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Clinical Reviews


The generalist’s guide to interstitial cystitis

How to diagnose and treat all but refractory cases of this not-so-uncommon disease

February 2006 · Vol. 18, No. 2

 

The typical patient voids 16 times a day and 2 or more times at night. In later stages of the disease, she may urinate as often as 60 times a day and every half hour at night, severely eroding her ability to hold a job, travel, or lead a normal life. In fact, her quality of life may be impaired as much as that of a person with end-stage renal disease.1,2 She sees an average of 4 doctors and endures irritative voiding symptoms for 4 years before her disease is identified. The cause is unknown.

Interstitial cystitis produces a wide spectrum of symptom severity, occurring episodically with spontaneous flare-ups and remission, or with continuous, intractable urinary urgency and pain. Until recently, women presenting with urinary urgency, frequency, and pain were presumed to have a urinary tract infection (UTI) or overactive bladder, and were often treated—to no avail—with multiple courses of antibiotics or anticholinergics.

Fortunately, interstitial cystitis is gaining recognition, and effective treatments are emerging. Usually the ObGyn—often the first physician a woman consults—need refer only the refractory cases to a specialist. This article describes the components of diagnosis and the most effective treatments, including use of the first-line agents amitriptyline (Elavil) and pentosan polysulfate sodium (Elmiron).

CASE Is overactive bladder the cause of stubborn symptoms?

“R.H.,” a healthy 48-year-old G2P2 with a 5-year history of urinary urgency and frequency, reports that she voids “at least 15 times per day.” She denies any urge incontinence, but says she experiences occasional stress incontinence if she has a bad cold. Four years ago, she saw a urologist for these symptoms, after her husband said he was tired of having to stop the car so she could go to the bathroom. The urologist diagnosed a “small bladder,” performed urethral “stretching,” and prescribed oxybutynin.

Her symptoms improved for about 6 months, but then progressed and have now worsened. She began taking tolterodine, 4 mg daily, 2 months ago, as prescribed by her primary care physician. The sensation of painful urgency has eased, but there has been no change in frequency. R.H. used to wake as often as 4 times a night with the urge to urinate, but since she began taking zolpidem tartrate (Ambien) as a sleep aid, she now wakes only 2 times every night.

Why are her symptoms so persistent?

This woman’s case is a classic example of interstitial cystitis masquerading as overactive bladder. Treatment with anticholinergic drugs may ease urgency symptoms slightly, but has no real effect on frequency.

This case has 5 hallmarks of the syndrome of interstitial cystitis:

  1. Urgency
  2. Frequency (more than 8 voids/day, taking fluid intake into account)
  3. Bladder pain
  4. Nocturia (more than twice)
  5. Absence of a genitourinary tract infection

Patients show signs of “battle fatigue”

Women with interstitial cystitis may be anxious, depressed, angry, and sleep-deprived. In some women, stress exacerbates the urinary symptoms and pain (as do certain common foods and beverages, especially citrus, tomatoes, and caffeine).

Approximately 60% of patients report dyspareunia, and many report chronic pelvic pain. In fact, 75% of women who report chronic pelvic pain also have irritative voiding symptoms. Therefore, it is important to ask about lower urinary tract symptoms whenever a woman presents with pelvic pain.3,4

Pain may be suprapubic, vaginal, perineal, or originate in the groin or lower back. Although 16% of patients present solely with pain, and 30% have only urinary frequency, most patients suffer from both symptoms.

Approximately 40% report premenstrual or ovulatory exacerbation of symptoms, although symptoms may improve during pregnancy.5 Voided volumes are usually small, despite the strong urgency, which does not always resolve. Pelvic pain may ease after voiding but recurs shortly.

Insidious, worsening course

Symptoms appear insidiously and worsen to a “final” stage within 5 to 15 years, at which point a plateau is reached with little further progression.6 Some experts suggest that the disease be classified as “early non-ulcerous” or “classic ulcerous.”

  • In early disease, bladder capacity exceeds 450 cc under anesthesia, with glomerulations and hemorrhage.
  • In classic disease, bladder capacity is less than 450 cc under anesthesia, and Hunner’s ulcers and fissures are evident. Hunner’s ulcers are described as “a central scar with small fibrin deposits before distension, and post-distension edema.”7

For now, however, there are no agreed-upon markers to distinguish the 2 types of disease.

The female-to-male ratio is 9:1, and about 500,000 to more than 1 million adults in the United States are thought to have interstitial cystitis.8 Caucasian women constitute 95% of patients, and the average age at diagnosis is 45 years. Thirty percent of women with interstitial cystitis are 30 years old or younger. Significantly more women with interstitial cystitis have had a hysterectomy than controls.9

For a diagnosis, skip the NIH criteria

Symptoms

Although the National Institutes of Health (NIH) established diagnostic criteria for research subjects, the criteria are overly stringent—60% of women with symptoms typical of interstitial cystitis do not qualify, but should not necessarily be excluded from diagnosis and treatment.

When a woman has the hallmark symptoms listed on page 57, but also reports continuous pain or dysmenorrhea, other pelvic pathology such as endometriosis should be considered, although interstitial cystitis should be included in the differential diagnosis of any woman reporting pelvic pain.

Incontinence is atypical. If present, it merits an incontinence evaluation to detect detrusor hyperreflexia or detrusor-sphincter dyssynergia.

Dysuria suggests a UTI, urethral diverticulum, urogenital atrophy, or vaginitis. Many patients present with an erroneous diagnosis of “recurrent UTIs.”

Diagnostic tools

Voiding diaries are useful and can be revealing. The Pelvic Pain and Urinary Frequency (PUF) scale, developed by Parsons, is helpful in predicting interstitial cystitis (see the Clip-and-save chart). The higher the score, the greater the likelihood of interstitial cystitis, particularly with a score of more than 8.

Another tool is the O’Leary-Sant Index, which measures pain, voiding symptoms, and quality of life.

Physical examination and laboratory studies

Perform a pelvic exam to rule out other diseases and pelvic pathology, including sexually transmitted diseases, urethral diverticulum, and pelvic masses. Typically, the pelvic exam in women with interstitial cystitis is negative except for suprapubic and/or trigonal tenderness.

Urinalysis, culture, and sensitivity are warranted but are usually negative.

Cytology should be analyzed if microscopic hematuria is present, or with other risk factors such as a history of smoking or age over 40.

Obtain cultures for sexually transmitted diseases if clinically indicated.

Urodynamic studies are not necessary to diagnose interstitial cystitis. However, if incontinence is present, a cystometrogram can confirm detrusor hyperreflexia. Otherwise the cystometrogram is normal except for heightened sensation or pain with bladder filling, or a bladder capacity of less than 350 cc.

The potassium sensitivity test: Useful but painful

Women with interstitial cystitis are thought to have increased bladder permeability that allows potassium to pass through to the detrusor muscle. Thus, the potassium sensitivity test often is used to diagnose the condition. The test is an office procedure in which 2 separate solutions are instilled into the bladder: 40 cc sterile water followed by 40 cc of a solution of 400 mEq potassium per liter of water. After each solution is instilled, the patient is monitored for symptoms. The test is positive when the patient responds only to the potassium.

The response may be marked and painful, and the bladder should be emptied immediately. Subsequent irrigation with sterile water may be necessary to alleviate the discomfort caused by the potassium solution. Symptoms provoked by the test generally subside after bladder emptying, but can persist and cause moderate distress, which limits the utility of this office-based test.

Parsons et al10 demonstrated an 81% positive response (197 of 244 women) to the test among women with pelvic pain, compared with 0 of 47 patients with no pelvic pain. They also found that 70% of patients with interstitial cystitis and 4% of controls had a positive response.

If a woman is extremely volume-sensitive during the water phase, the potassium phase may not be accurate. A false-positive response can be caused by infection or prior exposure to radiation or chemotherapy. A thorough history is imperative.

The gold standard: Cystoscopy under anesthesia

Cystoscopy with hydrodistention under general anesthesia is the surest way to diagnose interstitial cystitis or rule it out. Sterile water or saline is infused until bladder capacity is reached. Bladder rupture occurs in up to 10% of patients, so careful inspection during filling is crucial. After 5 minutes of distension, bladder volume is measured into a calibrated beaker. Terminal hematuria (the last 50 cc of effluent) often is noted.

Normal bladder capacity under anesthesia is 1,000 cc, but it is reduced in women with interstitial cystitis. Bladder capacity of 450 cc or less under anesthesia indicates a more contracted bladder and a later-stage disease. Glomerulations, petechiae, fissures, or (rarely) Hunner’s ulcers typically are visible, regardless of bladder volume. However, the presence of glomerulations does not necessarily make the diagnosis, because they can be found in asymptomatic women. Further, cystoscopic observations do not always correlate with the severity of symptoms (nor does positive biopsy always reflect interstitial cystitis).

Hydrodistention is not only diagnostic, but also can be therapeutic, as sympathetic nerve fiber density decreases afterward.11 However, the need for this procedure is under debate, due to the limitations described above. A bladder capacity less than 1,000 cc with the presence of glomerulations or petechiae and fissures, with or without the Hunner’s ulcers, constitutes a definitive diagnosis.

Cystoscopy under anesthesia is recommended because medical treatment can be costly and cause significant side effects. An accurate diagnosis should precede therapy to avoid misdirected therapy in a patient who does not have interstitial cystitis. Moreover, cystoscopy can rule out bladder neoplasms or other diseases. Some bladder carcinomas have been missed in women treated empirically for interstitial cystitis.12

Cystoscopic images “paint a thousand words.” When a woman sees her cystoscopy images, the picture indeed “paints a thousand words.” For many women, the images “justify” their symptoms and confirm that the disease is real.

CASE Don’t treat a UTI without a positive culture

“M.P.” is a healthy 44-year-old G2P2 with a history of recurrent UTIs. Approximately 14 months ago, while on vacation, she began having symptoms of urinary frequency, urgency, and lower abdominal pain that were relieved with voiding. She called her primary care physician, who prescribed levofloxacin and phenazopyridine over the phone for a presumed UTI. Since the patient was out of town, a urine culture was not obtained.

When M.P. returned from vacation, her symptoms recurred, so she underwent urinalysis, including culture and sensitivity, and began a 7-day course of nitrofurantoin (100 mg twice daily). When her symptoms did not improve by day 4, a second course of levofloxacin was given. The urine culture was sterile. As her physician recommended, M.P. increased her fluid intake, including water and cranberry juice. She also avoided sexual relations, since they exacerbated her symptoms, which improved overall but did not clearly abate.

Three months later her symptoms returned in full force.

How would you treat this patient?

Interstitial cystitis can produce symptoms consistent with a lower UTI, but urine cultures will be negative and the response to antibiotics will be minimal. Many patients call their physicians and report “another UTI.” However, if the woman is healthy with no history of renal disease or diabetes, consider interstitial cystitis. Obtain urine culture results from other physicians, if possible, to determine whether bacterial infection was ever confirmed.

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