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Interstitial Cystitis

- 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

- 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)

- Significant possible interaction - Refer to manufacturer's profile of each drug.

para>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

EPIDEMIOLOGY

  • 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 ageMild: 20 to 40 yearsSevere: 20 to 70 years
  • Pediatric considerations<10 years old and again at 13 to 17 yearsDaytime enuresis, dysuria without infection

Prevalence

In the United States:

  • Up to 1 million affected, but many cases likely are unreported
  • 0.052% but may be higher up to 10%

ETIOLOGY AND PATHOPHYSIOLOGY

  • Unknown but is not primarily psychosomatic
  • Possible causesSubclinical urinary infectionDamage to glycosaminoglycan mucus layer increasing bladder wall permeability to irritants such as ureaAutoimmuneMast cell histamine release
  • Neurologic upregulation/stimulation

RISK FACTORS

Unknown

COMMONLY ASSOCIATED CONDITIONS

  • 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

DIAGNOSIS

  • 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

HISTORY

  • Pelvic Pain and Urgency/Frequency Patient Symptom Scale: self-reporting questionnaire for screening potential interstitial cystitis patients (1)[B] (http://www.wgcaobgyn.com/files/urgency_frequency_pt_symptom_scale.pdf)
  • Frequent UTIs, vaginitis, or symptoms during the week before menses
  • O'Leary/Sant Voiding and Pain Indices (http://www.ichelp.org/wp-content/uploads/2015/06/OLeary_Sant.pdf)

PHYSICAL EXAM

  • Perineal/prostatic pain in men
  • Anterior vaginal wall pain in women

DIFFERENTIAL DIAGNOSIS

  • 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)

DIAGNOSTIC TESTS & INTERPRETATION

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 cytologyNormal: 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 visualizationHydraulic 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 testInsert 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 (KCl) 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

TREATMENT

GENERAL MEASURES

  • 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]

MEDICATION

  • 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.
  • 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 instillationsLidocaine, sodium bicarbonate, and heparin or pentosan polysulfate sodiumDimethyl sulfoxide (DMSO) every 1 to 2 weeks for 3 to 6 weeks, then PRNHeparin sometimes added to DMSOIntravesical liposomesOther agents: steroids, silver nitrate, oxychlorosene (Clorpactin)
  • ContraindicationNo anticholinergics for patients with close-angle glaucoma
  • Significant possible interactionRefer 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]

ISSUES FOR REFERRAL

  • Need for clarity with respect to diagnosis
  • Surgical intervention

ADDITIONAL THERAPIES

Myofascial physical therapy (targeted pelvic, hip girdle, abdominal trigger point massage) (6)[B]

SURGERY/OTHER PROCEDURES

  • 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

COMPLEMENTARY & ALTERNATIVE MEDICINE

Guided imagery

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

Not specifically needed unless symptoms are unresponsive to treatment

DIET

  • Variable effects from person to person
  • Common irritants include caffeine, chocolate, citrus, tomatoes, carbonated beverages, potassium-rich foods, spicy foods, acidic foods, and alcohol.

PATIENT EDUCATION

Interstitial Cystitis Association, 110 Washington St. Suite 340, Rockville, MD 20850; 1-800-HELPICA: http://www.ichelp.org/

PROGNOSIS

  • 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

COMPLICATIONS

Severe, with long-term, continuous high bladder pressure could be associated with renal damage.

REFERENCES

11 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):573-578.22 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):1545-1553.33 Dancel R, Mounsey A, Handler L. Medications for treatment of interstitial cystitis. Am Fam Physician. 2015;91(2):116-118.44 Foster HEJr, Hanno PM, Nickel JC, et al. Effect of amitriptyline on symptoms in treatment na ¯ve patients with interstitial cystitis/painful bladder syndrome. J Urol. 2010;183(5):1853-1858.55 Chen H, Wang F, Chen W, et al. Efficacy of daily low-dose sildenafil for treating interstitial cystitis: results of a randomized, double-blind, placebo-controlled trial-treatment of interstitial cystitis/painful bladder syndrome with low-dose sildenafil. Urology. 2014;84(1):51-56.66 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)

CODES

ICD10

  • N30.10 Interstitial cystitis (chronic) without hematuria
  • N30.11 Interstitial cystitis (chronic) with hematuria

ICD9

595.1 Chronic interstitial cystitis

SNOMED

  • 197834003 Chronic interstitial cystitis (disorder)
  • 79160001 Hunner's ulcer (disorder)
  • 36139001 Chronic ulcerating interstitial cystitis (disorder)

CLINICAL PEARLS

  • The potassium sensitivity test has been the most useful in confirming an initial diagnosis of interstitial cystitis.
  • Potassium sensitivity testInsert 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 KCl 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.