Interstitial Cystitis Workup

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 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 the following:

• Intravesical masses
• Stones
• Bladder diverticula
• Urethral diverticula
• Urethral stricture
• Meatal stenosis
• Findings suggestive of a neurogenic or nonneurogenic voiding dysfunction

Additional studies

Urethral and vaginal culture results must be negative 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.

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.

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. Contraindications to cystoscopy and bladder distention include anesthetic risk, history of prior rupture during distention, pregnancy, and urinary tract infection.

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 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.

Diagnostic hydrodistention

Diagnostic hydrodistention (ie, overdistention) is performed by placing the irrigation fluid at 80-100cm 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.

Glomerulations may also develop in various other bladder conditions, including neoplasia, infectious cystitis, radiation cystitis, and chemical cystitis, and when the bladder is defunctionalized (ie, in patients on dialysis) or chronically underfilled (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. Initially, however, many patients find that their symptoms are transiently exacerbated following this procedure.

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 that these are necessary 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 [CIS]) lesions. They are also performed to evaluate for detrusor mastocytosis. 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.

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.

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. Due to its lack of sensitivity and specificity, this test does not usually alter clinical decision-making and thus is generally not recommended.^[14]

By definition, urine culture results should be negative. No urine cytology findings specifically suggest 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. 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.

Keay et al 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, as compared with normal controls and patients with other urogenital diseases.^[15]

The sensitivity and specificity of APF activity, decreased HB-EGF levels, and increased EGF levels in patients with interstitial cystitis compared with control groups were 94% and 95%, 93% and 89%, and 87% and 91%, respectively. The results were promising, but these assays are currently experimental and are not commercially available.

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 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 findings 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, 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.

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.