Painful Bladder Syndrome

Painful bladder syndrome (interstitial cystitis/bladder pain syndrome) is a chronic condition (over 6 weeks, or 6 months in many definitions). It causes suprapubic pain, pressure or discomfort related to bladder filling, with urinary urgency and frequency, in the absence of infection or other identifiable pathology.

Prevalence is 0.5 to 2 percent in women (female-to-male ratio about 5 to 10:1). In men it overlaps with chronic prostatitis and pelvic pain syndrome.

Pathophysiology is multifactorial:

• Defective bladder urothelium glycosaminoglycan layer with increased permeability, allowing urinary potassium and toxins to penetrate (the epithelial leak theory).
• Mast cell activation and neurogenic inflammation.
• Sensory nerve upregulation and central sensitisation.
• Autoimmune mechanisms, and possible occult infection.

Two phenotypes are recognised:

• Hunner type (ulcerative), in 5 to 10 percent. Hunner lesions are red mucosal areas with fine vessels radiating to a central scar. This type is associated with inflammation, reduced bladder capacity, and a higher response to endoscopic treatment.
• Non-Hunner (the majority), with glomerulations on hydrodistension.

It is frequently associated with irritable bowel syndrome, fibromyalgia, vulvodynia, migraine, anxiety, depression and endometriosis.

• Suprapubic, pelvic, urethral or perineal pain that increases as the bladder fills and is relieved (temporarily) by voiding.
• Urinary frequency (more than 8 voids per day, often every 30 to 60 minutes, small volumes) and nocturia, and urgency not related to fear of incontinence.
• Dyspareunia, pain after intercourse, and worsening with certain foods (coffee, tea, alcohol, citrus, tomatoes, spicy foods, artificial sweeteners and carbonated drinks), stress and menses.
• Pain on bladder filling reproducible with suprapubic or anterior vaginal wall tenderness on examination; pelvic floor hypertonicity.
• Symptom flares and remission.
• Marked impact on sleep, work, sexual activity and mood.

Diagnosis is clinical, one of exclusion, based on the symptoms and negative testing.

• History, pain diary and voiding diary; validated questionnaires (O'Leary-Sant Symptom and Problem Index; Pelvic Pain and Urgency/Frequency score).
• Urinalysis and urine culture to exclude infection (including repeat cultures, cultures for atypical organisms where relevant), and urine cytology for those at risk of urothelial carcinoma (smokers over 40, haematuria); sexually transmitted infection tests.
• Physical and pelvic examination, assessing the pelvic floor, vulva and urethra.
• Post-void residual and, if needed, urodynamics (reduced capacity, sensory urgency at low volumes, absence of detrusor overactivity).
• Cystoscopy with hydrodistension (under anaesthesia) is performed when the diagnosis is uncertain or standard measures fail: Hunner lesions, glomerulations (petechial haemorrhages after distension to 80 cm H2O for 1 to 2 minutes) and low bladder capacity (below 400 mL under anaesthesia); bladder biopsy to exclude carcinoma in situ, tuberculosis, eosinophilic cystitis.
• Differential diagnoses: overactive bladder, recurrent urinary tract infection, urethral diverticulum, bladder cancer, endometriosis, chronic prostatitis, radiation cystitis, tuberculosis, and bladder stones.

Treatment is stepwise and individualised, beginning with conservative therapies. A multimodal approach is the rule.

• Education and behavioural therapy: reassure that it is a real and manageable condition, avoid trigger foods (an elimination diet with re-introduction), stress management, bladder training (timed voiding with gradual lengthening of intervals), and application of heat or cold to the suprapubic area.
• Pelvic floor physical therapy with myofascial release (for hypertonic pelvic floor, a common feature), biofeedback and relaxation. Avoid Kegel strengthening exercises when the pelvic floor is hypertonic.
• Oral medications:
  • Amitriptyline 10 mg at night, increasing by 10 to 25 mg every 1 to 2 weeks to 50 to 75 mg (maximum 100 mg); anticholinergic and sedating effects.
  • Pentosan polysulfate sodium 100 mg three times daily (or 100 mg once or twice daily in some regimens) for at least 3 to 6 months before judging benefit. Risks are pigmentary maculopathy with long term use (retinal examination baseline and yearly), and bleeding.
  • Hydroxyzine 10 to 50 mg at night (antihistamine for mast cell activity; limited evidence).
  • Cimetidine 400 mg twice daily; gabapentin 300 mg increasing to 1,800 mg daily or pregabalin for neuropathic pain; cyclosporine A 1.5 mg/kg twice daily for refractory Hunner type disease (monitor creatinine and blood pressure).
  • Analgesics: paracetamol, with limited use of non-steroidal drugs; avoid long term opioids.
  • Urinary alkalinisation with sodium bicarbonate or potassium citrate and phenazopyridine 200 mg three times daily for short term pain relief.
• Intravesical therapy by catheter (instillation, retained for 30 to 60 minutes):
  • Dimethyl sulfoxide 50 mL of 50 percent solution weekly for 6 to 8 weeks, then every 2 to 4 weeks for maintenance.
  • Hyaluronic acid (40 mg in 50 mL weekly for 4 weeks then monthly).
  • Chondroitin sulphate (2 percent 40 mL weekly for 6 weeks).
  • Heparin 10,000 to 25,000 units in 10 mL saline.
  • "Bladder cocktails" combining lidocaine (2 percent or alkalinised 4 percent, 10 to 20 mL), heparin, sodium bicarbonate and triamcinolone.
• Procedures:
  • Cystoscopic hydrodistension (diagnostic and therapeutic, benefit in 30 to 50 percent for 3 to 6 months).
  • Fulguration, laser ablation or triamcinolone injection of Hunner lesions (relief in 80 to 90 percent, with repeat as needed). This is the treatment of choice for the Hunner type.
  • Intradetrusor botulinum toxin A injection 100 to 200 units in refractory cases (retention risk, with self-catheterisation).
  • Sacral neuromodulation or tibial nerve stimulation for refractory frequency and pain.
• Surgery as a last resort for severe, refractory disease with a small contracted bladder: cystectomy with urinary diversion (and substitution cystoplasty), after multidisciplinary review. Pain may persist after surgery in some patients.
• Psychological support, treatment of comorbid conditions (irritable bowel syndrome, vulvodynia, fibromyalgia), and pain clinic referral.
• Prognosis: a chronic relapsing course with symptom control in most with a multimodal approach. Spontaneous remission occurs in some, and no cure is available.