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Interstitial Cystitis
Rebecca R. Yeager, MD
Montiel T. Rosenthal, MD
image BASICS
  • A condition of pain or discomfort in the bladder associated with a need to urinate frequently and urgently
  • A disease of unknown cause, probably representing a final common pathway from several etiologies
  • Likely, pathogenesis is disruption of urothelium, impaired lower urinary tract defenses and loss of bladder muscular wall elasticity. The symptoms in many patients are insidious, and the disease progresses for years before diagnosis is established.
  • Newer research implicates urine and serum inflammatory proteins antiproliferative factor, epidermal growth factor, heparin-binding epidermal growth factor, glycosaminoglycans, and bladder nitric oxide as contributing factors.
  • Mild: normal bladder capacity under anesthesia; ulceration, cracking, or glomerulation of mucosa (or not) with bladder distention under anesthesia; no incontinence symptoms wax and wane and may not progress. Interstitial cystitis is a bladder sensory problem.
  • Severe: progressive bladder fibrosis; small true bladder capacity under anesthesia; poor bladder wall compliance. In 5-10% of cases, Hunner ulcers present at cystoscopy; may have overflow incontinence and/or chronic bacteriuria unresponsive to antibiotics.
  • System(s) affected: renal/urologic
  • Synonym(s): urgency frequency syndrome; IC/bladder pain syndrome (BPS)
Pregnancy Considerations
Unpredictable symptom improvement or exacerbation during pregnancy; no known fetal effects from interstitial cystitis; usual problems of unknown effect on fetus with medications taken during pregnancy
  • Occurs predominantly among whites
  • Predominant sex: female > male (10:1)
  • Patients <30 years have predominant symptoms: dysuria, frequency, urinary urgency, pain in external genitals, and dyspareunia; and those >60 years more commonly have nocturia, urinary incontinence, or Hunner ulcer disease.
  • Predominant age
    • Mild: 20 to 40 years
    • Severe: 20 to 70 years
  • Pediatric considerations
    • <10 years old and again at 13 to 17 years
    • Daytime enuresis, dysuria without infection
In the United States:
  • Up to 1 million affected, but many cases likely are unreported
  • 0.052% but may be higher up to 10%
  • Unknown but is not primarily psychosomatic
  • Possible causes
    • Subclinical urinary infection
    • Damage to glycosaminoglycan mucus layer increasing bladder wall permeability to irritants such as urea
    • Autoimmune
    • Mast cell histamine release
  • Neurologic upregulation/stimulation
  • Fibromyalgia
  • Allergies
  • Chronic fatigue syndrome
  • Depression
  • Vulvodynia
  • Sexual dysfunction
  • Sleep disturbance
  • Migraines
  • Syncope
  • Dyspepsia
  • Chronic prostatitis
  • Chronic pelvic pain
  • Irritable bowel syndrome
  • Anal/rectal disease
  • Frequent, urgent, relentless urination day and night; >8 voids in 24 hours
  • Pain with full bladder that resolves with bladder emptying (except if bacteriuria is present)
  • Urge urinary incontinence if bladder capacity is small
  • Sleep disturbance
  • Dyspareunia, especially with full bladder
  • Secondary symptoms from chronic pain and sleeplessness, especially depression
  • Perineal/prostatic pain in men
  • Anterior vaginal wall pain in women
  • Uninhibited bladder (urgency, frequency, urge incontinence, less pain, symptoms usually decrease when asleep)
  • Urinary infection: cystitis, prostatitis
  • Bladder neoplasm
  • Bladder stone
  • Neurologic bladder disease
  • Nonurinary pelvic disease (STIs, endometriosis, pelvic relaxation)
Initial Tests (lab, imaging)
  • Urinalysis: normal except with chronic bacteriuria (rare)
  • Urine culture from catheterized specimen: normal except with chronic bacteriuria (rare) or partial antibiotic treatment
  • Urine cytology
    • Normal: reserve for men >40 years old and women with hematuria
Diagnostic Procedures/Other
  • Cystoscopy (especially in men >40 years old or women with hematuria)
    • Bladder wall visualization
    • Hydraulic distention: no improved diagnostic certainty over history and physical alone
  • No role for urodynamic testing
  • Intravesical lidocaine can help to pinpoint the bladder as the source of pain in patients with pelvic pain; this can be both diagnostic and therapeutic.
  • Potassium sensitivity test
    • Insert catheter, empty bladder, instill 40 mL H2O over 2 to 3 minutes, rank urgency on scale of 0 to 5 in intensity, rank pain on scale of 0 to 5 in intensity, drain bladder, instill 40 mL potassium chloride (KCI) 0.4 mol/L solution:
      • If immediate pain, flush bladder with 60 mL H2O and treat with bladder instillations.
      • If no immediate pain, wait for 5 minutes and rate the urgency and pain.
  • If urgency or pain >2, treat as above.
  • Pain or urgency >2 is considered a positive test and strongly correlates with interstitial cystitis if no radiation cystitis or acute bacterial cystitis is present.
Test Interpretation
  • Nonspecific chronic inflammation on bladder biopsies
  • Urine cytology negative for dysplasia and neoplasia
  • Possible mast cell proliferation in mucosa
  • Appropriate health care: outpatient
  • Self-care (eliminate foods and liquids that exacerbate symptoms on individual basis, fluid management) (2)[C]
  • Biofeedback bladder retraining (2)[C]
  • Randomized controlled trials of most medications for interstitial cystitis demonstrate limited benefit over placebo; there are no clear predictors of what will benefit an individual. Prepare the patient that treatment may involve trial and error.
  • P.569

  • Behavioral therapy combined with oral agents found improved outcomes compared to medications alone.
  • Intravesical injections of botulinum toxin are not effective in the treatment of ulcer-type interstitial cystitis.
First Line
  • Note: AUA consensus states medicines should be considered second-line therapy after patient education, stress reduction, behavior modification, and self-care (2)[C].
  • Pentosan polysulfate (Elmiron) 100 mg TID on empty stomach; may take several months (3 to 6) to become effective; rated as modestly beneficial in systematic drug review (only FDA-approved treatment for interstitial cystitis) (3)[C]
  • Amitriptyline: Most effective at higher doses (≥50 mg/day); however, initiate with lower doses to minimize side effects (4)[B].
  • Hydroxyzine 25 to 50 mg HS
  • Sildenafil 25 mg/day (5)[B]
  • Cimetidine 400 mg BID (2)[C]
  • Triple-drug therapy: 6 months of pentosan, hydroxyzine, doxepin
  • Antibacterials for bacteriuria
  • Oxybutynin, hyoscyamine, tolterodine, and other anticholinergic medications decrease frequency.
  • Prednisone (only for ulcerative lesions)
  • Montelukast has shown some benefit.
  • NSAIDs for pain and any inflammatory component
  • Bladder instillations
    • Lidocaine, sodium bicarbonate, and heparin or pentosan polysulfate sodium
    • Dimethyl sulfoxide (DMSO) every 1 to 2 weeks for 3 to 6 weeks, then PRN
    • Heparin sometimes added to DMSO
    • Intravesical liposomes
    • Other agents: steroids, silver nitrate, oxychlorosene (Clorpactin)
  • Contraindication
    • No anticholinergics for patients with close-angle glaucoma
  • Significant possible interaction
    • Refer to manufacturer's profile of each drug.
Second Line
  • Phenazopyridine, a local bladder mucosal anesthetic, usually is not very effective.
  • Intravesicular injection of botulinum type A for nonulcer interstitial cystitis
  • Cyclosporin A (2)[C]
  • Need for clarity with respect to diagnosis
  • Surgical intervention
Myofascial physical therapy (targeted pelvic, hip girdle, abdominal trigger point massage) (6)[B]
  • Hydraulic distention of bladder under anesthesia: symptomatic but transient relief
  • Cauterization of bladder ulcer
  • Augmentation cystoplasty to increase bladder capacity and decrease pressure with or without partial cystectomy. Expected results in severe cases: much improved, 75%; with residual discomfort, 20%; unchanged, 5%
  • Urinary diversion with total cystectomy only if disease is completely refractory to medical therapy
  • Sacral neuromodulation
Guided imagery
Patient Monitoring
Not specifically needed unless symptoms are unresponsive to treatment
  • Variable effects from person to person
  • Common irritants include caffeine, chocolate, citrus, tomatoes, carbonated beverages, potassium-rich foods, spicy foods, acidic foods, and alcohol.
Interstitial Cystitis Association, 110 Washington St. Suite 340, Rockville, MD 20850; 1-800-HELPICA: http://www.ichelp.org/
  • Mild: exacerbations and remissions of symptoms; may not be progressive; does not predispose to other diseases
  • Severe: progressive problems that usually require surgery to control symptoms
1. Parsons CL, Dell J, Stanford EJ, et al. Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecological cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology. 2002;60(4):573-578.
2. Hanno PM, Erickson D, Moldwin R, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193(5):1545-1553.
3. Dancel R, Mounsey A, Handler L. Medications for treatment of interstitial cystitis. Am Fam Physician. 2015;91(2):116-118.
4. Foster HE Jr, Hanno PM, Nickel JC, et al. Effect of amitriptyline on symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. J Urol. 2010;183(5):1853-1858.
5. Chen H, Wang F, Chen W, et al. Efficacy of daily low-dose sildenafil for treating interstitial cystitis: results of a randomized, double-blind, placebocontrolled trial—treatment of interstitial cystitis/painful bladder syndrome with low-dose sildenafil. Urology. 2014;84(1):51-56.
6. FitzGerald MP, Payne CK, Lukacz ES, et al. Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness. J Urol. 2012;187(6):2113-2118.
Additional Reading
Rais-Bahrami S, Friedlander JI, Herati AS, et al. Symptom profile variability of interstitial cystitis/painful bladder syndrome by age. BJU Int. 2012;109(9):1356-1359.
See Also
  • Urinary Tract Infection (UTI) in Females
  • Algorithm: Pelvic Girdle Pain (Pregnancy or Postpartum Pelvic Pain)
  • N30.10 Interstitial cystitis (chronic) without hematuria
  • N30.11 Interstitial cystitis (chronic) with hematuria
Clinical Pearls
  • The potassium sensitivity test has been the most useful in confirming an initial diagnosis of interstitial cystitis.
  • Potassium sensitivity test
    • Insert catheter, empty bladder, instill 40 mL H2O over 2 to 3 minutes; rank urgency on scale of 0 to 5 in intensity; rank pain on scale of 0 to 5 in intensity; drain bladder; and instill 40 mL KCI 0.4 mol/L solution.
  • Submucosal petechial hemorrhages and/or ulceration at the time of bladder distention and cystoscopy further support the diagnosis.
  • At present, there is no definitive treatment for interstitial cystitis.
  • Most patients with severe disease receive multiple treatment approaches. Regular multidisciplinary follow-up, pharmacologic therapy, avoidance of symptom triggers, and psychological and supportive therapy are all important because this disease tends to wax and wane. Monitor patients for comorbid depression.
  • Empowering patients to manage their symptoms, communicate regularly with their physicians, and learn as much as they can about this disease which may help them to optimize their outcome.