Interstitial Cystitis / Bladder Pain Syndrome / Hypersensitive Bladder

Introduction

Pain in the bladder can be caused by numerous disorders, such as bladder or genital infection, benign or malignant tumours, radiation, tuberculous cystitis, bladder or urethral obstruction, prostate disorders, endometriosis, pelvic/gynaecological disorders and chemical or drug-induced cystitis, including the recreational use of “street ketamine” by young people that has recently been causing great concern.

There is, however, a chronic painful bladder condition of unknown origin, described over 200 years ago and first referred to as interstitial cystitis (IC) in 1876. In 1914, Baltimore gynaecologist Guy Leroy Hunner described in detail “a rare type of bladder ulcer in women” which later became known as Hunner’s ulcer. Even though it was realised very early on that this was not in fact a true ulcer, the term Hunner’s ulcer persisted in use until very recently. It is currently more commonly described as a Hunner lesion. However, it is now believed that the majority of patients do not have lesions, but a chronic non-lesion form. These two types are sometimes described as the classic type (with lesions) and the non-classic type (without lesions).

Many new names for this enigmatic disorder have been suggested over the years. Today it is increasingly known as interstitial cystitis/bladder pain syndrome or painful bladder syndrome. The East Asian countries (Japan, Korea and Taiwan) prefer the term hypersensitive bladder (HSB), with or without pain, reserving interstitial cystitis for a disease with specific cystoscopic findings. Most patient organisations prefer to use the older term interstitial cystitis. This topic is currently under review by an ICS Standardisation Steering Committee Working Group on standardisation of terminology and definitions for Chronic Pelvic Pain Syndromes.

Symptoms

This distressing and potentially debilitating bladder symptom complex is characterised by an unpleasant sensation (pain, pressure or discomfort) perceived to be related to the bladder, associated with chronic lower urinary tract symptoms such as a frequent and urgent need to urinate, both day and night, in the absence of infection or other identifiable causes. Although the symptoms may initially resemble a bladder infection, urinalysis appears normal and a urine culture is negative. The pain typically increases as the bladder fills and may be temporarily alleviated when it is emptied. This pain may be suprapubic, in the bladder, urethra, vagina, penis, scrotum, testicles and perineum, may radiate to the lower back and groin and be felt throughout the pelvis. It may be burning or stabbing pain or a feeling of pressure or heaviness. Both male and female patients often experience pain with sexual activity. The course of the disease may be characterised by exacerbations and remissions (“flares”) or the pain may be persistent.

Prevalence

This bladder syndrome is believed to affect mainly women (approximately 80%) and is found worldwide in all races and all age groups, including children. While prevalence figures are still unclear and hampered by the many different definitions and methods of diagnosis around the world, it has been estimated that IC/BPS/HSB may affect around 300 per 100,000 females, although much higher figures have been seen in the United States. Of these, 10-50% may have the classic Hunner lesion subtype.

Associated Disorders

IC/BPS/HSB patients may also suffer from one or multiple associated disorders (comorbidities) such as allergy, multiple drug/chemical intolerance, gastrointestinal disorders, fibromyalgia, vulvar pain syndromes, depression, panic attacks and generalised autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and Sjogren’s syndrome.

Assessment

Assessment procedures vary considerably in different parts of the world. Due to the current lack of any specific marker, diagnosis is based on symptoms and exclusion of confusable diseases by history, a thorough physical examination, urinalysis and culture. In some countries, the initial diagnosis is based on symptoms and exclusions alone, while other countries insist on cystoscopy and biopsy. A cystoscopy under anaesthesia – with/without hydrodistension and with/without bladder biopsy - may provide information concerning bladder capacity, the presence of Hunner lesions, inflammation, or other pathology. The findings may provide support for a diagnosis and form guidance for the choice of treatment.

Treatment

Since there is as yet no cure for IC/BPS/HSB, treatment of this complex condition is challenging and aimed at alleviating the symptoms and improving the patient’s quality of life. Treatment is highly individual since no therapy exists that is equally effective for all patients and every patient is different. There are, nevertheless, many different treatments that can be tried, varying from conservative to invasive. Treatment may consist of diet and behavioural modification, pelvic floor rehabilitation, one or more oral drugs, intravesical treatment, neuromodulation or surgical interventions. Surgery with urinary diversion with or without bladder removal is considered to be a last resort, but in rare cases may be the only option for the severest patients. The two currently known subtypes - the classic inflammatory Hunner lesion subtype and the non-lesion subtype - require different treatment approaches. Effective treatments exist for patients with Hunner lesions and can greatly improve their quality of life. A holistic approach to treatment may produce the best results in all patients and certainly the presence of associated disorders should always be taken into account. Patient education plays an important role since it helps patients to understand why they are receiving a specific form of treatment and what it aims to achieve. IC support groups can also help a patient to cope with this disabling chronic condition.

Phenotyping

Current research is focusing on sub-typing (phenotyping) these patients with the ultimate aim of ensuring the most effective treatment per individual patient. There are great differences between the patients: some may have Hunner’s lesions, others not, some may have a contracted bladder with a very small bladder capacity, others a normal bladder capacity under anaesthesia. Some patients have bladder inflammation, others not. Some may have devastating pain, while other patients may have only frequency and urgency without any real pain. Some patients may have an associated autoimmune disease, others multiple pain syndromes. Understanding these different populations of patients (different phenotypes) may lead to better treatment in the future.

Impact

Painful bladder syndrome has a major impact on the patient’s quality of life. The frequent and urgent need to urinate means that the patient is constantly looking for the next toilet. This can present a serious obstacle to work, travel, social life and relationships and lead to social isolation and depression. Lack of sleep due to pain and frequent night-time urination causes fatigue, lack of concentration and irritability, while painful sexual activity may have a dramatic effect on relationships.

Conclusion

IC/BPS/HSB is an enigmatic, complex and difficult condition: difficult to diagnose, difficult to treat and difficult for the patient to cope with. Good physician/patient communication is of the utmost importance.

Suggested Reading

1. BLADDER PAIN SYNDROME: A Guide for Clinicians Edited by Nordling J, Wyndaele, JJ, Van de Merwe JP, Bouchelouche P, Cervigni M, Fall M. Published by Springer 2013.
2. The American Urological Association Guideline on Diagnosis & Treatment of Interstitial Cystitis/Bladder Pain Syndrome can be read online at: http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=ic-bps

A summary of this AUA Guideline was published in:

3. Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, Forrest JB, Gordon B, Gray M, Mayer RD, Newman D, Nyberg L Jr, Payne CK, Wesselmann U, Faraday MM. AUA Guideline for the Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome. J Urol. 2011 Jun;185(6):2162-70.
4. Homma Y, Ueda T, Tomoe H, Lin AT, Kuo HC, Lee MH, Lee JG, Kim DY, Lee KS. Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome. The interstitial cystitis guideline committee. Int J Urol 2013;20(8):742-3.
5. Homma Y. Hypersensitive bladder: Towards clear taxonomy surrounding interstitial cystitis. Int J Urol. 2013 Mar 21.
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9. Hunner GL. A rare type of bladder ulcer in women: report of cases. Boston Med Surg J 1915;172:660-4.
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12. Nickel JC, Shoskes D, Irvine-Bird K. Clinical phenotyping of women with interstitial cystitis/painful bladder syndrome: a key to classification and potentially improved management. J Urol. 2009 Jul;182(1):155-60.
13. Nickel JC, Tripp DA, Pontari M, Moldwin R, Mayer R, Carr LK, Doggweiler R, Yang CC, Mishra N, Nordling J. Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. J Urol. 2010;184(4):1358-63.
14. Nordling J, Fall M, Hanno P. Global concepts of bladder pain syndrome (interstitial cystitis). World J Urol. 2012 Aug;30(4):457-64.
15. Van de Merwe JP, Nordling J, et al. Diagnostic Criteria, classification, and Nomenclature for Painful Bladder Syndrome/Interstitial Cystitis: an ESSIC proposal. Eur Urol. 2008 Jan;53(1):60-7.
16. Warren JW, van de Merwe JP, Nickel JC. Interstitial cystitis/bladder pain syndrome and nonbladder syndromes: facts and hypotheses. Urology. 2011 Oct;78(4):727-32.