Interstitial cystitis, also known as bladder pain syndrome, is noninfectious bladder inflammation that causes pain (suprapubic, pelvic, and abdominal), urinary frequency, and urgency with incontinence. Diagnosis is by history and exclusion of other disorders clinically and by testing as needed. With treatment, most patients improve, but cure is rare. Treatment varies but includes dietary changes, bladder training, oral medications (eg, amitriptyline, pentosan, nonsteroidal anti-inflammatory drugs), and intravesical therapies.
Incidence of interstitial cystitis is unknown, but the disorder appears to be more common than once thought and may underlie other clinical syndromes (eg, chronic pelvic pain). White people are more susceptible, and 90% of cases occur in women (1). However, these demographic patterns may reflect disparities in access to care, referral practices, and diagnostic recognition rather than true biologic susceptibility.
The cause is unknown, but pathophysiology may involve loss of protective urothelial mucin, with penetration of urinary potassium and other substances into the bladder wall, activation of sensory nerves, and smooth muscle damage. Mast cells may mediate the process, but their role is unclear. (See also Overview of Voiding.)
General reference
1. Propert KJ, Schaeffer AJ, Brensinger CM, Kusek JW, Nyberg LM, Landis JR. A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. The Interstitial Cystitis Data Base Study Group. J Urol. 2000;163(5):1434-1439. doi:10.1016/s0022-5347(05)67637-9
Symptoms and Signs of Interstitial Cystitis
Interstitial cystitis is initially asymptomatic, but symptoms appear and worsen over years as the bladder wall is damaged. Suprapubic and pelvic pressure or pain occurs, usually with urinary frequency (up to 60 times/day) or urgency. These symptoms worsen as the bladder fills and diminish when patients void; in some people, symptoms worsen during ovulation, menstruation, seasonal allergies, physical or emotional stress, or sexual intercourse. Foods with high potassium content (eg, citrus fruits, chocolate, caffeinated drinks, tomatoes) may cause exacerbations. Tobacco, alcohol, and spicy foods may worsen symptoms. If the bladder wall becomes scarred, bladder compliance and capacity decrease, causing or worsening urinary urgency and frequency.
Diagnosis of Interstitial Cystitis
History and physical examination
Additional testing to exclude other conditions (eg,urinalysis, urine culture)
Cystoscopy with possible biopsy in selected patients to exclude other conditions with similar symptoms
Diagnosis is suggested by symptoms after testing (eg, urinalysis) has excluded more common disorders that cause similar symptoms (eg, urinary tract infections [UTI], pelvic inflammatory disease, chronic prostatitis or prostatodynia, diverticulitis) (1). Assessment of symptoms with a standardized symptom scale, such as the genitourinary pain index (GUPI) (2), the interstitial cystitis symptom index (ICS) (3), or visual analog scale (VAS) is helpful to establish baseline values and evaluate treatment .
Cystoscopy is not necessary to make the diagnosis of interstitial cystitis in uncomplicated cases, but should be considered if the diagnosis is unclear (1). Cystoscopic examination is useful in excluding urologic conditions that share signs and symptoms of interstitial cystitis and sometimes reveals benign bladder (Hunner) ulcers; biopsy of Hunner ulcers, when identified, is required to exclude bladder cancer. Urodynamic studies are also not routinely indicated but should be considered if outlet obstruction is suspected and in patients who do not respond to behavioral or medical therapies.
Diagnosis references
1. Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome. J Urol. 2022;208(1):34-42. doi:10.1097/JU.0000000000002756
2. Clemens JQ, Calhoun EA, Litwin MS, et al. Validation of a modified National Institutes of Health chronic prostatitis symptom index to assess genitourinary pain in both men and women. Urology. 2009;74(5):983-987.e9873. doi:10.1016/j.urology.2009.06.078
3. O'Leary MP, Sant GR, Fowler FJ Jr, Whitmore KE, Spolarich-Kroll J. The interstitial cystitis symptom index and problem index. Urology. 1997;49(5A Suppl):58-63. doi:10.1016/s0090-4295(99)80333-1
Treatment of Interstitial Cystitis
Nonpharmacologic interventions (behavioral interventions, education, stress management, manual physical therapy techniques
Medications (eg, amitriptyline, pentosan polysulfate sodium, nonsteroidal anti-inflammatory drugs [NSAIDs], cimetidine, hydroxyzine) Medications (eg, amitriptyline, pentosan polysulfate sodium, nonsteroidal anti-inflammatory drugs [NSAIDs], cimetidine, hydroxyzine)
Intravesical instillations (dimethyl sulfoxide, heparin, lidocaine)Intravesical instillations (dimethyl sulfoxide, heparin, lidocaine)
Procedures (eg, cystoscopy with hydrodistention)
Surgery for refractory symptoms
Choice of treatment
The treatment is individualized and typically involves a multimodal approach. Options include lifestyle or behavioral modifications, oral medications, intravesical instillations, procedures (eg, cystoscopy with hydrodistention), and rarely surgery (1). Surgery is considered in selected patients who have exhausted all other options.
Nonpharmacologic (or behavioral) interventions
While most patients improve with treatment, cure is rare. Treatment should involve education about normal bladder function, encouraging awareness of what is known and unknown about interstitial cystitis, and avoidance of potential triggers, such as tobacco, alcohol, foods with high potassium content, and spicy foods. Stress management techniques are useful to develop coping strategies to minimize stress-induced symptom exacerbation.
Manual physical therapy techniques such as massage and trigger point release in patients with pelvic floor muscle tenderness may help. Pelvic floor strengthening exercises (eg, Kegel exercises) are not recommended.
Pharmacotherapy
Oral medications that may be used include amitriptyline, pentosan polysulfate sodium, cimetidine, and hydroxyzine. No single medication has demonstrated superiority over another, and the choice is based on patient tolerance, preferences, and comorbidities (that may be used include amitriptyline, pentosan polysulfate sodium, cimetidine, and hydroxyzine. No single medication has demonstrated superiority over another, and the choice is based on patient tolerance, preferences, and comorbidities (2). Amitriptyline has demonstrated superiority over placebo for symptom improvement, but its use is often limited by adverse effects such as sedation and nausea. Pentosan polysulfate sodium may theoretically help replenish the bladder’s protective surface lining based on its proposed mechanism as a synthetic glycosaminoglycan analog, but this has not been proven. Improvement may not be noticed for 2 to 4 months, and there is risk of macular damage. Patients should have an ophthalmologic history prior to starting pentosan polysulfate sodium, and periodic retinal examinations are advised (1). Antihistamines may help by directly inhibiting mast cells or by blocking allergic triggers. Cimetidine may work by affecting histamine H2 receptors in the bladder to help reduce inflammation and pain.
Oral analgesics such as NSAIDs in standard doses may relieve pain.
Intravesical instillation of 15 mL of a solution containing pentosan, heparin, and lidocaine may benefit patients who are unresponsive to oral medications. Dimethyl sulfoxide instilled into the bladder through a catheter and retained for 15 minutes may deplete substance P and trigger mast cell granulation.of 15 mL of a solution containing pentosan, heparin, and lidocaine may benefit patients who are unresponsive to oral medications. Dimethyl sulfoxide instilled into the bladder through a catheter and retained for 15 minutes may deplete substance P and trigger mast cell granulation.
Intravesical hyaluronic acid is under study.
Procedures and major surgery
Cystoscopy with hydrodistention, cystoscopic resection of a Hunner ulcer, and sacral nerve root (S3) stimulation may help some patients.
Surgery (eg, partial cystectomy, bladder augmentation, neobladder reconstruction, and urinary diversion) is reserved for patients with intolerable pain refractory to all other treatments. Outcome is unpredictable; in some patients, symptoms persist.
Treatment references
1. Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome. J Urol. 2022;208(1):34-42. doi:10.1097/JU.0000000000002756
2. Imamura M, Scott NW, Wallace SA, et al. Interventions for treating people with symptoms of bladder pain syndrome: a network meta-analysis. Cochrane Database Syst Rev. 2020;7(7):CD013325. doi:10.1002/14651858.CD013325.pub2
Key Points
Interstitial cystitis is noninfectious bladder inflammation that may cause chronic pelvic pain and urinary frequency.
Diagnosis requires exclusion of other causes for symptoms (eg, UTIs, pelvic inflammatory disease, chronic prostatitis or prostatodynia, diverticulitis).
Cystoscopy and biopsy may be helpful to exclude conditions that may mimic interstitial cystitis.
Cure is rare, but most patients improve with treatment.
Treatments can include diet modification, physical therapy, and medications (eg, amitriptyline, pentosan polysulfate sodium, antihistamines such as hydroxyzine, cimetidine, dimethyl sulfoxide instillation, NSAIDs).Treatments can include diet modification, physical therapy, and medications (eg, amitriptyline, pentosan polysulfate sodium, antihistamines such as hydroxyzine, cimetidine, dimethyl sulfoxide instillation, NSAIDs).
Surgery is reserved for patients with intolerable pain refractory to all other treatments.
