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Bladder Pain Syndrome—Current Concepts and Management Guidelines

Bladder Pain Syndrome—Current Concepts and Management Guidelines

Review Article Bladder Pain Syndrome—Current Concepts and Management Guidelines

Jain A

To cite: Jain A. Bladder Pain Senior Consultant Urogynaecology Syndrome—Current Concepts Institute of and Robotic and Management Guidelines. Medanta The Medicity Pan Asian J Obs Gyn, Gurugram, Haryana, India May–Aug 2018, Vol. 1, Issue 1, (page 12-16). Received on:

Accepted on: ABSTRACT

Source of Support: /bladder pain syndrome (IC/BPS) is a chronic debilitating condition with increasing incidence globally. Despite of regular update of guidelines by different regulatory Conflict of Interest: bodies still there is a lack of consensus regarding the definition. It is still under reported in India. A single, standardised reporting method would help clini- cians to understand and communicate best treatment options to these patients. The purpose of this article is give an overview of the current guidelines regarding diagnosis and management of this disease. Keywords: Interstitial cystitis, Bladder pain syndrome, Chronic , Hunner’s lesion

BACkgRound suffering in a similar manner.5 Therefore more relaxed diagnosing criteria have been proposed by different Bladder Pain Syndrome/Interstitial cystitis(BPS/IC) is regulatory bodies including the one used by Japanese,6 considered as a chronic debilitating condition with a American Urological Association7 or by the European severely negative impact on a patient’s quality of life. Society for Study of Interstitial Cystitis.8 It was felt that Its prevalence ranges from 52 to 500/100,000 in females pelvic pain which was related to micturition cycle and compared to 8–41/100,000 in males,1 and its incidence presented with lower urinary tract symptoms could be is increasing globally. categorized as single entity ‘Bladder Pain Syndrome’.7 The term ‘Interstitial cystitis’ was first described by It included different terms in use like interstitial cystitis, Skene in 1887,2 who mentioned about destruction of painful bladder syndrome, , mucous membrane of bladder by , which under one category to avoid confusions. But still a single appeared to spread into the wall of . definition or diagnostic criteria for this condition, could Later Guy Leroy Hunner, a Boston gynaecologist, from not be agreed upon. Johns Hopkins, for the first time in 1914 described a Today most acceptable definition as proposed by the symptom complex of bladder pain associated with Society for Urodynamics and Female Urology (SUFU) is a unique cystoscopic finding of mucosal lesions, the “An unpleasant sensation (pain, pressure, discomfort) “elusive ulcer”, later termed Hunner’s ulcer.3 For a perceived to be related to the urinary bladder, number of years, this finding was the hallmark of IC. associated with lower urinary tract symptoms of more The ulcer was thought to be the cause of symptoms in than six weeks duration, in the absence of infection or these women. other identifiable causes.”9 With this, treatment can Based on this, this condition was first defined by the be started early after a relatively short symptomatic National Institute of Diabetes and Digestive and Kidney period, while definitions that require longer symptom Diseases in the late 1980s.4 Later it was noted in many durations (i.e., six months) can withhold the treatment studies that the diagnosis can be missed in more than for longer period, resulting in increased duration of 60% of patients once these strict criteria are applied, patient suffering. especially those without typical Hunner’s ulcer but

12 Bladder Pain Syndrome—Current Concepts and Management Guidelines

The European Association of Urology (EAU) also • History of neurological disease to rule out Neurogenic embraces the term BPS, but reserved the term IC bladder (‘Burning character’ of pain suggestive of for a subset of patients with findings of chronic neuropathic pain) inflammation extending submucosally; on , • Pain at anus or getting relieved after passing stools, hydrodistention, and/or bladder biopsy.8 may suggest an intestinal pathology. Other important points, which should be included in CLINICAL APPROACH TO A PATIENT history are WITH SUSPECTED IC/BPS • History suggestive of aetiology: to food or The diagnosis is based on the symptom complex with drugs/allergic bronchitis or bronchial asthma/other subjective perception of bladder as a source and after allergic disorders like Seasonal hay fever or urticaria/ excluding other identifiable causes for the symptoms. autoimmune disorders High clinical index of suspicion is the key to diagnosis. It • History of obstructive symptoms: in women due to is equally important not to over diagnose this condition. pelvic floor spasm, in men due to prostatic pathology or stricture • Recent change in diet, like health drinks, excessive HISTORY tea/green tea/coffee/dark or something Pain or discomfort in lower abdomen and/or urogenital else which the patient wasn’t used to earlier eg. area. change of diet due to geographical translocation. Patient will never have fear of leaking urine but would • Recent drug treatment for unrelated disease not be able to hold urine due to increase in pain with • History of associated diseases/co- morbidities like bladder filling. This vary symptom differentiate it from , , anxiety, OAB () as a cause of Urgency. or migraine.They might be of importance in The patients often learn to quickly empty their the identification of various phenotypes. bladder to avoid pain in BPS leading to increase in Frequency. At night also, the patient wakes up because of pain rather than a desire to pass urine due to full EXAMINATION bladder. General: Gait of the patient, Mental state of the patient, The classical presentation is immense urge with Somatic signs of anxiety like pallor, sweating etc. increasing suprapubic pain or discomfort as bladder Abdominal examination: any masses, any abdominal fills, which is usually relieved by voiding although soon tenderness especially suprapubic, previous surgical returning. Descriptions of discomfort may vary like scars. “pressure”, “burning”, “pricking” or “sharp”. Sometimes pain can be felt at locations other than suprapubic Local examination: Any area of tenderness in region like urethra, vagina, lower abdomen and back, perineum, tone of the pelvic floor muscle and trigger medial aspect of the thigh or inguinal area as referred points need to be noted. Any Myofascial bands must pain.9 also be looked for. Tenderness on pressing anterior History of following confusable diseases should also fornix may indicate presence of BPS. be elicited to exclude other causes. Neurological examination: If indicated • Prior pelvic surgery • Urinary stone disease INVESTIGATIONS • Pelvic inflammatory disease: presence of vaginal discharge The investigations are primarily aimed at excluding the • Vulvovaginitis: It will be associated with superficial diseases with specific aetiology ( Deep Dyspareunia indicates BPS). • Frequency volume chart gives a fair idea of the • Prior pelvic radiation functional bladder capacity. This serves a valuable • Infertility evidence to objectively evaluate the progress of • Pelvic : Pain intensity increases usually disease and its response to treatment. The voided around menstrual cycle. volume, spacing in between and the number of voids can be objective parameters for further intervention.

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• Urine analysis: The absence of pus cells in the • While evaluating a case of suspected BPS, all urinary sediments, leucocyte esterase (LE) or nitrite confusable disease entities must be carefully in the urine sample almost excludes the diagnosis excluded. Table 2 enlists such diseases which might of urinary infection. Presence of red blood cells in mimic BPS in clinical presentation. urine should indicate a detailed evaluation of the urinary tract starting with the urine cytology for MANAGEMENT OF IC/BPS PATIENT malignant cells. • Ultrasonography (optional)of the urinary tract to Education exclude any pelvic pathology likely to be the cause The management of these patients begins with detailed of symptoms, including significant post void residual discussion of the disease entity and prognosis. It must urine ( especially in presence of symptoms of voiding be emphasized that the treatment might be prolonged dysfunction). and the relief might be slow to appear. There could • Anesthetic challenge test (optional)is a simple test to be need to change during the course of demonstrate that the pain is indeed originating from treatment as this is a heterogeneous entity and so are bladder. 20 ml of 1% lignocaine may be instilled in the treatment modalities. bladder by a per urethral soft small calibre after evacuating any urine from the bladder. There is an immediate relief from pain which stays for Oral Non-specific almost an hour or more. This indicates that the pain Urine Alkalisers: Simply changing the acidic pH of is indeed originating from bladder. But this is not a urine to neutral or slightly alkaline can reduce the pain specific test as pain due to any bladder inflammation in such patients. would be relieved on instilling lignocaine in bladder. (Tryptomer) is a However, it is very useful when differentiating and has central and peripheral action. Apart from pelvic pain originating from uterus or adnexa (e.g. relieving neuropathic pain, it also stabilizes bladder 11 endometriosis) or colon. contractility by its anticholinergic effect. This should be • Symptom scores: O’Leary Saint symptom score and the treatment of choice in patients with the ‘burning’ Pain Frequency Urgency (PUF) score are useful for or ‘pricking’ character of pain. Its main side effects are 12 the follow-up and documentation of these patients. sedation and dryness of mouth. Dose: 10 mg at bedtime • Cystoscopy: The American Urological Association slowly escalated to 25 mg two times a day. (AUA) does not recommend cystoscopy in all cases of BPS, especially to confirm the diagnosis.7 However, (Atarax) is anti–. In patients European Society for Study of Interstitial Cystitis with history of allergies like seasonal rhinorrhea, (ESSIC) recommend cystoscopy in all cases.8 This urticarial or bronchial asthma should be considered for serves as a diagnostic investigation, as well as a use of this drug. Hydroxyzine is usually well tolerated therapeutic procedure, providing an opportunity to but has a sedative effect in some individuals. Dose: 10 perform hydrodistension and ablate Hunner’s lesions mg oral tablet at bed time but can be increased to 25 in the bladder. Therefore it should always be planned mg two to three times a day. under . Skeletal muscle relaxants like clonazepam or • Biopsy of any bladder lesion must be taken at cyclobenzaprine may be used if the symptoms are time of cystoscopy in order to exclude a different suggestive of pelvic floor spasm or on examination pathology like cystitis cystica, tubercular granuloma there are tender trigger points in levator ani muscle. or urothelial malignancy. Dose: Clonazepam (Clonotril) 0.25 mg at bed time; • Urodynamic evaluation in select cases to distinguish Cyclobenzparine (Skelebenz 15 mg) 15 mg at bed time. between this condition and neuropathic bladder, The main side effects of this class of drugs is sedation OAB or any other voiding dysfunction. and light headedness. • Laparoscopy reserved for cases where the chronic Analgesics like tramadol, Gabapentin and pregabalin. pelvic pain strongly suggests a cause other than These medicines must be used with caution as drug bladder. dependency is a frequent occurrence.

14 Bladder Pain Syndrome—Current Concepts and Management Guidelines

ORAL SPECIFIC MEDICATION of toxicity. There is still no published data in reference to direct comparison of with and PentosanPolysulphate (PPS) is a synthetic sulphated without alkalinisation or comparison of its different polysaccharide which may be used as oral tablet or concentrations. , urethral irritation, and intravesical instillation. It is estimated that 4-6% of bladder pain are reported AEs, which usually get this drug when ingested orally is excreted unchanged relieved within two weeks. in urine. It is expected to replenish the Glycosamine • Hyaluronic acid (recommended by RCOG Gr B and Glycan (GAG) layer of the urothelium which is Asian guidelines Gr c) responsible for the impermeability of the urothelium. • Chondroitin sulfate (recommended by Asian It is recommended in the dose of 100 mg three times a guidelines Gr c and RCOG Guidelines Gr D) and day, to be taken at least 1 hour before or 2 hours after Pentosanpolysulfate intravesical preparation meals to improve the bioavailability of drug. Usually the (recommended by Asian guidelines Gr c) are drug is well tolerated as the incidence of overall adverse commercially not available in India. events is almost 4% which include alopecia, diarrhoea, • Intravesical resiniferatoxinand Intravesical nausea, rash and rarely bleeding tendencies. A trial for Bacillus Calmette–Guérin are therapies that are not at least 3-6 months must be given before labelling a recommended for BPS. failure to treatment.

INTRAVESICAL TREATMENTS Cocktail Therapy The rationale is that combination might potentiate the The aim of administrating intravesicaltreatment is effect resulting in better outcome. to achieve high drug concentrations at the target, with few systemic side-effects. But the drawback is Few examples are: its invasiveness, which can be even painful and may 1. Anaesthetic cocktail: 1:1 mixture of 0.5% Marcaine increase the risk of infection. and 2% Lidocaine jelly, sulphate 10,000 IU, AUA Guidelines recommend it as second-line 40 mg and/or Gentamycin 80 mg treatments for BPS/IC (Option).7 2. Heparin cocktail: Heparin sulphate 25,000 IU/ Following agents have been recommended by various Hydrocortisone 200 mg/Physiological saline 50 ml14 guidelines: 3. DMSO cocktail: DMSO 50 cc/Sodium bicarbonate 44 • DMSO (recommended by AUA and RCOG guidelines meq/Kenalog 10 mg/Heparin 20,000 IU Gr C,13 Asian guidelines Gr B): Rapid absorption into 4. Heparin cocktail: Heparin 10,000 units/ml-2ml’s/ the bladder wall might lead to significant pain, if it Solucortef 125 mg/Gentamicin 80mg/2ml-2ml’s/ is held beyond 15-20 minutes after instillation. Most Sodium Bicarbonate 8.4% - 50ml’s/Marcaine 0.5% - patients recognized a garlic-like odour, and a few 50 ml’s patients felt bladder spasm possibly due to 5. Heparin cocktail with alkalinized lidocaine: Heparin degranulation. Caution should be taken while using it 40,000 IU/Lidocaine 2% 8 mL/Sodium bicarbonate in “cocktail” preparation, as there could be a chance 8.4% 3 mL of toxicity due to potential increase in absorption of some substances like lidocaine, in its presence. Limitations • Heparin (recommended by AUA and Asian guidelines 1. There is no data showing superior safety or efficacy Gr C, RCOG guideline Gr D): Intravesical dose ranges of these intravesical medications alone or in various from10,000 IU to 40,000 IU. Adverse Effects (AEs) combination in cocktails. are rare and minor. It is considered a safe option in 2. Mostly interval between instillation therapies is pregnancy also (RCOG Gr D).13 kept at 1-2 weeks but patients are using it as and • Lidocaine (recommended by AUA, RCOG and when required basis also. Currently no guideline Asian guidelines Gr B):Penetration into urothelium has clear recommendations in this regard. Various and therefore efficacy can be increased by adding clinically available GAG replenishing molecules are alkaline, but on other hand potential increase in Heparin, Pentosan Poly Sulphate, Hyaluronic acid, systemic absorption may increase the chances

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Chondroitin Sulphate, Combination of Hyaluronic REFERENCES acid and Chondroitin Sulphate. 1. Clemens JQ, Meenan RT, Rosetti MC, Gao SY, Calhoun EA. Prevalence and incidence of interstitial cystitis in a managed care population. J Urol. 2005;173:98-102. DIETARY MODIFICATION 2. Skene AJC. Diseases of Bladder and Urethra in Women. Most of these patients report association of symptom Wm Wood, New York, 1887. p. 167. 3. Hunner GL. Elusive ulcer of the bladder: further notes aggravation with certain food items, which may include on a rare type of bladder ulcer with report of 25 cases. coffee, tea, caffeinated drinks like coke and pepsi, Am J Obstet. 1918;78:374-95. chocolates, citrus fruits, apple, pineapple, carbonated 4. Wein A, Hanno P, Gillenwater J. Interstitial cystitis: an introduction to the problem. In: Hanno PM, Staskin DR, and alcoholic beverages, tomatoes, spices like red Krane RJ, Wein AJ (eds). Intersititial Cystitis. Springer- and green chillies, black pepper, artificial sweeteners, Verlag, London, 1990. pp. 13-15. vitamin C, and dairy products. It is usually suggested 5. Hanno PM, Landis JR, Matthews-Cook Y, Kusek J, Nyberg L Jr. The diagnosis of interstitial cystitis revisited: lessons to maintain a personal food dairy by stopping all learned from the National Institutes of Health Interstitial suspected food items for a time period till symptoms Cystitis Database study. J Urol. 1999;161(2):553-7. got relieved and then start these again one by one at 6. Homma Y, Ueda T, Ito T, Takei M, Tomoe H. Japanese interval of 3-4 days to notice any change in symptoms guideline for diagnosis and treatment of interstitial cystitis. Int J Urol. 2009;16(1):4-16. with any particular food item. In this way patients can 7. Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, learn themselves which food items are to be avoided in Erickson D, Fitzgerald MP, et al. AUA guideline for the near future to avoid recurrence of symptoms.15 diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011;185(6):2162-70. 8. Van de Merwe JP, Nordling J, Bouchelouche P, PAIN MANGEMENT Bouchelouche K, Cervigni M, Daha LK, et al. Diagnostic criteria, classification, and nomenclature for painful It is an important aspect of the treatment of BPS. Many bladder syndrome/interstitial cystitis: an ESSIC a time it becomes imperative to take help from the pain proposal. Eur Urol. 2008;53(1):60-7. 9. Hanno P and Dmochowski R: Status of international management teams which specialise in the treatment consensus on interstitial cystitis/bladder pain of chronic pains. They may include injection of local syndrome/painful bladder syndrome: 2008 snapshot. anesthetic agents at the trigger points, myofascial Neurourology and Urodynamics. 2009;28:274. relaxation or administration systemic analgesic agents. 10. Fall M, Logadottir Y, Peeker R. Interstitial cystitis is bladder pain syndrome with Hunner’s lesion. Int J Urol. 2014;21(Suppl 1):79-82. 11. Taneja R. Intravesical lignocaine in the diagnosis of SUMMARY bladder pain syndrome. Int Urogynecol J. 2010;21:321-4. The science of IC/BPS is ever evolving. The physicians 12. O’Leary MP, Sant GR, Fowler FJ Jr, Whitmore KE, have to remain abreast with the changing terminology Spolarich-Kroll J. The interstitial cystitis symptom index and problem index. Urology. 1997;49(Suppl 5A):58-63. and definitions in order to identify and treat these 13. Tirlapur SA, Birch JV, Carberry CL, Khan KS, Latthe PM, patients. Treatment of this condition should also Jha S, Ward KL, Irving A. On behalf of the Royal College include various modalities. Patient education is a very of Obstetricians and Gynaecologists. Management of bladder pain syndrome. BJOG. 2016;124:e46-e72. important ingredient of the treatment. It should also be 14. Taneja R, Jawade KK. A Rational combination of tried to identify potential etiological factors on clinical intravesical and systemic agents in the treatment of grounds e.g. history of allergies so that Interstitial cystitis. Scand J Nephrol Urol. 2007; 41:511-5. may be added in the treatment regime. The treatments 15. Asley Cox, Nicole Golda, Genevieve Nadeau, et al. CUA guideline: Diagnosis and treatment of interstitial are usually prolonged with reasonable relief in most cystitis/bladder pain syndrome. Can UrolAssoc J patients. 2016;10(5-6):E136-55. http://dx.doi.org/10.5489/ cuaj.3786 Published online, 2016.

Address for Correspondence Amita Jain Obstetrics-Gynaecology Fellow Urogynaecology (Australia) Senior Consultant Urogynaecology Institute of Urology and Robotic Surgery Medanta—The Medicity Gurugram, Haryana, India Mobile: 9871136110 [email protected]

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