eMedicine Specialties > Urology > Interstitial Cystitis

Interstitial Cystitis: Workup

Author: Eric S Rovner, MD, Professor, Department of Urology, Medical University of South Carolina
Contributor Information and Disclosures

Updated: Nov 24, 2009

Workup

Laboratory Studies

• 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.⁸
  • 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.

Imaging Studies

• 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.

Other Tests

• 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.

Diagnostic Procedures

• 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 Findings

No 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.

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