INTERSTITIAL CYSTITIS

Interstitial cystitis (IC) is a refractory bladder disorder of unknown aetiology. Patients suffer chronic urinary frequency, nocturia, urgency, and bladder/suprapubic pain, in the absence of any obvious cause. The presence of glomerulations on cystoscopic examination (petechiae seen after bladder wall distention) or Hunner's ulcers, may help confirm clinical suspicion.
IC is a diagnosis of exclusion . it is diagnosed once other causes for these symptoms have been excluded (e.g. cyclophosphamide, drug-induced, TB, radiation; bladder tumour; OAB presence of uninhibited bladder contractions on urodynamics excludes a diagnosis of IC).

Epidemiology
Predominantly affects females (~90%). Estimated female prevalence is 18.1 cases per 100,000 from European studies. American data suggests higher rates of 52 - 67 per 100,000.

Associated disorders
A higher prevalence of allergies, irritable bowel syndrome, fibromyalgia, focal vulvitis, and Sjogren's syndrome has been reported in IC.

Pathogenesis
IC appears to be a multifactorial syndrome. Possible contributing factors include:
- Increased mast cells. Studies have demonstrated increased mast cells in bladder smooth muscle (detrusor). Activated mast cells release histamine, which can cause pain, hyperaemia, and fibrosis in tissues.
- Defective bladder epithelium. An abnormal glycosaminoglycan (GAG) layer may allow urine to leak past the luminal surface, causing inflammation in muscle layers.
- Neurogenic mechanisms. Abnormal activation of sensory nerves causes release of neuropeptides, resulting in neurogenic inflammation.
- Reflex sympathetic dystrophy of the bladder. Excessive sympathetic activity.
- Urinary toxins or allergens.
- Bladder autoimmune response.

Evaluation
Exclude other causes for symptoms. History, examination (including pelvic in women and DRE in men), urinalysis, and culture are mandatory. IC symptom index questionnaire, voiding diaries, and urodynamics are useful. Diagnostic studies include:
- Cystoscopy 10% of patients will have pink ulceration of bladder mucosa (Hunner's ulcer). Under anaesthesia, the bladder should be distended twice (to 80 - 100cmH2O for 1 - 2min), and then inspected for diffuse glomerulations (>10 per quadrant in 3/4 bladder quadrants). Bladder biopsy is only indicated to rule out other pathologies. In conscious patients, bladder filling causes pain and reproduces symptoms.
- Intravesical KCl challenge In 75% of IC patients, installation of KCl into the bladder will provoke pain and symptoms.

Potential diagnostic markers under investigation include antiproliferative factor (APF), heparin-binding epidermal growth factor (HB-EGF), and insulin-like growth factor 1 (IGF1).

Treatment
- Oral medications. Tricyclics (amitriptyline) have anticholinergic, antihistamine, and sedative effects. Pentosan polysulphate (Elmiron) is an anti-inflammatory synthetic GAG analogue. Long-term analgesia
(NSAIDs, paracetamol). Opiates may be prescribed and monitored via pain clinics.
- Repeated intravesical drug installation. Dimethyl sulphoxide (DMSO) local anaesthetic; GAG analogues (pentosan polysulphate and hyaluronic acid/Cystostat); BCG; capsaicin, resiniferotoxin.
- Nerve stimulation. Transcutaneous electrical nerve stimulation (TENS); neuromodulation.
- Surgery. Transurethral resection, laser coagulation or diathermy of Hunner's ulcers, and bladder hydrodistention may be beneficial, otherwise surgery should only be considered after failed conservative treatments. Ultimately, urinary diversion cystectomy may be required.