Approach Considerations
The diagnosis of interstitial cystitis is most often made when long-standing urinary frequency, urgency, and pelvic pain exist in the absence of a readily identifiable etiology, such as urinary tract infection (UTI). Urinalysis and urine culture are mandatory. A voiding diary is helpful in establishing baseline voiding frequency.
Cystoscopy is considered by some clinicians to be mandatory in order to diagnose interstitial cystitis However, this is somewhat controversial because of the lack of specific or pathognomonic findings (except perhaps the very rare finding of a Hunner ulcer).
Urodynamic evaluation is optional, and finding detrusor overactivity or pelvic floor dysfunction may suggest an alternative diagnosis.
Imaging the bladder
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 magnetic resonance imaging (MRI), computed tomography (CT) scanning, and pelvic ultrasonography, may be performed when clinically indicated to evaluate for a suspected pelvic mass that is causing compression of the bladder or for an adjacent inflammatory process (eg, diverticulitis).
Patients with interstitial cystitis have pelvic floor hypertonicity on MRI, which manifests as shortened levator, increased posterior puborectalis angles, and decreased puborectal distances. [53]
Cystography and voiding cystourethrography may be used to evaluate the bladder for other causes of irritative lower urinary tract symptoms, including the following:
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Intravesical masses
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Stones
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Bladder diverticula
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Urethral diverticula
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Urethral stricture
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Meatal stenosis
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Findings suggestive of a neurogenic or nonneurogenic voiding dysfunction
Additional studies
Urethral and vaginal culture results should be obtained for pathologic organisms (eg, fungi and gonorrheal, chlamydial, and trichomonal species).
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 currently used primarily for research purposes and do not have a defined role in the diagnosis of interstitial cystitis. Antiproliferative factor (APF) has shown promise in research assays as a biomarker for worsened disease and is currently being investigated as a clinical marker. [8, 9]
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.
Cystoscopy
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, with bladder overdistention, is performed to help exclude other causes of symptoms suggestive of interstitial cystitis and to provide evidence for the diagnosis of interstitial cystitis. In addition, a biopsy of the bladder can be performed to evaluate for carcinoma in situ or other inflammatory conditions. Contraindications to cystoscopy and bladder distention include the following:
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Anesthetic risk
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History of prior rupture during distention
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Pregnancy
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Urinary tract infection
Cystoscopy is sometimes 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 distention 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.
Researchers from the University of Pittsburgh reported that ulcers of bladder mucosa and areas with angiogenesis can be easily detected by using a flexible cystoscope with a narrow-band imaging (NBI) system. In their study of 52 patients, Ueda et al identified conventional ulcers in 37 patients, matching the accuracy of conventional cystoscopy. Moreover, in an additional 13 cases, NBI identified abnormal areas without ulcers, which were later correlated with areas of petechial hemorrhage and glomerulation after hydrodistension. The authors suggest that this system is highly practical for the diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS), but it has yet to be widely adopted. [54]
Diagnostic hydrodistention
Diagnostic hydrodistention (ie, overdistention) is performed by placing the irrigation fluid at 60-80 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 escape 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 perhaps for some mild trabeculation. The diagnostic distention 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 50-100mL of effluent may be blood tinged (terminal pinking) in patients with interstitial cystitis. The bladder capacity may be reduced in patients with the ulcerative 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 raspberry-like in appearance and are graded as mild, moderate, or severe, depending on their numbers. Glomerulations represent the most consistent finding on 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 checkerboard-like or lattice-like 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. A systematic literature review by Wennevik et al found that glomerulations did not correlate with symptoms and were found in patients without IC/BPS. [55]
Glomerulations may also develop in various other bladder conditions, including the following:
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Neoplasia
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Infective cystitis
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Radiation cystitis
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Chemical cystitis
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Defunctionalized bladder (ie, in patients on dialysis)
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Chronically underfilled bladder (eg, patients who have undergone urinary diversion).
Relief of urinary frequency, urgency, and pain has been reported, at least temporarily, in as many as 60% of patients following bladder overdistention. Some studies have additionally shown that this relief is durable for periods up to and exceeding 1 month. [56] However, many patients find that their symptoms are transiently exacerbated immediately following this procedure.
Bladder Biopsy
Some centers advocate limiting the use of cystoscopy and biopsy in the evaluation and workup of patients thought to have interstitial cystitis; however, such a biopsy may be helpful to help exclude other disorders. Biopsies are performed primarily to help rule out other varieties of cystitis or malignant or premalignant (eg, carcinoma in situ) lesions. They are also performed to evaluate for detrusor mastocytosis, which some authors have used in directing therapy (see discussion below). Postoperative catheter drainage should be instituted in patients who undergo deep biopsies to reduce the chance of perforation, extravasation, or both.
No pathognomonic histologic findings exist for interstitial cystitis, although some authors have found increased numbers of mast cells in the detrusor muscle or submucosa in affected individuals. The finding of mast cells may suggest a potential role for antihistamine compounds in the treatment of the condition. However, this finding neither confirms nor excludes the diagnosis.
An increased activation of the extrinsic apoptotic pathway in biopsy samples has also been shown and may ultimately lead to a better understanding of the disease, but, again, no diagnostic criteria can be associated with this finding. [57]
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.
For this test, 40 mL of potassium chloride solution (40 mEq KCl/100 mL water) are instilled into the bladder for 5 minutes. [49] 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, and a diagnosis is made with an increase of 2 or more points on a pain or urgency scale. Patients who do not have interstitial cystitis may experience little or no pain from the solution. In patients who do experience pain, a rescue solution of heparin and lidocaine is instilled upon completion of the study. Because of its lack of sensitivity and specificity, this test does not usually alter clinical decision-making and thus is generally not used. [3]
Urine Studies
Urinalysis results are usually normal. Microscopic hematuria and pyuria are present in some patients. Much research is being undertaken to identify urine markers expressed in patients with interstitial cystitis to develop a noninvasive laboratory test. By definition, urine culture results should be negative.
The absence of any abnormal urine cytology findings specifically suggests a diagnosis of interstitial cystitis. A voided or catheterized urine specimen demonstrating cytologic changes consistent with dysplasia, carcinoma in situ, or frank cancer should prompt immediate further urologic evaluation.
Urodynamic Studies
Urodynamic studies are not part of the routine evaluation for interstitial cystitis. 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 increased sensation 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. Sphincter electromyography may show some increased activity caused by pain with bladder filling.
The prevalence of involuntary bladder contractions in patients with interstitial cystitis symptoms ranges from 0-14%; however, bladder contractions on filling cystometry studies 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.
Bladder compliance in patients with interstitial cystitis is usually normal. Postvoid residual volume should be minimal. Findings from pressure flow studies and free uroflow studies are usually unremarkable. True detrusor-sphincter dyssynergia excludes the diagnosis of interstitial cystitis.
