Basic Information

Definition

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. 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 weeks’ duration, in the absence of infection or other unidentifiable causes.

Synonyms

• Interstitial cystitis/bladder pain syndrome (IC/BPS)
• Painful bladder syndrome
• Tic douloureux of bladder

Epidemiology & Demographics

Incidence

21 cases per 100,000 women and four cases per 100,000 men annually

Prevalence

• 197 per 100,000 women and 41 per 100,000 men in the U.S.
• Because the disease is substantially underdiagnosed, it may actually affect one in five women and one in 20 men.
• More than 81% of women diagnosed with chronic pelvic pain and up to 84% of men initially diagnosed with chronic prostatitis actually have IC.
• More than 90% of patients diagnosed with overactive bladder who do not respond to anticholinergics are subsequently diagnosed with IC.

Predominant Sex and Age

• White women constitute 95% of patients with IC.
• Female/male ratio of 5 to 10:1.
• Most prevalent in fourth and fifth decades of life.

Physical Findings & Clinical Presentation

• 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.
• 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 (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.

Etiology

Unknown. Fig. 1 illustrates a hypothesis for etiologic cascade of painful bladder syndrome/interstitial cystitis.

Differential Diagnosis

• 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

Workup

• 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: with this test the 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’s 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’s potassium sensitivity test (PST).
• Urodynamics are unnecessary in diagnosis of IC.

Laboratory Tests

• 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.

Imaging Studies

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

• There is no consensus for optimal management.
• There is no cure for this disease.

Nonpharmacologic Therapy

• Avoidance of activities associated with flare-ups
• Avoidance of smoking
• Dietary restriction, 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

Acute and Chronic Rx

• 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.
• 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’s ulcers.
• 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 hr 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.

Surgery

• Major surgical intervention is not the mainstay of treatment.
• Patients whose condition is extreme and who are miserable may consider surgery if medications fail.
• Sacral neuromodulation (InterStim) is the current preferred surgical intervention.
• Laser ablation, fulguration, or resection is offered when Hunner’s ulcers are seen in cystoscopy.
• Augmentation cystoplasty is not recommended.
• Cystourethrectomy with urinary diversion is rarely done.

Complementary & Alternative Medicine

• 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 Algnot Plus, CystoProtek, Cysta-Q, aloe vera

Disposition

Referral

Comments

Prevention

Early identification and timely intervention improve patient outcome.

Patient & Family Education

• L.M. French, N. Bhambore: Interstitial cystitis/painful bladder syndrome. Am Fam Phys. 83 (10):1175–1181 2011

• A. Randel: American Urological Association approach to the diagnosis and management of IC/BPS. Am Fam Physician. 86:97–103 2012