Post on 29-Jun-2020
transcript
Gisela Chelimsky, MD Professor of Pediatrics
Medical College of Wisconsin USA
!! Spouse advisory board for Lundbeck and Ironwood (2014) Pharmaceutical
!! Many medications discussed are used “off label”
!! Appreciate the epidemiologic importance of comorbidities associated with chronic pelvic pain (CPP)
!! Understand the frequent comorbid conditions associated with CPP
!! Know the current understanding of order of development of comorbid conditions
!! Recognize differences in comorbid conditions in IC/BPS and MPP
!! Very prevalent !! They increase drastically the cost of medical
care !! They increase the number of procedures and
evaluations performed !! Often part of chronic overlapping pain
conditions
!! Conditions characterized by symptoms such as chronic pain, fatigue, sleep disturbances, and often disability
!! Other synonyms: "! Functional somatic syndromes "! Medically unexplained symptoms "! Somatoform disorders
!! The term chronic overlapping pain conditions implies that comorbidities are intrinsic
!! Until recently we have conceptualized these disorders as though they primarily involved the end organ
!! Each practitioners obtains a different history based on their specialty – practice medicine in silos
Rodriguez, M J Urol. 2009
!! Functional disorder n. A physical disorder in which the symptoms have no known or detectable organic basis but are believed to be the result of psychological factors such as emotional conflicts or stress. Also called functional disease
!! A functional disorder is a medical condition that impairs the normal function of a bodily process, but where every part of the body looks completely normal under examination, dissection or even under a microscope.
The American Heritage® Stedman's Medical Dictionary (dictionary.com)
Wikipedia
!! Strictly the second meaning, implying a change in function has impacted one or many end organ affected
!! Best example of differentiating a functional disease vs structural comes from GI disorder: irritable bowel syndrome (IBS), as opposed to structural GI disorders such as inflammatory bowel disease (IBD)
!!Think: hardware vs software
!! Most of the studies regarding comorbidities of pelvic pain were published after 2005
!! 2009: association between urologic conditions and IBS
Rodriguez, J Urol 2009
IBS CFS FM MHA Panic attacks
Depression
Clemens 2006
40% 16% 32%
Warren 2009
28% 9% 4% 36% 27% 42%
Nickel 2010
39% 18% 10% 30%
Clemens 2012
40% 22% 15% 25% 27% 55%
Our data 2016
50% 19% 22% 38% 3% 9%
Clemens Urology 2012
!! IC /BPS = 16185 ; non-IC/BPS = 32,370 !! No difference in age and gender; mean age of 46
years; 73.3 % women !! Average follow-up BPS/IC group (4.7 years); non-IC/
BPS group (5.4 years) !! No ICD codes for depression, anxiety or insomnia
before the index dx entry date !! IC/BPS had a significant higher incidence rate of
developing anxiety, depression, and insomnia than the matched controls (92.9 vs 38.4, 101.0 vs 42.2, 47.5 vs 23.0; per 10,000 person-year)
Chuang, Y Int Urol Nephrol 2015
!! Anxiety disorder: panic disorder, agoraphobia, specific phobia, social phobia, obsessive-compulsive disorder, posttraumatic stress disorder, acute stress disorder, and generalized anxiety disorder
!! 2,376 subjects (396 IC/BPS and 1,980 controls) 5.7 % had received an Anxiety Disorder (AD) diagnosis before the index date
!! IC/BPS group: 16.2% had an AD vs 3.6% controls (p < 0.001)
!! After adjusting for CPP, IBS, fibromyalgia, migraines, sicca syndrome, allergies, asthma, and OAB, the OR for prior AD among IC/BPS was 4.37 (95% CI = 2.16–8.85, P < 0.001) compared to the controls
!! 291 women aged 18-45!years with dx of IC/BPS and 873 randomly selected controls matched on age and index date of ambulatory care visit
!! IC/BPS: 29.9% had previous hx of dysmenorrhea vs 18.7% of controls
(adjusted odds ratio 1.59 (95% confidence interval 1.13-2.23, p!=!0.007) after adjusting for medical co-morbidities)
Chung, SD Acta Obstet Gynecol Scand. 2014
0
10
20
30
40
50
60
Percent of Each Comorbidity in IC/BPS +/- MPP
Percent
Our data: about 50% of IC/BPS have comorbid MPP
!! NIH-NIDDK MAPP group describes 2 phenotypes: "! Pelvic pain only (PP only) "! Pelvic pain and beyond (PP and beyond)
!! Two different disorders? "! PP beyond may be part of the chronic overlapping
pain conditions "! About 2/3 of women with IC/BPS have at least 1
comorbid diagnosis (Clemens Urology 2012)
Differences in pain distribution between IC/BPS subjects with PP only and PP beyond
Nickel JC, Tripp DA and the International Interstitial Cystitis Study Group. J Urol 2015
PP beyond: •! worse physical quality of
life •! greater sleep disturbance •! higher prevalence of IBS
and fibromyalgia •! more fatigue •! more psychiatric
conditions
PP only: •! worse sexual pain score
!! 164 consecutive patients at 6 month FU (mean 52 years, 69% female, median IBS duration 17 years)
!! Though 88% consulted GP, only 19% for IBS Sx !! Mean sick days:
"! For IBS: 1.7 "! For Comorbidities: 16.3 (p < 0.01)
!! Costs: "! IBS: 954 NOK "! Comorbid symptoms: 14854 NOK (p < 0.001)
!! Age, non-IBS diseases and somatic symptoms, not IBS severity: significant predictors for total costs
Johansson et al. BMC Gastroenterology 2010,10:31
Clemens UROLOGY 2012
Migraine (24 yrs) Depression (29 yrs) Panic attacks (31 yrs)
Fibromyalgia (38 yrs) Chronic fatigue syndrome (35 yrs)
IC/BPS (32 yrs) IBS (32 yrs)
Early
Late
Dysmenorrhea 84% IC/BPS
80%
IBS 75%
Fibromyalgia 69%
MPP 67% CFS 67%
CRPS 31%
Abdominal migraine 16%
CVS 9%
Migraine 85%
EARLY
LATE
Migraine 85%
MPP
CRPS 31%
migraine 16%
CVS 9%
Order of development of comorbidities when considering that if a disorder is not present at study enrollment, it may develop later
Adjustment disorder 84%
Syncope 76%
Migraine 74%
Dysmenorrhea 69%
IC/BPS 47% (NS)
Abdominal migraine
8%
PTSD 87%
EARLY
LATE
PTSD 87%
Syncope 76%
IC/BPS 47% (NS)
migraine
Anxiety 74%
MPP 36% (NS)
Anxiety 74%
Order of development of comorbidities when both comorbidities are present at study enrollment
Migraine Depression
Panic attacks
Fibromyalgia Chronic fatigue syndrome
IC/BPS IBS
Early
Late
Dysmenorrhea
IC/BPS
Abdominal migraine
Dysmenorrhea
migraine
Anxiety
MPP
PTSD Depression
Migraine
Syncope
IC/BPS
MPP
Clemens UROLOGY 2012
Anxiety Migraine
Our data
Are the comorbidities in IC/BPS similar as in MPP?
!! MPP: at least 3 months of non-cyclic CPP unrelated to bladder filling or emptying, AND a minimum NRS 4/10 using 2kg pressure in at least 2 of 5 examined pelvic floor TPs (levator ani, obturator internus, and midline perineum (Sanses, T 2015)
!! IC/BPS: at least 6 months of urgency, frequency, and bladder pain clearly linked to bladder filling and emptying
Tender-points in healthy controls, IC/BPS, MPP and IC/BPS with MPP
Sanses, T Clin J Pain 2016
P=0.05
0% 10% 20% 30% 40% 50% 60% 70%
Panic Reflex Syncope
Raynauds Dyspepsia
CIN CFS FM
Dysmenorrhea RA
POTS MCS TMJ
MHA Endometriosis
Asthma Adjustment Disorder
Autonomic Neuropathy CRPS
Syncopal Migraine Diabetes
IBS Generalized Anxiety
Dyspareunia SFIBS
CVS FAP
PTSD Abdominal migraine
IC
MPP
p<0.01 P=0.06
P=0.08
IC/BPS and MPP share most of the same comorbidities, except that MPP has higher prevalence of dysmenorrhea and PTSD
P=0.02 P=0.06
P=0.06
0% 10% 20% 30% 40% 50% 60% 70%
Panic
Reflex Syncope
Raynauds
Dyspepsia
CIN
CFS
FM
Dysmenorrhea
RA
POTS
MCS
TMJ
MHA
Endometriosis
Asthma
Adjustment Disorder
Autonomic Neuropathy
CRPS
Syncopal Migraine
Diabetes
IBS
Generalized Anxiety
Dyspareunia
SFIBS
CVS
FAP
PTSD
Abdominal migraine
Both dx
One dx
P=0.04
P=0.05
Having IC/BPS and MPP increases the prevalence of having dysmenorrhea, CFS, panic attacks and also FM and dyspepsia (p=0.06)
!! Two phenotypes of CPP: PP beyond, PP only !! Comorbidities are very common in IC/BPS PP
beyond, mainly IBS, chronic fatigue, fibromyalgia and depression
!! Migraine, depression, anxiety, PTSD and dysmenorrhea usually present before the onset of IC/BPS
!! Having IC/BPS and MPP increases the risk of other comorbidities
ICEPAC STUDY SUPPORTED BY NIDDK (R01DK083538) COLLABORATORS
!!ICEPAC Study Advisory Board: "! Debra Erickson, M.D. University of
Kentucky College of Medicine, Lexington, KY, USA
"! Kathleen Pajer, M.D., M.P.H. Children’s Hospital of Eastern Ontario, Ottawa, ON
"! Julian Thayer, Ph.D. The Ohio State University, Columbus, OH, USA
"! Ursula Wesselmann, M.D., Ph.D. UAB School of Medicine, Birmingham, AL, USA
"! Denniz Zolnoun, M.D., M.P.H. UNC School of Medicine, Chapel Hill, NC, USA
"! C.A.Tony Buffington, DVM, PhD, The Ohio State University, Columbus, OH, USA
!! Jeff Janata, PhD !! Tatiana Sanses, MD !! Adonis Hijaz, MD !! Sangeeta Mahajan, MD !! Robert Elston, PhD !! Elais Veizi, MD !! Brad Fenton, MD PhD !! Ajay Singla, MD
Supported by an Advancing Healthier Wisconsin grant 5520298