Interstitial Cystitis

From: 5 minutes clinical constult

Description
A disease of unknown cause probably representing a final common pathway from several etiologies. Likely pathogenesis is disruption of urothelium, impaired lower urinary track defenses and loss of bladder muscular wall elasticity. The symptoms in many patients are insidious and the disease progresses over years before the diagnosis is established.
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. A bladder sensory problem
Severe: Progressive bladder fibrosis. Small true bladder capacity under anesthesia. Poor bladder wall compliance. Often ulcers present at cystoscopy. May have overflow incontinence and/or chronic bacteriuria that is unresponsive to antibiotics
System(s) affected: Renal/Urologic
Synonym(s): Urgency frequency syndrome; Painful bladder syndrome

ALERT
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

Epidemiology
Caucasians predominant
Predominant sex:
Female > Male (10:1)
Predominant age:
20–40 for mild; 20–70 for severe
Pediatric considerations:
<10 years old and again at 13–17 yrs
Daytime enuresis, dysuria w/o infection

Prevalence
In the US:
Up to 500,000 affected. Many cases likely unreported
0.052%, but may be higher—up to 10% (1)[C]

Risk Factors
Unknown

Etiology
Unknown. 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 up regulation/stimulation

Commonly Associated Conditions
Fibromyalgia
Allergies
Chronic Fatigue Syndrome
Depression
Chronic Prostatitis
Chronic Pelvic Pain
Irritable Bowel Syndrome

Signs and Symptoms
Frequent, urgent, relentless urination day and night, >8 voids/24 hrs
Pain with full bladder that resolves with bladder emptying (except if bacteriuria 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 (PUF) Symptom Scale (2)[B]—self reporting questionnaire for screening potential interstitial cystitis patients
Frequent UTIs, vaginitis or symptoms in week before menses

Physical Exam
Perineal/Prostatic pain in males
Anterior vaginal wall pain in females

Diagnostic Tests and Interpretation
Lab
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 of age and women with hematuria

Diagnostic Procedures/Other
Cystoscopy (especially in men > 40 or women w/hematuria)
Bladder wall visualization
Hydraulic distention—no improved diagnostic certainty over H&P alone (3)[C]
No role for urodynamic testing
K+ Sensitivity Test (2)[B]:
Insert catheter, empty bladder, instill 40 ml H2O over 2–3 min, rank urgency at 0–5 in intensity, rank pain at 0–5 in intensity, drain bladder, instill 40 ml KCl 0.4 mol/L solution:
If immediate pain flush bladder w/60 ml H2O and treat w/bladder instillations
If no immediate pain wait 5 min and rate urgency and pain
If urgency or pain >2, treat as above
Pain or urgency >2 considered a positive test and strongly correlates with interstitial cystitis if no radiation cystitis nor acute bacterial cystitis

Pathological Findings
Nonspecific chronic inflammation on bladder biopsies
Urine cytology negative for dysplasia and neoplasia
Possible mast cell proliferation in mucosa

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
Non urinary pelvic disease (sexually transmitted diseases, endometriosis, pelvic relaxation)

Medication (Drugs)
First Line
Oxybutynin, hyoscyamine, and other anticholinergic medications decrease frequency.
Doxepin decreases frequency.
NSAIDs for pain and any inflammatory component
Pentosan polysulfate (Elmiron) 100 mg 3 times daily. May take several months to become effective (only FDA approved treatment for interstitial cystitis)
Triple drug therapy: 6 months of pentosan, hydroxyzine, doxepin
Antibacterials for bacteriuria
Prednisone (used for ulcerative lesions)
Montelukast
Hydroxyzine
Amitriptyline

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 as needed
Heparin sometimes added to DMSO
Other agents: Steroids, silver nitrate, oxychlorosene (Clorpactin)
Contraindications:
No anticholinergics with patients having closed-angle glaucoma
Significant possible interactions: Refer to manufacturer's profile of each drug.

Second Line
Note that phenazopyridine, a local bladder mucosal anesthetic, is usually not very effective.

Additional Treatment
General Measures
Appropriate health care: Outpatient (4)[B]
Eliminate foods and liquids that exacerbate symptoms on individual basis.
Biofeedback bladder retraining

Complementary and Alternative Therapies
Modified Thiele Massage (5)[C]—transvaginal of pelvic floor muscles

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 completely refractory to medical therapy

Follow-Up Recommendations
Patient Monitoring
Not specifically needed unless symptoms unresponsive to treatment

Diet
Variable effects from person to person
Common irritants include caffeine, chocolate, citrus, tomatoes, carbonated beverages, K+ rich foods, spicy foods, acidic foods, alcohol.

Patient Education
Interstitial Cystitis Association, 110 Wash. 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.

CLINICAL PEARLS
The potassium sensitivity test has been the most useful in confirming an initial diagnosis of interstitial cystitis. 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 multi-disciplinary follow-up, pharmacological therapy, avoidance of symptom triggers, psychological and supportive therapy are all important, as this disease tends to wax and wane. Monitor patients for depression as a co-morbidity. Empowering patients to be managers of their symptoms, to communicate regularly with their physicians, and to learn as much as they are able about this disease can help patients to optimize their outcome.

AUTHOR

Montiel T. Rosenthal, MD

BIBLIOGRAPHY
Parsons CL, Tatsis V. Prevalence if interstitial cystitis in young women. Urology 2004;64:866. [PMID:15533465]
Parsons CL, Dell J, 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;60:573–578. [PMID:12385909]
Ottem DP, Teichman JM. What is the value of cystoscopy with hydrodistention for interstitial cystitis? Urology 2005;66:494–499. [PMID:16140064]
Moldwin R, Evans R, et al. Rational. Approach to the Treatment of Patients with Interstitial Cystitis. Urology 2007;69(4A):73–81. [PMID:17462484]
OzamaI A, Rejba A, et al. Modified Thiele massage as therapeutic intervention for female patients with interstitial cystitis and high-tone pelvic floor dysfunction. Urology 2004;64:862. [PMID:15533464]