Definition
Persistent or recurrent pain, pressure or discomfort, perceived as coming from the urinary bladder
- Associated with LUTS i.e. urinary and frequency
- For at least 6 weeks (AUA) or 6 months (EAU)
- With other causes excluded
Traditional interstitial cystitis characterised by
- Hunner ulcers – linear cracks or fissuring of mucosa
- Glomerulations – small, dot-like bleeding points; discrete submucosal haemorrhages
Can be classified as Hunner ulcer (lesion positive) IC/BPS or non-lesion
| Hunner + | Hunner – |
| Older (40s mean age)
Respond to fulguration Proven histological abnormality Fewer co-morbidities / related conditions Smaller bladder capacity |
Younger
Normal cystoscopic findings More likely to be associated with other conditions like IBS, fibromyalgia, depression and other chronic pain conditions |
NIDDK definition for IC in the 1990s was very strict – BPS definition broadens the scope to include more patients.
Epidemiology
- Depends on definition and inclusion criteria
- 10 : 1 female to male
- 7 – 8 % prevalence
Pathophysiology
There are many proposed pathophysiological mechanisms:
- Leaky urothelium or defective GAG layer
- Allowing urinary irritants to then infiltrate detrusor muscle and nerves
- Mast cell mediated inflammation
- Sympathetic overactivity / neural mediated inflammation and dysfunction
- Autoimmune contributors or underlying autoimmune pathology
- Pelvic floor spasm or dysfunction and cross-sensitisation
All normal chronic pain mechanisms apply:
- Central sensitisation (amplified sensory input)
- Visceral hyperalgesia (increased sensitivity to pain, perhaps feeling pain in response to normal organ sensation)
- Cross sensitisation (pain in one area triggers another)
- All modulated by psychological input
History
- Deep pelvic or suprapubic pain
- May radiate to vagina, urethra, rectum
- Worst with bladder filling
- Relieved by emptying
- Triggered by foods, fluids, stress, periods
- Storage LUTS – frequency, urgency, nocturia
- Dysuria
- Associated pelvic symptoms -bowel dysfunction with constipation, dyspareunia
- Long duration of symptoms, often years, with significant flares
- Other pain syndromes, multiple previous investigations and different specialists involved
Examination
- Often normal
- Suprapubic tenderness
- Pelvic floor tenderness should be examined
- Genital exam otherwise is usually normal
Investigations and principles of diagnosis
The main goal of evaluation (history, exam and investigation) is to exclude other diagnoses before proceeding with treatment down an IC/BPS pathway.
| Diagnoses to exclude
|
||
| Bladder cancer
Carcinoma in situ Locally advanced cervical ca
|
Haemorrhagic cystitis
Eosinophilic cystitis |
Urethral stricture
Urethral diverticulum |
| UTI / recurrent UTI
Prostatitis TB / schistosomiasis |
Overactive bladder
Neuropathic bladder |
Pudendal neuralgia
Pelvic floor dysfunction |
| Bladder stone | Endometriosis | |
Investigations:
- Urine culture and microscopy
- Bloods – creatinine, inflammatory markers
- Bladder diary
- Questionnaires – e.g. PUF questionnaire, O’Leary Sant Index
- Ultrasound
- +/- urine cytology
- +/- PSA
- +/- STI screen
- +/- CT KUB or CT IVP
- Cystoscopy +/- hydrodistension +/- biopsy
Cystoscopy and hydrodistension may be diagnostic and occasionally therapeutic.
- Helps exclude other causes
- Distend the bladder for 1 – 2 minutes at 80 cm H20 to capacity
- Examine for glomerulations, ulcers and ‘waterfall bleeding’
- Measure the bladder capacity pre and post distension
- Assess for a pain response with bladder filling
Mechanism of potential therapeutic effect – ?disruption of sensory nerves
Management
Principles:
- No one silver bullet – focus on symptom control not cure
- May require multiple trials of different management
- Usually multidisciplinary – pain specialist, GP, physio, O+G, psychiatry/psychology
- Bespoke management for individual symptoms
- Requires buy-in from patient
1st line – simple interventions
- Education about the condition
- Identification, awareness and avoidance of triggers
- Simple analgesia
- Non pharmacological analgesia – heat packs, TENS etc
- Pelvic physiotherapy
- Psychology
- Acupuncture
2nd line – oral medications
- Amitriptyline
- Proven efficacy when combined with supportive therapies vs placebo (dose > 50 mg)
- Recommended by EAU guidelines
- Tricyclic antidepressant
- Anticholinergic activity
- Antihistamine activity
- Modulates serotonin and noradrenaline pathways
- Start at 10 mg, can titrate up as high at 150 mg daily, mostly 10 – 75 mg
- Causes drowsiness, take at night
- Titrate to side effects – sedation, dry mouth, constipation, increased appetite
- Caution in other anti-depressants, arrhythmias, elderly and history of cardiac disease
- Cimetidine
- Anti-histamine
- “limited data” as per EAU, recommended in AUA guidelines
- Elmiron (pentosan polysulfate)
- Synthetic polysaccharide, similar in structure to the GAG layer
- Recommended in EAU guidelines
- 100 mg TDS
- Expensive
- May take 3 months for effect
- Side effects
- Alopecia / hair loss
- Nausea, diarrhoea
- Visual changes / macular damage – emerging litigation – warn patients
- Hydroxyzine
- Other ‘heavy’ immunosuppressants have shown some success – azathioprine, cyclosporine, methotrexate
- Oral steroids not recommended as per EAU
3rd line – intravesical instillations
- DMSO
- Dimethyl sulfoxide
- Often administered in cocktail with heparin and/or steroids
- ? Desensitises nociceptive pathways in lower urinary tract
- Garlic-like breath from pulmonary excretion
- Weekly for 6 weeks, then monthly for 6 months
- May causes severe irritative urinary symptoms
- ‘Rimso-50’ is effective brand
- Local anaesthetics
- Combined heparin, lignocaine and sodium bicarb (to alkalinise urine and improve pharmacokinetics) reduces pain especially in short term
- Heparin
- May act as an exogenous GAG – can mimic its effects with anti-inflammatory effects, inhibition of fibroblast proliferation and inhibition of angiogenesis and smooth muscle proliferation
- No systemic absorption
- Intravesical steroids
- Chondroitin sulfate and hyaluronic acid (iAluRil)
- “may be effective” as per EAU
- Cocktails of above – e.g. lignocaine, DMSO, heparin and bicarbonate
4th line – surgical intervention
- Cystoscopy and hydrodistension
- Exclude other causes +/- diagnose Hunner lesions
- Distension to 80 cm H20 for < 5 minutes
- Assess capacity, pain response
- May provide some benefit, usually short-term, and may be associated with flare after procedure
- Resection of lesions
- Injection of triamcinolone to lesions (40 – 60 mg)
- Botox
- May have an anti-nociceptive effect
- Probably improves pain
- Trial of distension + botox vs distension alone had better outcomes for botox combined with distension
- 10 x trigonal injections may also have benefit
- Sacral neuromodulation
- “may be effective”
- Pudendal nerve stimulation
- Cystectomy
- Supratrigonal with augmentation
- Supratrigonal or total cystectomy with diversion
- Patient selection is key – must ensure pain is from bladder, not PSPS (polysymptomatic polysyndromic)
Treatments recommended against by EAU/AUA:
- Oral steroids
- Intravesical BCG
- Long term antibiotic
- High pressure long duration distension
| Management options for BPS/IC | |
| Simple | · Education
· Trigger identification and avoidance · Simple analgesia · Non pharmacological · Physio · Psychology · Acupuncture |
| Oral | · Amitriptyline
· Elmiron (pentosan polysulfate) · Anti-histamines – cimetidine, hydroxyzine · Immunosuppressants – cyclosporine, methotrexate, azathioprine |
| Intravesical | · DMSO
· Heparin · Local anaesthetics · Chondroitin sulfate / hyaluronic acid · Steroid |
| Surgical | · Cystoscopy and hydrodistension
· Botox (+/- hydrodistension) · Resection / fulguration / steroid to lesions · Neuromodulation · Cystectomy |