Interstitial Cystitis

Interstitial cystitis (bladder pain syndrome) is a chronic condition of pain, pressure or discomfort perceived to be related to the bladder, lasting more than 6 weeks, accompanied by urinary urgency or frequency, in the absence of infection or other identifiable cause. The terms interstitial cystitis and bladder pain syndrome are used together.

Epidemiology:

• Prevalence is about 0.5 to 3% in women depending on definition. Women are affected 5 to 10 times more often than men, with a mean onset of about 40 years.
• Frequently under-recognised and misdiagnosed as recurrent urinary tract infection or overactive bladder for years.

Phenotypes:

• Hunner lesion type (about 5 to 10%): red, inflamed mucosal lesions with a surrounding vascular pattern that crack and bleed on distension. These patients have more inflammation, a smaller bladder capacity, and respond to targeted therapy.
• Non-Hunner type: glomerulations (petechial haemorrhages after hydrodistension) are non-specific and found in asymptomatic people.

Proposed mechanisms:

• Urothelial barrier dysfunction (reduced glycosaminoglycan layer), mast cell activation, neurogenic inflammation, central sensitisation, autoimmune and infectious triggers, and pelvic floor muscle dysfunction.

Associations: irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, vulvodynia, migraine, anxiety, depression, endometriosis, and sleep disturbance. Pain syndromes outside the pelvis often coexist.

Complications and impact: severe reduction in quality of life, sexual dysfunction, depression, reduced bladder capacity, and in Hunner disease a risk of contracted bladder.

Core symptoms:

• Suprapubic or pelvic pain related to bladder filling and relieved partially by voiding.
• Urinary urgency and frequency (often 10 to 20 or more voids a day, with nocturia), with small voided volumes.
• Pain with specific foods and drinks (coffee, citrus, spicy foods, alcohol, carbonated beverages), stress, and sexual intercourse.
• Dyspareunia, perineal, vaginal, urethral or rectal pain. In men, penile, testicular or perineal pain.
• Symptoms fluctuate with flares and remissions. Hunner lesion disease has severe pain and frequency.

Examination:

• Suprapubic tenderness, anterior vaginal wall tenderness, tenderness of pelvic floor muscles (levator ani, obturator internus) on digital examination, and exclusion of prolapse and masses. Urethral or bladder base tenderness.
• Sensory testing and trigger points for myofascial pain.

Differential diagnosis (exclusion is part of diagnosis):

• Urinary tract infection (including tuberculosis, schistosomiasis, sexually transmitted infections), bladder cancer and carcinoma in situ, stones, radiation and drug-induced cystitis (ketamine, cyclophosphamide, tiaprofenic acid), overactive bladder, endometriosis, pelvic inflammatory disease, urethral diverticulum, prostatitis and chronic pelvic pain syndrome, pelvic floor myalgia, vulvodynia, and gynaecological or colorectal pathology.

Red flags: haematuria, age over 50 with new symptoms, smoking history, and abnormal cytology or imaging.

Diagnosis is clinical and one of exclusion:

• History with a bladder diary (voids, volumes, pain scores), validated tools (O'Leary-Sant Symptom and Problem Indices, ICSI/ICPI, Genitourinary Pain Index, visual analogue pain scale).
• Examination including pelvic and pelvic floor assessment.
• Urinalysis and urine culture (including repeated cultures during symptoms), urine cytology in smokers or those over 40 with haematuria, and nucleic acid tests for chlamydia, gonorrhoea, mycoplasma and trichomonas. Acid-fast bacilli culture for sterile pyuria.
• Post void residual by bladder scan, renal and bladder ultrasound, and additional imaging for suspected stones or masses.
• Uroflowmetry and urodynamics are not routine, but are helpful where voiding dysfunction is suspected. Urodynamics usually show low bladder capacity and sensory urgency, with early first desire to void.
• Potassium sensitivity test is not recommended because of poor specificity and pain.

Cystoscopy:

• Indicated for diagnosis of Hunner lesions, and exclusion of tumour, carcinoma in situ and stones in those with haematuria, refractory symptoms or atypical features.
• Hydrodistension under anaesthesia at 80 cm water pressure for 1 to 2 minutes shows glomerulations in a majority of patients, and capacity below 400 to 500 mL supports the diagnosis, but is not diagnostic. It may be therapeutic for a few months.
• Biopsy to exclude carcinoma in situ and other pathology (mast cell counts and chronic inflammation are non-specific). Hunner lesions show a dense lymphoplasmacytic infiltrate.

Management is stepwise and multimodal, guided by symptom response, and aims at improvement, since cure is uncommon.

Step 1: education and self-care (all patients)

• Explain the condition, avoid trigger foods guided by a food diary (elimination diet then reintroduction), manage stress, avoid tight clothing, apply heat or cold to the suprapubic region and perineum, timed voiding and gradual bladder training (increase interval by 15 to 30 minutes), and fluid management to avoid concentrated urine.
• Pelvic floor physiotherapy with myofascial release and trigger point therapy for tender muscles. Avoid strengthening exercises (Kegels) in hypertonic pelvic floor.
• Treat coexisting disorders (constipation, irritable bowel, vulvodynia, depression), and offer cognitive behavioural therapy and mindfulness.
• Simple analgesia: paracetamol 1 g every 6 hours, ibuprofen 400 mg every 8 hours with food. Phenazopyridine 200 mg three times daily for up to 2 days for flares. Urinary alkalinisation with calcium glycerophosphate or sodium bicarbonate for acid-related pain.

Step 2: oral and intravesical drug therapy

• Amitriptyline 10 mg at night, increased by 10 mg weekly to 50 to 75 mg (nortriptyline is an alternative). Response in about 60% at higher doses. Anticholinergic effects and sedation.
• Hydroxyzine 10 to 25 mg at night, increased to 50 to 75 mg, especially with allergic features.
• Pentosan polysulfate sodium 100 mg three times daily for at least 3 to 6 months, which helps about 30 to 40% of patients. Risks include pigmentary maculopathy (needs baseline and regular retinal examination), bleeding and gastrointestinal upset. Stop if no improvement after 6 months.
• Cimetidine 400 mg twice daily, gabapentin 300 mg at night titrated to 900 to 1800 mg/day, or pregabalin 75 to 150 mg twice daily for neuropathic pain. Montelukast and duloxetine 30 to 60 mg daily are used in selected cases.
• Intravesical therapy:
• Dimethyl sulfoxide (DMSO) 50% solution 50 mL held for 15 to 20 minutes, weekly for 6 to 8 weeks then monthly, which gives improvement in about 50 to 90% in some series.
• Heparin 10,000 to 25,000 units in 10 mL saline, three times weekly for several weeks.
• Alkalinised lidocaine 200 mg (1% 20 mL) buffered with sodium bicarbonate 8.4% 3 mL, instilled for 30 to 60 minutes, for short term relief of pain flares.
• Hyaluronic acid, chondroitin sulfate, or combination bladder instillation cocktails (lidocaine, heparin, triamcinolone and sodium bicarbonate) for a series of weekly instillations.
• Self-catheterisation for home instillation in motivated patients.

Step 3: cystoscopic procedures

• Hydrodistension under general or regional anaesthesia, with a response in about 30 to 50% for a limited time (months). It is a diagnostic and short-term treatment.
• Hunner lesions: fulguration, laser ablation, transurethral resection, or triamcinolone injection (10 mg/mL, 30 to 100 mg total divided around lesions) provides relief in about 80 to 90%, though recurrence is common, requiring repeat treatment every 6 to 18 months.

Step 4: refractory disease

• Intradetrusor botulinum toxin A 100 units (up to 200 units) in 20 to 30 sites, sometimes combined with hydrodistension, with benefits for 3 to 6 months. Risk of urinary retention (up to 10%) and need for intermittent self-catheterisation.
• Ciclosporin A 3 to 5 mg/kg/day (monitor renal function, blood pressure and drug levels) in Hunner lesion disease unresponsive to other treatments.
• Sacral neuromodulation (InterStim) for frequency, urgency and pain, with improvement in about 60% in selected patients. Percutaneous tibial nerve stimulation is another neuromodulatory option.
• Other options: monoclonal antibody therapy and other investigational drugs, low-level laser and shockwave therapy (emerging), and acupuncture.
• Opioids are generally avoided, but tramadol 50 mg every 6 hours or low-dose long acting opioids are considered in severe, refractory pain under pain specialist supervision.

Step 5: major surgery (last resort)

• Supratrigonal cystectomy with augmentation cystoplasty, or cystectomy with urinary diversion (ileal conduit or continent reservoir), reserved for end stage, small capacity bladders with intractable symptoms after failure of other therapies. Pain may persist in non-Hunner disease, so patient selection and counselling are essential. Hunner lesion disease responds better.

Follow-up

• Review every 1 to 3 months initially, using symptom scores and diaries to judge response and adjust therapy. Stop ineffective drugs after an adequate trial.
• Regular retinal monitoring if on pentosan polysulfate. Monitor creatinine and blood pressure on ciclosporin.
• Psychological support and multidisciplinary pain care are important, as flares are common and the condition is chronic.