The International Continence Society defines bladder pain syndrome, otherwise known as interstitial cystitis (IC), as a clinical syndrome consisting of suprapubic pain related to bladder filling and accompanied by other symptoms, such as increased daytime and nighttime frequency in the absence of proven infection or other obvious pathology.¹ The American Urological Association defines interstitial cystitis/bladder pain syndrome (IC/BPS) as an unpleasant sensation perceived to be related to the urinary bladder that is associated with lower urinary tract symptoms >6 wk duration, in the absence of infection or other unidentifiable causes.²

Interstitial cystitis

Interstitial cystitis/bladder pain syndrome (IC/BPS)

Painful bladder syndrome

Tic douloureux of bladder

• Urinary urgency, frequency (>8 in daytime), nocturia (>2 at night), and suprapubic pain are the most common symptoms
• Suprapubic pain is worse with bladder filling or urinating and relieved after emptying
• Dyspareunia and sexual dysfunction
• Symptoms lasting longer than 6 mo
• Intensity of symptoms waxes and wanes
• Insidious onset and worsens to the final stage within 5 to 15 yr
• Exercise, stress, sexual activity, ejaculation, certain foods with high potassium and acids (e.g., beer, spices, bananas, tomatoes, chocolate, strawberries, artificial sweeteners, oranges, cranberries, caffeine), menstruation, prolonged sitting, and activation of allergies exacerbate the symptoms
• Often associated with irritable bowel syndrome, migraine, endometriosis, skin sensitivities, multiple drug allergies, other allergies, vulvodynia, fibromyalgia, chronic fatigue syndrome, systemic lupus erythematosus, and mood disorders
• Dysphoric mood
• Lower abdominal tenderness
• Tender prostate in digital rectal examination
• Levator ani tenderness in female
• Tenderness of anterior vaginal wall/bladder neck in female

Unknown. Fig. E1 illustrates a hypothesis for etiologic cascade of painful bladder syndrome/interstitial cystitis.^1,2,6

• Chronic pelvic pain
• Overactive bladder
• Recurrent urinary tract infection
• Endometriosis
• Pelvic adhesions
• Vulvar vestibulitis
• Vulvodynia
• Urethral pain syndrome
• Chronic nonbacterial prostatitis
• Frequent vaginitis
• Benign prostatic hyperplasia

• IC can be considered a diagnosis of exclusion when no known cause of painful bladder can be identified.
• There is no definite diagnostic test.
• Validated questionnaires such as Pelvic Pain and Urgency/Frequency scale (PUF), O’Leary-Sant symptoms and problem index, and Wisconsin IC scale. PUF is the most commonly used.
• Voiding diary shows low-volume (<100 ml) and high-frequency voiding pattern.
• National Institute of Diabetes and Diseases of the Kidney diagnostic criteria misses 60% of IC patients and is not clinically used anymore.
• Anesthetic bladder challenge: Diagnostic test in which symptoms dissipate on instillation of an anesthetic cocktail into the bladder.
• Cystoscopy and hydrodistention under general anesthesia may show terminal hematuria (Fig. E2), glomerulation, Hunner ulcers (Fig. E3), and small bladder capacity of less than 350 ml. Cystoscopy and/or urodynamic testing should be considered when the diagnosis is in doubt, but the tests are not necessary to confirm an IC/BPS diagnosis in uncomplicated cases.
• Bladder biopsy is not essential for diagnosis of IC.
• Parson potassium sensitivity test (PST).
• Urodynamics are unnecessary in diagnosis of IC.

• Urine analysis and culture.
• Urine cytology should be performed if microscopic or gross hematuria is present, or with other risk factors such as smoking, age >40 yr, and other bladder cancer risk factors.
• Culture of sexually transmitted diseases if clinically indicated. Nonbacteriuric patients with pyuria should be screened for Chlamydia.
• Urine biomarkers (e.g., antiproliferative factor) are promising but not ready for clinical use.

CT or ultrasound of abdomen and pelvis may be considered to rule out other pathology.

• Avoidance of activities associated with flare-ups
• Avoidance of smoking
• Dietary restriction (Box E1), avoiding common irritants (e.g., coffee, citrus fruits)
• Physical therapy
• Exercise
• Behavioral therapy
• Bladder retraining
• Biofeedback
• Warm sitz bath, ice, heating pad
• Thiele massage (transrectal and transvaginal manual therapy of pelvic floor muscle) in presence of pelvic floor muscle tenderness and spasm
• Hydrodistention only gives temporary relief, so it is not commonly used anymore

• A course of empiric antibiotics if not tried yet. Long-term oral antibiotics are not recommended.
• Oral therapy is tried first.
• Pentosan polysulfate sodium (Elmiron) is the only FDA-approved and most effective oral therapy.
• Elmiron is associated with potential risk of macular damage, and therefore baseline retinal examination is recommended.
• Most treatment takes 3 to 6 mo before maximum benefit is seen.
• Adjunct oral therapy includes tricyclic antidepressants (amitriptyline), cimetidine, antihistaminics (hydroxyzine, montelukast), neuroleptics (gabapentin, topiramate), analgesics (NSAIDs, opioid analgesics), and occasionally antimuscarinics.
• Oral therapies can be used in combination.
• Antihistaminics are preferred for patients with an allergy history or those who show mast cells in bladder biopsy.
• Oral prednisone is used in presence of Hunner ulcers.
• Hunner lesions may require fulguration with laser/cautery and/or intralesional injection of triamcinolone.
• Other drugs rarely used for IC are cyclosporin A, interleukin-10, imatinib, methotrexate, suplatast, misoprostol, and quercetin.
• Growth factor inhibitors, gene therapy, RDP 58, and vitamin B₃ analogue (BXL 628) may represent future therapies.
• Intravesical treatment is used when oral medications fail, for acute flare-ups, or before the oral medications take full effect.
• Dimethyl sulfoxide (DMSO), heparin, lidocaine, hyaluronic acid, capsaicin, botulinum toxin A, chondroitin sulfate, steroids, and Elmiron are drugs used for intravesical treatment.
• DMSO is the only FDA-approved intravesical treatment.
• DMSO is used less often now because of its side effects, specifically a garlic-like odor or taste on breath or skin that lasts 72 h after treatment.
• Intravesical therapy typically involves mixture of heparin or Elmiron with lidocaine and sodium bicarbonate.
• Silver nitrate and Clorpactin have fallen out of favor.

• Major surgical intervention is not the mainstay of treatment.
• Patients whose condition is extreme with compromised quality of life may consider surgery (e.g., urinary diversion with or without cystectomy) if medications fail.
• Sacral neuromodulation (InterStim) is the current preferred surgical intervention.
• Laser ablation, fulguration, or resection is offered when Hunner ulcers are seen in cystoscopy.
• Augmentation cystoplasty is not recommended.
• Cystourethrectomy with urinary diversion is rarely done.

• Transcutaneous electric nerve stimulation
• Intravaginal electric nerve stimulation
• Acupuncture
• Urinary chelating agents such as Polycitra-K crystals, Urocit-K
• Prelief, an over-the-counter food additive
• Herbal remedies such as Algonot Plus, CystoProtek, Cysta-Q, aloe vera

Voiding diary and symptom questionnaire are helpful to monitor response to treatment.

• Urologist
• Pain specialist
• Physical therapist

• On average, these patients see five physicians and endure irritating voiding symptoms for 5 yr before the disease is identified.
• Besides symptom questionnaire and urine analysis, all other diagnostic tests are optional.
• PST is well tolerated.
• Negative cystoscopy does not rule out IC.

Early identification and timely intervention improve patient outcomes.

• IC support groups
• Interstitial Cystitis Association
• Interstitial Cystitis Network