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Causes
The cause of interstitial cystitis is unknown, though several theories have been put forward (these include autoimmune, neurologic, allergic and genetic). Regardless of the origin, it is clear that IC patients struggle with a damaged mucin, aka the GAG layer, aka bladdering lining. When this protective coating is damaged (perhaps via a UTI, excessive consumption of coffees or sodas, traumatic injury, etc.), urinary chemicals can "leak" into surrounding tissues causing pain, inflammation and urinary symptoms. Oral medications like Elmiron and medications which are placed directly into the bladder via a catheter work to repair and hopefully rebuild this damaged/wounded lining, allowing for a reduction in symptoms.

Recent work by the University of Maryland, Baltimore indicates that genetics are a factor in, and may even (in some cases) be the cause of IC. Two genes, FZD8 and PAND, are associated with the syndrome. FZD8, at gene map locus 10p11.2, is assocated with an antiproliferative factor secreted by the bladders of IC patients which "profoundly inhibits bladder cell proliferation," thus causing the missing bladder lining. PAND, at gene map locus 13q22-q32, is associated with a constellation of disorders (a "pleiotropic syndrome") including IC and other bladder and kidney problems, thyroid diseases, serious headaches/migraines, panic disorder, and mitral valve prolapse.

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Symptoms
It may well be that the symptoms of interstitial cystitis have multiple causes, and IC is actually several syndromes which will eventually be discerned. For example, patients with Hunner's Ulcers are believed to be the most advanced cases. They have larger "wounds" in the bladder that are much more difficult to treat. It is estimated that only 5 to 10% of patients have these ulcers. Far more patients may experience a very mild form of IC, in which they have no visible wounds in their bladder, yet struggle with symptoms of frequency, urgency and/or pain. Still other patients may have discomfort only in their urethra, while others struggle with pain in the entire pelvis. Some patients may experience pelvic floor tightness and dysfunction, while others have normal muscle tone.

Often the symptoms of IC are misdiagnosed as a "common" bladder infection (cystitis), however unlike cystitis, IC has not been conclusively proven to be a bacterial infection and the mis-prescribed treatment of antibiotics is ineffective. The symptoms of IC may also initially be attributed to prostatitis and epididymitis (in men) and endometriosis and uterine fibroids (in women).

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Diagnosis
Diagnosis has been greatly simplied in recent years with the development of two new methodologies. The Pelvic Pain Urgency/Frequency (PUF) Patient Survey, created by C. Lowell Parsons, is a short questionnaire that will help doctors identify if pelvic pain could be coming from the bladder. The KCL Test, aka the Potassium Sensitivity Test, uses a mild potassium solution to test the integrity of the bladder wall. Though the latter is not specific for IC, it has been determined to be helpful in predicting the use of compounds, such as pentosan, which are designed to help repair the GAG layer. The previous "gold standard" test for IC was the use of hydrodistention with cystoscopy. Researchers, however, determined that this visual examination of the bladder wall after stretching the bladder was also not specific for IC and that the test, itself, can contribute to the development of small glomerulations (aka petechial hemorrhages) often found in IC. Thus, a diagnosis of IC is one of exclusion, as well as a review of clinical symptoms.

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Treatment
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Diet
The foundation of therapy is a modification of diet to help patients avoid those foods which can will further irritate the damaged bladder wall. Common offenders include coffees, teas, herbal teas, green teas, all sodas (particularly diet), concentrated fruit juices, multivitamins, monosodium glutamate, chocolate, and potassium-rich foods such as bananas. Most IC support groups and many urology clinics have diet lists available.

The problem with diet triggers is that they vary from person to person: the best way for a person to discover his or her own triggers is to use an elimination diet. This is where someone cuts out all foods except the basics (e.g. potatoes, bread, rice, water) and then introduces new foods one at a time. Trying to discover which foods are one's own triggers without the use of an elimination diet is like trying to do a scientific experiment whilst altering 10 variables all at once.

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Bladder coatings
As recently as a decade ago, treatments available were limited to the use of astringent instillations, such as clorpactin or silver nitrate, designed to kill infection and/or strip off the bladder lining. In 2005, our understanding of IC has improved dramatically and these therapies are now no longer done. Rather, IC therapy is typically multi-modal, including the use of a bladder coating, an antihistamine to help control mast cell activity and a low dose antidepressant to fight neuroinflammation.

The two US FDA approved therapies for IC have had recent setbacks in various research studies. Oral Elmiron (aka pentosan polysulfate) is believed to provide a protective coating in the bladder, however data released in late 2005 by Alza Pharmaceuticals suggests that 84% of Elmiron is eliminated, intact, in feces. Another 6% is excreted via urine. Reference: Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers. Xenobiotica. 2005 Aug;35(8):775-84. In addition, the NIH funded ICCTG study of pentosan revealed results only slightly better than placebo.

DMSO, a wood pulp extract, is the only approved bladder instillation for IC yet it is much less frequently used in urology clinics. Research studies presented at recent conferences of the American Urological Association by C. Subah Packer have demonstrated that the FDA approved dosage of a 50% solution of DMSO had the potential of creating irreversible muscle contraction. However, a lesser solution of 25% was found to be reversible. Long term use is questionable, at best, particularly given the fact that the method of action of DMSO is not fully understood.

More recently, the use of a "rescue instillation" composed of elmiron or heparin, cystistat, lidocaine and sodium bicarbonate, has generated considerable excitement in the IC community because it is the first therapeutic intervention that can be used to reduce a flare of symptoms. Published studies report a 90% effectiveness in reducing symptoms.

Another bladder coating treatment is that of Cystistat(TM) which consists primarily of sodium hyaluronate. It is believed to replace the deficient GAG layer on the bladder wall. Like most other intravesical bladder treatments, this treatment requires the patient to lie for 20 - 40 minutes, turning over every ten minutes, to allow the chemical to 'soak in' and give a good coating, before it is passed out with the urine.

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Pelvic floor treatments
Pelvic floor dysfunction may also be a contributing factor thus most major IC clinics now evaluate the pelvic floor and/or refer patients directly to a physical therapist for a prompt treatment of pelvic floor muscle tension or weakness. Pain in the bladder and/or pelvis can trigger long term, chronic pelvic floor tension which is often described by women as a burning sensation, particularly in the vagina. Men with pelvic floor tension experience referred pain, particularly at the tip of their penis. In 9 out 10 IC patients struggling with painful sexual relations, muscle tension is the primary cause of that pain and discomfort. Tender trigger points, small tight bundles of muscle, may also be found in the pelvic floor.

Pelvic floor dysfunction is a fairly new area of specialty for physical therapists world wide. The goal of therapy is to relax and lengthen the pelvic floor muscles, rather than to tighten and/or strengthen them as is the goal of therapy for patients with incontinence. Thus, traditional exercises such as Kegels, can be helpful as they strengthen the muscles, however they can provoke pain and additional muscle tension. A specially trained physical therapist can provide direct, hands on, evaluation of the muscles, both externally and internally. While weekly therapy is certainly valuable, most providers also suggest an aggressive self-care regimen at home to help combat muscle tension, such as daily muscle relaxation audiotapes, stress reduction and anxiety management on a daily basis. Anxiety is often found in patients with painful conditions and can subconsciouly trigger muscle tension.

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Pain control
Pain control is usually necessary in the IC treatment plan. The pain of IC has been rated equivalent to cancer pain and should not be ignored to avoid central sensitization. The use of a variety of traditional pain medications, including opiates, is often necessary to treat the varying degrees of pain. Complementary therapies such as acupuncture, massage, and biofeedback are also beneficial to some patients. Even children with IC should be appropriately addressed regarding pelvic pain, and receive necessary treatment to manage it.

Electronic pain-killing options include TENS (a machine connected to sticky pads which one palces on their body at certain pressure points; the tens machine sends electrical impulses to the skin, using the human body as an 'earth'). PTNS stimulators have also been used, with varying degrees of success. This is similar to a TENS treatment, except a needle is used rather than sticky pads.

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Other treatments
Bladder distentions (a procedure which stretches the bladder capacity, done under general anaesthetic) have shown some success in reducing urinary frequency and giving pain relief to patients. However, many experts still cannot understand precisely how this can cause pain relief. Unfortunately, the relief achieved by bladder distentions is only temporary (weeks or months) and consequently, it is not really viable as a long-term treatment for Interstitial Cystitis: it is generally only used in extreme cases.

Surgical interventions are rarely used for IC. Neurostimulation techniques are not FDA approved for IC.

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