Interstitial cystitis

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Interstitial cystitis
Classification & external resources
ICD-10 N30.1
ICD-9 595.1
DiseasesDB 30832
MedlinePlus 000477
eMedicine med/2866 

Interstitial cystitis (commonly abbreviated to "IC") is a urinary bladder disease of unknown cause characterised by urinary frequency (as often as every 10 minutes), urgency, pressure and/or pain in the bladder and/or pelvis. [1] Pain typically increases as the bladder fills and reduces after voiding however some patients report pain with urination, often in the urethra. Patients may also experience nocturia, pelvic floor dysfunction and tension (thus making it difficult to start their urine stream), pain with sexual intercourse, discomfort and difficulty driving, travelling or working. Research has determined that the quality of life of IC patients is equivalent to end stage renal failure.

It is not unusual for patients to have been misdiagnosed with a variety of other conditions, including: overactive bladder, urethritis, urethral syndrome, trigonitis, prostatitis and other generic terms used to describe frequency/urgency symptoms in the urinary tract.

IC affects men and women of all cultures, socioeconomics and ages. Although the disease previously was believed to be a condition of menopausal women, growing numbers of men and women are being diagnosed in their twenties and younger. IC is not a rare condition ,however IC is more common in females then in men.[1] Early research suggested that IC prevalence ranged from 1 in 100,000 to 5.1 in 1,000 of the general population. New epidemiological data released in 2006 by Dr. Matt Rosenberg now suggests that up to 12% of women may have early symptoms of IC.

Contents

[edit] Nomenclature

The term "interstitial cystitis" has been hotly debated in recent years. In 2003/2004, researchers suggested that milder cases of IC should be known as painful bladder syndrome (PBS).[2] Thus, many journal articles referred to the condition as IC/PBS. The term "IC" was to be used solely for patients who met the very strict NIDDK research criteria. In 2006, yet another name change was proposed. The European Society For The Study of IC (ESSIC) (based in the Netherlands) suggested that the IC and IC/PBS be replaced with Bladder Pain Syndrome (BPS).[3] This change in nomenclature (as well as their proposed changes in the diagnostic methodology), was met with great opposition during the 2006 NIDDK Conference from patient groups and clinicians from around the world.

[edit] Causes

The cause of interstitial cystitis is unknown, though several theories have been put forward (these include autoimmune, neurologic, allergic and genetic).[4] Regardless of the origin, it is clear that the majority of IC patients struggle with a damaged urothelium, aka bladder lining. When the surface GAG layer 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 may be a factor in a small subset of patients. Two genes, FZD8 and PAND, are associated with the syndrome. FZD8, at gene map locus 10p11.2, is associated with an antiproliferative factor secreted by the bladders of IC patients which "profoundly inhibits bladder cell proliferation," thus causing the missing bladder lining.[5] 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.

[edit] 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", believed to be larger areas of bladder wall thinning, that can be much more difficult to treat. Some researchers believe that patients with Hunner's Ulcers may have an entirely different condition. It is estimated that only 5 to 10% of patients have these ulcers.[6] 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).

[edit] Diagnosis

Diagnosis has been greatly simplified 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.[7] The KCL Test, aka the Potassium Sensitivity Test, uses a mild potassium solution to test the integrity of the bladder wall.[8] Though the latter is not specific for IC, it has been determined to be helpful in predicting the use of compounds, such as pentosan polysulphate, 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.

In 2006, the ESSIC society proposed more rigorous and demanding diagnostic methods with specific classification criteria so that it cannot be confused with other, similar conditions. Specifically, they require that a patient must have pain associated with the bladder, accompanied by one other urinary symptom. Thus, a patient with just frequency or urgency would be excluded from a diagnosis. Secondly, they strongly encourage the exclusion of confusable diseases through an extensive and expensive series of tests including (A) a medical history and physical exam, (B) a dipstick urinalysis, various urine cultures, and a serum PSA in men over 40, (C) flowmetry and post-void residual urine volume by ultrasound scanning and (D) cystoscopy. A diagnosis of IC/PBS/BPS would be confirmed with a hydrodistention during cystoscopy with biopsy.

They also propose a ranking system based upon the physical findings in the bladder. Patients would receive a numeric and letter based score based upon the severity of their disease as found during the hydrodistention. A score of 1-3 would relate to the severity of the disease and a rating of A-C represents biopsy findings. Thus, a patient with 1A would have very mild symptoms and disease while a patient with 3C would have the worst available symptoms.[9]

[edit] Treatment

[edit] 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 alcohol, coffees, teas, herbal teas, green teas, all sodas (particularly diet), concentrated fruit juices, tomatoes, citrus fruit, cranberries, 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.[10][11]

[edit] 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.[12]

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.[13] In addition, the NIH funded ICCTG study of pentosan revealed results only slightly better than placebo.[14] The latter study was criticized, however, for targeting only the most severe IC patients who were also the least likely to respond (i.e. the NIDDK diagnostic criteria).

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.[15]

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.[16]

Other bladder coating therapies include Cystistat(TM) (sodium hyaluronate) and Uracyst(TM) (chondroitin). They are believed to replace the deficient GAG layer on the bladder wall. Like most other intravesical bladder treatments, this treatment may require 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.


[edit] 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.[17]

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 subconsciously trigger muscle tension.

[edit] 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.[18]

Electronic pain-killing options include TENS (a machine connected to sticky pads which one places 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.

[edit] 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.

[edit] Links to other conditions

It is important to note that some people with IC suffer from Anxiety disorder, and other conditions that may have the same etiology as IC. These include: irritable bowel syndrome (IBS), Fibromyalgia, Endometriosis, Vulvodynia, and chemical sensitivities. Men with IC are frequently diagnosed as having prostatitis, and there is an extensive overlap of symptoms and treatment between the two conditions, leading some researchers to posit that the conditions share the same etiology and pathology.

[edit] References

  1. ^ The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies ISBN 1-57224-210-8
  2. ^ NIDDK Interstitial Cystitis Summary - IC section of the NKUDIC
  3. ^ 2006 International Symposium: Frontiers in Painful Bladder Syndrome and Interstitial Cystitis - October 26-27, 2006 - Podium Sessions & Abstracts
  4. ^ NIDDK Interstitial Cystitis Summary - IC section of the NKUDIC
  5. ^ Numerous publications by Keay & colleagues available at PubmeD Keay, S, Zhang, C., Chai, T., Warren, J., Koch, K., Grkovic, D., Colville, H., Alexander, R. Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor in men with interstitial cystitis versus chronic pelvic pain syndrome. J. Urol. 2004; 63:22-26.
  6. ^ NIDDK Interstitial Cystitis Summary - IC section of the NKUDIC
  7. ^ Dr. Lowell Parsons website - includes references, protocols and publications.
  8. ^ Dr. Lowell Parsons website - includes references, protocols and publications.
  9. ^ ESSIC Society website - includes white papers, conference notes and protocols
  10. ^ "A Taste of the Good Life: A Cookbook for an IC Diet" ISBN 0-9665706-0-X
  11. ^ "Confident Choices: Customizing The IC Diet" ISBN 0-9767246-0-X
  12. ^ The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies ISBN 1-57224-210-8
  13. ^ Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers. Xenobiotica. 2005 Aug;35(8):775-84.
  14. ^ A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol. 2003 Sep;170(3):810-5.
  15. ^ AUA 2002 Abstract - DMSO: Does it change functional properties in the bladder wall Diethild Melchior*, C Subah Packer, Tomalyn C Johnson, Martin Kaefer, Indianapolis, IN
  16. ^ Parsons CL. Related Successful downregulation of bladder sensory nerves with combination of heparin and alkalinized lidocaine in patients with interstitial cystitis. Urology. 2005 Jan;65(1):45-8.
  17. ^ 13. Sandler, G. Pelvic Floor Dysfunction and Problem Trigger Points in Other Areas of the Body. June 2002 IC Network Feature Column
  18. ^ The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies ISBN 1-57224-210-8

[edit] See also

[edit] External links

US National Organizations & Resources

IC Conferences

IC Support Organizations

USA State Support Resources:

Research & Research Centers

Misc. Websites

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