience, patients with pelvic pain and minimal voiding symptoms represent a pharmacologic challenge, making an early pain-management clinic referral a useful adjunct.

In patients with significant voiding symptoms, the authors suggest an algorithm proposed by Hanno. Conservative treatment may include patient education, dietary manipulation, nonprescription analgesics, and pelvic floor relaxation. If the improvement in symptoms is inadequate, begin oral therapy with antispasmodics/antimuscarinics and nonnarcotic analgesics. In addition, a trial of amitriptyline for 8 weeks may be warranted. If amitriptyline fails, a trial of hydroxyzine for 8 weeks is suggested. If no response is observed, follow hydroxyzine with pentosan polysulfate sodium.

A 6- to 9-month course of pentosan polysulfate sodium (100 mg tid) is followed by a reassessment of interstitial cystitis symptoms. The authors have found that lower doses of this compound are not as effective, but we have not used the higher doses advocated by some authors. Additionally, adverse effects with pentosan polysulfate are dose dependent. One complication, particularly with long-term use, is macular disease, which may impair vision.[75, 76]

We attempt to try single-agent therapy first, moving down the ladder of medications, rather than treating patients with multiple agents from the outset. If conservative measures and medical therapy fail to provide adequate relief, surgical therapy should be considered.

Pain Management

Managing the pain component can be difficult in patients with interstitial cystitis. The etiology of the pain remains unclear, but various authors have postulated the etiology to be mediated centrally, peripherally, or locally via a neurogenic or inflammatory mechanism. Increasing evidence has implicated central mechanisms and sensitization in women with interstitial cystitis/bladder pain syndrome (IC/BPS). A study by Lai et al showed segmental hyperalgesia to mechanical stimulation in patients with IC/BPS.[77]

Additionally, it has been shown that there is excessive adrenergic stimulation in patients with IC/BPS, and iatrogenic stimulation shows heightened response in IC/BPS patients with pathologic findings of increased mucosal mastocytosis and increased sympathetic nerve density.[78]

Some patients require long-term pain medications, while others rely on these only during periods of symptomatic flares.

Agents used for pain relief include the following:

  • Anti-inflammatory drugs
  • Acetaminophen
  • Gabapentin (Neurontin)
  • Tricyclic antidepressants
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Various other agents

Most clinicians tend to avoid the extensive use of narcotics in patients with interstitial cystitis. When the pain component becomes unresponsive to nonnarcotic agents, referral to a chronic pain management facility may be helpful.

Transcutaneous electrical nerve stimulation (TENS) units, electrical stimulation (intravaginal), acupuncture, and intrathecal and intraspinal infusions have all been used. Topical anesthetics such as lidocaine have been applied directly to the bladder intravesically and have yielded some success.

Instillation Therapy

Patients in whom medical therapy fails may benefit from another bladder hydrodistention if the initial diagnostic hydrodistention was therapeutic. In the rare patient in whom a Hunner ulcer is seen on cystoscopy, cauterization or laser fulguration of the ulcer is recommended.[3]

If patients still do not respond, intravesical therapy may be initiated, beginning with weekly dimethyl sulfoxide (DMSO) therapy for 6 courses. Monthly maintenance DMSO instillations have been advocated by some clinicians in order to prevent flares, although data supporting this approach are lacking.

DMSO may be combined with steroids, bicarbonate, and heparin. Intravesical lidocaine may also be added. Some patients with refractory interstitial cystitis symptoms self-catheterize at home and instill a variety of these medications intravesically on an as-needed basis for symptom flares or simply for long-term therapy. In patients who respond poorly to DMSO, intravesical heparin or sodium oxychlorosene (Clorpactin) may be tried.

Long-term application of capsaicin, a component of hot pepper, has been associated with the desensitization of C fibers, the unmyelinated nerve fibers known for transmitting pain. Intravesical instillation of capsaicin has been limited in its use in interstitial cystitis because of the sensation of severe burning.

Resiniferatoxin, a capsaicin analogue, is 100-10,000 times more potent than capsaicin and is not associated with severe burning. However, resiniferatoxin has shown poor effectiveness after single administration, with no significant improvement in symptoms of interstitial cystitis, and adverse effects of dose-dependent pain and urgency symptoms.[79] A meta-analysis by Guo et al in 2013 showed that no significant improvement was achieved in patients treated with resiniferatoxin in terms of frequency, nocturia, incontinence, or involuntary detrusor contractions.[80] At this time, the AUA recommends against this treatment.[81]

Hyaluronic acid glycosaminoglycan replenishment therapy has yielded moderate results in non–placebo-controlled studies. In a study of weekly instillation of a 50-mL solution of phosphate-buffered solution containing 40 mg of sodium hyaluronate, 85% and 84% of patients reported symptomatic and quality-of-life improvement, respectively, with 50% of patients reporting a lasting effect at 5-year follow-up.[82] Patients in this study had demonstrated abnormal results on a modified potassium sensitivity test. Lower response rates are seen in patients without evidence of a urine-tissue barrier abnormality.[82] Currently, several studies with level 2b evidence support hyaluronic acid instillation. Patients report decreases in visual analog pain scores. Multicenter, randomized trials do not exist, however.[83]

In combination with hydrodistension, hyaluronic acid has been shown to maintain or prolong the effect of hydrodistension in some patients with IC/BPS.[84]

Additional smaller studies have shown that both hyaluronic acid and chondroitin sulfate produced sustained improvement in symptomatology (up to 3 y) in patients with refractory IC/BPS.[85] Unfortunately, other small studies have not been able to support the use of chondroitin sulfate as a monotherapy for IC/BPS, despite small improvements in pain scores.[86]

Intravesical bacillus Calmette-Guérin (BCG) has been hypothesized to suppress inflammation within the bladder. A randomized, placebo-controlled trial in patients with refractory interstitial cystitis revealed borderline statistical significance for global response assessment questioning, as well as most secondary outcome measures, including capacity, pain scores, urgency/frequency symptoms, and interstitial cystitis inventories.[87] As with resiniferatoxin, the AUA currently recommends against this treatment.[81]

Experimental therapies include treatment with intravesical liposomes, which are vesicles composed of concentric phospholipid bilayers.[88] These adsorb to cell surfaces and act as a delivery mechanisms for various chemicals. Animal models have shown decreased bladder sensitivity to potassium chloride,[89] and small human studies have shown promising results in reduction of frequency, nocturia, pain, urgency, and O'Leary-Sant scores.[90] While these results are initially promising, large, randomized trials are still lacking.

In animal models, direct transplantation of stem cells into the bladder has proved beneficial. In addition, animal experiments suggest that stem cells may provide an autologous cell source for bladder tissue regeneration, in patients requiring bladder augmentation.[91]

Hyperbaric oxygen is also an emerging treatment. As this has been successfully used to treat hemorrhagic cystitis from cyclophosphamide and radiation, it was used in a pilot study in patients with refractory IC/BPS.[92] Seven of 11 patients showed durable improvement in pain scores and urgency symptoms lasing over 2 years. This may also be a useful adjunct to DMSO instillation.[93]

Bladder Hydrodistention

Following diagnostic hydrodistention, therapeutic hydrodistention may be performed. This is usually performed at 60-80 cm water for less than 10 minutes. Hydrodistention at pressures greater than 100 cm water or for a duration exceeding 10 minutes is associated with adverse outcomes, including bladder rupture.[3]

The mechanism of action of bladder hydraulic distention is unknown. Hypotheses include neurapraxias by mechanical trauma and epithelial damage from mechanical trauma.

Surgical Therapies

Currently, no specific surgical therapies are directed towards interstitial cystitis. All surgical therapies currently used for treatment have been adapted from other therapeutic areas, and applied, sometimes successfully and sometimes not, to the population with interstitial cystitis.

Neuromodulation, or InterStim, is indicated for the treatment of some types of refractory voiding dysfunction, including urgency, frequency, and urge incontinence. This involves surgical placement of an electrode into the S-3 foramen to provide direct sacral nerve root stimulation. This technique has demonstrated some promising results in select patients with interstitial cystitis in some but not all studies, especially in the long term.

Studies in patients with interstitial cystitis refractory to conservative measures (ie, behavioral modification, diet, medications, hydrodistention) have found that sacral neuromodulation improved daytime frequency, nocturia, and mean voided volumes and decreased pain and interstitial cystitis symptom and problem index scores. In patients on long-term narcotics for refractory pain associated with interstitial cystitis, sacral neuromodulation has been shown to decrease (but not eliminate) narcotic requirements.

However, some authors have challenged these results. The frequency that arises in patients with IC/BPS is one in which patients void frequently to avoid pain with bladder filling. The studies showing benefit from sacral neuromodulation are all observational, small, single-center studies. Patients should be made aware that the indications for sacral neuromodulation are for voiding symptoms, and any effect on pain is unpredictable.

This should only be used as a fourth-line therapy.[94] A 2011 meta-analysis of sacral neuromodulation for chronic pelvic pain showed widely variable response rates and equally variable follow-up times, further questioning the use of this as a therapy for patients with IC/BPS.[95] However, as this has been shown to be a somewhat effective therapy in many patients, and as it is minimally invasive, it may be considered prior to any major invasive surgical interventions.[96]

In addition, sacral neuromodulation has been shown to normalize the abnormally high levels of antiproliferative factor (APF) and the abnormally low levels of heparin-binding epidermal growth factor in the urine of patients with interstitial cystitis.

Pudendal nerve stimulation has also been evaluated in patients with interstitial cystitis and has been compared with sacral nerve stimulation. In a small series, overall reduction in symptoms was 59% for pudendal nerve stimulation and 44% for sacral nerve stimulation.[97, 98, 99]

Botulinum toxin has been used for the treatment of interstitial cystitis as an isolated treatment, as well as in combination with other treatments. Results are mixed and patients should be counseled regarding the potential adverse effect of urinary retention.

Transurethral intradetrusor injection of onabotulinumtoxinA (OBA) coupled with therapeutic hydrodistention has been shown to be superior to hydrodistention alone in improving symptoms and bladder capacity in patients with interstitial cystitis. However, higher doses appear to increase the risk of postoperative voiding dysfunction and urinary retention. The use of intradetrusor OBA for this indication remains investigational.[100, 101, 102]

Multicenter trials investigating OBA use for refractory IC/BPS have shown significant benefit in a small number of patients, but overall no improvement in O'Leary-Sant scores.[103]

Other long-term studies have shown improvements in pain scores, with symptom relief lasting from 6-12 months, with an average duration of relief of 9.9 months.[104] Evidence indicates that location of injection of OBA is important. In a small 2011 study, investigators attempted to block urethral visceral afferent fibers with OBA. No improvement in pain symptoms was noted.[105] This is in contrast to other studies, in which OBA was injected directly into the detrusor muscle or trigone.[104] Unfortunately, the heterogeneity of studies with OBA has prevented effective meta-analysis, despite these studies suggesting a trend toward short-term benefit.[106]

Potential mechanisms for the effectiveness of OBA include down-regulation of vascular endothelial growth factor (VEGF) and an afferent sensory effect.[107]

Rarely indicated surgical therapies include the following:

  • Laser photoradiation (poor results)

  • Electrical stimulation

  • Transcutaneous electrical nerve stimulatio (TENS; more marked effect on bladder pain than on urinary frequency)

  • Peripheral denervation (rarely indicated)

  • Bladder augmentation (controversial because pain usually does not improve)

  • Urinary diversion (most invasive; usually reserved as last resort)

Indications for urinary tract reconstruction or urinary diversion are very limited in patients with interstitial cystitis. Candidates for these procedures should have exhausted all reasonable and available medical, pharmacologic, and behavioral therapies for their condition. They should also understand that even technically successful urinary tract reconstruction or urinary diversion still may not relieve the underlying symptoms of pain and urinary urgency.

Some studies have investigated a role for diversion in the absence of cystectomy as a therapy. Norus et al showed that no differences in symptoms were reported in patients who underwent ileal conduit after cystectomy compared with those who underwent ileal conduit without cystectomy, suggesting this as an appropriate option in carefully selected patients.[108] In a study by Peters in 2013, 10 women with previous ulcerative IC/BPS underwent cystectomy and urinary diversion (1 with a neobladder, 9 with ilealconduit). Despite 6 of the patients requiring reoperation, 8 of 9 reported significant improvements in quality of life and would make the same decision again. IC/BPS pain had resolved in 8 of 9 respondents in follow-up surveys.[21]

Surgeons should be reminded, however, that significant improvements were seen in those with ulcerative IC/BPS, and results in those with nonulcerative disease had poorer outcomes.[109]

However, as these therapies are highly invasive and evidence in the literature is composed only of very small studies, they should be reserved for patients who have been extensively counseled and in whom prior therapies have failed. As severe, refractory IC/BPS is considered by some to be an "orphan disease," treatments should be tailored to the individual to offer the best chance for a successful outcome.[109]

These reconstructive procedures are large surgical undertakings and, for the most part, are irreversible. Only limited success has been reported; thus, patients should be extensively counseled prior to undergoing this type of surgical therapy for interstitial cystitis.

 

Guidelines

Guidelines Summary

Guidelines of the diagnosis and management of interstitial cystitis/bladder pain syndrome (IC/BPS) have been issued by the following organizations:

  • American Urological Association (AUA)
  • Canadian Urologica Association (CUA)

The AUA evidence-based guidelines were initially published in 2011 and subsequently amended in 2014.[3] The Canadian Urological Association issued its evidenced-based guideline in 2016.[4]

Diagnosis

Tha AUA recommendations for diagnosis are as follows[3] :

  • A basic assessment that includes history, physical examination, and laboratory testing should be conducted both to confirm the presence of symptoms characteristic of IC/BPS and to rule out other conditions
  • Baseline voiding symptoms and pain levels should be documented, for use in assessment of response to treatment
  • Cystoscopy and/or urodynamics should not be used routinely but should be considered for complex presentations

The CUA recommendations are in agreement with AUA that all evauations should begin with history, physical examination, and laboratory testing and that baseline voiding and pain levels should be used to track response to treatment. However, the CUA recommends that cystoscopy be performed for most patients, to do the following[4] :

  • Rule out bladder cancer/carcinoma in situ
  • Identify Hunner lesions
  • Determine the effect of bladder filling and emptying on pelvic pain
  • Evaluate functional bladder capacity
  • Facilitate pelvic examination
  • Reassure the patient

The CUA considers cystoscopy optional only for young women with symptoms of IC/BPS but no risk factors for bladder cancer or other pelvic conditions.[4]

Additional CUA recommendations include the following[4] :

  • Ultrasound and/or other pelvic imaging is optional to rule out alternative clinical disorders, required for patients with hematuria
  • Optional intravesical anesthetic bladder challenge testing after cystoscopy to provide both relief to the patient, as well as provide diagnostic information and guide future therapy
  • Hydrodistension in select patients such as women unable to tolerate cystoscopy under local anesthesia

The AUA and CUA guidelines agree that urodynamics and bladder biopsy should not be used in routine care. Both guidelines recommend against potassium sensitivity diagnostic testing.[3, 4]

Treatment

Both guidelines offer treatment algorithms that begin with conservative management and progress to less conservative therapies if symptoms are not adquately controlled.[3, 4]

Overall management

Key AUA guideline recommendations for disease management include the following[3] :

  • Consider surgical treatments (other than fulguration of Hunner lesions) only after other treatment alternatives have been exhausted, or in the rare instance when an end-stage, small, fibrotic bladder has been confirmed and the patient's quality of life suggests a positive risk-benefit ratio for major surgery
  • Initial treatment type and level should depend on symptom severity, clinician judgment, and patient preferences
  • Multiple, simultaneous treatments may be considered if that is in the best interests of the patient
  • Baseline symptom assessment and regular re-assessment are required to gauge the efficacy of single and combined treatments
  • Treatments that fail to demonstrate efficacy should be stopped once a clinically meaningful interval has elapsed
  • Pain management should be continually assessed because of its importance to quality of life; if pain management is inadequate, consideration should be given to a multidisciplinary approach and the patient referred appropriately
  • The IC/BPS diagnosis should be reconsidered if no improvement occurs after multiple treatment approaches

Treatments that may be offered

The AUA guidelines divides treatments that can be offered into first-, second-, third, fourth-, fifth-, and sixth-line groups, based on the balance between potential benefits to the patient, potential severity of adverse events, and the reversibility of the treatment.[3] While the CUA guidelines are in general agreement regarding first-line treatment, subsequent treatments are not characterized in a detailed hierarchy.[4]

First-line treatments should be performed on all patients and include the following[3, 4] :

  • Patient education 
  • Self-care practices and behavioral modifications that can improve symptoms 
  • Stress management practices to improve coping techniques and manage stress-induced symptom exacerbations. 

In addition, the CUA recommends dietary restrictions of common food triggers for a period of 1 week to 3 months, with re-introduction of one item at a time and a waiting period of 3 days to identify potential offenders[4]

AUA second-line treatment recommentations include the following[3] :

  • Appropriate manual physical therapy techniques should be offered, if trained clinicians are available; however, pelvic floor strengthening exercises (eg, Kegel exercises) should be avoided
  • Multimodal pain management 
  • Amitriptyline, cimetidine, hydroxyzine, or pentosan polysulfate (PPS)
  • Dimethyl sulfoxide (DMSO), heparin, or lidocaine

CUA guidelines recommend pelvic floor physiotherapy for patients with pelvic floor muscle dysfunction (PFD). Massage, acupuncture, and trigger point injections are optional for patients with pelvic floor tenderness. 

The CUA recommends amitriptyline, cimetidine, hydroxyzine, or PSS as options after conservative therapies have failed, but notes that there is conflicting evidence of the effectiveness of PPS and expected benefits may be marginal in the majority of patients. In addition, CUA recommends gabapentin and quercetin, although evidence is weak.[4]

The CUA guidelines concur with the recommendations for DMSO, heparin and lidocaine.[4]

AUA third-line treatment recommentations include the following[3] :

  • Cystoscopy under anesthesia with short-duration, low-pressure hydrodistension 
  • If Hunner lesions are present, fulguration (with laser or electrocautery) and/or injection of triamcinolone 

AUA fourth-line treatment recommentations include the following[3] :

  • Intradetrusor botulinum toxin A (BTX-A); post-treatment intermittent self-catheterization may be required
  • A trial of neurostimulation may be performed and, if successful, implantation of permanent neurostimulation devices 

Overall, CUA guidelines concur with the AUA third- and fourth-line treatment recommendations. The guidelines do note that sacral neuromodulation (SNM) is not yet approved by Health Canada or the US Food and Drug Administration (FDA) for the treatment of IC/BPS, but is indicated for urgency frequency syndrome and urgency urinary incontinence.[4]

Cyclosporine is recommended by AUA as a fifth-line treatment[3] . CUA guidelines agree that due to its adverse side effects, cyclosporine should be considered a last resort in patients with inflammation and refractory disease. Close monitoring, including measurement of blood pressure, creatinine, and cyclosporine levels, is required.[4]

According to AUA, major surgery (eg, substitution cystoplasty, urinary diversion with or without cystectomy) is a sixth-line treatment for carefully selected patients for whom all other therapies have failed to provide adequate symptom control and quality of life.[3]  After weighing the invasiveness of surgery, the benign nature of IC/BPS, and multiple other treatment options available, the CUA concluded that major surgery should only be considered as an absolute last resort.[4]  

Treatments that should not be offered

The AUA recommends against the following treatments, due to a lack of evidence of efficacy, unacceptable adverse event profiles, or both[3] :

  • Long-term oral antibiotic administration 
  • Intravesical instillation of bacillus Calmette-Guerin (BCG) outside of clinical studies
  • High-pressure, long-duration hydrodistension 
  • Systemic long-term glucocorticoid administration 
 

Medication

Medication Summary

The goal of pharmacologic therapy in interstitial cystitis is to relieve symptoms. Medication may be administered orally or intravesically. Urinary analgesics include pentosan polysulfate sodium. (One report suggests a beneficial role for oral cimetidine.) Other agents used with less success include the following:

  • L-arginine
  • Nalmefene
  • Anticholinergic agents (eg, oxybutynin, oxybutynin XL, tolterodine [Detrol and Detrol LA])
  • Hyoscyamine
  • Corticosteroids
  • Antispasmodics
  • Immunosuppressives
  • Anti-inflammatory medications
  • Calcium channel blockers

Antihistamines, 1st Generation

Class Summary

Antihistamines inhibit binding to the H1 histamine receptor.

Hydroxyzine (Vistaril)

Hydroxyzine is an H1 histamine receptor blocker that may inhibit mast cell secretion and may suppress histamine activity in the subcortical region of the central nervous system (CNS). Adult dosing is 25-75mg/day orally. Hydroxyzine is a pregnancy category C drug.

Antidepressants, TCAs

Class Summary

Tricyclic antidepressants are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. They have central effects on pain transmission. They block the active reuptake of norepinephrine and serotonin.

Amitriptyline

Amitriptyline is an oral tricyclic antidepressant that inhibits reuptake of serotonin and/or norepinephrine at the presynaptic neuronal membrane, which increases concentration in the CNS. It may have anticholinergic and sedative effects. Adult dosing is 25-75 mg orally at bedtime. Amitriptyline is a pregnancy category D drug.

Analgesics, Urinary

Class Summary

Urinary analgesics relieve pain locally.

Pentosan polysulfate sodium (Elmiron)

Pentosan polysulfate sodium is a negatively charged, synthetic sulfated polysaccharide with an affinity for mucosal membranes. It repletes defects in the glycosaminoglycan layer. Adult dosing is 100mg orally 3 times daily. Pentosan polysulfate sodium is a pregnancy category B drug.

Urologics, Other

Class Summary

Instillation therapy may use dimethyl sulfoxide (DMSO). It may also use cauterizing agents for the removal of granulation tissue and dermatologic agents for their cleansing and disinfection and for the removal of necrotic debris.

Dimethyl sulfoxide (Rimso-50)

Dimethyl sulfoxide (DMSO) provides anti-inflammatory action, membrane penetration, antifungal activity, cryoprotective effects for living cells and tissues, collagen dissolution action, mast cell stimulation, nerve blockade, diuresis, cholinesterase inhibition, vasodilation, and muscle relaxation. It may be combined with heparin, steroids, or bicarbonate. In adults, instill 50mL of aqueous 50% solution directly into the bladder by catheter or Asepto syringe and allow it to remain for 20 minutes. DMSO is a pregnancy category X drug.

Antibacterials, Topical

Class Summary

Antimicrobials with antiseptic and astringent qualities may reduce morbidity.

Silver nitrate

Silver nitrate is used for its caustic, antiseptic, and astringent qualities. In adults, administer concentrations ranging from 1:5000 to 2% intravesically for 2-10 minutes. Silver nitrate is a pregnancy category C drug.

Oxychlorosene (Clorpactin WCS-90)

Sodium oxychlorosene exerts detergent action on bladder mucosa. It is reserved for patients in whom DMSO or silver nitrate instillations fail. In adults, administer 0.4% solution intravesically for 2-3 minutes at 60-80cm water pressure (4-6 treatments weekly). Sodium oxychlorosene is a pregnancy category C drug.

Anticoagulants, Hematologic

Class Summary

Anticoagulants prevent recurrent or ongoing thromboembolic occlusion of the vertebrobasilar circulation.

Heparin

Polysaccharide glycosaminoglycans may exert a protective effect on the bladder. Heparin has been shown to reduce relapses in patients who respond to DMSO. It is an analogue to the polysaccharide glycosaminoglycan lining of the bladder. Adult dosing is 10,000U intravesically in 10mL sterile water monthly. Polysaccharide glycosaminoglycans are pregnancy category C drugs.

 

Questions & Answers

Overview

What is interstitial cystitis/bladder pain syndrome (IC/BPS)?

How does the International Continence Society define interstitial cystitis/bladder pain syndrome (IC/BPS)?

How is interstitial cystitis/bladder pain syndrome (IC/BPS) diagnosed?

What biomarkers have been identified for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the most promising urinary biomarker for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is goal of treatment for interstitial cystitis/bladder pain syndrome (IC/BPS)?

How is response to treatment assessed in interstitial cystitis/bladder pain syndrome (IC/BPS)?

When was the first description of interstitial cystitis/bladder pain syndrome (IC/BPS) published?

What is the pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of the transitional cell apical membrane of the bladder in the pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of histaminergic and muscarinic neurotransmitter receptors in the pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the subgroups of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the characteristics of ulcerative interstitial cystitis (IC)?

What are the characteristics of nonulcerative interstitial cystitis (IC)?

What are the possible etiologies of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What evidence supports a genetic role in the etiology of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which clinical history suggests interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which autoimmune conditions are associated with interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which psychiatric conditions are associated with interstitial cystitis/bladder pain syndrome (IC/BPS)?

Why is it difficult to determine the prevalence of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the prevalence of interstitial cystitis/bladder pain syndrome (IC/BPS) in women in the US?

What is the global prevalence of interstitial cystitis/bladder pain syndrome (IC/BPS) in women?

Which patient groups is at highest risk for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the prevalence of interstitial cystitis/bladder pain syndrome (IC/BPS) among men and children?

What is the prognosis of interstitial cystitis (IC)?

What is the response of interstitial cystitis/bladder pain syndrome (IC/BPS) to treatment?

How does interstitial cystitis/bladder pain syndrome (IC/BPS) affect quality of life?

How does education and counseling affect the prognosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which associations provide patient support for interstitial cystitis/bladder pain syndrome (IC/BPS)?

Where can patient information on interstitial cystitis/bladder pain syndrome (IC/BPS) be found?

Presentation

What is the typical presentation of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the disease course of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the most prevalent feature of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS) can be reproduced urodynamically or with cystography?

What is the presentation of interstitial cystitis/bladder pain syndrome (IC/BPS) in men?

What are common comorbidities of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the significance of sleep difficulties in women with interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of questionnaires in the diagnosis of interstitial cystitis (IC)?

Which questionnaires have been validated for use in the evaluation of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the Pelvic Pain and Urgency/Frequency Patient Symptom Scale for interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which exams should be performed in the evaluation of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which physical findings may suggest diagnoses other than interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is included in the full exam of patients with suspected interstitial cystitis/bladder pain syndrome (IC/BPS)?

How is interstitial cystitis/bladder pain syndrome (IC/BPS) differentiated from provoked vestibulodynia disorder (PVD)?

How is provoked vestibulodynia disorder (PVD) treated?

Which physical findings are characteristic of interstitial cystitis/bladder pain syndrome (IC/BPS) in males?

What are the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) diagnostic criteria for interstitial cystitis (IC)?

What are the cystoscopic diagnostic criteria for interstitial cystitis (IC)?

What are subjective symptoms of interstitial cystitis (IC)?

What are the diagnostic exclusion criteria for interstitial cystitis (IC)?

DDX

How is interstitial cystitis/bladder pain syndrome (IC/BPS) diagnosed?

What is needed for a diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the differential diagnoses of interstitial cystitis/bladder pain syndrome (IC/BPS) associated with urinary frequency, urgency, and/or pain?

What are the differential diagnoses of interstitial cystitis/bladder pain syndrome (IC/BPS) associated with infectious or inflammatory conditions?

What are the gynecologic conditions included in the differential diagnoses of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the urologic conditions included in the differential diagnoses of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the neurologic conditions included in the differential diagnoses of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which GI conditions are included in the differential diagnoses of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Workup

When is the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS) most often made?

What is the role of cystoscopy in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of urodynamic evaluation in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of imaging studies in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which findings on MRI are characteristic of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of cystography and voiding cystourethrography in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of urethral and vaginal culture in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which assays are used in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of expressed prostatic secretions for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of cystoscopy in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

How is cystoscopy performed for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

How are ulcers of bladder mucosa and areas with angiogenesis detected in the evaluation of interstitial cystitis/bladder pain syndrome (IC/BPS)?

How is diagnostic hydrodistention performed in the evaluation of interstitial cystitis/bladder pain syndrome (IC/BPS)?

How is hydrodistention performed in the evaluation of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which findings from hydrodistention indicate interstitial cystitis/bladder pain syndrome (IC/BPS)?

How is a finding of glomerulations characterized in interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the diagnostic significance of a finding of glomerulations in the evaluation of interstitial cystitis/bladder pain syndrome (IC/BPS)?

In which bladder conditions are glomerulations seen?

How does hydrodistention affect the symptom of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of biopsy in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the pathognomonic histologic findings characteristic of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which histologic finding is diagnostic of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of potassium sensitivity testing in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of urine studies in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of urodynamic studies in the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Treatment

What are the challenges of treating interstitial cystitis/bladder pain syndrome (IC/BPS) in a primary care setting?

What is the treatment approach for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the treatment options for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of alternative, holistic, or complementary therapies in the treatment interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of counseling in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are behavioral treatment options for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the duration of behavioral therapy for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of diet in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which foods may be aggravating factors in interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of a food diary in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are theories for dietary exacerbations in interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which foods have been identified as least aggravating for patients with interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of medications in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the duration of drug treatment for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of pentosan polysulfate sodium in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of amitriptyline in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of anticholinergic agents in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of cyclosporine in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of mycophenolate mofetil (MMF) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of tanezumab in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of cimetidine in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the AUA treatment algorithm used for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the treatment algorithm for interstitial cystitis/bladder pain syndrome (IC/BPS) in patients with significant voiding symptoms?

What is the role of pentosan polysulfate sodium in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

How is pain managed in patients with interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which agents are used for pain relief in interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of narcotics in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are nonpharmacologic options for pain relief in interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the treatment options for interstitial cystitis/bladder pain syndrome (IC/BPS) if medical therapy fails?

What is the role of intravesical therapy for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of capsaicin in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of resiniferatoxin in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of hyaluronic acid in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the efficacy of hyaluronic acid in combination with hydrodistention for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of chondroitin sulfate in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of intravesical bacillus Calmette-Guérin (BCG) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of intravesical liposomes in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the use of hyperbaric oxygen in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of bladder hydrodistention in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the mechanism of action of hydrodistention for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of surgery in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of sacral neuromodulation in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the efficacy of sacral neuromodulation in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the indications for sacral neuromodulation in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of pudendal nerve stimulation in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of botulinum toxin in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of intradetrusor onabotulinumtoxinA (OBA) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the efficacy of intradetrusor onabotulinumtoxinA (OBA) for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are potential mechanisms for the effectiveness of intradetrusor onabotulinumtoxinA (OBA) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which surgical therapies are used rarely in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of urinary tract reconstruction or urinary diversion in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the role of diversion in the absence of cystectomy in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the limitations to reconstructive procedures for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Guidelines

Which organizations have issued guidelines for the diagnosis and management of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the American Urological Association (AUA) recommendations for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the Canadian Urological Association (CUA) recommendations for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are additional Canadian Urological Association (CUA) recommendations for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What do both the American Urological Association (AUA) and the Canadian Urological Association (CUA) recommend against for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which guidelines include an algorithm for treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the American Urological Association (AUA) treatment guidelines for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What is the American Urological Association (AUA) hierarchy for interstitial cystitis/bladder pain syndrome (IC/BPS) treatments?

What are the guidelines recommended first-line treatments for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the CUA recommended dietary restrictions for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the American Urological Association (AUA) second-line treatment recommendations for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the Canadian Urological Association (CUA) second-line treatment recommendations for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the American Urological Association (AUA) third-line treatment recommendations for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the American Urological Association (AUA) fourth-line treatment recommendations for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the Canadian Urological Association (CUA) third- and fourth-line treatment recommendations for interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are guidelines for the use of cyclosporine in interstitial cystitis/bladder pain syndrome (IC/BPS)?

What are the American Urological Association (AUA) recommendations for surgery to treat interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which treatments for interstitial cystitis/bladder pain syndrome (IC/BPS) are recommended against by the AUA?

Medications

Which medications are used in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS)?

Which medications in the drug class Anticoagulants, Hematologic are used in the treatment of Interstitial Cystitis?

Which medications in the drug class Antibacterials, Topical are used in the treatment of Interstitial Cystitis?

Which medications in the drug class Urologics, Other are used in the treatment of Interstitial Cystitis?

Which medications in the drug class Analgesics, Urinary are used in the treatment of Interstitial Cystitis?

Which medications in the drug class Antidepressants, TCAs are used in the treatment of Interstitial Cystitis?

Which medications in the drug class Antihistamines, 1st Generation are used in the treatment of Interstitial Cystitis?