Interstitial cystitis

Signs and symptoms

The most common symptoms of IC are suprapubic pain, urinary frequency, painful sexual intercourse,

In general, symptoms may include painful urination described as a burning sensation in the urethra during urination, pelvic pain that is worsened with the consumption of certain foods or drinks, urinary urgency, and pressure in the bladder or pelvis. Other, more severe symptoms include chronic inflammation, ulcuration (Hunner's leasions), fybrotic scar tissue and stiffness of the bladder.

During cystoscopy, 5–10% of people with IC are found to have Hunner's ulcers. A person with IC may have discomfort only in the urethra, while another might struggle with pain in the entire pelvis. Interstitial cystitis symptoms usually fall into one of two patterns: significant suprapubic pain with little frequency or a lesser amount of suprapubic pain but with increased urinary frequency.

Association with other conditions

Some people with IC/BPS have been diagnosed with other conditions such as irritable bowel syndrome (IBS), fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), allergies, Sjögren syndrome, which raises the possibility that interstitial cystitis may be caused by mechanisms that cause these other conditions. There is also some evidence of an association between urologic pain syndromes, such as IC/BPS and CP/CPPS, with non-celiac gluten sensitivity in some people.

In addition, men with IC/PBS are frequently diagnosed as having chronic nonbacterial prostatitis, and there is an extensive overlap of symptoms and treatment between the two conditions, leading researchers to posit that the conditions may share the same cause and pathology.

Causes

The cause of IC/BPS is not known. However, several explanations have been proposed and include the following: autoimmune theory, nerve theory, mast cell theory, leaky lining theory, infection theory, and a theory of production of a toxic substance in the urine. Other suggested etiological causes are neurologic, allergic, genetic, and stress-psychological including exposure to abuse in childhood or adulthood. In addition, recent research shows that those with IC may have a substance in the urine that inhibits the growth of cells in the bladder epithelium. An infection may then predispose those people to develop IC. Evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/BPS possibly due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. Research has shown a proliferation of nerve fibers is present in the bladders of people with IC which is absent in the bladders of people who have not been diagnosed with IC.

Regardless of the origin, most people with IC struggle with a damaged urothelium, or bladder lining. When the surface glycosaminoglycan (GAG) layer is damaged (via a urinary tract infection (UTI), traumatic injury, etc.), urinary chemicals can "leak" into surrounding tissues, causing pain, inflammation, and urinary symptoms. Oral medications like pentosan polysulfate and medications placed directly into the bladder via a catheter sometimes work to repair and rebuild this damaged/wounded lining, allowing for a reduction in symptoms. Most literature supports the belief that IC's symptoms are associated with a defect in the bladder epithelium lining, allowing irritating substances in the urine to penetrate into the bladder—a breakdown of the bladder lining (also known as the adherence theory). Deficiency in this glycosaminoglycan layer on the surface of the bladder results in increased permeability of the underlying submucosal tissues.

GP51 has been identified as a possible urinary biomarker for IC with significant variations in GP51 levels in those with IC when compared to individuals without interstitial cystitis.

A proposed mechanism for interstitial cystitis is the autoimmune mechanism. Some studies have noted the link between IC, anxiety, stress, hyper-responsiveness, panic, and abuse. Biopsies on the bladder walls of people with IC may contain larger counts of mast cells than healthy bladder walls. Mast cells, which contain histamine granules, respond to allergic stimuli. In this theory, Mast cells are activated in response to antigen detection in the bladder wall. The activation of mast cells triggers the release of histamine, amongst other inflammatory mediators. Additionally, another proposed mechanism is increased activity of unspecified nerves in the bladder wall. An unknown toxin or stimuli may activate nerves within the bladder wall, causing the release of neuropeptides. These neuropeptides can induce a secondary cascade which stimulates pain in the bladder wall.

Genes

Some genetic subtypes, in some people, have been linked to the disorder.

• An antiproliferative factor is secreted by the bladders of people with IC/BPS 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 IC/BPS and other bladder and kidney problems, thyroid diseases, serious headaches/migraines, panic disorder, and mitral valve prolapse.

Diagnosis

A diagnosis of IC is one of exclusion, as well as a review of clinical symptoms. as well as other potential disorders.

The KCl test, also known as the potassium sensitivity test, is no longer recommended. The test uses a mild potassium solution to evaluate the integrity of the bladder wall.

For complicated cases, the use of hydrodistention with cystoscopy may be helpful. Researchers, however, determined that this visual examination of the bladder wall after stretching the bladder was not specific for IC and that the test, itself, can contribute to the development of small glomerulations (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 person must have pain associated with the bladder, accompanied by one other urinary symptom. Thus, a person 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 would be confirmed with a hydrodistention during cystoscopy with biopsy.

They also propose a ranking system based upon the physical findings in the bladder.

Differential diagnosis

The symptoms of IC/BPS are often misdiagnosed as a urinary tract infection. However, IC/BPS has not been shown to be caused by a bacterial infection and antibiotics are an ineffective treatment. IC/BPS is commonly misdiagnosed as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men, and endometriosis and uterine fibroids (in women).

Treatment

In 2011, the American Urological Association released consensus-based guideline for the diagnosis and treatment of interstitial cystitis. Further reviews of multiple studies and guidelines have updated these recommendations.

They include treatments ranging from conservative to more invasive:

1. First-line treatments – education, dietary modification, exercise, physical therapy, first-line analgesics (nonsteroidal anti-inflammatory drug with paracetamol and gastric protection), stress management, support groups, and psychotherapy including cognitive behavioral therapy
2. Second-line treatments – oral medications (amitriptyline, cimetidine), bladder instillations (DMSO, heparinor lidocaine)
3. Third-line treatments – treatment of Hunner's lesions (laser, fulguration or triamcinolone injection), hydrodistention (low pressure, short duration)
4. Fourth-line treatments – botulinum toxin (BTX-A), neuromodulation (sacral or pudendal nerve)
5. Fifth-line treatments – cyclosporine A
6. Sixth-line treatments – surgical intervention (urinary diversion, augmentation, cystectomy)

The American Urological Association guidelines also listed several discontinued treatments, including long-term oral antibiotics, intravesical bacillus Calmette Guerin, intravesical resiniferatoxin), high-pressure and long-duration hydrodistention, and systemic glucocorticoids.

Bladder distension

Bladder distension while under general anesthesia, also known as hydrodistention (a procedure which stretches the bladder capacity), has shown some success in reducing urinary frequency and giving short-term pain relief to those with IC. Recent studies show pressure on pelvic trigger points can relieve symptoms. The relief achieved by bladder distensions is only temporary (weeks or months), so is not viable as a long-term treatment for IC/BPS. The proportion of people with IC/BPS who experience relief from hydrodistention is currently unknown and evidence for this modality is limited by a lack of properly controlled studies. Bladder rupture and sepsis may be associated with prolonged, high-pressure hydrodistention.

Bladder instillations

Bladder instillation of medication is one of the main forms of treatment of interstitial cystitis, but evidence for its effectiveness is currently limited.

The disadvantages of installations are severe pain in the urethra, caused by the catheter that is used to administer the instillation, bladder pain and the fact that most installations need to be held in the bladder for at least two hours, whereas some patients have to urinate (far) more frequent than once every two hours. This causes severe pain and/or affects the treatment because the instillation did not sit in the bladder long enough.

About DMSO:

50% solution of DMSO had the potential to create irreversible muscle contraction. However, a lesser solution of 25% was found to be reversible. Long-term use of DMSO is questionable, as its mechanism of action is not fully understood though DMSO is thought to inhibit mast cells and may have anti-inflammatory, muscle-relaxing, and analgesic effects. Other agents used for bladder instillations to treat interstitial cystitis include: heparin, lidocaine, chondroitin sulfate, hyaluronic acid, pentosan polysulfate, oxybutynin, and botulinum toxin A. Preliminary evidence suggests these agents are efficacious in reducing symptoms of interstitial cystitis, but further study with larger, randomized, controlled clinical trials is needed.

Diet

Diet modification is often recommended as a first-line method of self-treatment for interstitial cystitis, though rigorous controlled studies examining the impact diet has on interstitial cystitis signs and symptoms are currently lacking. Individuals with interstitial cystitis often experience an increase in symptoms when they consume certain foods and beverages. Avoidance of these potential trigger foods and beverages such as tomatoes, cranberries, caffeine-containing beverages including coffee, tea, and soda, alcoholic beverages, chocolate, citrus fruits, hot peppers, and artificial sweeteners may be helpful in alleviating symptoms. The foundation of therapy is a modification of diet to help people avoid those foods which can further irritate the damaged bladder wall.

The mechanism by which dietary modification benefits people with IC is unclear. Integration of neural signals from pelvic organs may mediate the effects of diet on symptoms of IC.

Medications

Nonsteroidal anti-inflammatory drug and paracetamol and gastric protection combined with other conservative measures can be an effect first-line treatment.

As a second-line treatment, amitriptyline has been shown to be effective in reducing symptoms such as chronic pelvic pain and nocturia The antihistamine hydroxyzine failed to demonstrate superiority over placebo in treatment of people with IC in a randomized, controlled, clinical trial. However, when hydroxyzine is used in combination with pentosan polysulfate sodium it may be more effective than pentosan polysulfate sodium on its own, but large-scale studies are needed.

As a last-line treatment the calcineurin inhibitor cyclosporine A has been studied as a treatment for interstitial cystitis due to its immunosuppressive properties. A prospective randomized study found cyclosporine A to be more effective at treating IC symptoms than pentosan polysulfate, but also had more adverse effects.

In one study, the antidepressant duloxetine was found to be ineffective as a treatment, although a patent exists for use of duloxetine in the context of IC, and is known to relieve neuropathic pain.

Pelvic floor treatments

Urologic pelvic pain syndromes, such as IC/BPS and CP/CPPS, are characterized by pelvic muscle tenderness, and symptoms may be reduced with pelvic myofascial physical therapy.

This may leave the pelvic area in a sensitized condition, resulting in a loop of muscle tension and heightened neurological feedback (neural wind-up), a form of myofascial pain syndrome. Current protocols, such as the Wise–Anderson Protocol, largely focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as trigger points), physical therapy to the area, and progressive relaxation therapy to reduce causative stress.

Pelvic floor dysfunction is a fairly new area of specialty for physical therapists worldwide. 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 people with urinary incontinence. Thus, traditional exercises such as Kegel exercises, which are used to strengthen pelvic muscles, 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.

A therapeutic wand can also be used to perform pelvic floor muscle myofascial release to provide relief.

Surgery

Surgery is rarely used for IC/BPS. Surgical intervention is very unpredictable, and is considered a treatment of last resort for severe refractory cases of interstitial cystitis. Some people who opt for surgical intervention continue to experience pain after surgery. Typical surgical interventions for refractory cases of IC/BPS include: bladder augmentation, urinary diversion, transurethral fulguration and resection of ulcers, and bladder removal (cystectomy).

Neuromodulation can be successful in treating IC/BPS symptoms, including pain. Percutaneous tibial nerve stimulation stimulators have also been used, with varying degrees of success. Percutaneous sacral nerve root stimulation was able to produce statistically significant improvements in several parameters, including pain.

Alternative medicine

There is little evidence looking at the effects of alternative medicine though their use is common. There is tentative evidence that acupuncture may help pain associated with IC/BPS as part of other treatments. Despite a scarcity of controlled studies on alternative medicine and IC/BPS, "rather good results have been obtained" when acupuncture is combined with other treatments.

Biofeedback, a relaxation technique aimed at helping people control functions of the autonomic nervous system, has shown some benefit in controlling pain associated with IC/BPS as part of a multimodal approach that may also include medication or hydrodistention of the bladder.

Prognosis

IC/BPS has a profound impact on quality of life. A 2007 Finnish epidemiologic study showed that two-thirds of women at moderate to high risk of having interstitial cystitis reported impairment in their quality of life and 35% of people with IC reported an impact on their sexual life. Other research has shown that the impact of IC/BPS on quality of life is severe

International recognition of interstitial cystitis has grown and international urology conferences to address the heterogeneity in diagnostic criteria have recently been held. IC/PBS is now recognized with an official disability code in the United States of America.

Epidemiology

Interstitial cystitis affects men and women of all cultures, socioeconomic backgrounds, and ages. Although the disease was previously believed to be a condition of menopausal women, growing numbers of men and women are being diagnosed in their twenties and younger. While BPS is not a rare condition, severe IC is. Early research suggested that the number of BPS cases ranged from 1 in 100,000 to 5.1 in 1,000 of the general population. In recent years, the scientific community has achieved a much deeper understanding of the epidemiology of interstitial cystitis. Recent studies have revealed that between 2.7 and 6.53 million women in the USA have symptoms of IC and up to 12% of women may have early symptoms of IC/BPS. Further study has estimated that the condition is far more prevalent in men than previously thought ranging from 1.8 to 4.2 million men having symptoms of interstitial cystitis.

The condition is officially recognized as a disability in the United States.

History

Philadelphia surgeon Joseph Parrish published the earliest record of interstitial cystitis in 1836 describing three cases of severe lower urinary tract symptoms without the presence of a bladder stone. In 2002, the United States amended the Social Security Act to include interstitial cystitis as a disability. The first guideline for diagnosis and treatment of interstitial cystitis is released by a Japanese research team in 2009. The American Urological Association released the first American clinical practice guideline for diagnosing and treating IC/BPS in 2011 and has since (in 2014 and 2022) updated the guideline to maintain standard of care as knowledge of IC/BPS evolves.

Names

Originally called interstitial cystitis, this disorder was renamed to interstitial cystitis/bladder pain syndrome (IC/BPS) in the 2002–2010 timeframe. In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) began using the umbrella term urologic chronic pelvic pain syndrome (UCPPS) to refer to pelvic pain syndromes associated with the bladder (e.g., interstitial cystitis/bladder pain syndrome) and with the prostate gland or pelvis (e.g., chronic prostatitis/chronic pelvic pain syndrome).

In 2008, terms currently in use in addition to IC/BPS include painful bladder syndrome, bladder pain syndrome and hypersensitive bladder syndrome, alone and in a variety of combinations. These different terms are being used in different parts of the world. The term "interstitial cystitis" is the primary term used in ICD-10 and MeSH. Grover et al. said, "The International Continence Society named the disease interstitial cystitis/painful bladder syndrome (IC/PBS) in 2002 [Abrams et al. 2002], while the Multinational Interstitial Cystitis Association have labeled it as painful bladder syndrome/interstitial cystitis (PBS/IC) [Hanno et al. 2005]. Recently, the European Society for the study of Interstitial Cystitis (ESSIC) proposed the moniker, 'bladder pain syndrome' (BPS) [van de Merwe et al. 2008]."

References

References

1. (2010). "From interstitial cystitis to chronic pelvic pain.". Journal of Medicine and Life.
2. (2005). "Stedman's Medical Eponyms". Lippincott Williams & Wilkins.
3. (May 2015). "Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment.". The Journal of Urology.
4. (16 July 2012). "Interstitial cystitis/bladder pain syndrome fact sheet".
5. (2007). "Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review". [[The Journal of Urology]].
6. (2012). "Treatment of interstitial cystitis in women". Taiwanese Journal of Obstetrics and Gynecology.
7. (2010). "Cross-talk and sensitization of bladder afferent nerves". Neurourology and Urodynamics.
8. Harvard Health Publishing. (25 March 2020). "Diagnosing and treating interstitial cystitis".
9. Peters, Dr. Jill. ""Interstitial Cystitis" Paul Perry, MD, Chairman, Obgyn.Net Editorial Advisory Board, Chronic Pelvic Pain interviews Jill Peters, MD". Obgyn.Net Conference Coverage from International Pelvic Pain Society—Simsbury Connecticut—April/May, 1999.
10. (2009). "Genetics and Phenotyping of Urological Chronic Pelvic Pain Syndrome". The Journal of Urology.
11. (2015). "Gluten Sensitivity". Annals of Nutrition and Metabolism.
12. (2012). "Non-coeliac gluten sensitivity". BMJ.
13. "Gluten and CP/CPPS". Prostatitis Network.
14. PubMed Health. (2011). "Prostatitis-nonbacterial-chronic". U.S. National Library of Medicine.
15. "Interstitial Cystitis (Painful Bladder Syndrome)". PubMed Health Glossary.
16. (June 2017). "Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome". Archives of Gynecology and Obstetrics.
17. National Institute of Diabetes and Digestive and Kidney Diseases. (2012). "Interstitial Cystitis/Painful Bladder Syndrome". National Institutes of Health.
18. "Interstitial Cystitis: Etiology". MedScape Reference.
19. "Understanding Interstitial Cystitis". MD Conversation / peer-reviewed.
20. (September 2007). "Fact or fiction—is abuse prevalent in patients with interstitial cystitis? Results from a community survey and clinic population". Journal of Urology.
21. (2012). "Causes". Mayo Clinic.
22. (2006). "Pentosan Polysulfate". Drugs.
23. (May 2007). "Interstitial cystitis/painful bladder syndrome: Symptom recognition is key to early identification, treatment". Cleveland Clinic Journal of Medicine.
24. (2002). "The Role of Pentosan Polysulfate in Treatment Approaches for Interstitial Cystitis". Reviews in Urology.
25. "Adult Conditions / Bladder / Interstitial Cystitis". American Urological Association Foundation.
26. (2007). "A Seat on the Aisle, Please!: The Essential Guide to Urinary Tract Problems in Women". Springer.
27. "American Urological Association -".
28. (2007). "Diagnosis of Interstitial Cystitis/Painful Bladder Syndrome in Patients With Overactive Bladder Symptoms". Reviews in Urology.
29. (January 2008). "Diagnostic Criteria, Classification, and Nomenclature for Painful Bladder Syndrome/Interstitial Cystitis: An ESSIC Proposal". European Urology.
30. (2022). "Interstitial Cystitis". StatPearls Publishing.
31. (2015). "The enigma of men with interstitial cystitis/bladder pain syndrome". Translational Andrology and Urology.
32. (2011). "AUA Guidelines Diagnosis and Treatment of Interstitial Cystitis". American Urological Association.
33. (May 2018). "Guideline of guidelines: bladder pain syndrome". BJU International.
34. (October 2024). "Bladder Pain Syndrome (BPS): A Comprehensive Review of Treatment Strategies and Management Approaches". Research and Reports in Urology.
35. (September 2015). "Nutritional Considerations for Patients with Interstitial Cystitis/Bladder Pain Syndrome". Journal of the Academy of Nutrition and Dietetics.
36. (2008). "Summation model of pelvic pain in interstitial cystitis". Nature Clinical Practice Urology.
37. (2009). "Antidepressant Drugs for Chronic Urological Pelvic Pain: an Evidence-Based Review". Advances in Urology.
38. (2011). "Safety and effectiveness of an internal pelvic myofascial trigger point wand for urologic chronic pelvic pain syndrome". Clin J Pain.
39. (2008). "Functional and Chronic Anorectal and Pelvic Pain Disorders". Gastroenterology Clinics of North America.
40. (7 October 2021). "Physical Therapy".
41. (2017). "Efficacy of a therapeutic wand in addition to physiotherapy for treating bladder pain syndrome in women: a pilot randomized controlled trial".
42. (2010). "Sacral neuromodulation stimulation for IC/PBS, chronic pelvic pain, and sexual dysfunction". International Urogynecology Journal.
43. (2013). "Neuromodulation of Pelvic Visceral Pain: Review of the Literature and Case Series of Potential Novel Targets for Treatment". Pain Practice.
44. (2008). "Posterior Tibial Nerve Stimulation Twice a Week in Patients with Interstitial Cystitis". Urology.
45. (7 December 2015). "Complementary therapies for bladder pain syndrome: a systematic review". International Urogynecology Journal.
46. (2002). "Complementary and Alternative Therapies as Treatment Approaches for Interstitial Cystitis". Reviews in Urology.
47. (2008). "Die Komplexität chronischer Beckenschmerzen am Beispiel der Interstitiellen Zystitis". Aktuelle Urologie.
48. (2008). "Treatment of interstitial cystitis with hydrodistention and bladder training". International Urogynecology Journal.
49. (2004). "Multimodal therapy for interstitial cystitis". The Journal of Reproductive Medicine.
50. (1997). "Interstitial Cystitis". Lippincott-Raven.
51. (2004). "Interstitial Cystitis:The Paradigm Shifts". Reviews in Urology.
52. IC Network. "Conferences".
53. (2007). "Interstitial cystitis/painful bladder syndrome: Symptom recognition is key to early identification, treatment". Cleveland Clinic Journal of Medicine.
54. Robert M. Moldwin. (1 October 2000). "The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies". New Harbinger Publications.
55. (2011). "Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States". Journal of Urology.
56. "Harvard Medical School Family Health Guide: Treating interstitial cystitis". Harvard Medical School.
57. "Policy Interpretation Ruling Titles II and XVI: Evaluation of Interstitial Cystitis". Social Security Administration.
58. (2009). "Interstitial Cystitis: An Unsolved Enigma". Clinical Journal of the American Society of Nephrology.
59. (2009). "Japanese guideline for diagnosis and treatment of interstitial cystitis". International Journal of Urology.
60. "Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome (2022)". American Urological Association.
61. (2007). "Multi-disciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network". NIDDK.
62. (May 2020). "A Comprehensive Review of the Diagnosis, Treatment, and Management of Urologic Chronic Pelvic Pain Syndrome". Curr Pain Headache Rep.
63. (2011). "Role of inflammation in bladder function and interstitial cystitis". Therapeutic Advances in Urology.