Calderdale and Huddersfield

Diagnosis and Management of Interstitial Cystitis

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Guidelines on the Diagnosis and Management of Interstitial Cystitis

Purpose of guideline

Locations where this guideline applies

Scope

Overview 2

Background 2

Local Issues 2

National Issues 2

Guideline at a Glance 3

Flow Chart or Algorithm 7

Reference Pages 8

References, including national guidelines 9

Guideline developed by: 10

List of interested groups 10

Distribution list and areas where guideline should be readily available 10

Arrangements for training 10

List of changes and dates of changes 11

Equality Impact Assessment 12

Equality Impact Assessment Tool 13

Overview

Background

Interstitial cystitis (IC) can be defined as: an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six weeks duration, in the absence of infection or other identifiable cause.IC infers an inflammatory process which has not been proven in all cases. Therefore IC has become synonymous with the term Bladder Pain Syndrome (BPS), a preferred term used by the European Society for the Study of Interstitial Cystitis (ESSIC)ii.The true prevalence of IC is unknown and varies depending on the diagnostic criteria used in each study. The RAND Interstitial Cystitis Epidemiology (RICE) study is the most comprehensive epidemiological study of its type. It was conducted as a two-stage survey of approximately 150,000 United States households to identify and interview women with IC/BPS symptoms, they concluded that between 2.7 and 6.5 percent of United States women have symptoms consistent with a diagnosis of IC/BPS.iii Other European studies have shown a lower prevalence.

The exact pathogenesis is unclear, complicating the diagnosis and treatment. One theory includes a deficiency in the glycosaminoglycan (GAG) layer protecting the bladder mucosa causing urine infiltration and submucosal inflammation, stimulating sensory nerve fibres. Mast cell activation, toxic agents in the urine and auto antibodies have also been proposed to play a roll. Infection is not commonly thought to cause IC but can initiate and worsen symptoms. Insert your text about scene setting here.

Diagnosis

Diagnosis should be based on symptoms, exclusion of other diseases, with or without cystoscopy evidence of Hanner’s ulcers. A careful history should be taken eliciting symptoms including suprapubic pressure or pain, urinary frequency, urgency, notaria and dyspareunia .Commonly pain occurs on bladder filling and is relieved on emptying. It is important to differentiate frequency due to the sensation of needing to void and that of the desire to void to become pain free. IC is not commonly associated with urinary incontinence.Co-existing conditions such as irritable bowel syndrome and fibromyalgia are common. It is important to ascertain the impact of the symptoms on the woman’s quality of life and how they impact on her activities of daily living. This will help assess the impact of treatment later on. Pelvic examination may elicit pain in the region of the bladder.

Investigations

A voiding diary should be obtained. A low volume frequency voiding pattern is characteristic of IC. The O´Leary/Sant Voiding and Pain Indices questionnaire (appendix 1) does not help establish a diagnosis but can be used at initial assessment to evaluate response to treatment. A urine culture should be obtained to rule out urinary tract infection. Haematuria has been shown to be present in up to 40% of patients with IC.iv.Urine cytology may be considered if the patient is at risk of bladder cancer, i.e. smoker.

Cystoscopy can exclude bladder cancer, vesicle stones, urethral diverticula and intravesicular foreign bodies. The only agreed cystoscopic finding in IC is the presence of Hunner’s lesions, well-demarcated reddish mucosal lesions lacking in the normal capillary structure which bleed easily on touch. The absence of Hunner’s lesions however does not exclude a diagnosis of IC.

Hydrodistention at the time of cystoscopy may produce glomerulations. Glomerulations are common in IC but can also be seen in other conditions such as chronic pelvic pain and endometrisosis.v.Bladder biopsy is not useful in diagnosing IC, as no specific histological findings are known. However it may play a role in ruling out bladder carcinoma.vi

Urodynamics can help identify concomitant voiding dysfunction, however there are no urodynamic criteria for IC. The patient may experience pain on bladder filling, but can have normal filling pressures and compliance. A reduced bladder capacity without demonstrable detrusor over activity can be suggestive of IC.vii 12-20% of patients with IC will have detrusor overactivity demonstrated on urodynamics.viii

Management

The pathophysiology of IC is poorly understood, along with a lack of quality treatment studies, meaning targeting treatment is difficult. The aim of treatment is for improvement in quality of life using the most conservative method that is effective to alleviate the troublesome symptom or symptoms.

Patient education is paramount. They must understand the diagnosis, the chronic nature of the disorder and that there is no one single treatment available to cure the symptoms.

First line treatments are conservative measures. These include; stress reduction to avoid heightened pain sensitivity, avoiding bladder irritants such as caffeine and citrus fruits, eliminating certain foods from the diet to determine if dietary intake exacerbates symptoms, application of heat or cold over the bladder and pelvic floor muscle relaxation.

A large trial undertaken by the National Institute of Diabetes and Digestive and Kidney Diseases showed life style changes and a placebo medication improved 46% of patients moderately or markedly on the Global Response Assessment.ix

Pharmacological measures

There is no single recommended treatment for Interstitial cystitis. There are quite a few options.

Intravesicular installation

Sodium hyaluronate - Sodium hyaluronate is claimed to have anti-inflammatory, analgesic, muscle relaxant and collagenolytic effects. Sodium hyaluronate is a viscous solution consisting of a high molecular weight (500,000-730,000 daltons) fraction of purified natural sodium hyaluronate in buffered physiological sodium chloride. Hyaluronic acid is a natural complex sugar of the glycosaminoglycan family and is a long-chain polymer containing repeating disaccharide units of Na-glucuronate-N-acetylglucosamine. 50 ml are instilled into the bladder and retained for 30 minutes. It is done weekly once for four weeks.

Pentosanpolysulfate (PPS) - There is conflicting evidence for PPS use when compared to a placebo. One trial using PPS 200mg bd over a four month period showed similar rates of symptom improvement compared to placebo (56% v’s 49% respectively).x Whereas one study showed 28% of patients had symptomatic relief of IC compared to 13% of patients in the placebo group.xi There are few side effects to taking the medication.

Others

Dimethylsulfoxide (DMSO) - In a randomized studyxii, an 80% improvement rate was reported. Usually a solution of 50% DMSO diluted by physiological saline or distilled water is instilled into the bladder, and retained in the bladder for 10 to 20 min.

Oral preparations

Antibiotics - Antibiotics have been shown to have a small benefit, though not statistically significant, when compared to placebo.xiii As some theories consider microorganisms are implicated in the pathogenesis of IC, a trial of antibiotics is not completely unjustified.

Hydroxyzine Hydrochloride - The use of antihistamines aims to manage mast cell dysfunction. Hydroxyzine has been shown to be effective at reducing symptoms by 40% and by greater amounts in those with allergies.xiv The best dose to use is not known. Starting with a low dose of 10mg and gradually increasing as required will help reduce unwanted side effects such as drowsiness. Hydroxyzine is often best taken at night for this reason.

Cimetidine - Cimetidine has also been widely studied and has shown to be effective, especially at reducing pelvic pain and nocturia when given at doses of 400mg bd over a three month period.xv Other trials using 300mg bd and 200mg tds also resulted in significant symptom improvementxvi xvii

Amitriptyline - Amitriptyline is thought to inhibit mast cell activity by blocking histamine H1 receptor and to modify pain transmission in the central nervous system by inhibiting serotonin and noradrenalin reuptake. Randomized control trials have shown Amitriptyline, taken at a starting dose of 25mg and titrated over several weeks to 100mg, improves symptoms in 63% of IC patients when taken over a 4 month period.xviii Other studies suggest doses of less than 50mg have no significant difference on symptoms when compared to placebo.xix The side effects are common and include dry mouth, sedation, blurring of vision and nausea.

Botulinum Toxin A - Botulinum toxin inhibits release of calcitonin gene-related peptide (CGRP) and substance P from afferent nerves and weakens pain response induced by acetic acid or cyclophosphamide. Small studiesxx have shown an improvement in symptom scores when 100 to 200 units are injected in 20 to 30 areas of the bladder.

Hydrodistention - There are different methods for hydrodistention, a common one involves filling the bladder, under general or spinal anaesthesia, with saline to a pressure of 80cmH2O for a few minutes. It is thought that hydropressure causes ischaemia and metabolic acidosis, degenerating afferent nerves leading to reduced bladder pain and increased bladder capacity. Studies have shown up to 60% of patients were without symptoms for 3 to 12 months.xxi Bladder perforation is a known complication.

Pentosan polysulfate (PPS) - PPS instilled intravesically, may directly replenish the deficient GAG layer. Giving 300mg of intravesicular PPS twice weekly for 10 weeks then a maintenance dose monthly has been shown to improve quality of life.xxii One studyxxiii has shown benefits in using intravesicular installation of PPS along with oral PPS when compared to Intravesicular PPS and a placebo.

Resiniferatoxin - Resiniferatoxin is a naturally occurring chemical found in resin spurge. It is an ultra-potent analogue of capsaicin, a C-fibre afferent neurotoxin, which may alleviate the symptoms by desensitizing bladder afferents. Small studiesxxiv have proven some benefit over a three month period when 10nM was infused daily for 10 days and also when 10nM infused once weekly for 4 weeks xxv . However it has not been compared to placebo. A Cochrane review found pain on installation was more common with Resiniferatoxin.xxvi

O´Leary/Sant Voiding and Pain Indices

INTERSTITIAL CYSTITIS SYMPTOM INDEX / INTERSTITIAL CYSTITIS PROBLEM INDEX
1. During the past month, how often have you felt the strong need to urinate with little or no warning? / During the past month, how much has each of the following been a problem for you?
1. Frequent urination during the day?
0_____ Not at all / 0_____ No problem
1_____ Less than 1 in 5 times / 1_____ Very small problem
2_____ Less than half the time / 2_____ Small problem
3_____ About half the time / 3_____ Medium problem
4_____ More than half the time / 4_____ Big problem
5_____ Almost always
2. During the past month, have you had to urinate less than 2 hours after you finished urinating? / 2. Getting up at night to urinate?
0_____ Not at all / 0_____ No problem
1_____ Less than 1 in 5 times / 1_____ Very small problem
2_____ Less than half the time / 2_____ Small problem
3_____ About half the time / 3_____ Medium problem
4_____ More than half the time / 4_____ Big problem
5_____ Almost always
3. During the past month, how often did you most typically get up at night to urinate? / 3. Need to urinate with little warning?
0_____ Never / 0_____ No problem
1_____ Once / 1_____ Very small problem
2_____ 2 times / 2_____ Small problem
3_____ 3 times / 3_____ Medium problem
4_____ 4 times / 4_____ Big problem
5_____ 5 times
6_____ 5 or more times
4 . During the past month, have you experienced pain or burning in your bladder? / 4. Burning, pain, discomfort, or pressure in your bladder?
0_____ Not at all / 0_____ No problem
1_____ Once / 1_____ Very small problem
2_____ A few times / 2_____ Small problem
3_____ Fairly often / 3_____ Medium problem
4_____ Almost always / 4_____ Big problem
5_____ Usually
Total Score______ / Total Score______

Algorithm for the Management of Interstitial Cystitis

Reference Pages

Hanno P, Dmochowski R. Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot. Neurourol Urodyn. 2009;28(4):274-86

2 Joop P. V M, Jørgen N et al. Diagnostic Criteria, Classification, and Nomenclature for Painful Bladder Syndrome/Interstitial Cystitis: An ESSIC ProposalEuropean Urology, 2008; 53(1)60-67

3 Berry SH, E. M. S. M. e. a., 2011. Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J Urol, 186, p. 540

4 Gomes CM, Sánchez-Ortiz RF, Harris C et al. Significance of heamaturia in patients with interstitial cystitis: review of radiographic and endoscopic findings. Urology. 2001 Feb;57(2):262-5

5 Chung MK, Chung RP, Gordon D: Interstitial cystitis and endometriosis in women with chronic pelvic pain. The ‘evil twins’ syndrome. JSLS 2005; 9:25

6 Hanno P, Levin RM, Monson FC, et al. Diagnosis of interstitial cystitis. J Urol. 1990;143:278–281

7 Awad SA, MacDiarmid S, Gajewski JB et al.Idiopathic reduced bladder storage versus interstitial cystitis. J Urol. 1992 Nov;148(5):1409-12

8 Kirkemo A, Peabody M, Diokno AC et al. Associations among urodynamic findings and symptoms in women enrolled in the Interstitial Cystitis Data Base (ICDB) study. Urology. 1997, 49:76

9 Foster HE, Kreder K, Fitzgerald MP et al. Effect of Amitriptyline on symptoms in newly diagnosed patients with interstitial cystitis/painful bladder syndrome. J Urol 2010; 183: 1853

10 Holm-Bentzen M, Jacobsen F, Nerstrom B et al. A prospective double-blind clinically controlled multicentre trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and realetd painful bladder disease. J Urol 1987; 138:503

11 S. GrantMulholland, Affiliations

Departments of Urology, Thomas Jefferson UniversityHospital, and University of Pennsylvania Hospital, Philadelphia, Pennsylvania

University of California,San Diego Medical Center, San Diego, California, USA

Tufts University School of Medicine, and Boston University School of Medicine, Boston, Massachusetts

Grannum R.Sant, Affiliations