Interstitial cystitis (IC) is a chronic, painful
inflammatory condition of the bladder wall. Although there is no cure for IC, many
treatment options are currently available. This overview is designed to help physicians
and patients develop a step-by-step treatment plan.
Since IC symptoms vary from patient to patient, it is
important to consider which treatment, or combination of treatments, is appropriate for
each individual. Physicians and patients should discuss all viable treatment options.
WHAT IS INTERSTITIAL CYSTITIS?
Interstitial cystitis (IC) is a chronic
inflammatory condition of the bladder wall. Its cause is unknown. Symptoms are similar to
a urinary tract infection (UTI), also known as common cystitis. However, common cystitis
is caused by bacteria and can be successfully treated with antibiotics.
Unlike common cystitis, IC is believed not to be caused
by bacteria and does not respond to conventional antibiotic therapy. It is important to
note that IC is not a psychosomatic disorder nor is it caused by stress.
WHO IS AFFECTED?
IC can affect people of any age, race or sex. It is,
however, most commonly found in women. A recent study estimates that there may be more
than 700,000 cases of IC in the US.
However, this is considered an underestimation because IC
is often undiagnosed or misdiagnosed. [Curhan, et al, "Epidemiology of Interstitial
Cystitis: A Population-Based Study," Journal of Urology, February 1999, pp. 549-552]
WHAT ARE THE SYMPTOMS?
Some or all of these symptoms may be present:
Frequency: Day and/or night frequency of urination
(up to 60 times in 24 hours in severe cases). In early or very mild cases, frequency is
sometimes the only symptom. Some patients experience mild, moderate or severe nighttime
frequency, while others may experience no nighttime voiding. The absence of nighttime
voiding does not exclude the diagnosis of IC.
Urgency: The sensation of having to urinate
urgently, which may also be accompanied by pain, pressure or spasms.
Pain: Can be in the pelvic region, bladder,
urethral or vaginal areas. Pain is also frequently associated with sexual intercourse. Men
with IC may experience testicular, scrotal and/or perineal pain, and painful ejaculation.
The absence of pain does not exclude the diagnosis of IC.
Other Disorders: Some patients also report muscle
and joint pain, migraines, allergic reactions and gastrointestinal problems, as well as
the more common symptoms of IC described above. It appears that IC has an as yet
unexplained association with certain other chronic diseases and pain syndromes such as
vulvar vestibulitis, fibromyalgia and irritable bowel syndrome. [Alagiri, et al,
"Interstitial Cystitis: Unexplained Associations With Other Chronic Disease and Pain
Syndromes," Supplement to the journal, Urology, May 1997, pp. 52-57]. Many IC
patients, however, have only bladder symptoms.
HOW IS IC DIAGNOSED?
Most IC patients have difficulty obtaining a
diagnosis. To make a proper diagnosis of IC:
Take urine cultures to determine if there is a
bacterial infection present.
Rule out other diseases and/or conditions that
have symptoms resembling IC. These diseases may include bladder cancer, kidney disorders,
tuberculosis of the bladder, vaginal infections, sexually transmitted diseases,
endometriosis, radiation cystitis and neurological or rheumatologic disorders.
Perform a cystoscopy with hydrodistention if no
infection is present and no other disorder is discovered. Cystoscopy during a routine
office visit may not reveal the characteristic abnormalities of IC.
It is necessary to distend the bladder under general or
regional anesthesia in order to see glomerulations (pinpoint hemorrhages) on the bladder
wall which are the hallmark of this disease, and are present in 90 percent of IC patients.
Five to 10 percent of IC patients have ulcers on the bladder wall, which are called
Hunner's ulcers or patches. Ten percent of IC patients show no cystoscopic signs of
pinpoint hemorrhages or ulcers, yet still have the symptoms of IC. If cystoscopy is
performed in the doctor's office, using only local anesthesia, the diagnosis of IC may be
missed. Also, this "in office" procedure may be too painful for some IC
patients. A biopsy of the bladder wall may be necessary to rule out other diseases such as
bladder cancer and to assist in the diagnosis of IC. IC is not associated with bladder
cancer.
Bladder distention: Under general anesthesia, the
bladder is stretched by filling it with water. This is part of the diagnostic procedure
for IC, and it may be therapeutic as well for some patients.
A COMPREHENSIVE TREATMENT PLAN
Non-invasive techniques, such as diet modification &
self-help, may be used in combination with other, more aggressive treatment modalities,
and are considered a first step in relieving IC symptoms. Response to treatment is
individual.
Diet & Self-Help: A diet low in
acidic foods, and avoiding beverages such as coffee, tea, carbonated and/or alcoholic
drinks, may be helpful in reducing IC symptoms. Prelief®, an over-the-counter dietary
supplement, may help IC patients better tolerate acidic foods and beverages.
Self-help measures include stress-reduction techniques,
pelvic floor relaxation exercises, biofeedback, and bladder-retraining (once pain is under
control).
Transcutaneous Electrical Nerve
Stimulation (TENS): This device, which is worn externally, may help to relieve bladder
pain.
The following Oral Medications may be
added if more relief is needed:
Tricyclic antidepressants:
Used for their anti-pain properties, and prescribed in lower dosages for treating IC than
would be used for treating depression. Benefits include: anticholinergic effects which
help decrease urinary frequency; sedative effects; and the blockage or reuptake of certain
neurotransmitters that cause the brain to misinterpret or ignore pain impulses.
The most common tricyclic antidepressants used to treat
IC are: amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®),
doxepin (Sinequan®), and imipramine (Tofranil®). Also, Selective Serotonin Reuptake
Inhibitors (SSRIs), such as paroxetine (Paxil®), may be helpful.
Antihistamines:
Useful in treating IC, especially for IC patients with concurrent allergies. The most
widely used antihistamine to treat IC is hydroxyzine. It affects mast cell degranulation
which is thought to play a part in some IC patients' symptoms. It also has sedative and
anxiety reducing effects. Hydroxyzine is available in two oral forms--hydroxyzine pamoate
(Vistaril®), and hydroxyzine hydrochloride (Atarax®). Vistaril has a slightly higher
absorption rate. Atarax is available in liquid form for patients allergic to fillers or
dyes used in the capsules or pills. Cromolyn sodium (Gastrocrom®), a mast cell inhibitor,
may also help to relieve IC symptoms in some patients.
Elmiron (pentosan
polysulfate sodium): FDA-approved in 1996. It is the only oral medication approved
specifically for use in IC. Thought to work by restoring a damaged, thin, or
"leaky" bladder surface. Eases the pain and discomfort of IC.
Pain Medications:
For mild to moderate IC pain, tricyclic antidepressants may be useful. Also,
anticonvulsants such as gabapentin (Neurontin®) and clonazepam (Klonopin®) are currently
being used to treat chronic pain, as are muscle relaxants such as Valium® and Baclofen®.
Short-acting opioid analgesics such as Vicodin® and Percocet® may be used to treat
moderate, intermittent IC pain. OxyContin®, MS-Contin® and Duragesic® are long-acting
analgesics that are useful in treating chronic, severe IC pain. [Brookoff D. The Causes
and Treatment of Pain in Interstitial Cystitis, p. 177-192. In Sant, GR (ed Cystitis.
Lippincott-Raven, New York, 1997. Reprints of this article are available through the ICA.]
Other oral medications
include: Antispasmodics (Urised®) and anticholinergics (Detrol®, Ditropan XL®,
Levsin®); H2 Blockers, such as Tagamet® and Zantac®; urinary alkalinizing agents,
Bicitra® and Polycitra-K®; adrenergic blockers, Cardura®, Flomax® and Hytrin®;
leukotriene inhibitors such as Singulair® (montelukast); and combination medications such
as Urimax® (antispasmodic plus analgesic).
A combination of these treatments may be needed. An
example of an individualized treatment plan might include diet modification, combined with
the regular use of a tricyclic antidepressant; Elmiron; plus an opioid analgesic for
breakthrough pain.
The following Bladder Instillations may
be added to the treatment protocol, if necessary:
DMSO (dimethyl sulfoxide),
Rimso®-50: approved for use in IC in 1978. Instilled directly into the bladder. Believed
to work as an anti-inflammatory agent. DMSO can be combined with steroids, heparin, and/or
local anesthetics.
Heparin: has both
anti-inflammatory and surface protective actions. Heparin may mimic the activity of the
bladder's mucous lining, temporarily "repairing" the glycosaminoglycans (GAG)
layer.
Other bladder instillations include:
Clorpactin WCS-90® (oxychlorosene sodium) -- can
be very painful and requires general anesthesia, although it has been used in dilute form
in the office setting.
Silver nitrate -- used infrequently, and
considered an outdated therapy.
Electromotive Drug Administration
(EMDA®)
EMDA is a newly developed controlled medication delivery system created by Physion.
EMDA is proposed as an alternative to conventional administration of medications for
urologic conditions. EMDA utilizes an electric current to send an accelerated, directional
movement of medication (in an intravesical solution) deep into bladder tissues. The rate
of medication administration can be controlled by varying the intensity of the current.
The potential uses of EMDA therapy for IC include the delivery of local anesthetics,
anti-inflammatories, bladder coating agents and other medications directly and deeply into
the bladder wall.
Surgery:
Laser Surgery: has
been successfully used to treat Hunner's ulcer (or patch), present in 5 to 10 percent of
IC patients. No other uses for treating IC with lasers have been clinically proven,
therefore laser surgery should be reserved for the ulcerative form of IC only.
Surgery:
considered only as a last resort. Several types of surgeries have been used to treat IC,
including bladder augmentation, urinary diversion and construction of an internal pouch.
Serious complications can result from surgery, and these procedures may not relieve pain
(see the ICA Fact Sheet, IC & Surgery).
Treatments NOT effective for IC:
Urethral dilatation
Urethrotomy
CLINICAL TRIALS USING
EXPERIMENTAL THERAPIES CURRENTLY UNDERWAY & AVAILABLE TO IC PATIENTS
IMPORTANT: The following treatments are not yet
approved by the U.S. Food & Drug Administration for use in IC. However, patients may
participate in clinical studies of these treatments. Check the Research section of
www.ichelp.org for further information on current clinical trials, including site
locations.
Bacillus Calmette-Guerin
The National Institutes of Health (NIH) IC Clinical Trials Group has begun enrollment
for a double-blind, placebo-controlled, multi-center study of BCG (bacillus Calmette
Guerin). This is an intravesical treatment (instilled into the bladder). While its exact
mechanism of action in IC is not yet known, BCG is thought to work by boosting the immune
system.
Cystistat®
Bioniche Life Sciences, Inc., a Canadian biopharmaceutical company, has begun a
multi-center, placebo-controlled study of Cystistat® (sodium hyaluronate) for the
treatment of interstitial cystitis (IC). Intravesical administration of sodium hyaluronate
is thought to act by direct contact with the defective mucosal lining of the bladder (a
widely accepted theory for the cause of IC symptoms) and replacing the deficient GAG
layer.
InterStim®
The neuromodulation device by Medtronic, Inc., called InterStim® Therapy for Urinary
Control, is now being considered as a potential IC treatment when other more conservative
therapies have failed. Although it is not yet approved for the treatment of IC,
pre-clinical trials have been completed and FDA studies are currently underway. InterStim
consists of a small, surgically implanted device that is used to send mild electrical
pulses to nerves located in the lower back (just above the tailbone). These nerves
influence the bladder and surrounding muscles that manage urinary function. The InterStim
system is surgically placed under the skin, typically in the lower back.
SI-7201(Sodium hyaluronate)
Seikagaku Corporation is conducting a double-blind, placebo-controlled multi-center
clinical study evaluating the safety and effectiveness of intravesical instillations of
sodium hyaluronate solution (SI-7201). SI-7201 is thought to work by providing a coating
on the lining of the bladder.
EXPERIMENTAL TREATMENTS BEING
CONSIDERED FOR STUDY
IMPORTANT: The following treatments are not yet
approved by the U.S. Food & Drug Administration for use in IC, and have not yet
undergone clinical trials. They are not currently available to IC patients in the U.S.
RTX® (resiniferatoxin)
RTX® is the brand name of resiniferatoxin, a new substance that is being proposed as
a potential intravesical therapy for IC. When placed directly into the bladder, RTX works
by "deadening" the sensory nerve fibers of the bladder. When used to treat IC,
RTX has the potential to help not only urgency and frequency, but also bladder pain. RTX
is not currently available for use in IC in the U.S. However, clinical studies are being
planned.
Botulinum Toxin
Researchers are investigating the use of intravesical botulinum toxin for the
treatment of IC. By studying the nerve pathways that are affected by botulinum toxin, they
hope to provide new targets and treatments for IC. This treatment is not currently
available for use in IC in the U.S. However, clinical studies are being planned.
IMPORTANT RESEARCH ADVANCES
Markers: Of particular importance
is the work on IC urinary markers. A unique protein in the urine of IC patients had been
isolated. This protein, called APF (antiproliferative factor), may prevent the growth of
new, healthy bladder cells in IC patients. APF was not found in urine specimens from
patients without any urologic symptoms or from those who have acute urinary tract
infections or other urologic conditions. This protein may be directly responsible for
preventing repair of the damaged epithelial lining in IC patients. In addition, it has
been discovered that heparin-binding epidermal growth factor-like growth factor (HB-EGF),
known to be important for epithelial cell proliferation and wound healing, is
significantly decreased in IC patient urine specimens.
Additional studies have confirmed increased levels of
APF, EGF, IGFBP-3 (insulin-like growth factor binding protein-3) and interleukin-6 (IL-6)
in urine samples from patients with IC, and have also demonstrated decreased levels of
HB-EGF, cyclic GMP and methylhistamine.
The results of further research could lead to
identification of agents that will suppress the production of APF, or enhance the
production of HB-EGF, both resulting in the formation of a healthy bladder lining. APF may
ultimately provide a non-invasive clinical test for IC. This would have a major impact on
early diagnosis and treatment.
Genetics: Recent studies indicate a
higher-than-expected prevalence of IC among first degree relatives of index IC cases,
concordance among monozygotic twins for IC, and several families with IC in multiple
generations. These findings are consistent with an inherited susceptibility to IC. Linkage
analysis and positional cloning can be used to identify location of susceptibility gene(s)
to IC. The rapid progress being made in sequencing the human genome will facilitate
identification of such genes.
