- Author: Eric S Rovner, MD; Chief Editor: Edward David Kim, MD, FACS
History of the Procedure
- Urologic causes -Bladder cancer or carcinoma in situ (CIS), radiation cystitis, overflow incontinence, acontractile detrusor, prostatodynia,chronic pelvic pain syndrome, bladder outlet obstruction (eg, urinary retention with overflow incontinence), large postvoid residual volume, or open bladder neck (eg, intrinsic sphincteric deficiency, urolithiasis,urethritis)
- Prevalence: Reports on the prevalence of interstitial cystitis conflict depending on the country of origin and the criteria used for diagnosis. In the United States, Curhan et al showed a prevalence of 60-70 cases per 100,000 women, whereas reports from Europe indicate a prevalence of 18 cases per 100,000 women and only 3-4 cases per 100,000 women in Japan. These marked differences are likely due to differences in diagnostic criteria, varying from all-encompassing clinical criteria (eg, those from the National Institute of Diabetes & Digestive & Kidney Diseases [NIDDK] of the US National Institutes of Health) to very strict criteria based on a pathologic diagnosis. The incidence rate of interstitial cystitis is 2.6 cases per 100,000 women per year in the United States.
- Race: Of patients with interstitial cystitis, 94% are white. Interstitial cystitis appears to be slightly more common in Jewish women.
- Sex: Approximately 90% of patients with interstitial cystitis are female. Household size, marital status, number of male sexual partners, educational status, and parity are not statistically different between patients with interstitial cystitis and healthy controls.
- Age: Median age at presentation is 40 years. However, Close et al from Seattle have shown that interstitial cystitis may occur in children. In their series, the median age of onset was 4.5 years, with a mean age of diagnosis of 8.2 years. The children had diffuse glomerulations and terminal hematuria. Of the 16 children in the study, 15 improved after bladder hydrodistention.
- Family history: Although interstitial cystitis has not traditionally been considered a hereditable condition, a recent study from the University of Maryland reports a higher occurrence of interstitial cystitis in monozygotic versus dizygotic twins, suggesting the disease has at least a partial genetic predisposition.
- Associated medical conditions: Patients with interstitial cystitis are more likely to have undergone prior gynecologic surgery and/or to have a history of UTIs and are 10-12 times more likely to report childhood bladder problems. Interstitial cystitis is associated with several chronic illnesses, including inflammatory bowel disease, systemic lupus erythematosus, irritable bowel syndrome, fibromyalgia, and atopic allergy. In addition, several psychiatric conditions have been associated with interstitial cystitis, including anxiety disorder, depression, and adjustment reactions.
- Pathogenic role of mast cells in the detrusor and/or mucosal layers of the bladder
- Deficiency in the glycosaminoglycan layer on the luminal surface of the bladder, resulting in increased permeability of the underlying submucosal tissues to toxic substances in the urine
- Infection with a poorly characterized agent (eg, a slow-growing virus or extremely fastidious bacterium)
- Production of a toxic substance in the urine
- Neurogenic hypersensitivity or inflammation mediated locally at the bladder or spinal cord level
- Manifestation of pelvic floor muscle dysfunction or dysfunctional voiding
- Autoimmune disorder
National Institute of Diabetes and Digestive and Kidney Diseases criteria
- Glomerulations in at least 3 quadrants of the bladder and at least 10 glomerulations per quadrant
- Classic Hunner ulcer
- Pain associated with the bladder
- Urinary urgency
- Cystometric bladder capacity larger than 350 mL in a conscious patient with either gas or liquid filling
- Intense urge to void when patient's bladder has been filled with 100 mL of gas or 150 mL water during cystometry at a fill rate of 30-100 mL/min
- Demonstration of phasic involuntary bladder contractions on cystometry findings at a fill rate of 30-100 mL/min (Note that, although this is an exclusion criterion as per the NIDDK, detrusor instability may be present in as many as 14% of patients with a clinical diagnosis of interstitial cystitis.)
- Duration of symptoms less than 9 months
- Symptoms relieved by antimicrobials, urinary antiseptics, anticholinergics, or antispasmodics
- Frequency of micturition of less than 8 times per day
- Diagnosis of bacterial prostatitis or cystitis within a 3-month period
- Presence of ureteral or bladder calculi
- Active genital herpes
- Uterine, cervical, vaginal, or urethral cancer
- Urethral diverticulum
- Cyclophosphamide or other chemical cystitis
- Tuberculous cystitis
- Radiation cystitis
- Benign or malignant bladder tumors
- Patient younger than 18 years
- No urine cytology findings specifically suggest a diagnosis of interstitial cystitis (IC).
- A voided or catheterized urine specimen demonstrating cytologic changes consistent with dysplasia, CIS, or frank cancer should prompt immediate further urologic evaluation.
- Urinalysis results are usually normal. Microscopic hematuria and pyuria are present in some patients. By definition, urine culture results should be negative.
- Urethral and vaginal culture results also must be negative for pathologic organisms (eg, fungi and gonorrheal, chlamydial, and trichomonal species).
- Findings from other urine studies, such as voided cytology or bladder lavage cytology, may help exclude other diagnoses such as CIS and transitional cell carcinoma.
- No serologic or hematologic abnormalities are known to be specific for interstitial cystitis.
- Various assays for stress protein genes, glycosaminoglycans, mast cell tryptase, Tamm-Horsfall protein autoantibodies, and others have been suggested by numerous investigators; however, these assays are presently used primarily for research purposes and do not have a defined role in the diagnosis of interstitial cystitis.
- In men, expressed prostatic secretions yield no findings specific for interstitial cystitis; nonetheless, localizing cultures and microscopic examination should be performed to exclude bacterial prostatitis.
- Much research is being undertaken to identify urine markers expressed in patients with interstitial cystitis to develop a noninvasive laboratory test.
- Keay et al has reported that urine samples in patients with interstitial cystitis contain a factor (antiproliferative factor [APF]) that inhibits bladder epithelial growth. They also found that APF influences changes in specific levels of bladder epithelial growth factors including significantly decreased levels of heparin-binding epidermal growth factor (HB-EGF) and increased levels of epidermal growth factor (EGF) in patients with interstitial cystitis compared to normal controls and patients with other urogenital diseases.
- The sensitivity and specificity of APF activity, decreased HB-EGF levels, and increased EGF levels in patients with interstitial cystitis compared with control groups was 94% and 95%, 93% and 89%, and 87% and 91%, respectively. The results are promising, but these assays are currently experimental and are not commercially available.
- No known radiographic, ultrasonographic, or other imaging findings are specific for interstitial cystitis.
- Unless indicated to help exclude alternative diagnoses, radiographic studies have only a limited role in the evaluation of interstitial cystitis. Cross-sectional imaging, including MRI, CT scanning, and pelvic ultrasonography, may be performed when clinically indicated to evaluate for a suggestive pelvic mass that is causing compression of the bladder or for an adjacent inflammatory process (eg, diverticulitis).
- Cystography and voiding cystourethrography may be used to evaluate the bladder for other causes of irritative lower urinary tract symptoms, including intravesical masses, stones, bladder diverticula, urethral diverticula, urethral stricture, meatal stenosis, or findings suggestive of a neurogenic or nonneurogenic voiding dysfunction.
- Urodynamic studies are not part of the routine interstitial cystitis evaluation.
- Few urodynamic findings are consistent in patients with interstitial cystitis, and findings specific for the syndrome do not exist.
- On filling cystometry, most patients have a hypersensitive bladder with a decreased volume at all filling intervals. Pain with bladder filling that reproduces the patients' interstitial cystitis symptoms is very supportive of a diagnosis of interstitial cystitis.
- Bladder compliance in patients with interstitial cystitis is normal.
- The prevalence rate of involuntary bladder contractions in patients with interstitial cystitis symptoms ranges from 0%-14%; however, when observed on filling cystometry studies, bladder contractions are commonly cited as mitigating evidence against a diagnosis of interstitial cystitis, as per the NIDDK criteria.
- Volitional bladder contractions in patients with interstitial cystitis are quite similar to those in healthy persons.
- Findings from pressure flow studies and free uroflow studies are usually unremarkable.
- Sphincter electromyography findings may show some increased activity caused by pain with bladder filling. True detrusor-sphincter dyssynergia excludes the diagnosis of interstitial cystitis. Postvoid residual volume should be minimal.
- Biopsies are primarily performed to help rule out other varieties of cystitis and malignant or premalignant (CIS) lesions. They are also performed to evaluate for detrusor mastocytosis.
- Endoscopic findings: Aside from a thorough history and physical examination, cystoscopy is described as the most important diagnostic tool for assessing a patient who may have interstitial cystitis.
- Cystoscopy is performed to help exclude other causes of symptoms suggestive of interstitial cystitis and to provide evidence for the diagnosis of interstitial cystitis. Sometimes, cystoscopy is performed without anesthesia; however, bladder hypersensitivity with filling and pelvic pain may limit the examination considerably. Importantly, patients who can tolerate several hundred milliliters of fluid during bladder filling, with manipulation and examination, without general anesthesia probably do not have interstitial cystitis.
- In general, cystoscopy is performed while the patient is under anesthesia in order to provide sufficient distension to examine for coexisting urethral and bladder pathology (eg, transitional cell carcinoma) and features of interstitial cystitis such as Hunner ulcers and glomerulations. Bladder capacity values are also recorded.
- Diagnostic hydrodistention (ie, overdistension): This is performed by placing the irrigation fluid at 80-100 cm water above the patient's bladder. Fluid is run into the bladder under gravity until it slows to a drip. Manual compression of the urethra around the cystoscope sheath should be performed as the bladder fills to help prevent the egress of fluid and to ascertain the true bladder capacity.
- Continuous intravesical observation of the bladder wall is necessary to note perforation and extravasation as the bladder is filled. A seemingly large bladder capacity or exceedingly prolonged filling time without deceleration of the filling rate may indicate bladder perforation.
- Examination of the fully distended bladder should be unremarkable, except for perhaps some mild trabeculation. The diagnostic distension is typically held for 1-2 minutes, and then the bladder is drained. The amount of drainage (bladder capacity under anesthesia) and the color of the effluent are recorded. Characteristically, the last 50-100 mL of effluent may be blood tinged (terminal pinking) in patients with interstitial cystitis.
- The bladder capacity may be reduced in patients with the classic or ulcer variety of interstitial cystitis, whereas the bladder capacity is normal or only slightly reduced in patients with the nonulcerative form of interstitial cystitis.
- Reinspection of the bladder may reveal diffuse pinpoint petechial hemorrhages within the bladder (ie, glomerulations). These lesions are small, hemorrhagic, and raspberrylike in appearance and are graded as mild, moderate, or severe based on severity. Glomerulations represent the most constant finding after cystoscopy in patients with interstitial cystitis. Typically, the glomerulations are present in at least 3 quadrants of the bladder, sparing the trigone. These glomerulations may appear in a checkerboardlike or latticelike configuration or may appear as splotchy areas over a section of the bladder. Glomerulations noted only along the posterior wall suggest trauma from the cystoscope sheath and not necessarily any pathologic process such as interstitial cystitis.
- Glomerulations are not specific for interstitial cystitis, although some authors state that glomerulations are not present in healthy bladders. Others have speculated that the appearance of glomerulations may simply be a manifestation of chronic bladder underfilling due to hypersensitivity or sensory urgency rather than any specific primary pathologic process such as interstitial cystitis. Glomerulations may also develop in various other bladder conditions, including neoplasia, infectious cystitis, radiation cystitis, and chemical cystitis, and in patients with a defunctionalized bladder (patients on dialysis) and other conditions in which the bladder has been chronically underfilled (eg, patients who have undergone urinary diversion).
- The classic description of interstitial cystitis is a reddened bladder with a reduced capacity and fissures and scars that crack and bleed after distension. These findings with the classic Hunner ulcer are exceedingly rare. Mucosal cracks, ulcers, and fissures are much more common than the classic Hunner ulcer. Most patients with interstitial cystitis have a normal bladder capacity (>400 mL), some degree of glomerulations, and terminal pinking following hydrodistention. The finding of a Hunner ulcer should be noted with caution because previous biopsy or transurethral resection sites sometimes can appear quite similar to a Hunner ulcer. Hunner ulcers are discreet patches of denuded (ie, ulcerated) bladder wall, which are thought to be highly specific for the diagnosis of interstitial cystitis. Unfortunately, these are observed in fewer than 10% of patients.
- In general, the cystoscopic findings, including severity of glomerulations and amount of bleeding, do not correlate with symptom severity or treatment response.
- In summary, endoscopic features of interstitial cystitis prior to hydrodistention include a normal urethral lumen, Hunner ulcers (rare), and an absence of lesions or masses (intrinsic or extrinsic) suggestive of other pathology or disease processes. Following hydrodistention to 80 cm water pressure for 1-2 minutes, the following may be identified: (1) glomerulations (petechial hemorrhages), (2) submucosal hemorrhages, and (3) bloody effluent upon drainage (terminal pinking). In classic or ulcerative interstitial cystitis, observed in approximately 10% of patients, decreased bladder capacity (< 400 mL), ulcers, or scars may be seen. In nonulcerative disease (90%), bladder capacity is usually more than 400 mL and ulcers, scars, or mucosal cracking are usually absent.
- Potassium sensitivity test: Some authors have found that certain subgroups of patients with interstitial cystitis have increased urothelial permeability to certain intravesical constituents. This potential property is exploited in the potassium sensitivity test as a diagnostic test for interstitial cystitis.
- In patients with interstitial cystitis or other conditions of the bladder that affect urothelial permeability, the patient experiences acute and severe pain with intravesical instillation of the potassium chloride solution. Patients who do not have interstitial cystitis experience little or no pain from the solution.
- This test is controversial because its operating characteristics (eg, sensitivity, specificity) have not been clearly defined. It has not been widely adapted for clinical use.
Histologic FindingsNo pathonomic histologic findings exist for interstitial cystitis. As noted above, some authors have found increased numbers of mast cells in the detrusor muscle or submucosa in affected individuals. However, this finding neither includes nor excludes the diagnosis.
Medical TherapyThe therapy for interstitial cystitis (IC) begins with extensive patient education regarding the chronic nature of the disease and realistic assessments of the condition, prognosis, and potential responses to therapy. Ongoing reassurance and physical and emotional support are important as the diagnostic evaluation progresses and therapies are applied. Only rarely will patients with interstitial cystitis have an immediate, complete, and durable response to any particular therapy. They must be counseled at length regarding the lack of universally effective therapies. Often, referral to one of the local interstitial cystitis support groups, especially a local chapter of theInterstitial Cystitis Association, can be helpful in providing a continuing network of support for the patient.Ideally, in clinical practice, the treatment of interstitial cystitis should be initiated with the least invasive, least expensive, and most reversible therapy. In general, this consists of a program of dietary and fluid management, time and stress management, and behavioral modification. Thereafter, treatments are applied in a progressively more invasive step-wise fashion until some degree of symptomatic relief is obtained.Interventions might include various pharmacological agents (eg, pentosan polysulfate sodium [Elmiron], antihistamines, tricyclic antidepressants, analgesics, anti-inflammatory agents), intravesical therapy (ie, medications intermittently instilled directly into the bladder via a catheter), electrical stimulation, and complementary therapies such as acupuncture and hypnosis.Managing the pain component can be difficult in patients with interstitial cystitis. The etiology of the pain remains unclear, but various authors have postulated the etiology to be mediated centrally, peripherally, or locally via a neurogenic or inflammatory mechanism. Some patients require long-term pain medications, while others rely on these only during periods of symptomatic flares. Anti-inflammatory agents, acetaminophen, gabapentin (Neurontin), tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and various other agents are used. Most clinicians tend to avoid the extensive use of narcotics in patients with interstitial cystitis. When the pain component becomes unresponsive to nonnarcotic agents, referral to a chronic pain management facility may be helpful.Transcutaneous electrical nerve stimulation (TENS) units, electrical stimulation (intravaginal), acupuncture, and intrathecal and intraspinal infusions have all been used. Topical anesthetics such as lidocaine have been applied directly to the bladder intravesically and have yielded some success.
Behavioral therapyFollowing each intervention, the patient is reassessed for response. Unfortunately, therapies are often applied in a haphazard "hit-and-miss" fashion, combining numerous different therapies before truly assessing the patient's response to each therapy. This approach is sometimes partly driven by unrealistic patient demands and expectations regarding the success of various therapeutic interventions. Again, patients must receive extensive counseling regarding the nature and prognosis of their condition and its response to therapy. This is critically important, and such counseling must be initiated prior to embarking on invasive interventions for which no proven overwhelming benefit may be achieved.Biofeedback and pelvic floor rehabilitation (ie, Kegel exercises), bladder training programs (ie, progressively increasing the voiding interval over the course of weeks to months), and other behavioral measures are excellent initial interventions and have been used by some authors with some success. The urinary frequency and urgency components seem to respond better to these interventions than the pelvic pain component.Various dietary measures have been examined as therapy of interstitial cystitis. These dietary measures and the previously mentioned behavioral measures can be effective when used alone, but can also be complementary to virtually all other interventions for interstitial cystitis. Certain foods, including coffee, alcohol, tomatoes, vinegar, spicy foods, chocolate, and particular fruits and vegetables, have been implicated in aggravating symptoms of interstitial cystitis and, in the opinion of some authors, can precipitate symptomatic flares. Avoiding these food items or substituting other food items is often advised. Not uncommonly, patients are instructed to fill out a food diary, recording the relationship between the consumption of various food and drink items and their interstitial cystitis symptoms. In this manner, items that provoke or exacerbate the interstitial cystitis symptom complex can be eliminated from the diet in a methodical fashion.Ultimately, the decision to abandon or augment behavioral therapy and to pursue other therapeutic options is made by both the patient and physician when a general lack of progress occurs or when symptoms progress. Very few, if any, studies have looked at the minimal duration of time necessary to assess response to behavioral therapy in patients with interstitial cystitis. Furthermore, an optimal behavioral program has also not been defined. Given the chronic nature of the condition and the possibility of spontaneous improvement or remission, progressively more invasive and expensive treatment should be initiated with caution. Generally, if tolerated by the patient, a trial of 3-6 months of behavioral therapy is warranted prior to proceeding to more invasive or expensive therapies.
Oral medicationOral medications should be considered only after the aforementioned conservative measures have failed. With the exception of Elmiron, the drugs listed in Medications are not specific for the treatment of interstitial cystitis; however, all of them have demonstrated some degree of efficacy in controlled or uncontrolled studies. The duration of individual pharmacotherapy is variable. The clinical studies on Elmiron seem to suggest that maximal effects are not observed until the patient has been on drug therapy for 5-6 months. Other medications are dispensed and their effects are reevaluated as per the expected pharmacokinetics. For example, steady-state serum levels of many tricyclic antidepressants are not attained until 6-8 weeks of stable dosing. Only at this time can the drug dose be safely and reasonably adjusted.A National Institutes of Health (NIH)–funded study compared placebo with oral pentosan polysulfate sodium, hydroxyzine, and a combination of both. Using pentosan polysulfate sodium alone or in combination with hydroxyzine was shown to be slightly beneficial, but this was not significant.In a randomized, double-blind, placebo-controlled study, amitriptyline has been shown to provide statistically significant improvement in the O'Leary-Sant interstitial cystitis symptom and problem index, pain, and urgency intensity when compared to placebo. Common adverse effects include dry mouth, weight gain, constipation, and sedation.Anticholinergic agents such as oxybutynin and tolterodine can be used to treat the urinary frequency component of the condition; however, these agents can impair bladder emptying and thus may exacerbate pelvic pain. They should be used with caution in patients with interstitial cystitis.Cyclosporine A was recently compared to Elmiron in a randomized prospective nonblinded comparative study. In the cyclosporine A arm, micturition frequency was significantly reduced and clinical response rates were superior; however, treatment-related toxicity was increased in this group. While these preliminary studies are promising, continued evaluation and conservative patient selection are necessary.The authors' algorithm for treatment is largely based on whether the patient has predominantly a pelvic pain component or an urgency/frequency component. In the authors' experience, patients with pelvic pain and minimal voiding symptoms represent a pharmacological challenge, making an early pain clinic referral a useful adjunct.In patients with significant voiding symptoms, the authors suggest an algorithm proposed by Hanno. Conservative treatment may include patient education, dietary manipulation, nonprescription analgesics, and pelvic floor relaxation. If an improvement in symptoms is inadequate, begin oral therapy with either antispasmodics and nonnarcotic analgesics or with amitriptyline for 8 weeks. If amitriptyline fails, a trial of hydroxyzine for 8 weeks is suggested. If no response is observed, follow hydroxyzine with Elmiron.A 6- to 9-month course of Elmiron (100 mg tid) is followed by a reassessment of interstitial cystitis symptoms. The authors have found that lower doses of this compound are not as effective but have not used the higher doses advocated by some authors. In the authors' experience, the better plan is to try single-agent therapy first, moving down the ladder of medications, rather than treating patients with multiple agents from the outset. If conservative measures and medical therapy fail to provide adequate relief, surgical therapy should be considered.Although interstitial cystitis has been reported in children, the condition is observed almost exclusively in adults; therefore, pediatric dosages are not included.
Instillation therapyPatients in whom medical therapy fails may benefit from another bladder hydrodistention if the first hydrodistention was therapeutic earlier. When Hunner ulcers are identified, laser fulguration has been shown to be therapeutic. If patients still do not respond, intravesical therapy may be initiated, beginning with weekly dimethyl sulfoxide (DMSO) therapy for 6 courses. Monthly maintenance DMSO instillations have been advocated by some clinicians in order to prevent flares, although data supporting this approach are lacking. DMSO may be combined with steroids, bicarbonate, and heparin. Intravesical lidocaine may also be added. Some patients with refractory interstitial cystitis symptoms self-catheterize at home and instill a variety of these medications intravesically on an as-needed basis for symptom flares or simply for long-term therapy. In patients who respond poorly to DMSO, intravesical heparin or sodium oxychlorosene (Clorpactin) may be tried.Raymond Rackley, MD, from the Cleveland Clinic, has developed an intravesical formula that they have found to be highly successful in otherwise resistant or difficult cases. They use 50 mL of 1% lidocaine solution, in which they dissolve one tablet of sodium bicarbonate (650 mg), a 100-mg tablet of Elmiron, and a 200-mcg tablet of misoprostol (Cytotec), a synthetic prostaglandin E1 analog. This is allowed to sit for 1 hour and is then instilled into the bladder through a catheter; the patient is asked to retain it for as long as possible. The procedure is repeated as often as necessary to achieve relief, typically starting at 3-4 times per day in severe cases.Long-term application of capsaicin, a component of hot pepper, has been associated with the desensitization of C fibers, the unmyelinated nerve fibers known for transmitting pain. Intravesical instillation of capsaicin has been limited in its use in interstitial cystitis because of the sensation of severe burning; however, resiniferatoxin, a capsaicin analogue, is 100-10,000 times more potent than capsaicin and is not associated with severe burning. Resiniferatoxin has shown poor effectiveness after single administration, with no significant improvement in symptoms of interstitial cystitis, and side effects of dose-dependent pain and urgency symptoms.Hyaluronic acid glycosaminoglycan replenishment therapy has yielded moderate results in non–placebo-controlled studies. Weekly instillation of a 50-mL solution of phosphate-buffered solution containing 40 mg of sodium hyaluronate was performed in patients with an abnormal modified potassium test finding. Eighty-five and 84% of patients reported symptomatic and quality-of-life improvement, respectively, with 50% of patients reporting a lasting effect at 5-year follow-up. However, lower response rates are found in patients without evidence of a urine-tissue barrier abnormality.Intravesical bacillus Calmette-Guérin (BCG) has been hypothesized to suppress inflammation within the bladder and was evaluated for treatment of refractory interstitial cystitis. A randomized placebo-controlled trial revealed the treatment arm to have borderline statistical significance for global response assessment questioning, as well as most secondary outcome measures, including capacity, pain scores, urgency/frequency symptoms, and interstitial cystitis inventories.Patients in whom all forms of noninvasive therapy fail, including a referral to a pain clinic, should be considered candidates for sacral neuromodulation or other investigational protocols.
MedicationsAntihistamines inhibit binding to H1 histamine receptor. Hydroxyzine (Atarax, Vistaril) is an H1 histamine receptor blocker that may inhibit mast cell secretion and may suppress histamine activity in subcortical region of CNS. Adult dosing is 25-75 mg/d PO. Hydroxyzine is a pregnancy category C drug.Tricyclic antidepressants increase the synaptic concentration of serotonin and/or norepinephrine in the CNS. Amitriptyline (Elavil) is an oral tricyclic antidepressant that inhibits reuptake of serotonin and/or norepinephrine at the presynaptic neuronal membrane, which increases concentration in the CNS. It may have anticholinergic and sedative effects. Adult dosing is 25-75 mg PO hs. Amitriptyline is a pregnancy category D drug.Urinary analgesics relieve pain locally. Pentosan polysulfate sodium (Elmiron) is a negatively charged synthetic sulfated polysaccharide with an affinity for mucosal membranes. It repletes defects in the glycosaminoglycan layer. Adult dosing is 100 mg PO tid. Pentosan polysulfate sodium is a pregnancy category B drug. Other agents used with less success include L -arginine, nalmefene, anticholinergic agents (eg, oxybutynin, oxybutynin XL, tolterodine [Detrol and Detrol LA]), hyoscyamine, corticosteroids, antispasmodics, immunosuppressives, anti-inflammatories, and calcium channel blockers. In addition, a recent report suggests a beneficial role for oral cimetidine. Intravesical agents are described below.Renal and genitourinary agents are used for the symptomatic relief of interstitial cystitis. Dimethyl sulfoxide, ie, DMSO (Rimso-50) provides anti-inflammatory action, membrane penetration, antifungal activity, cryoprotective effects for living cells and tissues, collagen dissolution action, mast cell stimulation, nerve blockade, diuresis, cholinesterase inhibition, vasodilation, and muscle relaxation. It may be combined with heparin, steroids, or bicarbonate. In adults, instill 50 mL of aqueous 50% solution directly into bladder by catheter or Asepto syringe and allow to remain for 20 min. Dimethyl sulfoxide is a pregnancy category X drug.Cauterizing agents are used for the removal of granulation tissue. Silver nitrate is used for its caustic, antiseptic, and astringent qualities. In adults, administer concentrations ranging from 1:5000 to 2% intravesically for 2-10 min. Silver nitrate is a pregnancy category C drug.Dermatological agents are used for their cleansing and disinfection and for the removal of necrotic debris. Sodium oxychlorosene (Clorpactin WCS-90) exerts detergent action on bladder mucosa. It is reserved for patients in whom DMSO or silver nitrate instillations fail. In adults, administer 0.4% solution intravesically for 2-3 min at 60-80 cm water pressure (4-6 treatments qwk). Sodium oxychlorosene is a pregnancy category C drug.Polysaccharide glycosaminoglycans may exert a protective effect on the bladder. Heparin has been shown to reduce relapses in patients who respond to DMSO. It is an analog to polysaccharide glycosaminoglycan lining of the bladder. Adult dosing is 10,000 U intravesically in 10 mL sterile water monthly. Polysaccharide glycosaminoglycans is a pregnancy category C drug.
Bladder hydraulic distensionFollowing diagnostic hydrodistention, a therapeutic hydrodistention may be performed. This is usually performed at 80-100 cm water for 8-10 minutes.After draining the bladder from the therapeutic hydrodistention, bladder biopsy may be performed on areas that appear abnormal. Biopsy should be deep enough to sample the detrusor muscle. Unfortunately, no pathognomonic histological findings exist for interstitial cystitis. Biopsies are primarily performed to help rule out other varieties of cystitis or malignant or premalignant (eg, CIS) lesions. In all cases, biopsy should be performed following hydrodistention.In the authors' opinion, postoperative catheter drainage should be instituted in patients who undergo deep biopsies to reduce the chance of perforation, extravasation, or both. Although some centers advocate limiting the use of cystoscopy and biopsy in the evaluation and workup of patients thought to have interstitial cystitis, the authors believe these are necessary to help exclude other disorders such CIS and bladder calculi.The mechanism of action of bladder hydraulic distension is unknown. Hypotheses include neurapraxias by mechanical trauma and epithelial damage from mechanical trauma.
Emerging surgical therapiesSacral neuromodulation has been approved by the US Food and Drug Administration (FDA) for medically refractory frequency, urgency, and urge incontinence and is showing promising results in patients with interstitial cystitis. Several authors have studied sacral neuromodulation in patients with interstitial cystitis refractory to conservative measures (behavioral modification, diet, medications, hydrodistention). Sacral neuromodulation improved daytime frequency, nocturia, and mean voided volumes and decreased pain and interstitial cystitis symptom and problem index scores. In addition, sacral neuromodulation has been shown to normalize the abnormally high levels of APF and the abnormally low levels of HB-EGF in the urine of patients with interstitial cystitis.Pudendal nerve stimulation has also been evaluated in patients with interstitial cystitis and compared to sacral nerve stimulation. In a small series, overall reduction in symptoms was 59% for pudendal nerve stimulation and 44% for sacral nerve stimulation.[20, 21, 22]Transurethral intradetrusor injection of botulinum toxin type A coupled with therapeutic hydrodistention has been shown to be superior to hydrodistention alone in improving symptoms and bladder capacity in patients with IC. However, higher doses appear to increase the risk of postoperative voiding dysfunction and urinary retention following this procedure. The use of intradetrusor botulinum A toxin for this and other urological conditions remains investigational.[11, 10, 12]
Rarely indicated surgical therapies
- Laser photoradiation (poor results)
- Electrical stimulation
- TENS (more marked effect on bladder pain than on urinary frequency)
- Peripheral denervation (rarely indicated)
- Bladder augmentation (controversial results because pain component does not improve in most patients)
- Urinary diversion (most invasive, usually reserved as last resort)
Follow-upNo established guidelines exist for monitoring patients with interstitial cystitis. This is not surprising given the wide spectrum of severity of patient symptoms.