Bladder pain syndrome / Interstitial cystitis

Transcription

1 Bladder pain syndrome / Interstitial cystitis Terminology The term bladder pain syndrome/interstitial cystitis (BPS/IC) is defined as the presence of chronic pain, pressure, or pelvic discomfort lasting 6 months or more, perceived in relation to the bladder and accompanied by at least one other urinary symptom, such as the persistent desire to urinate or frequency. The term BPS allows the diagnosis of interstitial cystitis (IC) to be reserved for patients with typical cystoscopic and histological characteristics. Classic criteria for BPS/IC The following criteria used for defining IC have been elaborated by the NIDDK (National Institute of Diabetes, Digestive and Kidney): Suprapubic pain or urinary urgency associated with bladder filling. Frequency (at least 8 times) and nocturia (at least once). Presence of Hunner ulcers or diffuse glomerulations (10 per quadrant in at least 3 quadrants) in cystoscopy performed after bladder distention (under anesthesia and with intravesical pressures greater than 80 cm of water pressure). A urodynamic study should show intense urgency with less than 150 ml of bladder filling and a bladder capacity <350 ml. The presence of involuntary contractions rules out IC. Factors that rule out IC: the presence of known causes for symptoms (UTI, vaginitis, herpes, radiation, lithiasis, or bladder diverticula); improvement of symptoms with antimicrobials, antispasmodics, anticholinergics, or urinary antiseptics; or being under 18 years of age. European Society criteria for the study of BPS/IC The European Society for the study of BPS/IC (ESSIC) has proposed standardized diagnostic criteria to facilitate comparisons between studies. A diagnosis should be made depending on the results of a cystoscopy with hydrodistention and a biopsy: Biopsy Cystoscopy and hydrodistention Not performed Normal Glomerulations Hunner lesion Not performed XX 1X 2X 3X Normal XA 1A 2A 3A Not conclusive XB 1B 2B 3B Positive XC 1C 2C 3C a Cystoscopy: Grade 2 Glomerulations (equimosis, severe submucosal bleeding) and grade 3 (Global and diffuse bleeding of bladder mucosa). b With or without glomerulations. c Histology shows detrusor inflammatory infiltrate or mast cells, granulation tissue or intrafascicular fibrosis. Etiology No specific primary cause of BPS/IC has been definitively proven to date. Various theories have been proposed, several of which are probably interrelated. Abnormalities of the bladder epithelium. Activation of bladder mast cells. Allergic or autoimmune processes. Neurogenic inflammation. Impaired innervation on a local (bladder) or general level. Presence of toxic substances in the urine as an antiproliferative factor produced by the bladder cells of patients with BPS/IC

2 Symptoms Affects women (90%) with an average age of 40 years, but can occur at any age. Perineal or pelvic pain upon bladder filling resulting in frequency and nocturia. There may be constant pain that worsens with bladder filling. Urinary urgency is common. Hematuria presents in 24 41% of cases. Non causal factors that exacerbate symptoms: - Foods: citric fruits, tomatoes, ethanol, chocolate, spices. - Menstruation: as a possible effect of gonadal hormones on bladder sensation. - Stress. Associated diseases: allergic processes, irritable bowel syndrome, fibromyalgia, systemic lupus, inflammatory bowel disease, focal vulvitis or vulvar vestibular syndrome, and Sjögren s syndrome. Diagnosis Essential examinations: - Medical history and voiding diary. - Physical exam: to rule out other causes. - Urinalysis and urine culture. Essential examinations depending on symptoms and presentation: - Urodynamic study. - Cystoscopy under anesthesia with hydrodistention. - Bladder biopsy: useful for ruling out other pathologies. - Urine cytology. Examinations that have not been proven useful: - Potassium sensitivity test: is not helpful in diagnosing BPS/IC. Examinations that are still under study: - Urinary markers: urinary antiproliferative factor. First line treatments (oral medications) No treatment is 100% effective in all patients. A combination of various treatments, progressively invasive depending on the response, is usually necessary. The following oral drugs have shown efficacy in at least one randomized clinical trial. Heparinoids: - Sodium Pentosanpolysulphate (ELMIRON ): is the second drug (and the only oral drug) approved by the FDA for BPS/IC. Mechanism of action: seems to replace the deficient layer of glycosaminoglycans, inactivate proinflammatory components, and inhibit histamine secretion from mast cells; it also exerts antiinflammatory effects such as complement inhibition. Dose: 100 mg/day, since higher doses (300 mg/day) are not effective (due to very low oral bioavailability). Requires at least 3 6 months for the treatment to reach its maximum effect. Tricyclic antidepressants: - Amitriptyline (TRYPTIZOL ): basic treatment for BPS/IC. Its efficacy is due to its central and peripheral anticholinergic effects, the sedative effect of its central antihistaminic action, and its nociceptive modulatory effects on the CNS. It also blocks the presynaptic reuptake of serotonin and noradrenaline. The usual dose is mg/day oa. - Imipramine (TOFRANIL ): effective in only 9% of patients. - Duloxetine has no proven efficacy. Antihistamines: - Hydroxyzine (ATARAX ): central antihistaminic effect. Requires gradual dose introduction, starting with 10 mg/day until a maximum dose of 75 mg/day is reached.

3 H2 receptor antagonists: - Cimetidine (TAGAMET ): effective in patients with severe inflammation. Direct immunomodulatory effect on H2 receptors of T cells. The recommended dose is 400 mg/day. Inmunosuppressive drugs: - Corticosteroids: have traditionally proven to be ineffective, being useful only in patients with Hunner ulcers (50% efficacy). Their role in patients with no ulcers remains undetermined. Oral drugs Generic name Brand name Oral dose (mg/day) Duration Pentosan polysulfate ELMIRON 3 caps of 100 mg 3 6 months Amitriptyline TRYPTIZOL 1 3 tabs of 25 mg 3 6 months Hydroxyzine ATARAX 1 3 tabs of 25 mg 3 6 months Cimetidine TAGAMET 1 tab of 400 mg 3 6 months Second line treatments (intravesical medications): Polar solvents: - 50% Dimethyl sulfoxide (RIMSO 50 ): the first drug approved by the FDA for the treatment of IC. Administered once a week for 6 weeks with individualized maintenance. The instilled dose is 50 ml during 15 minutes. To relieve the pain caused by DMSO, 2.5% Lidocaine can be instilled for 5 minutes with subsequent evacuation of the liquid, followed by administration of DMSO. Its efficacy is due to its antiinflammatory and analgesic effects due to the changes in afferent bladder innervation and the elimination of free radicals that it causes. Its use with other products has not led to greater efficacy. Heparins: - Calcium heparin (CALCIPARINE ): the available clinical evidence is based on clinical studies without a placebo. Its mechanism of action is due to its antiinflammatory effect. Usually used in combination with local anesthetics such as Lidocaine. The normal dose is 2 vials of 5000 IU in 25 ml of distilled water instilled into the bladder for 30 minutes. Mucopolysaccharides: - Hyaluronic acid (CYSTISTAT ): has shown efficacy in clinical studies without a placebo. The applied dose is 40 mg/week for 4 6 weeks and then monthly maintenance. Intravesical drugs Generic name Brand name Intravesical dose Duration Dimethyl sulfoxide RIMSO ml (50%) 15 min/week 6 wks Calcium Heparin CALCIPARINE IU in 25 ml 30 min/wk 6 wks Hyaluronic acid CYSTISTAT 40 mg for 30 min/wk 6 wks Third line treatments (surgical treatment) Bladder distention under anesthesia: after an initial diagnostic distention, the bladder is distended to 80 cm of H2O pressure for 8 minutes. If a biopsy is performed, it should be done after the second distention due to the decreased risk of rupture. Its effect is temporary (6 months) with an improvement rate of 50 61% and marked improvement in 12 16%. Its mechanism of action is unknown, but is probably due to changes in the afferent nerve endings of the bladder produced by distention. Fulguration of Hunner ulcers: the results are similar to ulcer resection. The initial response is good, but with relapses in 45% of cases, although response to retreatment is good. Augmentation cystoplasty: not recommended since it is not effective. Sacral nerve neurostimulation (MEDTRONIC INTERSTIM ): in long term studies, responses have been observed to last months, although results in the literature are controversial. Cystectomy and orthotopic diversion: indicated in patients with Hunner ulcers and diminished bladder capacity in exploration under anesthesia. Whether to preserve or resect the

4 trigone remains controversial, since pain and recurrent ulcers can occur in the trigone or urethra. Urinary diversion without cystectomy: the last option. Indicated in cases with low bladder capacity under anesthesia. The cessation of pain is not guaranteed. Other treatments Physical therapy (pelvic floor rehabilitation): effective in patients with increased muscle tone at the pelvic level with pain points in that area (trigger points).

5 Management of BPS/IC Infection Treatment Medical history Physical examination Voiding diary Urinalysis/Urine culture Cystoscopy +/ biopsy Citology Urodynamic testing Hematuria Workup Detrusor Hyperactivity BPS/IC Treatment Dietary counseling Analgesics Pelvic floor relaxation techniques Severe symptoms Oral or intravesical drugs Reevaluation Bladder Hyperactivity Hunner s lesion Bladder hydrodistension Antimuscarinics TUR/laser More agressive therapies: Neuromodulation Urinary diversion