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bladder pain syndrome / interstitial cystitis

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bladder pain syndrome is highly prevalent. it is a diagnosis of exclusion. the biggest hurdle in management is diagnosis. more often than not patients suffering with BPS move from pillar to post, from a clinician to another, often getting urethral dilatations, receiving NSAIDS and even antipsychotics (having been labelled as 'psychiatric' patient).
once diagnosis is made, treatment is multipronged and based on phenotype - the concept is called UPOINT. interstitial cystitis is a small but significant minority (moreover ulcerative type) of BPS.
Gabapentin, amitriptyline and pentosan polysulfate are cornerstone pharmacotherapeutic agents for IC/BPS

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bladder pain syndrome / interstitial cystitis

  1. 1. Interstitial cystitis – bladder pain syndrome ​Dr Mayank Mohan Agarwal ​MS, MRCS(Ed), ​DNB, MCh (PGI, Chd) ​VMMF and IAUA Fellowships Uro-Oncology, Pelvic Floor Reconstruction (MSKCC, NY; UCLA, LA; WFUBMC, NC)​ Formerly Associate Professor of Urology, PGIMER, Chandigarh (India) Formerly Consultant & Head of Urology, NMC specialty hospital, Abu Dhabi (UAE) Consultant and Head of Urology Aster Ramesh Cardiac and Multispecialty Hospitals Guntur (AP), India
  2. 2. INTRODUCTION • Bourque (1951): Aunt Minnie description of IC “We have all met........patients who suffer chronically from their bladder; .......distressed.......constantly, having to urinate often, .......day and night, and suffering pains every time they void. .......these miserable patients are unhappy, ........finally influence their general state of health physically ......and mentally ......”
  3. 3. SUMMARY • ETIOLOGY • PRESENTATION • WORKUP • MANAGEMENT
  4. 4. Definition • IC / BPS o Chronic (>6-12wk) symptoms of pain emanate from the bladder and/or pelvis o Urinary urgency (for pain) and/or frequency o In the absence of another identified cause – Clinical diagnosis ‘of exclusion’ • IC o The above with o “typical cystoscopic and histological features,”
  5. 5. Classification • European society for study of IC classification: 2008
  6. 6. Classification • European society for study of IC classification: 2008
  7. 7. Classification • European society for study of IC classification: 2008
  8. 8. Epidemiology • Prevalence 10% • Strict criteria – – USA 60/100,000 – Europe 20/100,000 – Japan 3/100,000 • Mostly women (90%) • Median age 40y (children to old age)
  9. 9. ETIOPATHOGENESIS
  10. 10. Pelvic floor dysfunction INSULT autoimmune infection Neurogenic inflammn Trauma / overdistensn Damage to epithelium Leakage into interstitium Immuno- stimulation C-fibre activation Mast cell activation NON-NOCICEPTION PROGRESSIVE BLADDER INJURY APF REPAIR<<DAMAGE
  11. 11. PRESENTATION • Recurrent pelvic pain or discomfort (pressure, burning, throbbing, etc.) • at least 4-6 weeks’ duration • Increases with bladder filling and /or decreases with micturition in the absence of definable pathology • associated with urinary frequency and/ or urgency
  12. 12. PRESENTATION • Recurrent pelvic pain or discomfort (pressure, burning, throbbing, etc.) • at least 4-6 weeks’ duration • Increases with bladder filling and /or decreases with micturition in the absence of definable pathology • associated with urinary frequency and/ or urgency
  13. 13. • Incontinence very uncommon • Other symptoms – dyspareunia, pelvic pain • Part of CPPS • Other associations – – Allergies – Irritable bowel syndrome – Fibromyalgia – SLE – Anxiety / depression PRESENTATION CPPSU-CPPSBPSIC
  14. 14. Workup • No consensus on minimum and optimal workup • No shortcut to detailed History & examination that’s where is remains underdiagnosed and mistreated • Diagnosis of exclusion – what all to exclude • Tools – – Questionnaires – Urine-analysis – Imaging – Urodynamics – Cystoscopy Mycobacterial infections CIS Endometriosis Other inflammatory conditions
  15. 15. Questionnaires • NOT FOR DIAGNOSIS • For objectively assessing severity and effect of therapy – University of Wisconsin IC scale – O’Leary-Sant IC symptom index – Pelvic pain and urgency/frequency scale (PUF) – Genitourinary pain index (GUPI) • Research tools • Clinical practice – (bio)feedback Questions related to bladder, pelvic pain and sex
  16. 16. Urine-analysis • ALWAYS – – microscopy and bacterial culture • PREFERABLE – (MUST if sterile pyuria, µ-hematuria) – Urine cytology for malignant cells (x 3 days) NOT first morning sample – Urine for AFB µ-s & c/s or PCR (genexpert, LPA) (x 3-5 days) MUST be first morning (or overnight collection) • INVESTIGATIONAL – Nanobacteria culture – Antiproliferative factor
  17. 17. Imaging Ultrasonography • Extension of clinical examination • Readily available • Surprises not uncommon CT / MRI rarely needed
  18. 18. Urodynamics • Not routinely indicated in ‘pure’ BPS symptoms • Possible indications – – U/UUI predominant presentation • DO (~15% coexist) • Compliance (generally normal in IC) – Voiding phase dysfunction (VUDS): • DUA not uncommon – Doubtful history especially when refractory to medication
  19. 19. •55 F •Severe perineal pain A/W voiding X 3 years •Lump like feeling in perineum •Hysterectomy 1 yr back PAIN
  20. 20. •55 F •Severe perineal pain A/W voiding X 3 years •Lump like feeling in perineum •Hysterectomy 1 yr back PAIN
  21. 21. 55F, LUTS X 1 year - straining, urgency for suprapubic pain on full bladder, frequency of urine. recurrent UTI like symptoms. hematuria and severe pelvic pain on postponing urination. O/E pelvic floor tone increased, no tender pointsCT / urine cytology / urine culture - WNL. partial benefit with gabapentin and tizanidine.
  22. 22. 55F, LUTS X 1 year - straining, urgency for suprapubic pain on full bladder, frequency of urine. recurrent UTI like symptoms. hematuria and severe pelvic pain on postponing urination. O/E pelvic floor tone increased, no tender pointsCT / urine cytology / urine culture - WNL. partial benefit with gabapentin and tizanidine. 55 F, LUTS X 1 year - straining, urgency for suprapubic pain on full bladder, frequency of urine. recurrent UTI like symptoms. hematuria and severe pelvic pain on postponing urination. O/E pelvic floor tone increased, no tender pointsCT / urine cytology / urine culture - WNL. partial benefit with gabapentin and tizanidine.
  23. 23. 55 F, LUTS X 1 year - straining, urgency for suprapubic pain on full bladder, frequency of urine. recurrent UTI like symptoms. hematuria and severe pelvic pain on postponing urination. O/E pelvic floor tone increased, no tender pointsCT / urine cytology / urine culture - WNL. partial benefit with gabapentin and tizanidine.
  24. 24. 55 F, LUTS X 1 year - straining, urgency for suprapubic pain on full bladder, frequency of urine. recurrent UTI like symptoms. hematuria and severe pelvic pain on postponing urination. O/E pelvic floor tone increased, no tender pointsCT / urine cytology / urine culture - WNL. partial benefit with gabapentin and tizanidine.
  25. 25. CYSTOSCOPY • Micropyuria • Microhematuria • Severe symptoms – particularly small fixed capacity on bladder diary and scalding pain • Chronic smoker – male more than 40 • Failure of initial therapy
  26. 26. CYSTOSCOPY Glomerulations Hunner’s ulcer / scar YES NO Biopsy Hydrodistension Fulguration Re-distension YES NO Conclude ALWAYS - ALWAYS UNDER ANESTHESIA
  27. 27. • Therapeutic distension – 80-100 cmH2O for ~ 8 mins • UNDER VISION • Initial efficacy ~60% Capacity excellent fair <600ml 26% 29% >600ml 12% 43% • Short lasting <3m • Non-ulcer IC, number of glomerulations ≠ symptoms Badenoch 1971; Hamer 1992; Hanno & Wein 1991
  28. 28. Dietary modification Long list of ‘what to avoid’ by IC foundation • Irritants – tea, coffee, cola, tobacco, chocolate, spicy • High potassium content – fruits, dry fruits, juices • Organic – preservative, ‘sugar-free’ Often prohibitive Avoid what you can not tolerate
  29. 29. Pelvic floor dysfunction INSULT autoimmune infection Neurogenic inflammn Trauma / overdistensn Damage to epithelium Leakage into interstitium Immuno- stimulation C-fibre activation Mast cell activation NON-NOCICEPTION PROGRESSIVE BLADDER INJURY APF REPAIR<<DAMAGE
  30. 30. Pelvic floor dysfunction INSULT autoimmune infection Neurogenic inflammn Trauma / overdistensn Damage to epithelium Leakage into interstitium Immuno- stimulation C-fibre activation Mast cell activation NON-NOCICEPTION PROGRESSIVE BLADDER INJURY APF REPAIR<<DAMAGE PENTOSAN POLYSULFATE AMITRIPTYLINE GABAPENTIN HYDROXYZINE MONTELEUKAST CYCLOSPORINE AZATHIOPRINE
  31. 31. UPOINT (CPPS ≡ BPS/IC) • URINARY • PSYCHOLOGICAL • ORGAN SPECIFIC • INFECTION • NEUROLOGICAL • TENDERNESS Nickel et al. phenotype directed management of IC/BPS. Urology 2014; 84: 175
  32. 32. Management Behavioral modification Fluid and diet modification Stress management EDUCATION PFMT, relaxation biofeedback Thiel’s massage Trigger point release Gabapentin PPS Hydroxyzine Montelukast Amitriptyline Nortriptyline Cyclosporine Tacrolimus Azathioprine Oral medications Invasive treatment Intravesical DMSO PPS cocktail Botox Interstim
  33. 33. Management Behavioral modification Fluid and diet modification Stress management EDUCATION PFMT, relaxation biofeedback Thiel’s massage Trigger point release Gabapentin PPS Hydroxyzine Montelukast Amitriptyline Nortriptyline Cyclosporine Tacrolimus Azathioprine Oral medications Invasive treatment Intravesical DMSO PPS cocktail Botox Interstim
  34. 34. PPS: is it effective? • Better than placebo – Pain – 16.6% – Urgency – 13% – Frequency – 16.6% – Nocturia – nil • Better than ‘nothing’ – – 34% vs 18% Hwang et al. Efficacy of PPS in IC. Urology 1997 Sant et al. Pilot trial of oral PPS and hydroxyzine. J urol 2003
  35. 35. PPS: is it effective? • Better than placebo – Pain – 16.6% – Urgency – 13% – Frequency – 16.6% – Nocturia – nil • Recent evidence contradictory Hwang et al. Efficacy of PPS in IC. Urology 1997 Nickel et al. PPS in IC/BPS: Insights from RCT. J urol 2015
  36. 36. PPS: what’s the correct dose • RCT – 3 groups 300 – 600 – 900mg /d • No placebo group? • Percentage of patients with 50–100% improvement on PORIS (Patient’s Overall Rating of Symptom Index) • 300mg/d 0 10 20 30 40 50 60 4wk 8wk 12wk 16wk 24wk 32wk 300 mg/day 600 mg/day 900 mg/day Nickel et al. RCT dose ranging PPS for IC. Urology 2005.
  37. 37. PPS: early or late? • Retrospective secondary analysis of the RCT (n = 128) • Dose 300mg/d x 32 weeks • Better if started within 6 months of diagnosis Nickel et al. timing of initiation of PPS after IC diagnosis: effect on symptom improvement. Urology 2008
  38. 38. PPS in combination • Oral PPS 200mg bid • intravesical PPS 200mg / 30 min 0 20 40 60 80 100 treatment placebo Davis et al. oral + intravesical PPS: RCT. J urol 2008
  39. 39. • Oral PPS 300mg/d • Subcutaneous heparin PPS in combination 0 5 10 15 20 25 30 responders at 3m responders at 6m PPS + heparin PPS Ophoven et al. PPS + heparin for IC. Urology 2005
  40. 40. Strategy for management Initiate with • Behavioral modification • Diet modification • First line Medications – – Gabapentin – ± amitriptyline – ± hydroxyzine or montelukast • If cystoscopically confirmed IC  initiate on PPS
  41. 41. Minimize Antibiotic use Hospital and surgical hygiene

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