Interstitial cystitis

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Interstitial cystitis
ICD-10 N30.1
ICD-9 595.1
DiseasesDB 30832
MedlinePlus 000477

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Steven C. Campbell, M.D., Ph.D. Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [1]

Synonyms and Keywords: Painful bladder syndrome

Overview

Interstitial cystitis (commonly abbreviated to "IC") is a urinary bladder disease of unknown cause characterized 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, and discomfort and difficulty driving, traveling or working. The pathogenesis of interstitial cystitis includes epithelial dysfunction, mast cell activation, and bladder sensory nerve up-regulation.[2] Interstitial cystitis must be differentiated from other types of cystitis (bacterial, hemorrhagic), prostatitis, epididymitis, endometriosis, uterine fibroids, bladder stones, lower ureteral stones, urogenital prolapse, and genital cancers.[3][4] Females are more commonly affected with interstitial cystitis than males. The female to male ratio may range from 5:1 to 10:1. The median age at diagnosis ranges from 42-46 years.[5] Laboratory findings consistent with the diagnosis of interstitial cystitis include negative urine cultures and the absence of erythocytes and leukocytes on urinalysis.[6]

Historical Perspective

In 1836, Philadelphia surgeon Joseph Parrish published the earliest record of interstitial cystitis by describing three cases of severe lower urinary tract symptoms without the presence of a bladder stone. The term "interstitial cystitis" was coined by Dr. Alexander Skene in 1887 to describe the disease.[3]

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).[6] 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).[7] 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.

Pathophysiology

Pathogenesis

The pathogenesis of interstitial cystitis includes:[2]

  • Epithelial dysfunction
  • Mast cell activation
  • Bladder sensory nerve up-regulation

The urothelium acts as a barrier against damage to the bladder. The urothelium produces a mucous layer which regulates the entry of potassium in the bladder interstitium. Damage to the urothelium results in the production of cytokines which activate mast cells in the interstitium. Mast cell activation is further triggered by the diffusion of excess potassium into the bladder interstitium.[4]

The cause of interstitial cystitis is unknown, though several theories have been put forward (these include autoimmune, neurologic, allergic and genetic).[8] Regardless of the origin, it is clear that the majority of IC patients struggle with a damaged urothelium, or bladder lining. When the surface GAG layer is damaged (via a UTI, excessive consumption of coffee or sodas, traumatic injury, etc.), urinary chemicals can "leak" into surrounding tissues, causing pain, inflammation, and urinary symptoms. Oral medications like Elmiron and medications that are placed directly into the bladder via a catheter work to repair and rebuild this damaged/wounded lining, allowing for a reduction in symptoms.

Genetics

Some genetic subtypes have been linked to the disorder:[3]

  • An antiproliferative factor is secreted by the bladders of people with interstitial cystitis which inhibits bladder cell proliferation, thus possibly causing the missing bladder lining.
  • PAND, at gene map locus 13q22–q32, is associated with a constellation of disorders (a "pleiotropic syndrome") including interstitial cystitis and other bladder and kidney problems, thyroid diseases, serious headaches/migraines, panic disorder, and mitral valve prolapse.

Recent work at 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.[9] 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.

Associated 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. Interstitial cystitis may be associated with:[3]

Differentiating Interstitial Cystitis from other diseases

Interstitial cystitis must be differentiated from:[3][4]

Cystitis must be differentiated from other diseases that cause lower urinary tract irritation symptoms, such as: dysuria, urgency and frequency in addition to urethral dyscharge , the differential list include: urethritis, cervicitis, vulvovaginitis, epididimitis, prostatitis , and syphilis.[10][11][12][13]

Disease Findings
Cystitis Bladder inflammation, Features with increased frequency and urgency, dysuria, and suprapubic pain. Is more common among women. E.coli is the most common pathogen[14][15][16][17].
Urethritis infection of the urethra,causes dysuria and urethral discharge[12][18][19]
Bacterial vulvovaginitis Presents with dysuria and pruritus, Vaginal discharge and odor are almost always present, caused by Gardnerella species[20].
Cervicitis Often asymptomatic,some women have an abnormal vaginal discharge and vaginal bleeding (especially after sexual intercourse)[21]
Prostatitis bacterial infection of the prostate,causes discomfort during ejaculation[22]
Epididymitis Presents with scrotal pain and swelling accompanied by fever and lower urinary tract irritation symptoms(dysuria and frequency)[23].
Syphilis Presents with generalized systemic symptoms such as malaise, fatigue, headache and fever. Skin eruptions may be subtle and asymptomatic. It is classically described as 1) non-pruritic bilateral symmetrical mucocutaneous rash; 2) non-tender regional lymphadenopathy; 3) condylomata lata; and 4) patchy alopecia.[11]

Epidemiology and Demographics

Females are more commonly affected with interstitial cystitis than males. The female to male ratio may range from 5:1 to 10:1. The median age at diagnosis ranges from 42-46 years.[5]

Diagnosis

Symptoms

Common symptoms of interstitial cystitis include:[3]

  • Suprapubic pelvic pain
  • Urinary urgency and increased frequency
  • Pain during urination
  • Pain during sexual intercourse

Laboratory Findings

Laboratory findings consistent with the diagnosis of interstitial cystitis include negative urine cultures and the absence of erythocytes and leukocytes on urinalysis.[6]

Treatment

Diet

The foundation of therapy is a modification of diet to help patients avoid those foods which can further irritate the damaged bladder wall. Common triggers include alcohol, coffees, teas, herbal teas, green teas, all sodas (particularly diet), concentrated fruit juices, tomatoes, citrus fruit, cranberries, the B vitamins, vitamin C, 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.[24][25]

Medication

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.[26]

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.[27] In addition, the NIH funded ICCTG study of pentosan revealed results only slightly better than placebo.[28] 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.[29]

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.[30]

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.

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.[31]

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.

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.[32]

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.

Other treatments

Bladder distensions (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.

References

  1. The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies ISBN 1-57224-210-8
  2. 2.0 2.1 Sant GR (2002). "Etiology, pathogenesis, and diagnosis of interstitial cystitis". Rev Urol. 4 Suppl 1: S9–S15. PMC 1476007. PMID 16986036.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Interstitial Cystitis. Wikipedia.https://en.wikipedia.org/wiki/Interstitial_cystitis. Accessed on February 15, 2016
  4. 4.0 4.1 4.2 French LM, Bhambore N (2011). "Interstitial cystitis/painful bladder syndrome". Am Fam Physician. 83 (10): 1175–81. PMID 21568251.
  5. 5.0 5.1 Moutzouris DA, Falagas ME (2009). "Interstitial cystitis: an unsolved enigma". Clin J Am Soc Nephrol. 4 (11): 1844–57. doi:10.2215/CJN.02000309. PMID 19808225.
  6. 6.0 6.1 6.2 Interstitial Cystitis/Painful Bladder Syndrome. NIDDK. http://www.niddk.nih.gov/health-information/health-topics/urologic-disease/interstitial-cystitis-painful-bladder-syndrome/Pages/facts.aspx. Accessed on February 16, 2016
  7. 2006 International Symposium: Frontiers in Painful Bladder Syndrome and Interstitial Cystitis - October 26-27, 2006 - Podium Sessions & Abstracts
  8. NIDDK Interstitial Cystitis Summary - IC section of the NKUDIC
  9. 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.
  10. Kurowski K (1998). "The woman with dysuria". Am Fam Physician. 57 (9): 2155–64, 2169–70. PMID 9606306.
  11. 11.0 11.1 Moore, Zack S; Seward, Jane F; Lane, J Michael (2006). "Smallpox". The Lancet. 367 (9508): 425–435. doi:10.1016/S0140-6736(06)68143-9. ISSN 0140-6736.
  12. 12.0 12.1 Taylor-Robinson D (1996). "The history of nongonococcal urethritis. Thomas Parran Award Lecture". Sex Transm Dis. 23 (1): 86–91. PMID 8801649.
  13. Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.
  14. Stephen Bent, Brahmajee K. Nallamothu, David L. Simel, Stephan D. Fihn & Sanjay Saint (2002). "Does this woman have an acute uncomplicated urinary tract infection?". JAMA. 287 (20): 2701–2710. PMID 12020306. Unknown parameter |month= ignored (help)
  15. W. E. Stamm (1981). "Etiology and management of the acute urethral syndrome". Sexually transmitted diseases. 8 (3): 235–238. PMID 7292216. Unknown parameter |month= ignored (help)
  16. W. E. Stamm, K. F. Wagner, R. Amsel, E. R. Alexander, M. Turck, G. W. Counts & K. K. Holmes (1980). "Causes of the acute urethral syndrome in women". The New England journal of medicine. 303 (8): 409–415. doi:10.1056/NEJM198008213030801. PMID 6993946. Unknown parameter |month= ignored (help)
  17. Leonie G. M. Giesen, Grainne Cousins, Borislav D. Dimitrov, Floris A. van de Laar & Tom Fahey (2010). "Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs". BMC family practice. 11: 78. doi:10.1186/1471-2296-11-78. PMID 20969801.
  18. Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.
  19. Brill JR (2010). "Diagnosis and treatment of urethritis in men". Am Fam Physician. 81 (7): 873–8. PMID 20353145.
  20. Daniel V. Landers, Harold C. Wiesenfeld, R. Phillip Heine, Marijane A. Krohn & Sharon L. Hillier (2004). "Predictive value of the clinical diagnosis of lower genital tract infection in women". American journal of obstetrics and gynecology. 190 (4): 1004–1010. doi:10.1016/j.ajog.2004.02.015. PMID 15118630. Unknown parameter |month= ignored (help)
  21. Kimberly A. Workowski & Gail A. Bolan (2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. PMID 26042815. Unknown parameter |month= ignored (help)
  22. Felix Millan-Rodriguez, J. Palou, Anna Bujons-Tur, Mireia Musquera-Felip, Carlota Sevilla-Cecilia, Marc Serrallach-Orejas, Carlos Baez-Angles & Humberto Villavicencio-Mavrich (2006). "Acute bacterial prostatitis: two different sub-categories according to a previous manipulation of the lower urinary tract". World journal of urology. 24 (1): 45–50. doi:10.1007/s00345-005-0040-4. PMID 16437219. Unknown parameter |month= ignored (help)
  23. A. Stewart, S. S. Ubee & H. Davies (2011). "Epididymo-orchitis". BMJ (Clinical research ed.). 342: d1543. PMID 21490048.
  24. "A Taste of the Good Life: A Cookbook for an IC Diet" ISBN 0-9665706-0-X
  25. "Confident Choices: Customizing The IC Diet" ISBN 0-9767246-0-X
  26. The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies ISBN 1-57224-210-8
  27. Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers. Xenobiotica. 2005 Aug;35(8):775-84.
  28. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol. 2003 Sep;170(3):810-5.
  29. 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
  30. 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.
  31. 13. Sandler, G. Pelvic Floor Dysfunction and Problem Trigger Points in Other Areas of the Body. June 2002 IC Network Feature Column
  32. The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies ISBN 1-57224-210-8

See also

External links

de:Interstitielle Zystitis



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