Transcript No Slide Title

Painful Bladder
Syndrome/Interstitial Cystitis:
A New Paradigm Emerging
C. Lowell Parsons
Professor of Surgery/Urology
School of Medicine
University of Ca. San Diego
1
Major Themes
 PBS/IC Misdiagnosis is Common
 Epithelial Damage and Urinary
Potassium Associated with PBS/IC
 Prevalence Better Appreciated Now
 PBS/IC Case Studies
2
PBS/IC History
 In 1980 little known about pathogenesis
 PBS/IC was only known to exist and only
the very severe form was recognized and
diagnosed
 Only hypothetical causes suggested, e.g.
maybe infectious or autoimmune
 PBS/IC often misdiagnosed as UTI, OAB,
gynecologic problem
3
What is PBS/IC?
 A disease of the urinary bladder
 It causes frequency and urgency of urination,
pelvic pain and urinary incontinence
 Can flare suddenly after sexual activity
 Causes pain with sex often first symptom
 Flares the week before the menstrual cycle
 May flare with allergy season
4
PBS/IC Symptoms/Lower
Urinary Symptoms
 Frequency, Urgency primarily bladder
symptoms
 Dysuria is a urethral symptom
 Pain from bladder refers anyplace in
pelvis, Labia, Scrotum, Perineal,
Abdominal, Medial thighs.
 This referred pain confuses origin
5
What is PBS/IC?
 PBS/IC may begin at age 16-20 with
frequency
 Symptoms may become very severe
and debilitating
 Flares
6
Where Does Interstitial
Cystitis Begin?
SEVERITY OF SYMPTOMS:
A SPECTRUM OF DISEASE
“Recurrent
UTI”
misdiagnosis
“Urethral
Syndrome”
“Overactive
Bladder”
Prostatitis
Mild/Moderate
Interstitial
Cystitis
GYN Dx’s
NIH
Cases
Advanced
Interstitial
Cystitis
7
Overlap Between OAB and PBS/IC
Painful Bladder
Syndrome/
• Frequency
• Urgency
• Pain
Slide courtesy of GR Sant, MD.
8
PUF Diagnostic Questionnaire
for PBS/IC Symptoms
 Developed to identify PBS/IC patients
 Also determines disease severity
 Widely used by Urologists and
Gynecologists
 Validated by Kushner and Moldwin
2006
9
PUF: Pelvic Pain and Urgency/
Frequency Patient Symptom Scale
Circle the answer that best describes how you feel for each question.
1 How many times do you void during waking hours?
2 a. How many times do you void at night?
b. If you get up at night to void, to what extent does
it usually bother you?
3
0
1
2
3
4
3-6
7-10
11-14
15-19
20+
0
1
2
3
4+
None
Mild
Symptom
Score
Bother
Score
Moderate Severe
Are you currently sexually active?
YES _____
NO_____
4 a. If you are sexually active, do you now have or have you
ever had pain or urgency to urinate during or after
Never Occasionally
Usually
Always
Never Occasionally
Usually
Always
sexual intercourse?
b. Has pain or urgency ever made you avoid sexual intercourse?
5 Do you have pain associated with your bladder or in
your pelvis, vagina, lower abdomen, urethra, perineum,
testes, or scrotum?
6 Do you still have urgency shortly after urinating?
7 a. When you have pain, is it usually—?
b. How often does your pain bother you?
8 a. When you have urgency, is it usually—?
b. How often does your urgency bother you?
Never Occasionally
Usually
Always
Never Occasionally
Usually
Always
Mild
Never Occasionally
Mild
Never Occasionally
Moderate Severe
Usually
Always
Moderate Severe
Usually
Always
SYMPTOM SCORE (1, 2a, 4a, 5, 6, 7a, 8a)
BOTHER SCORE (2b, 4b, 7b, 8b)
TOTAL SCORE (Symptom Score + Bother Score) =
10
PBS/IC Prevalence Higher
 Original estimates in the 1980s only
40K in US
 With PUF Questionnaire Rosenberg and
Hazzard (2005) found prevalence much
higher
 Rand Study also validates much higher
PBS/IC prevalence of 3-8 million in US
 PBS/IC estimated 3-10 million in US
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The Role of the
Epithelium in the
Pathogenesis of PBS/IC
12
Bladder Epithelium Damaged
 Cystoscopy reveals bladder damage
Normal Healthy Bladder
PBS/IC Bladder with
visible damage
13
Mucus GAG Layer Regulates
Epithelial Permeability
GAG: Glycosaminoglycan
14
Epithelial Mucus GAG Layer
Schematic
Water
hydrates
GAG Layer
Micrograph
15
The Role of Urinary Potassium in
the Generation of Bladder
Symptoms and Tissue Injury
16
Healthy bladders sequester
bladder contents
25
 Healthy bladders
20
 Protamine damage
allows leakage
 Heparin treatment
mostly restores
bladder’s ability to
sequester contents
% Leak of Solute Urea
prevent leakage of 15
contents (% instilled10
urea)
25
20
Normal
Protamine
Heparin
5
15
N
P
H
0
10
5
0
*SG&O 1990
17
PBS/IC Patients have Damaged
Bladders that Leak
35
% Leak of Solute Urea
30
25
20
15
Normal
Protamine
IC
IC Ulcers
10
5
0
Normals=41 IC=56 J.Urol 1991
18
Fate of Urinary Potassium
Muscle
Mucus
An
_
K
+
K
+
Vessels
Prostate
+
K
Nerve
Mast
cell
19
The Etiology of
Symptoms in the Lower
Urinary Tract
20
PBS/IC Differential Diagnosis
 Recurrent UTI
 Urethral Syndrome
 Neurogenic Bladder
 Detrusor instability, OAB
 Pelvic Floor dysfunction
 Radiation, Cytoxan cystitis
 Vaginitis
 Tb, Schistosomiasis
 PBS/IC
21
Diagnosis by Tradition, Sex,
Specialist, Sub-committee
 25 yr. Old female with 12 voids per
day, flare of urgency, pain with sex,
intermittent dysparuenia, Neg U/A:
Sees GU- Recurrent UTI
Sees Gyn- Endometriosis, yeast
infection
 25 yr. Old Male with 12 voids per day,
Flare of urgency, pain with sex,
intermittent painful ejaculations, Neg
U/A: Prostatitis
22
PBS/IC/Prostatitis in
Men
23
Potassium Sensitivity in
Prostatitis Patients
Group
N
KCl Positive
________________________________
Prostatitis*
41
34 (83%)
Normals*
43
0
Patients**
31
26 (84%)
*Parsons Et al Journal of Urology Sept. 2002
**Hassan et al Int Journ Urol Aug 2007
24
Unifying Hypothesis: Common
Symptoms of Lower Urinary Tract
 Lower Urinary Epithelial Dysfunction has
increased urothelial permeability
 Potassium diffusion into bladder wall
causes symptoms: Pain, Muscle Spasms
and tissue damage
 PBS/IC, OAB, CP/CPPS, Urethral
Syndrome, UFS, Recurrent UTI’s, Gyn CPP,
V/V
 PBS/IC is merely the severe form of this
disease
25
Therapy Principles for PBS/IC
 Correct Epithelial Dysfunction
 Inhibit Neural Hyperactivity
 Control Allergies
26
Therapies for PBS/IC
 Discovery that Heparin and PPS (Elmiron®)
repaired experimentally injured human and
rodent bladders led to following treatments
 Elmiron® - oral drug approved in 1997
 Urigen developing URG101 - a combination of
intravesical Heparin and alkalinized Lidocaine
for immediate relief of bladder pain and
restoration of bladder mucus GAG layer
27
PBS/IC Case Studies
28
GU Pediatric Case Study (#1)
 9 yr old female taken out of diapers age 5
but had several incontinent episodes per
day
 Main symptoms are severe urgency,
chronic lower abdominal pain that is
increasing, intense symptoms flares
treated as UTI’s
 Some urine cultures positive for E. coli,
many negative culture reports,
cystoscopy- normal UO’s, cystitis cystica
29
GU Pediatric Case Study (#1)
 What is diagnosis?
 Traditional Urology Diagnosis?
 What to do for therapy?
 After this workup a urinary diversion
was recommended and patient self
referred to UCSD
30
GU Pediatric Case Study (#1)
 Used Therapeutic solution containing
Heparin+lidocaine+NaBicarb
 Immediate relief of 75%+ of symptoms
 Daily after 3 weeks of solution plus Elmiron-
no incontinence, urge and pain 75%+ gone;
Patient wanted to cath herself and did so
 3 months later, no urge or pain no
incontinence for 2 months
 5 months after Rx only oral Elmiron
31
Urology Case Study (#2)
 21 yr old female referred with Dx of
recurrent “UTI”
 3 years of 5-6 “UTI’s” per year
 Pain and Symptoms during and after sex,
now tends to avoid sex
 Antibiotics make her Better, Last two C&S’s
sterile, She voids 12 per day, 1 x nocturia
when “uninfected”
 U/A- no RBCs, no WBC’s, no bacteria. What
is her diffential diagnosis
32
Pelvic Pain Symptoms
GU Bladder Pain: PBS/IC Gyn Pelvic Pain:
 Dyspareunia
 Dyspareunia
 Menstrual/
 Perimenstrual flare
perimenstrual flare
 Flares after sex
 Flares after sex
 Pain (lower
 Pain (lower abdomen,
abdomen, vulva,
vulva, urethra, vagina,
urethra, vagina,
medial thighs,
medial thighs,
perineum)
perineum)
 Voiding symptoms
 Voiding symptoms
33
Gynecology Case Study (#3)
 25 yr. Old female presents with Chronic
dyspareunia for 6 years, progressing
 Labial pain and lower abdominal pain
(increases week before menses)
 No vaginal discharge, good health
 What is her differential Diagnosis?
34
Major Take Aways
 PBS/IC Misdiagnosis is Common
 Pain is referred, flares
 PBS/IC can be mild to severe symptoms
 Prevalence Better Appreciated Now
 PUF Questionnaire for better PBS/IC
diagnosis
 RAND and other studies validate much
larger PBS/IC prevalence
35