DELAYED DIAGNOSIS. Mean time to diagnosis = 4-7 years Mean # of physicians = 8 NIDDK criteria underdiagnoses >60%

Transcription

1 DELAYED DIAGNOSIS Mean time to diagnosis = 4-7 years Mean # of physicians = 8 NIDDK criteria underdiagnoses >6% 1

2 PREVALENCE 1,, 9,, 8,, 7,, 6,, 5,, 4,, 3,, 2,, 1,, NHS "Prostatitis" "Endometriosis" The Normal Bladder Bladder lumen Intracellular adhesion molecules GAG layer/mucus Epithelial cells Extracellular matrix Slide courtesy of C. Lowell Parsons, MD 2

3 ChS J Urol 24;171:1554 E-cadherin Uroplakin ZO-1 (tight junctions) Normal IC BLADDER PERMEABILITY Parsons et al SGO 199 % Urea absorption IC Control Baseline Protamine 3

4 POTASSIUM STIMULATION J Urol 1998; 159: % positive Control Protamine Heparin Urgency Pain MAST CELLS Saban et al: Am J Physiol Renal Physiol 22; 283F616 4

5 MAST CELLS Urol 1997; 49 (supp): 18 Detrusor mastocystosis Allergic rhinitis premenstrual flares irritable bowel syndrome, fibromyalgia multiple drug allergies NEURAL UPREGULATION A δ myelinated fibers (mechanoreceptors) Unmyelinated C fibers (nociceptors) ATP P2X 3 Histamine Substance P 5

6 CENTRAL PATHWAYS C-fos DRG, spinal cord DLC on-off-neutral Pelvic Floor Spasm in IC Bladder inflammation Pelvic floor dysfunction Slide Courtesy of Grannum Sant, MD. 6

7 Proposed Etiology of IC Bladder Insult More injury Epithelial Layer Damage Mast cell activation and histamine release Potassium leak into interstitium Activation of C-fibers and release of substance P CLINICAL PICTURE Urgency, frequency, nocturia, pain dyspareunia lack of incontinence negative UA and C&S failed prior antibiotics, anticholinergics 7

8 Flares and Remissions Common Causes of Flares Perimenstrual Sexual intercourse Diet Stress Cystitis/vaginitis Allergies 8

9 HOW DOES IC PRESENT? J Urol 21: 166: UTI's Symptom Endometriosis Urge-freq-pain INTERSTITIAL CYSTITIS TIMELINE Severity of Symptoms A Spectrum of Disease Recurrent UTI misdiagnosis Urethral Syndrome Mild/Moderate Interstitial Cystitis NIH Cases Advanced Interstitial Cystitis 9

10 Number of People Voids per Day Normal Subjects vs. IC Patients Normal Subjects N=48 IC Patients N= CL Parsons et al., Urology : Number of Voids per Day Normal Avg=6.5; IC Avg=16.5 1

11 URINALYSIS Standing order for C&S when symptomatic Catheterize for C&S Hematuria workup? DEFINITION Urgency, frequency, or pain in the absence of defined urinary pathology ignore NIDDK criteria no pathologic markers 11

12 POTASSIUM TEST J Urol 1998; 159: Fr catheter 4 ml water / saline 4 cc.4 M KCl 5 minutes 5 minutes immediate pain rank urgency (-5) rank pain (-5) rank urgency (-5) rank pain (-5) positive test URETHRAL SYNDROME VS. IC K test + % Urethral syndrome IC 12

13 PELVIC PAIN / ENDOMETRIOSIS K test + % IC Control 1 PUF VS. PST Urol 22; 6: % PST Positive PST % (n=56) (n=2) (n=61) PUF score (n=114) (n=75) (n=56) PUF Score n=334 patients. 48 normals. Parsons CL et al. Urology. 22;6:

14 PROSTATITIS VS. MALE IC J Urol 1999: 162: 369, J Urol 1999: 162: 214, Urol 1995; 45: 587; J Urol 23; 17: 818 mean age years perineal, abdominal, testis, penile pain AUA-SS, dysuria, dyspareunia Prostate expressate not useful 67% no inflammation 6% diagnosed IC (glomerulations), 75% improve after hydrodistension Glomerulations as Seen on Cystoscopy 14

15 Hunner s Ulcer THINK IC Recurrent UTI overactive bladder chronic prostatitis chronic pelvic pain / endometriosis 15

16 PRINCIPLES OF THERAPY treat triggers treat epithelium treat allergies treat neural up-regulation ELMIRON EFFICACY 4 double blind studies all showed significant pain relief versus placebo Parsons, CL, J Urol1987 Sep;138(3):513-6 Bade, JJ, Br J Urol 1997 Feb;79(2): Holm-Bentzen M, J Urol Sep;138(3):53-7 Mullholand, SG, Urology 199 Jun;35(6):

17 Pentosan Polysulfate Sodium (Elmiron ) 8 Percentage of Patients With Moderate Improvement or Better Percentage of Patients to 5 Positive response in pain (n=144) Positive overall response (n=1416) 6 to to to to 29 3 to 35 Months on pentosan polysulfate sodium Hanno PM. Urology. 1997; 49(suppl 5A): Elmiron Dose-Ranging Trial % of Patients Completing, With PORIS 5% mg 6 mg 9 mg Time, wk 34 PORIS = Patient s overall rating of improvement of symptoms. 17

18 PPS FOR CHRONIC NONBACTERIAL PROSTATITIS Nickel et al: Urol 2; 56: p< p<.5 p<.5 p<.5 Baseline 12 weeks 24 weeks SFQ SSI CPSI QOL Reduction in Total NIH-CPSI Change From Screening/Baseline (Intent-to-Treat Patients) PPS Placebo Change From Screening/Baseline Baseline Week 4 Week 8 Week 12 Week 16-7 P=.2 P=.2 Nickel JC et al

19 Reduction in Pain Change From Screening/Baseline (Intent-to-Treat Patients) Baseline Week 4 Week 8 Week 12 Week 16 Change From Screening/Baseline P=.4 P=.4 PPS Placebo Nickel JC et al. 22. PPS AND HYDROXYZINE J Urol 23; 17: 81 Response rate % placebo hydroxyzine PPS combo 19

20 Elmiron Atarax TIMELINE J Urol 23; 17: 81 Elmiron Atarax Elavil Elmiron Atarax Elavil/neurontin DMSO Hydrodistension Interstim Recurrent UTI diagnosis Urethral syndrome Mild/moderate Interstitial Cystitis NIH cases Advanced IC 2