Download A 38-Year-Old Woman with Urinary Frequency

INTERSTITIAL CYSTITIS
A 38-Year-Old Woman with Urinary Frequency,
Urgency, and Pelvic Pain
Case Study and Commentary, Kenneth M. Peters, MD
INSTRUCTIONS
The following article, “A 38-Year-Old Woman
with Urinary Frequency, Urgency, and Pelvic
Pain,” is a continuing medical education (CME) article. To
earn credit, read the article and complete the CME evaluation form on page 52.
OBJECTIVES
After participating in the CME activity, primary
care physicians should be able to:
1. Recognize the classic presentation of interstitial cystitis
2. Know the differential diagnosis for the complaint of
urinary frequency, urgency, and pelvic pain
3. Describe tests used to diagnose interstitial cystitis
4. Recognize the importance of pain control in the treatment of interstitial cystitis
5. Describe the therapies used to treat interstitial cystitis,
including behavioral therapy, oral agents, intravesical
instillations, and neuromodulation
CASE STUDY
Initial Presentation
A visibly upset 38-year-old woman presents to her
new internist with the complaint of urinary frequency, urgency, and pelvic pain.
History
She says that her symptoms began 2 years ago after a documented urinary tract infection. The symptoms have worsened
over the past 2 years. She is frustrated because she has seen
3 different physicians during this time and no one has been
able to help her. She said that 1 physician prescribed antibiotics for “recurrent urinary tract infections,” but her symptoms never resolved. A voiding cystourethrogram was
performed that demonstrated no urethral or bladder abnormalities. An intravenous pyelogram also was normal. Her last
physician told her that there is “nothing wrong.”
Upon questioning, the patient states that she voids approximately 15 times during the day and 3 to 4 times per night. She
denies any incontinence. She has pain in her suprapubic area,
which is worse with a full bladder. She also reports severe dys42 JCOM July 2001 Vol. 8, No. 7
pareunia, which is putting a stress on her marriage. Past medical history is remarkable for mitral valve prolapse and irritable bowel symptoms. A previous laparoscopy performed by
her gynecologist showed no endometriosis. She takes ibuprofen 600 mg 3 times per day for her pain but this gives only
minimal relief. She has tried anticholinergics and urinary analgesics without improvement.
She states that she is very sensitive to medications but has
no definite allergies. She does not drink caffeinated beverages
and limits her fluid intake in hope of decreasing her daily
voids. She denies cigarette use and rarely uses alcohol due to
a worsening effect on her bladder symptoms. Both her parents are alive and have no significant medical problems.
Physical Examination
Physical examination reveals a distraught, thin female.
Height is 5'10", weight is 130 lb, blood pressure is
120/60 mm Hg, pulse is 70 bpm. General system examination is unremarkable. A vaginal examination demonstrates
normal external genitalia and no vaginal prolapse or discharge. There is no urethral fullness or tenderness. Significant tenderness is elicited with palpation of the bladder neck
area and along the levator muscles of the vagina. A rectal
examination demonstrates good sphincter tone and intact
anal wink reflex; no rectal mass or tenderness is elicited. A
postvoid residual measurement is 10 mL.
Laboratory Findings
Laboratory testing reveals a normal blood count and normal
levels of serum electrolytes, blood urea nitrogen (BUN), and
creatinine. A urinalysis is completely normal and culture
demonstrates no growth.
Voiding Diary
Voiding diary documents 14 voids per day. The maximum
voided volume is 175 mL and average voided volume is
95 mL. She has 3 nighttime voids with volumes ranging
between 60 mL and 75 mL.
From the Department of Urology, William Beaumont Hospital, Royal Oak, MI.
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CASE-BASED REVIEW
• What is the working diagnosis in this patient?
The differential diagnosis includes bacterial cystitis, interstitial cystitis, endometriosis, bladder cancer, urethral diverticulum, renal calculi, bladder calculi, sexually transmitted diseases, urinary retention, and pelvic malignancies. Infectious
etiologies are unlikely secondary to negative cultures and
unresponsiveness to antibiotics. Endometriosis and pelvic
malignancies have been ruled out by laparoscopy. There is
no evidence of urethral diverticulum on examination and
voiding cystourethrogram. The renal collecting system and
ureters were normal on intravenous pyelography, ruling out
stones as the cause of her symptoms. Although not applicable in this case, it should be noted that the finding of hematuria in a patient with irritative voiding symptoms mandates
an evaluation of the upper urinary tract, bladder cystoscopy,
and urine cytology to rule out bladder cancer.
Interstitial cystitis (IC) must be considered a very likely
diagnosis in the above scenario. IC patients often suffer for
years and seek multiple medical opinions before their disease
is diagnosed and effective treatment is initiated. The most
common complaints are urinary urgency, frequency, and
pelvic pain [1]. Sixty percent of IC suffers complain of pain
with sexual intercourse, and for many the pain is so severe
that they abstain altogether [2–4]. Most IC patients have been
treated with antibiotics for recurrent infections, although a
review of medical records usually fails to reveal documented
infections. IC patients often have other associated disorders
such as fibromyalgia, irritable bowel symptoms, and migraine
headaches. Many IC patients have seasonal allergies and sensitivities to medications and foods [5]. Although this patient
represents a classic presentation, it should be noted that IC
presents in a multitude of ways, with waxing and waning
symptoms, and with varying degrees of severity. Table 1 presents a brief self-administered questionnaire that can be handed to patients in the office to assess and monitor symptoms.
Initial Management
The primary care physician responds empathically
toward the patient, stating that he hears how frustrated she is. He tells her that he suspects she may have IC,
and that it is not unusual for patients with IC to have trouble
obtaining a diagnosis. He provides some education about IC
and recommends some behavioral therapies that may
relieve her symptoms. He refers her to a urologist for further
workup and evaluation.
• What behavioral therapies should be employed in the
treatment of IC?
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Diet and Self-Help
Diet modification and behavioral therapies are considered
the first step in relieving IC symptoms. Many patients with
IC are sensitive to various food items [6]. Patients should be
instructed to avoid caffeinated beverages and alcohol and
should be advised to eat a diet low in acidic foods (eg, tomatoes, citrus), which may worsen their bladder symptoms
(Table 2). Calcium glycerophosphate (Prelief), an over-thecounter dietary supplement that neutralizes the acid in
foods, may help improve IC symptoms, although no good
clinical trials have been published [7]. Most subjects with
irritative voiding symptoms dehydrate themselves in hopes
that they will void less. In IC, the protective barrier of the
bladder is likely compromised; this may allow the irritative
solutes in the urine (eg, potassium) to infiltrate the detrusor
muscle, causing bladder irritation and nerve upregulation.
Thus, patients who may have IC should be encouraged to
increase their water intake, diluting the urine and causing
less bladder irritation.
In addition to dietary restrictions and fluid management,
pelvic floor exercises and relaxation therapy should be emphasized [8]. Stress has been shown to worsen the symptoms
of IC, and stress management may help alleviate pain, urgency and frequency associated with IC [9]. A patient information sheet detailing self-help measures for IC is provided
on page 46.
Presentation to Urologist
The patient presents to a urologist, who reviews the
case and agrees that the symptoms are suggestive of
IC. Her tells her that he would like to schedule a diagnostic
procedure to help rule out other conditions and confirm the
diagnosis. As the patient’s pain is severe (8/10 on a standard
pain scale) and poorly controlled on nonsteroidal antiinflammatory drugs (NSAIDs), the urologist begins the patient on oxycontin 10 mg twice daily. This is titrated up to
40 mg twice daily, which gives her good pain relief. She is
educated regarding opioid use, including possible side effects (eg, constipation, sleepiness) and the potential for tolerance and withdrawal and is warned not to crush or chew the
tablets. For the first time in 2 years, the patient is hopeful that
her suffering will be alleviated.
• What methods are commonly employed to diagnose IC?
Diagnostic Testing
One can often make the diagnosis of IC on history alone after
ruling out other causes that can mimic the disease such as
documented bacterial cystitis, endometriosis, bladder cancer, and urethral diverticulum. Unfortunately, there are no
available urine or serum markers for IC, although several
Vol. 8, No. 7 July 2001 JCOM 43
INTERSTITIAL CYSTITIS
Table 1. Voiding and Pain Indices
Intersitial Cystitis Symptom Index
Interstitial Cystitis Problem Index
Q1.
During the past month, how much has each of the following been a
problem for you?
Q1. Frequent urination during the day?
0. _____ No problem
1. _____ Very small problem
2. _____ Small problem
3. _____ Medium problem
4. _____ Big problem
Q2. Getting up at night to urinate?
0. _____ No problem
1. _____ Very small problem
2. _____ Small problem
3. _____ Medium problem
4. _____ Big problem
Q3. Need to urinate with little warning?
0. _____ No problem
1. _____ Very small problem
2. _____ Small problem
3. _____ Medium problem
4. _____ Big problem
Q4. Burning, pain, discomfort, or pressure in your bladder?
0. _____ No problem
1. _____ Very small problem
2. _____ Small problem
3. _____ Medium problem
4. _____ Big problem
Add the numerical values of the checked entries; total score: ________
Q2.
Q3.
Q4.
Add
During the past month, how often have you felt the strong need
to urinate with little or no warning?
0. _____ Not at all
1. _____ Less than 1 time in 5
2. _____ Less than half the time
3. _____ About half the time
4. _____ More than half the time
5. _____ Almost always
During the past month, have you had to urinate less than 2
hours after you finished urinating?
0. _____ Not at all
1. _____ Less than 1 time in 5
2. _____ Less than half the time
3. _____ About half the time
4. _____ More than half the time
5. _____ Almost always
During the past month, how often did you most typically get up
at night to urinate?
0. _____ None
1. _____ Once
2. _____ 2 times
3. _____ 3 times
4. _____ 4 times
5. _____ 5 or more times
During the past month, have you experienced pain or burning
in your bladder?
0. _____ Not at all
2. _____ A few times
3. _____ Almost always
4. _____ Fairly often
5. _____ Usually
the numerical values of the checked entries; total score: ________
Reprinted with permission from O’Leary MP, Sant GR, Fowler FJ, et al. The interstitial cystitis symptom index and problem index. Urology 1997;
49 Suppl 5A:62.
promising markers are under investigation [10–14]. In their
1987 and 1988 workshops on IC, the National Institutes of
Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK)
developed a research definition for IC [15] (Table 3). The
NIDDK criteria were found to be far too restrictive to be
used as a clinical diagnosis for IC [16].
Hydrodistension
The gold standard for the diagnosis of IC has been bladder
hydrodistension under a general or regional anesthetic
[17,18]. This is performed in an operating room setting
where a complete cystoscopy can be performed to assess the
urethra and bladder. This will help rule out bladder cancer
44 JCOM July 2001 Vol. 8, No. 7
or urethral diverticulums. After inspection of the bladder, the bladder is filled by gravity drainage at 80 to
100 cm/H2O pressure to its capacity. Upward pressure
along each side of the urethra is often needed to maximally
distend the bladder to prevent leakage around the cystoscope. The bladder is allowed to distend until no more
water will run into the bladder, and this is allowed to dwell
for 2 minutes. The bladder is drained into a pitcher and the
volume measured. Typically with IC there is terminal hematuria seen when the bladder is drained. The average normal
bladder capacity under an anesthetic is 1115 mL, and the
average IC bladder capacity is 575 mL; however, in nonulcerative IC, the bladder capacity can be normal [19]. Upon
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CASE-BASED REVIEW
reinspecting the bladder, the vast majority of patients will
have glomerulations seen in all sectors of the bladder, the
hallmark of IC.
Approximately 15% of IC patients will have deep cracks
or ulcers on their bladder wall, which have been termed
Hunner’s ulcers and are associated with more severe symptoms [20]. Unfortunately, cystoscopic findings are not
pathognomonic for IC and one must make a clinical decision regarding the presence or absence of these findings
[21]. A bladder biopsy can be performed for pathologic evaluation and to rule out bladder cancer. The majority of IC
patients have chronic inflammation seen on pathology examination. Special stains can be performed to look for mast
cells, which if present may give more support to treat an
individual with an antihistamine. If ulcerative lesions are
present, these should be biopsied and the entire involved
area should be gently cauterized, which often leads to improvement in symptoms.
Patients with IC should be informed that their symptoms
may worsen for 2 to 3 weeks after a hydrodistension, after
which they usually fall to their baseline. In 50% of cases, a
marked improvement in symptoms may occur that can last
for many months. If an IC patient responds well to a hydrodistension, it can be repeated in the future as a part of multimodal treatment.
Potassium Sensitivity Test
A second test that is becoming popular for the diagnosis of
interstitial cystitis is the potassium sensitivity test. This test is
based on the hypothesis that there is increased epithelial permeability in the bladder of IC patients and that instilling a
potassium solution in the bladder will provoke symptoms of
urgency, frequency, and pain [22–24]. To perform this test,
2 solutions are placed in the bladder for 3 to 5 minutes.
Solution 1 is 45 mL of sterile water and solution 2 contains
400 mEq/L of KCl. After instilling the solution, the patient is
asked if it provokes symptoms on a scale of 0 to 5. A test is
considered positive when the patient does not react to water
but states the KCl caused symptoms to increase 2 points or
more on this scale. Studies have shown that 70% of IC subjects have a positive test compared with 4% of control subjects. The pain caused by this test can be alleviated by rinsing the bladder with water and instilling heparin and
bupivacaine hydrochloride into the bladder. The benefit of
the potassium sensitivity test is that it can be done in an
office setting, does not require cystoscopy, and may lead to a
more rapid initiation of treatment for the IC. The drawback
is that it does not allow inspection of the bladder for other
causes of symptoms, it evokes acute pain in the nonanesthetized patient, and it does not provide the patient the
opportunity to have a clinical improvement in symptoms
from a hydrodistension.
Table 2. Foods to Avoid in Interstitial Cystitis
Fruit
Apples
Apricots
Bananas
Cantaloupe
Citrus (fruit and
juice)
Cranberry juice
Cranberries
Grapes
Nectarines
Peaches
Pineapples
Plums
Pomegranates
Condiments
Mayonnaise
Soy sauce
Vinegar
Salad dressing
Vegetables
Avocados
Fava beans
Lima beans
Onions
Rhubarb
Tomatoes
Meat/fish/dairy
Anchovies
Caviar
Corned beef
Aged cheeses
Yogurt
Sour cream
Processed meats and
fish
Bread
Rye
Sourdough
Beverages
Carbonated
beverages
Caffeinated
beverages
Coffee
Tea
Alcohol
Additives
Aspartame
Saccharine
Nitrates/nitrites
Other
Nuts
Chocolate
Tofu
“Junk” food
Spicy food
• What is important to know regarding pain control in IC?
Pain Management
Pain control is a serious problem for the IC patient and should
be an integral component of the treatment regimen [25,26].
Once the pain is under control, treatments directed at IC are
usually more effective. Combination opioid/NSAID preparations such as codeine plus acetaminophen (Tylenol #3),
hydrocodone plus acetaminophen (Vicodin, Loracet, Norco),
or propoxyphene napsylate plus acetaminophen (Darvocet)
can be the initial pain medication used. It is recommended
that the total daily dose of acetaminophen not exceed 4 g per
day to prevent liver toxicity. Therefore, one must be aware of
the amount of acetaminophen in each tablet prescribed and be
certain that the number of pills taken per day does not exceed
the recommended dose (Table 4). If the maximum dose of the
combination product fails to adequately control the patient’s
pain, the patient can be switched to a pure opioid, such as oxycodone or morphine. The dosage is titrated upward until adequate pain relief is achieved. Nonopioid medications such as
acetaminophen or ibuprofen can be taken concurrently. In
patients not previously treated with opioids, oxycontin can be
started at a dose of 10 mg every 12 hours and can be titrated
upward every 2 to 3 days until the most beneficial dose with
the minimal side effects is achieved. Patients previously on
continued on page 47
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Vol. 8, No. 7 July 2001 JCOM 45
CASE-BASED REVIEW
continued from page 45
Table 3. NIDDK Research Criteria for Interstitial Cystitis
Inclusion criteria
01. Glomerulations or Hunner’s ulcer on cystoscopic examination
after hydrodistension under anesthesia
02. Pain associated with the bladder or urinary urgency
Exclusion criteria
01. Awake cystometric bladder capacity greater than 350 cc
02. Absence of intense urge to void with bladder filled to 100 cc
of gas or 150 cc of water during cystometry, at fill rate of
30–100 cc/min
03. Demonstration of involuntary bladder contractions on cystometry
04. Duration of symptoms less than 9 months
05. Absence of nocturia
06. Symptoms relieved by antimicrobials, urinary antiseptics, anticholinergics, or antispasmodics
07. Frequency of urination while awake less than 8 times per day
08. Diagnosis of bacterial cystitis or prostatitis within 3 months
09. Bladder or lower ureteral calculi
10. Active genital herpes
11. Uterine, cervical, vaginal, or urethral cancer
12. Urethral diverticulum
13. Cyclophosphamide or any type of chemical cystitis
14. Tuberculous cystitis
15. Radiation cystitis
16. Benign or malignant bladder tumors
17. Vaginitis
Table 4. Acetaminophen Levels in Commonly Prescribed
Opioid Compounds
Trade Name
Opioid
Tylenol #3
Darvocet-N 100
Vicodin
Vicodin ES
Lorcet 10/650
Norco 10/325
Codeine 30 mg
Propoxyphene 100 mg
Hydrocodone 5 mg
Hydrocodone 7.5 mg
Hydrocodone 10 mg
Hydrocodone 10 mg
Acetaminophen
300
650
500
750
650
325
mg
mg
mg
mg
mg
mg
Max
Pills/Day
12
06
08
05
06
12
the appropriate specialist for treatment of these associated
disorders should be considered.
Operative Procedure
The urologist performs a cytoscopy and hydrodistension under a spinal anesthetic. The urethra and bladder initially appear unremarkable. Following hydrodistention,
the bladder is found to have a capacity of 600 mL with associated terminal hematuria. On reinspection of the bladder, there
is noted to be diffuse petechial hemorrhages in all sectors of the
bladder and a deep ulcer seen at the right dome of the bladder
consistent with IC. Biopsies are taken and the ulcerative area is
completely cauterized. The patient is discharged to home in
good condition with instructions to follow up in 3 weeks.
18. Age younger than 18 years
NIDDK = National Institutes of Arthritis, Diabetes, Digestive and Kidney
Diseases.
opioids can be started at a dose of 20 mg every 12 hours and
titrated accordingly. Long-acting opioids such as oxycontin
are very effective in controlling pain, have a simple dosing
schedule, and remove the peaks and troughs of pain associated with intermittent opioids. Patients must understand that
under no circumstances should a sustained-release opioid
tablet be broken, crushed, or chewed. This can result in the
rapid release of a large dose of opioid, which can be lifethreatening. The type and dose of narcotics prescribed must
be individualized and take into account other sedative medications the patient currently takes.
Physicians not comfortable prescribing opioids should
refer the IC patient to a pain specialist. In any case, referral
to pain clinics knowledgeable in IC may be of benefit.
Various opioids or neuroleptics can be tried, along with
nerve blocks or implantable pain pumps to treat the severe
pain that can be associated with IC. In addition, many IC
subjects complain of associated problems such as fibromyalgia, irritable bowel syndrome, and vulvodynia. Referral to
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Follow-up
The patient returns to the office and the urologist reviews the
findings. The biopsies show chronic inflammation of the
bladder. The patient is very relieved to finally have a diagnosis. She also states that her symptoms have improved
since the hydrodistension. Her pain is very well controlled
and she has decreased her oxycontin to 20 mg twice daily.
Both her daytime frequency and nocturia have improved.
The patient is instructed to begin pentosan polysulfate sodium (Elmiron) 100 mg 3 times daily and hydroxyzine HCl to
be titrated over a 1-month period from 25 mg to 75 mg as a
single dose at night. She was also given information about
the Interstitial Cystitis Association (www.ichelp.org) as a
source of information and support.
• What pharmacologic treatments are directed at IC?
Oral Agents
A multimodality approach is the most effective means of
treating IC. The patient needs to understand that this is a
chronic condition and she needs to actively participate in her
Vol. 8, No. 7 July 2001 JCOM 47
INTERSTITIAL CYSTITIS
treatment. Once behavioral therapy [8] is optimized, oral
medications may be utilized if additional symptom relief is
needed.
Elmiron (Pentosan Polysulfate)
The only FDA-approved oral therapy for IC is pentosan
polysulfate (PPS). PPS is a glycosaminoglycan (GAG) that
binds tightly to the bladder mucosa. One theory in IC is that
the bladder mucosa is “leaky” and PPS may help rebuild the
natural bladder barrier leading to improvement in symptoms. PPS has been studied in several double-blind, placebocontrolled trials in the United States. In subjects meeting the
NIDDK criteria for IC, 38% of those receiving PPS at a dose
of 100 mg 3 times per day for 3 months reported a 50% reduction in bladder pain compared with 18% of placebotreated subjects [27]. An open-label physician usage study
that enrolled 2809 patients between 1986 and 1996 demonstrated that 61% of patients on PPS for a minimum of
3 months developed improvement in pain or discomfort and
this improvement was sustained while subjects were taking
PPS [28]. An IC patient must commit to taking PPS for 3 to
6 months before determining that it is ineffective and, in
addition, if symptom improvement is achieved, PPS may
need to be continued indefinitely to maintain the improvement. PPS is a well tolerated drug, with 1% to 4% of patients
complaining of alopecia (reversible upon discontinuation),
gastrointestinal upset, headache, liver function abnormalities, or abdominal pain. PPS should not be given in conjunction with routine use of therapeutic doses of aspirin or
NSAIDs. PPS appears to help a subset of IC patients and has
a good side-effect profile. PPS should be considered a firstline therapy for IC; however, since it may require several
months before any clinical improvement is seen, it should
not be used as a single agent.
Hydroxyzine
Hydroxyzine is an antihistamine and is used primarily in the
treatment of atopic dermatitis, urticaria, and allergic rhinitis.
There is some evidence that mast cells may be involved in the
pathogenesis of IC [29]. Hydroxyzine can reduce bladder
mast cell degranulation, and anecdotal evidence suggests it
may be effective in the treatment of IC [30–34]. Hydroxyzine
may be more effective in IC patients who are found to have
increased mast cells on bladder biopsy or those with seasonal
allergies. Hydroxyzine is also a sedative and in the short-term
often improves quality of sleep and decreases nocturia. With
prolonged use, both daytime and nighttime IC symptoms
may improve. Hydroxyzine should be started at a dose of
25 mg at night and titrated based on side effects to 75 mg per
night. The dose may need to be increased during allergy season. No controlled clinical studies on the efficacy of hydroxyzine for IC have been published.
48 JCOM July 2001 Vol. 8, No. 7
Antidepressants
Antidepressants can aid in the treatment of IC [35–37] and
can be combined with PPS as an initial treatment regimen.
Patients with chronic pain and sleep deprivation often develop clinical depression [26]. In addition, tricyclic antidepressants have been used for chronic pain disorders by increasing
the pain threshold. Low-dose amitriptyline (10 mg to 75 mg)
taken at night can be very effective in improving sleep and
diminishing urinary frequency and bladder pain. Patients
should be cautioned that tricyclic antidepressants can cause
weight gain and daytime sedation. The sedative side effects
will usually diminish with continued usage. The dose should
be slowly titrated to minimize symptoms. Some IC patients
will benefit from selective serotonin reuptake inhibitors, such
as fluoxetine or sertraline. These are nonsedating and should
be given once per morning. No good controlled clinical trials
on the use of antidepressants for IC have been performed;
however, they clearly can provide some symptomatic relief in
the treatment of IC.
• What intravesical therapies have been used for the
treatment of IC?
Intravesical Therapy
Intravesical therapies for IC have been a mainstay of treatment for many years [38,39].
Dimethyl Sulfoxide
Dimethyl sulfoxide (DMSO) is the only approved intravesical therapy for this disease. DMSO is an unusual compound.
It first was developed as an industrial solvent and may aid in
delivering other compounds, such as steroids and heparin,
into the detrusor muscle. Clinically, DMSO is thought to have
anti-inflammatory properties and mast cell stabilizing effects.
Studies on DMSO have been poorly controlled due to the
unique “garlic-like” odor that patients possess after being
instilled with this medication. A “cocktail” of medication
comprising 50 mL of DMSO, 100 mg of hydrocortisone, and
20,000 units of heparin is instilled in the bladder and retained
for 15 to 20 minutes once per week for 6 to 8 weeks. Bladder
symptoms may initially worsen; however, some IC patients
will experience symptomatic relief from this treatment. The
symptom improvement is often short-lived and is best after
the first course of DMSO. Subsequent treatments with this
medication tend not to be as effective.
Heparin
Intravesical heparin can be used in the treatment of IC
[40–45]. Heparin is a GAG-type compound and binds
tightly to the bladder mucosa. Similar to PPS, heparin may
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CASE-BASED REVIEW
help rebuild the protective GAG layer of the bladder and
improve bladder symptoms. Again, no controlled trials have
been performed on this compound. Patients are taught intermittent self-catheterization and instill 25,000 units of heparin
in their bladder in a 15 mL volume on a daily basis. The
patients hold this medication until their next void. Only 1%
to 3% of oral PPS is excreted in the urine, whereas heparin
therapy delivers a large bolus of this GAG compound directly to the bladder mucosa. Daily intravesical heparin can be
initiated in conjunction with beginning oral pentosan polysulfate. The heparin can be withdrawn after 8 to 12 weeks
and the patient maintained with oral therapy. This has the
potential to shorten the time interval required to achieve a
therapeutic effect from GAG therapy. If the patient cannot
tolerate PPS, intravesical heparin can be continued indefinitely. Heparin is not absorbed through the bladder mucosa,
so anticoagulation effects are not a concern.
Bacillus Calmette-Guerin
Intravesical Bacillus Calmette-Guerin (BCG) for the treatment of IC is in phase III clinical trials. A phase II doubleblind, placebo-controlled trial demonstrated a 60% clinical
response to BCG compared to a 27% placebo response rate
[46]. Subjects who received a single 6-week course of BCG
and responded were followed for over 2 years; 90% continued to have marked clinical improvement in both pain and
frequency symptoms despite no other therapy for their IC
[47]. BCG is a weakened strain of the tuberculosis bacteria
and has been used effectively for years in the treatment of
superficial bladder cancer. The exact mechanism of action of
BCG in bladder cancer is unknown, but it is thought to act
by stimulating an immune response in the bladder. There is
some evidence that IC may be secondary to an immune
imbalance in the bladder [48–55]. Intravesical BCG may correct this imbalance, leading to long-term clinical improvement. Fifty mg of BCG diluted in 50 mL of normal saline is
instilled in the bladder once per week for 6 weeks. Patients
are asked to retain the solution for as long as they can for up
to 2 hours. Bladder symptoms tend to worsen during the
instillation period of BCG due to its irritative effects, and
clinical improvement usually is not seen for at least 3 to
6 months. Because PPS is known to tightly bind to BCG and
may prevent attachment of the vaccine to the bladder lining,
patients should not be receiving PPS while being treated
with intravesical BCG.
Other
Other intravesical therapies need to be performed under a
general or regional anesthetic. These include sodium oxychlorosene [56] and silver nitrate. The utility of these treatments is in question and their use has mostly fallen out of
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favor. These treatments are very caustic to the bladder and
may lead to destruction of the bladder mucosa and formation of a new, more intact bladder lining. A voiding cystourethrogram should be performed to rule out vesicoureteral reflux before instilling these medications.
• Is there a role for surgical therapy in the treatment of IC?
Surgery for IC
Radical surgery for interstitial cystitis is rarely indicated and
should be used as a last resort. Augmenting the bladder or
diverting the urine while leaving the bladder in place is
often doomed to failure. Removing the bladder with urinary diversion may be effective in very select, end-stage
cases; however, this should not be considered the standard
of care for IC. Patients choosing this mode of therapy need
to be aware that this may not resolve the pain associated
with IC [57].
A new treatment that shows promise for refractory IC
patients is sacral nerve modulation (Medtronic, Inc., Minneapolis, MN). This technology is approved for urinary
urgency, frequency, urge incontinence, and idiopathic urinary
retention. The benefit of sacral nerve stimulation is that a temporary electrode can be placed via a percutaneous approach
and the integrity of the sacral nerves can be identified; the
patient can feel the stimulation prior to having a permanent
implant and the efficacy of sacral nerve stimulation can be
determined by measuring urgency, frequency, and pain with
the temporary electrode in place. If the patient has a positive
response to the temporary device, a permanent implant can
be placed in the operating room and programmed via an
external programmer similar to a cardiac pacemaker. Early
evidence suggests that sacral nerve modulation may be very
effective in treating refractory interstitial cystitis [58,59].
• Does IC occur in men?
IC in Men
Men presenting with symptoms of genital pain, perineal
pain, frequency, or dysuria are often labeled as having
chronic abacterial prostatitis. In fact, the majority of these
men have characteristic findings of IC upon cystoscopy and
hydrodistension and will respond to standard IC therapies
[60–63]. IC is more prevalent in men than previously
thought, and it is imperative that the clinician have a high
level of suspicion for IC in the man with chronic prostatitis
symptoms.
Vol. 8, No. 7 July 2001 JCOM 49
INTERSTITIAL CYSTITIS
Three Months Later
The patient returns 3 months after beginning PPS
and hydroxyzine and states she is 75% improved.
Her pain is manageable and her urgency and frequency is
much less. Overall, she is happy with her symptoms and
will continue on her current treatment.
Summary
This case highlights the typical presentation and treatment of
IC. It is important to consider IC in the differential diagnosis
of frequency, urgency, and pelvic pain with negative urine
cultures. Too often patients with IC go undiagnosed and are
told that nothing is wrong with them. Justifying their symptoms with a diagnosis is often therapeutic. Patients with IC
must understand that it is a chronic condition and there is no
single treatment that will cure the disease. They need to be
involved in the decision-making process regarding the treatment plan and be proactive in managing the disease with
dietary changes and stress reduction. The pain associated
with IC can be severe and needs to be treated. If the physician
is not comfortable treating the pain, the patient should be
referred to a pain clinic. Managing IC must be individualized
and physicians must include oral therapies, intravesical
instillations, and neuromodulation in their treatment regimen. The vast majority of IC patients can lead very manageable and productive lives.
Corresponding author: Kenneth M. Peters, MD, Dept. of Urology,
William Beaumont Hospital, 3601 W. 13 Mile Road, Royal Oak, MI
48073.
Financial disclosures: Dr. Peters is a member of the Speakers Bureau,
Alza Pharmaceuticals.
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Copyright 2001 by Turner White Communications Inc., Wayne, PA. All rights reserved.
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