Definitions of IC: U.S. perspective. Edward Stanford MD MS FACOG FACS Western Colorado

Transcription

1 Definitions of IC: U.S. perspective Edward Stanford MD MS FACOG FACS Western Colorado

2 PURPOSE OF A DEFINITION? Identifies with specificity those patients who are most likely to have the disease. Identifies those patients eligible for selective treatments. Allows us a way to follow patients for diagnosis of other possible disorders and to adjust treatments (early or late).

3 PURPOSE OF A DEFINITION? How effective are current definitions? How effective are current treatments? What

4 Micturition normal Afferent signals from the LUT A delta mechanosensitive, myelinated, both nociceptive and non-nociceptive C-fibers does not respond to distention, unmyelinated, activated by cold, heat, chemical irritation

5 Micturition normal Control neural circuits in the brain and spinal column Coordination of activity of smooth muscle in the urethral sphincter and pelvic floor muscles Involves sympathetic, parasympathetic, and somatic neurons Sensation of bladder filling = stimulation of mechano-sensitive axons alerts brain of capacity

6 Micturition normal Sympathetic during filling relaxes detrusor stimulates urethral sphincter Parasympathetic during micturition contracts detrusor relaxes urethral sphincter Somatic innervation maintains active tone of PFM stimulation of the striated muscle of the external urethral sphincter

7 Micturition normal Cortex inhibitory Brain stem facilitatory Pontine on-off switch to LUT between storage and emptying

8 Micturition normal Receptors Muscarinic (M3)

9 IC Purinergic neurotransmission via - adenosine 5 triphosphate (ATP) pathway - vanilloid and purinergic (P2X3) pathway Confirming inflammatory role - increased numbers of - substance P (released by C-fibers) containing neurons - substance P receptors (neurokinin-1) mrna - increased NGF (nerve growth factor)

10 DEFINITIONS - NIH Originally to enroll patients in research trials and relied upon cystoscopic findings (1988) Now symptom based Syndrome pain, urgency, frequency, no infection Chronic, fluctuating symptoms No specific treatments Exact causation unknown Most often diagnosed as a UTI (Porru)

11 DEFINITIONS ESSIC 2007 Bladder pain syndrome (BPS) Chronic (>6 months) pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom like persistent urge to void or frequency Confusable diseases - exclude Cystoscopy with hydrodistension Bladder biopsies Cognitive, behavioural, emotional and sexual symptoms should be addressed

12 ESSIC 2007 Cystoscopy with hydrodistension Not done Normal Glomerulations2 Hunner s ulcer3 Not done XX 1X 2X 3X Normal XA 1A 2A 3A Biopsy Inconclusive XB 1B 2B 3B Positive3 XC 1C 2C 3C 1 cystoscopy: glomerulations grade II-III 2 with or without glomerulations 3 histology showing inflammatory infiltrates and/or detrusor mastocytosis and/or granulation tissue and/or intrafascicular fibrosis

13 ESSIC Definition only diagnosed 74% of 156 patients diagnosed with BPS/IC 53% of 150 CPP patients (Cheng 2012)

14 DEFINITIONS Classic ulcerated Non-ulcer Invasive cystoscopy with hydrodistention Hunner s ulcers relatively uncommon (3-10%) Glomerulations seen in asymptomatic patients (32% Cheng et al 2012)

15 PATHOGENESIS Changes in urothelial permeability Sensory nerve stimulation Mast cell activation

16 DIFFERENTIAL DIAGNOSIS Urinary UTI (30 patients) 60%? hematuria Gyn GI Endometriosis 38 85% Vulvar vestibulitis 20% IBS 35%

17 Coexistence of Pathology Bladder Epithelial Dysfunction: IC 64 patients: 69% IC 64% adhesions 28% endometriosis 20% vulvar vestibulitis Vulvar Vestibulitis Pelvic Pathology: biopsy-proven endometriosis, adhesions Stanford et al JMIG 2006

18 Stanford et al AJOG 2008 IC: Database

19 Misdiagnosis ICD-9 Diagnosis N % Abdominal pain 1, UTI Cystitis Dysuria Frequency Pelvic pain, NOS Hematuria Vaginitis Lumbago Cervicalgia

20 Misdiagnosis ICD-9 Diagnosis N % Incontinence, NOS Endometriosis* SUI Myalgia/Myositis Urge incontinence* Cervicitis Urinary symptoms, NOS Female Genital symptoms, NOS Urethritis Nocturia Mixed incontinence Urinary retention Bladder symptoms, NOS Urethral stricture Abdominal swelling

21 Concomitant disorders Concomitant disorder N Mean SD p value Age seen None Age at initial diagnosis One One None PUF score at diagnosis One >One None Stanford SGS 2009 One > One

22 TESTING THE DEFINITIONS

23 DIAGNOSIS Symptoms pain, urgency, frequency PST UD Markers Questionnaires

24 PAIN Reportedly affects 100% 11% may not have pain Usually with bladder filling The bladder fills are different rates during the day Suprapubic 80% Perineal 70% Genital 40% Overlapping mechanisms functional pain syndromes Pelvic visceral pain Sacral neuromodulation Hydrodistension Resinaferatoxin (RTX)

25 UTI Recurrent UTI 204 patients, IC diagnosis 24 months Actual recurrent UTIs, 7% Most common diagnosis in patients with recurrent UTI stone 93% have sterile urine with symptoms of recurrent UTI Stanford EJ, McMurphy C Int Urogyn J 2007

26 HEMATURIA Benign microscopic hematuria 100 women, IC, prospective, low risk of GU malignancy 24% with MH, no gross hematuria PUF 17 (mean) PST positive in 92%, 8 with cysto pos findings Likelihood of a pos PST or pos cysto findings with MH same PST correlated with cysto findings MH likely an incidential finding in IC patients Stanford et al Urology 2006

27 UROTHELIAL PERMEABILITY PST not recommended Only test for IC pain on an awake patient GAG hyaluronic acid and chondroitin

28 Results vary URODYNAMICS

29 MARKERS None useful in diagnosing IC APF

30 QUESTIONNAIRES ICSI PUF

31 INTERSTITIAL CYSTITIS Syndrome Unknown etiology Commonly associated with concomitant disorders No test to confirm diagnosis Definitions are not supported