Transcript Interstitial Cystitis Lecture

Overview of Interstitial Cystitis
for the Primary Care Physician
WVU WOMENS HEALTH CURRICULUM – Revisions 9/2008
Stanley Zaslau, MD, MBA, FACS
Program Director & Associate Professor
Section of Urology
West Virginia University
Objectives
• In this lecture, participants will learn:
– Incidence, epidemiology and pathogenesis of
Interstitial Cystitis (IC)
• Understand the role of the urothelium in the
prevention and treatment of IC.
– Key concepts in the physical examination of the
IC patient
– Understand the concept of multimodal therapy
for the treatment of IC.
Objectives
• In this lecture, participants will learn:
– Key treatments of IC
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Antidepressants
Gabapentin
Intravesical therapy
Pentosan polysulfate
Neuromodulation
– Sexual dysfunction in the IC patient –
pathogenesis and treatment strategies
Introduction
• Challenge to diagnose
• “Traditional” view recognizes patients with
end-stage disease
• A continuum--rather than a “fixed” disease
• Confused with other GU or GYN disorders
Definition
• First reported in 1915
• NIH criteria established in 1987
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characterize IC syndrome patient
describe advanced disease
do not define IC
criteria represent a small part of the IC
population
Interstitial Cystitis (IC)
Definition
• Interstitial cystitis is urgency, frequency,
and pain in the absence of a defined
etiology
C. Lowell Parsons, MD
The triad of urinary urgency, frequency, and
bladder or pelvic pain in the absence of
bacterial infection or other definable pathology
is the definition of interstitial cystitis
Grannum Sant, MD
“Better” Definitions
• Clinical syndrome
• Gradually progressive
• Time line concept:
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20’s:
30’s:
40’s:
60’s:
mild, intermittent urgency with UTI
urethral syndrome (persistent -Cx)
meets NIH criteria for IC
severe, constant symptoms c/w IC
Clinical Picture of IC
Urgency
Pelvic
Frequency
Pain
± Incontinence
• Urgency, frequency, nocturia, chronic
pelvic pain (CPP)
• Pain associated with sexual intimacy
• +/- incontinence
• Negative culture and sensitivity
1. Parsons CL.
Epidemiology
• Affects 2.5 million women in US
• Significant number of men affected
• Studies:
– Finnish: incidence 1.2 cases/100,000 people
• prevalence of 10-11/100,000
– Held: 44,000 cases in US; prevalence of
450,000 cases
– May only reflect end-stage disease
Epidemiology
• More recent studies
– 284 UCSD Female MS attending lectures
– All filled out PUF questionnaire
• 8 items
• symptom, bother and total score
– pelvic pain
– urgency
– frequency
– 24% had scores > 10
Parsons, et al Urol 2002
Increasingly a Concern in Women
• Estimated prevalence of self-reported IC in women
is 1.5 million1
• IC is often misdiagnosed or underdiagnosed
– 38% of women scheduled for laparoscopy
for suspected endometriosis were
cystoscopically confirmed to have IC2
• IC may be a common cause of Chronic Pelvic Pain (CPP)
– 80% to 85% of women with CPP of unidentified etiology shown
to have pain of bladder origin3
1. Curhan GC et al. J Urol. 1999;161:549-552.
2. Clemons JL et al. 2002;100:337-341.
3. Parsons CL et al. Obstet Gynecol. 2001;98:127-132.
Possible Presentations
Refractory Patients
New Patients
Recurrent UTI
Symptoms
Overactive
Bladder
Treatment
Failures
Consider
IC
Failed
Endometriosis
Therapy
Nonbacterial
Prostatitis
1. Parsons CL et al. Female Patient. May 2002(suppl):12-17.
2. Chung MK et al. JSLS. 2002;6:311-314.
3. Miller JL et al. Urology. 1995;45:587-590.
• Urgency
• Frequency
• Pain
– Dyspareunia
Diagnostic considerations for the
Primary Care Physician
• For patients with:
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urgency
frequency
dysuria
painful with sexual intercourse
negative urine cultures and urine cytologies
SUSPECT INTERSITIAL CYSTITIS
Physical Examination
• Females
– anterior vaginal wall tenderness
– suprapubic tenderness
– pelvic floor dysfunction
• Males
– suprapubic tenderness
– sphincter spasm
– tender rectal examination
IC Evaluation Tools for the
Primary Care Physician
• Routine testing for the PCP
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urine analysis
urine culture
urine cytology
voiding diary
• Additional testing to be undertaken by the
urologist
– cystourethroscopy and urodynamics
– KCL testing
Voids per day
• Statistics (mean)
– Normal population: 6.5times/day
– IC population: 16.5 times/day
Anesthetic Bladder Capacity
• Normal people: 1100 cc
• IC patients: 575 cc
Clinical Approach to IC: A Primer for
the Primary Care Physician
Male
Female
• History
– ICSI
– PUF
• History
– ICSI
– CPSI
– PUF
• Physical exam
• Physical exam
• Urinalysis and/or culture
• Urinalysis and/or culture
• Elective tests
• Elective tests
– PPMT
– Potassium
sensitivity test
– Cystoscopy and
hydrodistention
– Cystometrogram
– Urine for cytology
– Potassium
sensitivity test
– Cystoscopy and
hydrodistention
– Cystometrogram
– Urine for cytology
1.
ICSI = Interstitial Cystitis Symptom Index.
PUF = Pelvic Pain and Post-Prostate Massa
Pathogenesis
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Vascular insufficiency
Epithelial leak
Role of Urinary Potassium
Neural Up-regulation
Mast Cells
Epithelial Leak
• Leak --> impaired migration of solutes
across epithelium
• “Leak assay” studies (75% + in IC)
• Potassium sensitivity test + in 90%
– suggest leaky epithelium
– may suggest neurological inflammatory
component
Role of Urinary Potassium
• Principle toxic substance in urine is
potassium
• Toxic to human cells
• Urine concentration 75 mEq/L
• Levels > 15 mEq/L depolarize sensory
nerves and muscle
Role of Urinary Potassium
• Effects of excessive K+ back diffusion:
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vascular destruction
lymphatic destruction
sensory nerve & muscle depolarization
up-regulation of mast cells
induction of substance P and up-regulation of
pain fibers
– disease progression
Potassium Sensitivity
May Be a Good Predictor of IC
• Detects abnormal bladder epithelial
permeability
• Positive in 70% to 90% of IC patients
• 81% of gynecologic patients with
pelvic pain had increased potassium
sensitivity
1. Parsons CL et al. J :1054-1057.
Role of Urinary Potassium
• Sodium chloride instillation does not cause
symptoms
• Conclusion:
– individual potassium sensitivity:
• useful diagnostic tool for IC
• useful even in patients with mild symptoms
• useful when one is unsure of the diagnosis
Neural Up-regulation
• Up-regulation of sensory nerves in the
bladder
• Seen in severe forms of IC
• Difficult to treat
• Can persist after treatment of epithelial
defect
Mast Cells
• Role not fully understood
• Present in IC and non-IC bladders
• Causative or secondary role in IC?
– Cause: degranulate & produce symptoms
– Secondary: response to epithelial leak
• Interact with sensory nerves & release
neurotransmitters that activate pain
Glycosaminoglycan (GAG) Layer in IC
• GAG, a mucoprotein, is a component of bladder epithelium
• GAG may be essential for bladder protection
– Irritants and toxins in urine
– Bacterial adherence
• GAG deficiency may result in pathologic
changes associated with IC
– Permeability of urothelium
– Inflammatory/allergic response
Lilly JD, Parsons CL.;171:493-496.
Vicious Cycle of IC
Bladder Insult
More Injury
Epithelial Layer
Dysfunction
Mast Cell Activation
and Histamine
Release
Potassium Leak
into Interstitium
Activation of C-fibers and
Release of Substance P
Principles of Treatment--Multimodal
• Dietary guidelines
• Stabilize the urothelium
– pentosan polysulfate
• Modulate neural activity
– Tricyclic antidepressants like amitriptyline,
gabapentin
• Stabilize mast cells
– Antihistamines, ex. Hydroxyzine
• Stabilize the pelvic floor
– sacral neuromodulation
Pentosan Polysulfate
• Mechanism: re-establish GAG layer function
and decrease K+ leak
• The only FDA-approved oral therapy proven
effective for IC pain or discomfort
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Reduces painful symptoms long-term
Dose: 100 mg TID (200 mg BID)
Full effect takes up to 6 months
Side effects: headache, GI upset, hair loss
Antihistamines
• Role: blockade of mast cell release of
histamine
• Dose: 25 mg to 75 mg qHS
• Useful:
– allergy sufferers (spring/fall)
• Adverse: sedative properties
Antidepressants
• Role: decrease neural pain, decrease
urgency and frequency (Ach effect)
• Dose: 25 mg to 100 mg qHS amitriptyline
• Some patients respond to lower doses (10
mg)
• SSRI can also be considered (watch for
drug-induced FSD
Gabapentin
• Role: inhibit neural up-regulation and
neurogenic spinal cord inflammation
• Use: chronic unrelenting pain
• Dose: 300 mg to 2400 mg/day
• Side effects: sedation
• Advise: careful dose titration to balance
sedative properties
Intravesical Agents
• Dimethyl Sulfoxide (DMSO)
– Principle FDA approved intravesical agent
– Instilled once weekly for at least 6 weeks
– Cocktails: DMSO, sodium bicarbonate,
heparin, triamcinolone, bupivicaine
– 50% objective response rate
Sacral Neuromodulation
• Rationale
– Disrupt afferent inputs to the bladder and pelvic
floor that cause pathologic voiding
– Specifically help regulate
• capsaicin-sensitive C-afferent neurons
– originate from sacral parasympathetic plexus
– may relieve pelvic pain/muscle spasm
• neural input through the pelvic nerve
– may aid in detrusor contraction
Sacral Neuromodulation
• Goals of sacral neuromodulation Therapy
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Improve pelvic pain
Improve urinary frequency
Improve voided volumes
Improve overall symptom scores
• IC Symptom Index
• Chronic Prostatitis Symptom Index
Sacral Neuromodulation
• Potential uses of sacral neuromodulation
– Refractory urinary urge incontinence
– Non-obstructive urinary retention
– Refractory urinary urgency and frequency
• Interstitial Cystitis
Sacral Neuromodulation Current
Literature
• Refractory Urgency/Frequency (IC) Comiter C.
– 25 patients, prospective study
– Mean age 47 years
– Trial of sacral nerve stimulation
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50% improvement in frequency
50% improvement in nocturia
50% improvement in voided volume
50% improvement in pain
– 17/25 qualified for permanent implant
Sacral Neuromodulation Current
Literature
• Prospective study for refractory IC
– Mean follow up: 14 months
– Parameters:
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Daytime frequency: 17 ---> 8.7 voids (p<0.01)
Nocturia: 4.5 ---> 1.1 voids (p<0.01)
Mean Voided Volume: 111 cc ---> 264 cc (p<0.01)
Pain (1-10 scale): 5.8/10 to 1.6/10 (p<0.01)
IC Symptom Index: 16.5 ---> 6.8 (p<0.01)
Sacral Neuromodulation Current
Literature
• Prospective study for refractory IC
– 16/17 (94%) had improvement in all parameters
at last follow up
• Conclusions
– Sacral neuromodulation is safe and effective
treatment of dysfunctional voiding/pelvic pain
– Useful treatment for refractory IC symptoms
Comiter CV. J Urol 2003 Apr;169(4):1369-73.
Sacral Neuromodulation Current
Literature
• West Virginia University Hospital Experience
– Collaborative model (Pain Treatment Center and
Urology)
– All patients evaluated with cystoscopy and
urodynamics prior to test stimulation
– 2 stage approach (test stimulation -> permanent implant
Sacral Neuromodulation Current
Literature
• West Virginia University Hospital Experience
– To date:
• 210 test stimulations
• 195 permanent implants
– 80 implants have refractory urgency/frequency (IC)
• Mean age 51 years
• Mean follow up is 2 year (longest out is 3 years)
• All with improvement in symptoms and voided volume as well
as decline in pelvic pain/bladder spasm
Zaslau S, et al. West Virginia Medical Journal, August, 2003
Sexual Problems Affecting the IC
Patient
• Pain associated with intercourse
– Entry dyspareunia
– Deep dyspareunia
Entry Dyspareunia
• “Pain at the opening”
– Atrophic vaginitis
• post menopausal women
• estrogen loss
• Tx: topical or oral estrogen replacement
– Vaginitis
• infectious (fungal)
• Tx: oral or topical antifungal agents
Entry Dyspareunia
• Herpes vulvitis
– must rule out other causes first!
• Vulvodynia
– vulvar pain of unknown cause
– “feels like dragging sandpaper thru open
wound”
• Infectious vulvitis
– glandular enlargement; tx: antibiotics
Deep Dyspareunia
• Most common type of dyspareunia in IC
• Sources of pain:
– Vaginal infections
– Vaginal dryness
• estrogen loss
• psychological stress
Deep Dyspareunia
– Bladder pain
• pain in front portion of vagina
• caused by penile pressure on bladder trigone
– Pain from other pelvic abnormalities
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endometriosis
ovarian diseases
pelvic infections
diverticulosis
Deep Dyspareunia
– Pain from pelvic floor muscles
• most common source of pain for IC patient
• pelvic floor spasm occurs in 70% of IC patients
• can prevent penile insertion
Vicious cycle of muscle spasm
1. SPASM OF PELVIC MUSCLES
2. FEAR OF PAIN WITH PENETRATION
PENILE PENETRATION
3. MORE MUSCLE TIGHTENING
4. PENIS PENETRATES INTO SPASTIC,
TENDER MUSCLES
5. FURTHER TIGHTENING OF MUSCLES
IC and Female Sexual Dysfunction
(FSD)
• 100 patients with IC
• FSFI administered
– Assess 6 domains of sexual function
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Desire
Arousal
Orgasm
Lubrication
Satisfaction
Pain
IC and FSD
• Results:
– Mean age 39 years
– Impairment in all domains “50-75% of the
time”
• Conclusions
– FSD in IC involves more than pelvic pain
Zaslau, S et al FSFF, Vancouver, BC 2002
FSD in IC: 1st 400 Patients
• 400 IC patients
• FSFI administered on line at IC-Network
• Compared to two groups
– Controls (131)
– Female sexual arousal disorder (129)
FSD in IC 1st 400 Patients
• Results
– Statistically significant decrease in all domains
when compared to controls
– Stastically significant decrease in all domains
when compared to Arousal Disorder Group
– Lowest scores: pain
Zaslau, et al AUA 2003, Chicago, IL.
Conclusions: IC and FSD
• Global sexual dysfunction affecting all
domains
• May be age related and progressive
• Pain domain has lowest scores
• Treatment is multimodal and may involve
counseling, sex therapy and physical
therapy
General Treatment Principles
• Talk to your partner
– create “game plan” to deal with partner needs
– role for physician, social worker, sex therapist
• Don’t focus only on penetration
– Shift major focus to foreplay, full body
massage, deep kissing, fondling, oral-genital
contact
General Treatment Principles
• Watch out for medication effects on
orgasm
– medications can cause fatigue and/or loss of
sexual desire
– antidepressants impair orgasm
• Go slow
– forget the terrible memories
– Relax to prevent pelvic muscle spasm
– Go slow with insertion and thrusting
General Treatment Principles
• Lots of lubrication
– aids in penetration
– especially helpful in vulvodynia
• Be in control
– goes along with going slow
– let the patient call the shots
– communicate!
General Treatment Principles
• Find the right position
– There is no “perfect position”
– Goal: minimize vaginal tenderness, adjust
vault-penis angle and partner weight
– Missionary: most discomfort for female
partner (penile-->bladder base pressure)
– Female superior: more control for IC female
General Treatment Principles
• Go one step at a time
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Step-wise approach for vaginal penetration
First goal: NOT penis in vagina = orgasm!
Don’t focus on vaginal entry initially
Instead: superficial penetration and maximize
foreplay
General Treatment Principles
• Avoid intercourse during flares
– Flare can be related to menses
– Increased urinary frequency and pelvic pain =
flare
– Focus away from intercourse and onto
foreplay!
• Take advantage of remissions
– take things slow; “roll with the punches”
General Treatment Principles
• Take a warm bath after sex
– can relax pelvic floor muscles
– can be therapeutic after sex
– however, warmth can be irritating!
• Avoid urinary tract infections
– void before and after sexual relations
• Avoid use of diaphragm
– can increase UTI and pelvic pain/irritation
General Treatment Principles
• Use vaginal dilators/biofeedback
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can relax vaginal vault
patient in total control of insertion
step-wise treatment strategy
minimizes anxiety
General Treatment Principles
• Read and learn more about IC
– Interstitial Cystitis Association
(www.ichelp.org)
– Interstitial Cystitis Network
(www.ic-network.com)
Summary
• Interrelationships between conditions:
– Overactive Bladder
• No bacteriuria
• No bladder pain
– Urinary Tract Infection
• Bacteriuria and bladder pain
– Interstitial Cystitis
• Bladder pain and no bacteriuria
Summary (continued)
• The prevalence of IC is much higher than previously estimated
• IC should be considered in patients who have failed standard
therapy for endometriosis (prior to hysterectomy), OAB, or
have symptoms of recurrent/chronic UTI and do not improve
on antibiotics
• Increase awareness of IC as part of CPPS differential diagnosis
• Symptoms of CP/CPPS appear to be similar to IC
• Treatment of IC is multimodal (pentosan polysulfate,
antidepressants, antihistamines, role for sacral neuromodulation
in treatment failures)
*NBP = non-bacterial
References – 1
• Peters KM, Killinger KA, Carrico DJ, Ibrahim IA,
Diokno AC, and Graziottin A: Sexual Function
and Sexual Distress in Women with Interstitial
Cystitis: A Case Control Study. Urology. 2007;
70(3): 543-547.
• Zaslau S, Triggs J, Morgan L, Osborne J, Subit M,
Riggs D: “Characterization of Female Sexual
Dysfunction in Patients with Interstitial Cystitis.”
Presented at the American Urological Society
Meeting, Chicago, IL, April 27, 2003.
References - 2
• Zaslau S, Subit MJ, Mohseni HF, Riggs D, Jackson B,
Kandzari S: “Sexual Dysfunction in Patients with
Interstitial Cystitis.” Presented at the American
Urogynecology Meeting, Hollywood, FL, September 12,
2003.
• Zaslau S, Subit MJ, Mohseni HF, Riggs D, Jackson B,
Kandzari S. “Sexual Dysfunction in Patients with
Interstitial Cystitis: Initial Analysis of Under 40 Cohort.”
Presented at the Mid-Atlantic Section of the American
Urological Society Meeting, Boca Raton, FL, October 2629, 2003.
References - 3
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Zaslau S: Blueprints in Urology, 1st ed. Boston,
MA: Blackwell Science, Inc., 2004.
Zaslau S: SOAP Notes in Urology, 1st ed.
Baltimore, MD: Lippincott Williams and
Wilkins, Inc., 2006.
Messing EM. Interstitial cystitis and related
syndromes. In: Campbell’s Urology, 6th Edition.
Walsh PC, Retik AB, Stamey TA, Vaughan ED
Jr (eds). Philadelphia: WB Saunders Co.,
Volume 1, Chapter 24, pp. 982-1005, 1992.