Fibromyalgia Identification and Diagnosis

Fibromyalgia
Identification and Diagnosis
PBP00930O © 2010 Pfizer Inc. All rights reserved. Printed in USA/May 2010
Chronic Pain and Fibromyalgia
Pathophysiology of Fibromyalgia
Clinical Features and Diagnosis of Fibromyalgia
2
The Burden of Chronic Pain
• Pain is the most common reason for physician visits1
– Roughly 1 in 5 adults suffers from chronic pain2,3
• Chronic pain has detrimental effects
– Impaired daily activities, lost work productivity2,4
– Poorer general health, increased risk for cardiovascular
morbidity, depression, anxiety2,3,5,6
– Greater health care utilization7
– Erosion of trust in health care providers8
– Negative effect on partner/caregiver9
• Fibromyalgia (FM) is a chronic, widespread pain condition
that is distinct from other types of chronic pain10
1. Abbott FV, Fraser MI. J Psychiatry Neurosci. 1998;23(1):13-34.
2. Smith BH et al. FamPract. 2001;18(3):292-299.
3. Gureje O et al. JAMA. 1998;280(2):147-151.
4. Stewart WF et al. JAMA. 2003;290(18):2443-2454.
5. Chung OY et al. Anesth Analg. 2008;107(3):1018-1025.
6. Bruehl S et al. Clin J Pain. 2005;21(2):147-153.
7. Blyth FM et al. Pain. 2004;111(1-2):51-58.
8. Waters D, Sierpina VS. Pain Physician. 2006;9(4):353-360.
9. Reich JW et al. Arthritis Rheum. 2006;55(1):86-93.
10. Woolf C. Ann Intern Med. 2004;140(6):441-451.
3
C
FM Is a Chronic Pain Condition and Is Distinct
from Other Types of Pain1
Pain is the most common reason for physician visits2
Nociceptive
Pain
Neuropathic
Pain
Inflammatory
Pain
Central Pain
Amplification
(eg, burns, cuts)
(eg, herpes zoster, pDPN)
(eg, rheumatoid arthritis,
psoriatic arthritis)
(eg, FM)
Painful
Stimuli
Neuronal
Damage
Inflammation
Abnormal Pain
Processing by CNS
pDPN=painful diabetic peripheral neuropathy.
1. Woolf C. Ann Intern Med. 2004;140(6):441-451.
2. Abbott FV, Fraser MI. J Psychiatry Neurosci. 1998;23(1):13-34.
4
C
FM Is Characterized by Chronic
Widespread Pain and Tenderness1
• American College of Rheumatology (ACR)
criteria for the classification of FM include2:
– Chronic widespread pain (core feature)
for ≥3 months
• Pain above and below the waist
• Pain on left and right sides of body
• Pain in the axial skeleton
– Pain at ≥11 of 18 tender points when
palpated with 4 kg/cm2 of digital pressure
• New preliminary diagnostic criteria are
intended as an alternative to, not a
replacement for, the ACR criteria3
Diagram Showing 18 Tender Points
The ACR criteria are2:
• Sensitive (88.4%) – proportion
of patients correctly identified as
having the condition
• Specific (81.1%) – proportion
of patients correctly identified as
not having the condition
1. Wolfe F et al. Arthritis Rheum. 1995;38(1):19-28.
2. Wolfe F et al. Arthritis Rheum. 1990;33(2):160-172.
3. Wolfe F et al. Arthritis Care Res. 2010;62(5):600-610.
5
C
FM Epidemiology and Risk Factors
• Prevalence of FM in United States is estimated to be
2% to 5% of the adult population1,2
– FM is often underdiagnosed/misdiagnosed3
– Diagnosis takes an average of 5 years4
• Most common in individuals aged 25 to 60 years5
• Risk factors include:
– Genetic: increased incidence among first-degree relatives,
associated with genetic markers6,7
– Environmental: physical trauma, infections, social stressors8
– Gender: more common in women1,5,9
1.
2.
3.
4.
Wolfe F et al. Arthritis Rheum. 1995;38(1):19-28.
Lawrence RC et al. Arthritis Rheum. 2008;58(1):26-35.
Buurma AK et al. Fibromyalgia. Waltham, MA: Decision Resources; July 2009.
National Fibromyalgia Association Web site. www.fmaware.org/site/
PageServer?pagename=fibromyalgia_diagnosed. Accessed
January 27, 2010.
5.
6.
7.
8.
9.
Weir PT et al. J Clin Rheumatol. 2006;12(3):124-128.
Arnold LM et al. Arthritis Rheum. 2004;50(3):944-952.
Buskila D, Sarzi-Puttini P. Arthritis Res Ther. 2006;8(5):218.
Mease PJ. J Rheumatol. 2005;32(suppl 75):6-21.
Wolfe F, Rasker JJ. Fibromyalgia. In: Kelley’s Textbook of Rheumatology.
Philadelphia, PA: Saunders; 2008: chap 38.
6
The Clinical Challenge: Patient Cycling
Contributes to Underdiagnosis
Dx with comorbid
condition
~5 million individuals
with FM symptoms1
94% present to HCP2
Refer or
switch HCP
In a practice with
30 patients/day, 1-3 may
have FM symptoms3
Cycling4
(average of 5 years5)
Tx but then
re-present
Overall
diagnosis
rate is low2
Switch/add Tx;
switch/add Dx
Obstacles to Earlier Diagnosis4,5
 No definitive laboratory tests
for diagnosis
 FM not suspected early in
“cycling” process
 Multiple symptoms
 Confounding comorbidities
 Symptom descriptions do not
always facilitate diagnosis
HCP=health care provider.
1. Lawrence RC et al. Arthritis Rheum. 2008;58(1):26-35.
2. Buurma AK et al. Fibromyalgia. Waltham, MA: Decision Resources; July 2009.
3. Turk D, McCarberg B. The Black Book of Fibromyalgia. New York, NY:
MBL Communications, Inc; 2009.
4. Data on file. Pfizer Inc, New York, NY.
5. National Fibromyalgia Association Web site.
www.fmaware.org/site/PageServer?pagename=
fibromyalgia_diagnosed. Accessed January 27, 2010.
7
Chronic Pain and FM: Summary
• FM is a distinct chronic pain disorder characterized by
widespread pain and tenderness1
• In the United States, FM affects 2% to 5% of adults2,3
• FM is challenging to diagnose; rate of diagnosis is low4
• Diagnosis takes an average of 5 years5
1.
2.
3.
4.
5.
Wolfe F et al. Arthritis Rheum. 1990;33(2):160-172.
Wolfe F et al. Arthritis Rheum. 1995;38(1):19-28.
Lawrence RC et al. Arthritis Rheum. 2008;58(1):26-35.
Buurma AK et al. Fibromyalgia. Waltham, MA: Decision Resources; July 2009.
National Fibromyalgia Association Web site. www.fmaware.org/site/
PageServer?pagename=fibromyalgia_diagnosed. Accessed January 27, 2010.
8
Chronic Pain and Fibromyalgia
Pathophysiology of Fibromyalgia
Clinical Features and Diagnosis of Fibromyalgia
Conducting the Manual Tender Point Survey
9
C
Central Amplification: Leading Theory
for Abnormal Pain Processing in FM
Perceived pain
Ascending
input
Normal Pain Processing
Descending
modulation
Pain
stimuli
Nociceptive afferent fiber
Perceived pain
(hyperalgesia/allodynia)
Increased release of
glutamate and
substance P
Pain Processing in FM
Decreased release of norepinephrine and serotonin
Pain
amplification
Woolf CJ. Ann Intern Med. 2004;140(6):441-451.
Gottschalk A, Smith DS. Am Fam Physician. 2001;63(10):1979-1986.
Induction of central amplification leading
to abnormal pain processing
Minimal
stimuli
10
C
FM: An Amplified Pain Response
Subjective Pain Intensity
10
Pain in FM
8
Hyperalgesia
6
(eg, when a pinprick causes an
intense stabbing sensation)
4
Allodynia
Pain
amplification
response
Normal Pain
Response
(eg, hugs that feel painful)
2
0
Stimulus Intensity
Adapted from Gottschalk A, Smith DS. Am Fam Physician. 2001;63(10):1979-1986.
11
C
fMRI Study Supports the Amplification of
Normal Pain Response in Patients With FM
Patients with FM experienced
high pain with low-grade stimuli
14
Pain Intensity
12
Overlapping regions of brain
activation were seen in patients
with FM after low pain stimuli
and in normal subjects after
high pain stimuli
10
8
6
4
2
0
1.5
2.5
3.5
Stimulus Intensity, kg/cm2
FM (n=16)
Subjective pain control
Stimulus pressure control
4.5
Red: Activated by low-intensity stimulus in FM patients
(n=16)
Blue: Activated only by high-intensity stimulus in controls
Yellow: Area of overlapping activation
fMRI=functional magnetic resonance imaging.
Gracely RH et al. Arthritis Rheum. 2002;46(5):1333-1343.
12
Elevated Substance P and Glutamate
Are Found in CSF of FM Patients
Pain Neurotransmitter Levels
50
42.8
40
P<.001
30
20
16.3
10
0
FM Patient
(n=32)
Glutamate2
Glutamate Concentration, µg/mL
Substance P Concentration,
fmoles/mL†
Substance P1*
Control
(n=30)
2.5
2.36
P<.003
2.0
1.37
1.5
1.0
0.5
0
FM Patient
(n=20)
Control
(n=20)
*CSF (cerebrospinal fluid) sample collected via lumbar puncture in FM and
healthy controls and substance P levels assessed by radioimmunoassay.
† fmoles/mL = femtomole/mL = 10-15 mole/mL.
1. Russell IJ et al. Arthritis Rheum. 1994;37(11):1593-1601.
2. Sarchielli P et al. J Pain. 2007;8(9):737-745.
13
Pathophysiology of FM: Summary
• Central amplification is a leading theory of FM
pathophysiology1
• fMRI data support FM as a disorder of central pain
amplification2
– Areas activated by high-intensity stimuli in control patients
were activated by low-intensity stimuli in patients with FM
• Elevated pain neurotransmitters (eg, substance P,
glutamate) seen in patients with FM3-5
– May contribute to pain amplification
1. Staud R, Rodriguez ME. Nat Clin Pract Rheum. 2006;2(2):90-98.
2. Gracely RH et al. Arthritis Rheum. 2002;46(5):1333-1343.
3. Russell IJ et al. Arthritis Rheum. 1994;37(11):1593-1601.
4. Bradley LA et al. Arthritis Rheum. 1996;(suppl 9):212. Abstract 1109.
5. Sarchielli P et al. J Pain. 2007;8(9):737-745.
14
Chronic Pain and Fibromyalgia
Pathophysiology of Fibromyalgia
Clinical Features and Diagnosis of Fibromyalgia
Conducting the Manual Tender Point Survey
15
C
Clinical Presentation of FM
• Chronic widespread pain and tenderness are the defining features
of FM1-3
• FM is often accompanied by sleep disturbance
and fatigue2
• Patients with FM may also present with other
comorbid symptoms or conditions, including1,3,4:
–
–
–
–
–
–
IBS
Cognitive dysfunction
Numbness or tingling
Mood disorders
Morning stiffness
Headaches/migraines
IBS=irritable bowel syndrome.
1. Wolfe F et al. Arthritis Rheum. 1995;38(1):19-28.
2. Wolfe F, Rasker JJ. Fibromyalgia. In: Kelley’s Textbook of Rheumatology. Philadelphia, PA: Saunders; 2008.
3. Mease P. J Rheumatol. 2005;32(suppl 75):6-21.
4. Weir PT et al. J Clin Rheumatology.2006;12(3):124-128.
16
C
Clinical Features of FM Pain
• Pain in all 4 quadrants of the body, including1:
Location
Duration
– Pain above and below the waist, on the left and right sides of the body,
and in the axial skeleton
• Chronic, lasting at least 3 months1
• Allodynia: pain experienced from nonpainful stimuli2
– eg, hugs, handshakes
Quality
• Hyperalgesia: an amplified response to painful stimuli2
– eg, pinprick, stubbed toe
• Patient descriptors of pain3,4
– “Flu-like,” “dull,” “aching”
Pain/Tenderness
Measures
• Manual Tender Point Survey (MTPS) exam5
• Visual analog scale (VAS), numeric rating scale (NRS),
pain diagram2,3,6
Other
• Pain worsens with overactivity, stress, life events2,3
1. Wolfe F et al. Arthritis Rheum. 1990;33(2):160-172.
2. Wolfe F, Rasker JJ. Fibromyalgia. In: Kelley’s Textbook of Rheumatology. Saunders; 2008.
3. Goldenberg DL. Clinical Management of Fibromyalgia. West Islip, NY: Professional Communications, Inc; 2009.
4. Staud R. Arthritis Res Ther. 2006;8(3):208-214.
5. Okifuji A et al. J Rheumatol. 1997;24(2):377-383.
6. Johnson C. J Chiropr Med. 2005;4(1):43-44.
17
C
FM Often Seen With Other Chronic
Medical Conditions1-5
Other Pain States
• IBS
• Pelvic pain syndromes
• Painful bladder syndrome
(interstitial cystitis)
• Headaches/migraines
• Neck and back pain
Infection and Inflammation
• Hepatitis C
• Lyme disease
• Crohn’s disease
Psychological Disorders
• Depression
• Anxiety disorders
• Posttraumatic stress disorder
Rheumatic Disorders
• Osteoarthritis
• Rheumatoid arthritis
• Systemic lupus erythematosus
Consider FM in patients with chronic conditions who also
suffer from chronic widespread pain, fatigue, and sleep disturbance
1. Chakrabarty S, Zoorob R. Am Fam Physician. 2007;76(2):247-254.
2. Wolfe F, Rasker JJ. Fibromyalgia. In: Kelley’s Textbook of Rheumatology.
Philadelphia, PA: Saunders; 2008.
3. Weir PT et al. J Clin Rheumatol. 2006;12(3):124-128.
4. Mease P. J Rheumatol. 2005;32(suppl 75):6-21.
5. Hershfield NB. Can J Gastroenterol. 2005;19(4):231-234.
18
C
Diagnosing FM:
ACR Classification Criteria
According to ACR criteria, FM can be diagnosed if patient has:
1. Widespread pain for ≥3 months in all 4 quadrants of body1
– Widespread pain is defined as:
• Pain above and below the waist
• Pain on the left and right sides of the body
• Pain in the axial skeleton
2. Pain on palpation in ≥11 of 18 tender points1
– MTPS provides standardized approach to tender point assessment2
The ACR criteria are1:
• Sensitive (88.4%) – proportion of patients correctly identified as having the condition
• Specific (81.1%) – proportion of patients correctly identified as not having the condition
1. Wolfe F et al. Arthritis Rheum. 1990;33(2):160-172.
2. Okifuji A et al. J Rheumatol. 1997;24(2):377-383.
19
Preliminary Diagnostic Criteria for FM
According to the preliminary criteria, FM can be diagnosed
based on an HCP-administered questionnaire:
1. Widespread pain index (WPI)
– The number of painful body regions
2. Symptom severity (SS) scale that assesses the severity of:
–
–
–
–
Fatigue
Waking unrefreshed
Cognitive symptoms
Quantifies the occurrence of other somatic symptoms
3. Pain and symptoms present for 3 months or longer
The preliminary criteria:
• Not meant to replace current ACR classification criteria, but to offer an alternative method of FM diagnosis
• Accurately identified 88% of the same FM cases initially identified by the 1990 ACR classification criteria
Wolfe F et al. Arthritis Care Res. 2010;62(5):600-610.
20
C
Clinical Approach to FM Diagnosis
1. Patient history
– Chronic widespread pain for ≥3 months1
– Multiple visits with pain, fatigue, sleep complaints2
– Other associated conditions/symptoms2
• IBS, morning stiffness, migraines,
mood disorders, etc
2. MTPS exam3 (refer to slides for specific instructions on
conducting the physical exam)
3. Other physical exam and/or lab assessments to rule
out or establish coexistence of other disorders2
1. Wolfe F et al. Arthritis Rheum. 1990;33(2):160-172.
2. Mease PJ. J Rheumatol. 2005;32(suppl 75):6-21.
3. Okifuji A et al. J Rheumatol. 1997;24(2):377-383.
21
Telltale Descriptions of FM:
Listening to Patients
Common descriptions of
FM symptoms from patients1,2
“I feel like I always
have the flu.”
“No matter how
much sleep I’ve had,
I always feel like a
truck ran me over
when I wake up.”
“I hurt all over.”
“I’m always tired
and run-down.”
1. Wolfe F et al. Arthritis Rheum. 1990;33(2):160-172
2. Goldenberg DL. Clinical Management of Fibromyalgia. West Islip, NY: Professional Communications, Inc; 2009.
22
Identifying Widespread Pain in
Possible FM Patients
Pain drawings can help identify
widespread pain in possible FM patients1
Pain severity can be evaluated
using assessment scales2,3
Visual Analog Scale (VAS)2*
No
pain
Very
severe
pain
*Actual scale should be 100 mm in length.
Numeric Rating Scale (NRS)3
No
pain
Back
1
2
3
4
5
6
7
8
9
10
Most
pain
Front
Adapted from pain drawing provided courtesy of L Bateman.
1. Silverman SL, Martin SA. In: Wallace DJ, Clauw DJ, eds. Fibromyalgia & Other Central
Pain Syndromes. Philadelphia, PA: Lippincott, Williams & Wilkins; 2005:309-319.
2. Bigatti SM, Cronan TA. J Nurs Meas. 2002;10(1):5-14.
3. Johnson C. J Chiropr Med. 2005;4(1):43-44.
23
Importance of “Seeing” the Whole
Patient When Diagnosing FM
• Specialists often diagnose from the viewpoint of their training
• PCPs have the opportunity to look at the whole patient
The psychiatrist sees
depression
The otolaryngologist
sees TMJ syndrome
The gastroenterologist
sees IBS
The gynecologist
sees PMS
The cardiologist
sees noncardiac
chest pain
Weir PT et al. J Clin Rheumatology. 2006;12(3):124-128.
The rheumatologist
sees FM
The neurologist sees
chronic headache
24
Differentiating Selected Conditions From FM:
Key Clues to Make a Confident Diagnosis
Condition
Clinical Presentation
Typical Patient
Characteristics
Diagnostic
Tests
FM
Chronic widespread pain; sleep
disturbance; morning stiffness; IBS;
fatigue; headache; mood symptoms
F > M (2-9:1)
Onset: 25-60 y
2%-5% of US adults
MTPS, labs
typically within
normal limits
Myofascial pain
syndrome
Localized muscle pain arising from
trigger points; muscle stiffness;
sleep disturbance
Onset: 27-50 y
45%-54%
Palpation of
trigger points
Osteoarthritis
Stiffness; gelling; crepitus; joint pain
(knee, hip, hand)*
Onset: ↑ with age†
~12%†
Radiographs
DIP/PIP nodules
Hypothyroidism
Weight gain; cold intolerance; fatigue;
muscle aches
F > M (2-8:1)
~5%
Serum TSH
Rheumatoid
arthritis
Symmetric swelling of joints, insidious
onset; morning stiffness (>1 hour)
F > M (2-3:1)
Onset: 30-50 y
~0.5%-1%
RF, anti-CCP,
ESR, CRP,
radiographs
Polymyalgia
rheumatica
Weakness; pain in girdle muscles
(neck, shoulders, thighs); stiffness
F > M (2:1)
Onset: >50 y
0.5-0.7%
ESR, CRP,
response to
prednisolone
Systemic lupus
erythematosus
Photosensitivity; fever; skin rash;
fatigue; joint/muscle pain
F > M (9:1)
Onset: 15-44 y
~0.05%
ANA, ESR, CRP,
anti-DNA
Polymyositis
Symmetric proximal muscle
weakness; pain
F > M (2-3:1)
Onset: >20 y (esp 45-60)
~0.005%-0.01%
CPK, EMG
Data from Goldman L, Ausiello D. Cecil Textbook of Medicine. 23rd ed. Philadelphia, PA: Saunders Elsevier; 2007, unless otherwise noted.
*Hunter DJ et al. Rheum Dis Clin North Am. 2008;34(3):623-643. †Bitton R. Am J Manag Care. 2009;15(8 suppl):S230-S235.
25
Diagnosis of FM Results in Reduced
Health Care Utilization and Associated Costs
− Testing increases considerably
in 5 years before diagnosis
− Rates decline or stabilize after
diagnosis
200
FM Case
Matched Control
150
95% CI
100
FM is associated with heavy
utilization of health care
resources for at least 10 years
prior to diagnosis2
FM Diagnosis
50
− Labs and imaging
− Physician referrals
− Medications
•
Rate of Diagnostic Testing*
Per 100 Person-Years: FM vs Control2
Failure to diagnose FM can
lead to excessive costs1
Rate per 100 Person-Years
•
-10
-5
0
5
Years Relative to Index Date
*Diagnostic testing defined as all laboratory tests requested by general practitioner (UK study).
1. Annemans L et al. Arthritis Rheum. 2008;58(3):895-902.
2. Hughes G et al. Arthritis Rheum. 2006;54(1):177-183.
26
Patient Satisfaction and Health Status
Improves After FM Diagnosis
– Allows patients to begin
appropriate therapy
• Improves health status
over the long term2
– Greater satisfaction with health
– Lesser number of major and
minor symptoms
Failure to diagnose FM can:
• Aggravate symptoms3
• Promote distrust of health care
providers and fear regarding
missed diagnosis3
Lesser
4
satisfaction
Patient Health Dissatisfaction
A diagnosis of FM:
• Brings a sense of relief
to patients1
Greater
satisfaction
Patient Satisfaction Improves
After an FM Diagnosis2
3.0
Lower number indicates
improved patient satisfaction
3
2.2 *
2
1
0
Baseline
Postdiagnosis
n=100
*Statistically significant vs baseline (P value not provided)
as a change in the 5-point Likert scale.
1. Undeland M, Malterud K. Scand J Prim Health Care. 2007;25(4):250-255.
2. White KP et al. Arthritis Rheum. 2002;47(3):260-265.
3. Goldenberg DL. Clinical Management of Fibromyalgia. West Islip, NY: Professional Communications, Inc; 2009.
27
Clinical Features and Diagnosis of FM:
Summary
• Chronic widespread pain and tenderness are the defining
features of FM1,2
– Often accompanied by sleep disturbance, fatigue, other comorbidities
• The FM diagnosis should be based on patient characteristics,
not on exclusion3
• FM diagnosis guided by:
– Patient-reported symptoms4
– History of chronic widespread pain1
– MTPS exam5
• Abnormal laboratory values should trigger an investigation
of co-occurring conditions4
• Receiving an FM diagnosis reduces costs and improves
health status6,7
1. Wolfe F et al. Arthritis Rheum. 1990;33(2):160-172.
2. Wolfe F et al. Arthritis Rheum. 1995;38(1):19-28.
3. Chakrabarty S, Zoorob R. Am Fam Physician. 2007;76(2):247-254.
4. Mease P. J Rheumatol. 2005;32(suppl 75):6-21.
5. Okifuji A et al. J Rheumatol. 1997;24(2):377-383.
6. White KP et al. Arthritis Rheum. 2002;47(3):260-265.
7. Altomonte L et al. Reumatismo. 2008;60(suppl 1):70-78.
28