There are widespread definitions for the condition, Bladder Pain Syndrome (BPS). The European Society for the Study of BPS (ESSIC) in 2008 defined BPS as ‘pelvic pain, pressure or discomfort perceived to be related to the bladder, lasting at least 6 months, and accompanied by at least one other urinary symptom, for example persistent urge to void or frequency, in the absence of other identifiable causes’.¹

More recently, the American Urological Association has described BPS as ‘an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes’.²

BPS may be associated with negative cognitive, behavioural, sexual or emotional consequences, as well as symptoms suggestive of sexual dysfunction according to the European Association of Urology. In 2016, The Royal College of Obstetricians and Gynaecologists, together with The British Society of Urogynaecology, issued a Green-top guideline on the management of BPS.³

Bladder Pain Syndrome is a chronic condition with an unknown aetiology. Over the years, there have been many definitions and criteria surrounding this unfathomable condition. It is now generally accepted as a diagnosis of exclusion with no definitive diagnostic or confirmatory test.

A large American study found prevalence rates of 2.3% - 6.5%. BPS is between 2 and 5 times more common in women than in men.⁴ A systematic review found the most commonly reported symptoms of BPS to be bladder/pelvic pain, urgency, frequency and nocturia.⁵ However, the prevalence of this condition remains elusive in many parts of the world, due to the variations in consensus in defining the symptoms and diagnostic criteria.

A number of expert panels, including the ESSIC¹ American Urological Association², European Association of Urology⁷ and International Consultation on Incontinence6, have published symptom-based diagnostic criteria for BPS. All include the symptoms of pain related to the bladder, at least one other urinary symptom, absence of identifiable causes and minimum duration of symptoms of 6 weeks² to 6 months.

CLINICAL PRESENTATION

Despite the multi-faceted nature of BPS, certain fundamental principles in the assessment and management of this condition remain.

A combination of thorough medical history and physical examination should by undertaken by the clinician in the approach to BPS.

Building Rapport
Establishing rapport and empathy with the affected patient is vital in understanding the complexity of the symptoms and adverse impact on the quality of life. This is similar to the management of chronic pelvic pain syndromes. Patients should be encouraged to talk about their symptoms and any theories that they have about the origins of the pain. This allows engagement in further investigations and management of their condition.^8,9

Symptoms Assessment
It is important to explain that BPS is a chronic condition with periods of fluctuating symptom severity, where symptoms may be life-long.

Symptoms assessment forms the basis of the initial evaluation. Symptoms include suprapubic pain related to bladder filling, urgency, increased daytime and night-time frequency, in the absence of any identifiable pathology or infection. The location of the pain has been described in several studies and the most commonly reported sites are the bladder, urethra and vagina. The description of the pain ranges from pressure and aching to a burning sensation.

Aggravating and Alleviating Factors
A study of 565 patients with the condition was used to identify factors that can aggravate and alleviate the condition. Voiding was found to relieve the pain in 57% - 73% of patients. Pain was aggravated by stress (61%), sexual intercourse (50%), constrictive clothing (49%), acidic beverages (54%), coffee (51%) and spicy foods (46%).

The Events Preceding IC study of 158 women with BPS10-12 found that pain worsened with certain food or drink, and/or worsened with bladder filling, and/or improved with urination in 97% of patients.

Excluding Other Potential Causes
Due to its nature of diagnosis of exclusion, it is imperative that other potential causes of bladder pain or lower urinary tract symptoms have to be considered, such as urinary tract infections, sexually transmitted infections, other bladder diseases (e.g., calculi, tumours etc.), as well as previous pelvic surgery.

The location of the pain, and relationship to bladder filling and emptying should be established.

The characteristics of the pain, including trigger factors and onset, correlation with other events and description of the pain, should be recorded.

Careful exploration into the woman’s history for any physical or sexual abuse should also form part of the clinical assessment.

Physical examination should be performed to rule out urinary retention, hernias and painful trigger points on abdominal palpation. A genital examination should also be done to rule out atrophic changes, prolapse, vaginitis and trigger point tenderness over the urethra, vestibular glands, vulvar skin or bladder. Features of dermatosis, including vulvar or vestibular disease, should be looked for. Superficial or deep vaginal tenderness, and tenderness of the pelvic floor muscles, should be assessed during the course of the examination.

A bimanual pelvic examination is helpful to rule out uterine, cervical or adnexal pathology.

WORK-UP

Both a 3-day bladder diary (frequency volume chart) and a food diary should be employed to determine the urinary habits, as well as to identify if specific foods cause a flare-up of symptoms, respectively.

Urine should be tested to rule out a UTI, as this is a prerequisite for diagnosis of BPS. Investigations for urinary ureaplasma and chlamydia can be considered in symptomatic patients with negative urine cultures and pyuria.

In those with persistent microscopic or macroscopic haematuria, urine cytology should be tested for the suspicion of urological malignancy. Cystoscopy and a referral to urology should then be initiated accordingly.

Bladder Pain Syndrome is a diagnosis of exclusion.¹ Hence, other conditions should be excluded as follows:

• malignancy, e.g., bladder carcinoma/carcinoma in situ, cervical, uterine or ovarian cancer
• infection of the urinary or genital tract
  
• overactive bladder
• radiation cystitis or drug-mediated cystitis, e.g., cyclophosphamide, ketamine
  
• bladder outlet obstruction or incomplete bladder emptying
• calculus of the bladder or lower ureter
• urethral diverticulum
• pelvic organ prolapse
• endometriosis
  
• pudendal nerve entrapment or pelvic floor muscle-related pain
  
• irritable bowel syndrome
• diverticular disease of the bowel

INITIAL MANAGEMENT

The management choices for BPS are multi-varied. These range from a spectrum of conservative to invasive multi-disciplinary treatments, depending on the severity of the symptomatology.

Once BPS has been diagnosed, it is imperative to address the patient’s expectations and the impact of the symptoms on her quality of life, prior to tailoring an individualised therapy together with the patient.

Conservative treatments encompass dietary modification, stress management and analgesia. Dietary avoidance of caffeine, alcohol, acidic foods and drinks (citrus fruits, carbonated drinks, chocolates and tomatoes¹¹) may bring about improvement in symptoms.

Stress reduction (such as relaxation techniques, music listening and meditation) and regular exercises have also reported symptomatic improvement.¹³ Different selections and cocktails of analgesia may be useful in treating the key symptom of pain in this condition.

Early referral to a pain specialist should be considered in patients with chronic refractory symptoms. There is, however, limited evidence on the benefits of acupuncture.

Oral amitriptyline or cimetidine may be considered when first-line conservative treatments have failed. A systematic review of two randomised controlled trials using increasing titrated doses of amitriptyline between 10 mg and 100 mg over a 4-month period showed trends in improvement in urinary urgency, frequency and pain scores in both trials compared with non-treated patients.¹⁴ One RCT compared 36 patients treated with a 3-month course of 400 mg cimetidine orally versus placebo twice daily. All patients had symptomatic improvements, but these were more pronounced in the treatment group, especially for pain and nocturia.

The small sample size and short duration of follow-up are limiting factors in this study.¹⁵ Cimetidine is currently not licensed to treat BPS and should only be commenced by a clinician specialised to treat this condition.

Multimodal therapy may be considered if single drugs are unsuccessful, but should be commenced by specialists with expertise and consideration of multidisciplinary input.

If either conservative or pharmacological treatments have been unsuccessful, other invasive therapies may be considered or added using an individualised approach, under the guidance from a multi-disciplinary input (physiotherapist, pain team, clinical psychologist, urologist, urogynaecologist).

Several intra-vesical treatments using various medications may be enlisted by the multi-disciplinary team.^{16 -21}

BPS AND PREGNANCY

Woman can be advised that the effect of pregnancy on the severity of BPS symptoms can be variable. A patient survey conducted by the Interstitial Cystitis Association in 1989 showed that there was a wide variation in the perception of BPS symptoms during the pregnancy and the puerperium.²³

BPS was also not affected by the mode of delivery. BPS treatment options considered safe in pregnancy include oral amitriptyline and intravesical heparin.^{23, 24} Currently, there is inadequate robust evidence underlying the rest of the therapies.^{25, 26}

GPs can call for appointments through the GP Appointment Hotline at 6321 4402 for more information.

Dr Lim Shau Khng Jason is an obstetrician, gynaecologist and urogynaecologist at the Department of Obstetrics & Gynaecology (O&G) at Singapore General Hospital. He completed his subspecialty fellowship in Urogynaecology and Advanced Female Pelvic Floor Reconstructive Surgery in England, at the University College London Hospitals and John Radcliffe Hospital in Oxford.

His areas of clinical practice include obstetrics (childbirth), general gynaecology, female pelvic floor reconstructive surgery (urinary incontinence and pelvic organ prolapse), benign gynaecology minimally-invasive surgery, postpartum pelvic floor preventive medicine and intrapartum management and obstetric emergencies.

Dr Lim also pioneered and leads the Postnatal Assessment Service in the Department of O&G at the SGH, the first of its kind for postpartum service in Singapore. He is also an Adjunct Assistant Professor at the Yong Loo Lin School of Medicine, NUS, as well as at the Duke-NUS Graduate School of Medicine for undergraduate studies. His postgraduate academic undertakings includes the SingHealth Residency Transitional Year Core Faculty and SingHealth PGY1 Core Faculty, as well as Core Faculty under the SingHealth Residency O&G Programme.

References

1. Van de Merwe JP, Nordling J, Bouchelouche P, Bouchelouche K, Cervigni M, Daha LK, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol 2008;53:60–7.
2. American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Linthicum, MD: AUA; 2014.
3. Royal College of Obstetricians and Gynaecologists. Management of Bladder Pain Syndrome. Green-top Guideline No. 70, RCOG/BSUG Joint Guideline. December 2016.
4. Konkle KS, Berry SH, Elliott MN, Hilton L, Suttorp MJ, Clauw DJ, et al. Comparison of an interstitial cystitis/bladder pain syndrome clinical cohort with symptomatic community women from the RAND Interstitial Cystitis Epidemiology study. J Urol 2012;187:508–12.
5. Bogart LM, Berry SH, Clemens JQ. Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review. J Urol 2007;177:450–6.
6. Hanno P, Lin A, Nordling J, Nyberg L, van Ophoven A, Ueda T, et al.; Bladder Pain Syndrome Committee of the International Consultation on Incontinence. Bladder Pain Syndrome Committee of the International Consultation on Incontinence. Neurourol Urodyn 2010;29:191–8.
7. Fall M, Baranowski AP, Fowler CJ, Lepinard V, Malone-Lee JG, Messelink EJ, et al.; European Association of Urology. EAU guidelines on chronic pelvic pain. Eur Urol 2004;46:681–9.
8. McGowan L, Luker K, Creed F, Chew-Graham CA. How do you explain a pain that can’t be seen?: the narratives of women with chronic pelvic pain and their disengagement with the diagnostic cycle. Br J Health Psychol 2007;12:261–74.
9. Price J, Farmer G, Harris J, Hope T, Kennedy S, Mayou R. Attitudes of women with chronic pelvic pain to the gynaecological consultation: a qualitative study. BJOG 2006;113:446–52.
10. Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Waxell T, et al. Increased prevalence of interstitial cystitis: previously unrecognised urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology 2002;60:573–8.
11. Warren JW, Brown J, Tracy JK, Langenberg P, Wesselmann U, Greenberg P. Evidence-based criteria for pain of interstitial cystitis/painful bladder syndrome in women. Urology 2008;71:444–8.
12. Tincello DG, Walker AC. Interstitial cystitis in the UK: results of a questionnaire survey of members of the Interstitial Cystitis Support Group. Eur J Obstet Gynecol Reprod Biol 2005;118:91–5.
13. O’Hare PG 3rd, Hoffmann AR, Allen P, Gordon B, Salin L, Whitmore K. Interstitial cystitis patients’ use and rating of complementary and alternative medicine therapies. Int Urogynecol J 2013;24:977–82.
14. Giannantoni A, Bini V, Dmochowski R, Hanno P, Nickel JC, Proietti S, et al. Contemporary Management of the painful bladder: a systematic review. Eur Urol 2012;61:29–53.
15. Thilagarajah R, Witherow RO, Walker MM. Oral cimetidine gives effective symptom relief in painful bladder disease: a prospective, randomised, double-blind placebo-controlled trial. BJU Int 2001;87:207–12.
16. Matsuoka PK, Haddad JM, Pacetta AM, Baracat EC. Intravesical treatment of painful bladder syndrome: a systematic review and meta-analysis. Int Urogynecol J 2012;23:1147–53.
17. Nickel JC, Moldwin R, Lee S, Davis EL, Henry RA, Wyllie MG. Intravesical alkalinised lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome. BJU Int 2009;103:910–8.
18. Barua JM, Arance I, Angulo JC, Riedl CR. A systematic review and meta-analysis on the efficacy of intravesical therapy for bladder pain syndrome/interstitial cystitis. Int Urogynecol J 2016;27:1137–47.
19. Tirumuru S, Al-Kurdi D, Latthe P. Intravesical botulinum toxin A injections in the treatment of painful bladder syndrome/interstitial cystitis: a systematic review. Int Urogynecol J 2010;21:1285–300.
20. Dimitrakov J, Kroenke K, Steers WD, Berde C, Zurakowski D, Freeman MR, et al. Pharmacologic management of painful bladder syndrome/ interstitial cystitis: a systematic review. Arch Intern Med 2007;167:1922–9.
21. Parsons CL, Housley T, Schmidt JD, Lebow D. Treatment of interstitial cystitis with intravesical heparin. Br J Urol 1994;73:504–7.
22. Thakkinstian A, Nickel JC. Efficacy of intravesical chondroitin sulphate in treatment of interstitial cystitis/bladder pain syndrome (IC/BPS): Individual patient data (IPD) meta-analytical approach. Can Urol Assoc J 2013;7:195–200.
23. Erickson DR, Propert KJ. Pregnancy and interstitial cystitis/painful bladder syndrome. Urol Clin North Am 2007;34:61–9.
24. Simon LJ, Landis JR, Erickson DR, Nyberg LM. The Interstitial Cystitis Data Base Study: concepts and preliminary baseline descriptive statistics. Urology 1997;49 Suppl 5A:64–75.
25. Bjørn AM, Ehrenstein V, Nohr EA, Nørgaard M. Use of inhaled and oral corticosteroids in pregnancy and the risk of malformations or miscarriage. Basic Clin Pharmacol Toxicol 2015;116:308–14.
26. Onwude JL, Selo-Ojeme DO. Pregnancy outcomes following the diagnosis of interstitial cystitis. Gynecol Obstet Invest 2003;56:160–2.