Transcript Fibromyalgia disease overview DOWNLOAD (1.90 MB PPT file)

Fibromyalgia: A Chronic Widespread
Neurologic Pain Condition
Disease Overview and Diagnosis
PBP00542 © 2009 Pfizer Inc. All rights reserved. Printed in USA/August 2009
1
What is Fibromyalgia?
• Pathogenesis of Fibromyalgia
• Clinical Features and Diagnosis
of Fibromyalgia
• Management of Fibromyalgia
• Summary
2
Categorization of Pain Conditions
Nociceptive Pain
Neuropathic Pain
Inflammatory Pain
Central Pain
Amplification
(ie, Burn)
(ie, Herpes zoster)
(ie, Rheumatoid arthritis)
(ie, Fibromyalgia)
Noxious stimuli
Neuronal damage
Inflammation
Acute Pain
Courtesy of Woolf C. Ann Intern Med. 2004;140:441-451.
Abnormal pain
processing by CNS
Chronic Pain
3
Fibromyalgia (FM): A Chronic Widespread
Neurologic Pain Condition
FM is a neurological condition associated with chronic
widespread pain (CWP) and tenderness1
American College of Rheumatology
(ACR) criteria for the diagnosis
of FM:2
– Chronic widespread pain
• Pain for ≥3 months
• Pain above and below the waist
• Pain on left and right sides of body
and axial skeleton
– Pain at ≥11 of 18 tender points when
palpated with 4 kg of digital pressure
Diagram showing 18 tender points
ACR criteria are both sensitive
(88.4%) and specific (81.1%)2
1. Wolfe F, et al. Arthritis Rheum. 1995;38(1):19-28.
2. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
4
Epidemiology of FM
FM is one of the most common CWP conditions1
Prevalence in United States is estimated to be 2%-5%
of the adult population1
FM is highly underdiagnosed2
• Only 1 in 5 is diagnosed
• Diagnosis takes an average of 5 years3
Impacts a wide range of patients2
• Most patients are between 25 and 60 years of age
• Women more likely to be diagnosed than men
1. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28.
2. Weir PT, et al. J Clin Rheumatol. 2006;12:124-128.
3. National Pain Foundation. Available at: http://nationalpainfoundation.org/articles/849/facts-and-statistics. Accessed July 21, 2009.
5
Risk Factors for FM
Genetic factors1
– Relatives of FM patients are at higher risk for FM
• First-degree relatives are significantly more likely to have FM
(Odds ratio=8.5; P =0.0002)
• Have significantly more tender points
Environmental factors2
– Physical trauma or injury
– Infections (Lyme disease, hepatitis C)
– Other stressors (eg, work, family, life-changing events)
Gender3
– Women are diagnosed with FM about 7 times as often as men
1. Arnold LM, et al. Arthritis Rheum. 2004;50(3):944-952.
2. Mease PJ. J Rheumatol. 2005;32(suppl 75):6-21.
3. Arnold LM, et al. Arthritis Rheum. 2004;50(9):2974-2984.
6
• What is Fibromyalgia?
Pathogenesis of Fibromyalgia
• Clinical Features and Diagnosis
of Fibromyalgia
• Management of Fibromyalgia
7
The Normal Pain Processing Pathway
3. A signal is sent via
the ascending tract
to the brain, and
perceived as pain
Pain
Perceived
4. The descending tract carries
modulating impulses back to
the dorsal horn
2. Impulses from afferents
depolarize dorsal horn
neurons, then, extracellular
Ca2+ diffuse into neurons
causing the release of Pain
Associated Neurotransmitters
– Glutamate and Substance P
Glutamate
1. Stimulus sensed by
the peripheral nerve
(ie, skin)
1. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.
2. Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
Substance P
8
Central Sensitization: A Theory for
Neurological Pain Amplification in FM
Central sensitization is believed to be an underlying cause of the
amplified pain perception that results from dysfunction in the CNS1
– May explain hallmark features of generalized heightened pain sensitivity2
• Hyperalgesia – Amplified response to painful stimuli
• Allodynia - Pain resulting from normal stimuli
Theory of central sensitization is supported by:
– Increased levels of pain neurotransmitters3,4
• Glutamate
• Substance P
fMRI data demonstrates low intensity stimuli in patients with FM
comparable to high intensity stimuli in controls5
fMRI = functional magnetic resonance imaging
1. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.
2. Williams DA and Clauw DJ. J Pain. 2009;10(8):777-791.
3. Sarchielli P, et al. J Pain. 2007;8:737-745.
4. Vaerøy H, et al. Pain. 1988;32:21-26.
5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
9
Central Sensitization Produces Abnormal
Pain Signaling
Perceived pain
Ascending
input
After nerve injury, increased input to the dorsal
horn can induce central sensitization
Nerve dysfunction
Descending
modulation
Nociceptive afferent fiber
Induction of central sensitization
Perceived pain
(hyperalgesia/allodynia)
Increased release of pain neurotransmitters
glutamate and substance P
Minimal
stimuli
Pain
amplification
Increased pain perception
1. Adapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
2. Woolf CJ. Ann Intern Med. 2004;140:441-451.
10
FM: An Amplified Pain Response
Subjective pain intensity
10
Pain in FM
Normal pain
response
8
Hyperalgesia
6
(when a pinprick causes an
intense stabbing sensation)
4
Allodynia
Pain
amplification
response
(hugs that feel painful)
2
0
Stimulus intensity
Adapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1986.
11
fMRI Study Supports the Amplification of
Normal Pain Response in Patients With FM
14
Pain intensity
12
10
8
6
4
2
0
1.5
2.5
Stimulus intensity
3.5
4.5
(kg/cm2)
Patients with FM experienced high
pain with low grade stimuli
FM (n=16)
Subjective pain control
Stimulus pressure control
fMRI = functional magnetic resonance imaging
Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
(n=16)
Red: Activation at low intensity stimulus in patients with FM
Green: Activated only at high intensity stimulus in controls
Yellow: Area of overlap (ie, area activated at high
intensity stimuli in control patients was activated by low
intensity stimuli in patients with FM)
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Patients With FM Have Elevated Pain
Neurotransmitter Substance P in Their CSF
Substance P concentration
(fmoles/mL)†
In 3 separate clinical studies, substance P, a pain
neurotransmitter, was elevated in FM patients1-3
50
40
P<0.001
P<0.001
42.8
43
FM patients
Healthy control subjects
30
P<0.03
20
10
19.26
17
16.3
12.83
0
Russell 1994
*1
*2
*3
Russell 1995
Bradley
n=32
n=24
n=14
n=30
n=24
n=10
CSF = cerebrospinal fluid
sample collected via lumbar puncture in FM and healthy controls and SP levels assessed by radioimmunoassay
†fmoles/mL = femtomole/mL = 10-15 mole/mL
1. Russell IJ, et al. Arthritis Rheum. 1994;37:1593-1601.
2. Russell IJ, et al. Myopain 1995: Abstracts from the 3rd World Congress on Myofascial Pain and Fibromyalgia; July 30 - August 3, 1995; San Antonio, TX.
3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109.
13
*CSF
Patients With FM Have Elevated Pain
Neurotransmitter Glutamate in Their CSF
CSF level of glutamate (µg/mL)
CSF Levels of Glutamate
2.5
P<0.003
FM patient
Control
2.0
1.5
Sarchielli et al measured
CSF levels of glutamate in
20 FM patients and 20
age-matched controls
Significantly higher levels
of glutamate were found in
FM patients compared
with controls
1.0
0.5
0
FM patient
CSF = cerebrospinal fluid
Sarchielli P, et al. J Pain. 2007;8:737-745.
Control
14
FM Pathophysiology: Summary
Central sensitization is a leading theory of FM
pathophysiology1
Elevated pain neurotransmitters in CSF of patients with
FM2-4
– Several studies showed elevated levels of glutamate and
substance P
– Elevated levels suggest that this may contribute to pain
amplification
fMRI data supports FM as a disorder of central pain
amplification5
– Areas activated by high intensity stimuli in control patients were
activated by low intensity stimuli in patients with FM
CSF = cerebrospinal fluid
fMRI = functional magnetic resonance imaging
1. Staud R and Rodriguez ME. Nat Clin Pract Rheum. 2006;2:90-98.
2. Russell IJ, et al. Arthritis Rheum. 1994;37:1593-1601.
3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109.
4. Sarchielli P, et al. J Pain. 2007;8:737-745.
5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
15
• What is Fibromyalgia?
• Pathogenesis of Fibromyalgia
Clinical Features and Diagnosis
of Fibromyalgia
• Management of Fibromyalgia
16
Clinical Features of FM
Chronic Widespread Pain1,2
• CORE criteria of FM
• Pain is in all 4 quadrants of the body ≥3 months
• Patient descriptors of pain include:4
• Aching, exhausting, nagging, and hurting
Tenderness2
• Sensitivity to pressure stimuli
• Hugs, handshakes are painful
• Tender point exam given to assess tenderness
• Hallmark features of FM4
• Hyperalgesia
• Allodynia
Other Symptoms2,3,5
• Fatigue
• Pain-related conditions/symptoms
• Chronic headaches/migraines, IBC, IC, TMJ, PMS
• Subjective morning stiffness
Other
Symptoms
• Neurologic symptoms
• Nondermatomal paresthesias
• Subjective numbness, tingling in extremities
• Sleep disturbance
• Non-restorative sleep, RLS
1. Leavitt F, et al. Arthritis Rheum. 1986;29:775-781.
2. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28.
3. Roizenblatt S, et al. Arthritis Rheum. 2001;44:222-230.
4. Staud R. Arthritis Res Ther. 2006;8(3):208-214.
5. Harding SM. Am J Med Sci. 1998;315:367-376.
17
Widespread Pain and Tenderness
are the Defining Features of FM
In patients with FM, pain involves more areas
than other chronic pain conditions
*
Chronic Pain Controls
FM patients
98
100
*
85
*
*
80
72
69
% of patients
79
60
51
46
40
24
20
0
Widespread pain
Thoracic pain
Lumbar pain
Cervical pain
*P<0.001
Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
18
Patients With FM Present With
a Global Pain Disorder
While the ACR classification
criteria focuses on 18 points,
patients do not usually speak
of tender points1
This is a pain drawing—a
patient colors all areas of the
body in which they feel pain2
The diagram shows that the
pain of FM is widespread1
ACR = American College of Rheumatology
1. Wolfe F, et al. Arthritis Rheum. 1990:33:160-172.
Back
Front
Adapted from pain drawing provided courtesy of L Bateman.
2. Silverman SL and Martin SA. In: Wallace DJ, Clauws DJ, eds. Fibromyalgia & Other Central Pain
Syndromes. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2005:309-319.
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ACR-Recommended Manual Tender Point
Survey* for the Diagnosis of FM
LOW CERVICAL –
Anterior aspects of C5, C7
intertransverse spaces
TRAPEZIUS –
Upper border of trapezius,
midportion
OCCIPUT –
At nuchal muscle
insertion
FOREHEAD
SUPRASPINATUS –
SECOND RIB SPACE –
At attachment to medial
border of scapula
about 3 cm lateral to sternal
border
ELBOW –
RIGHT FOREARM
Muscle attachments to
Lateral Epicondyle
GLUTEAL –
Upper outer quadrant of
gluteal muscles
KNEE –
Medial fat pad of knee
proximal to joint line
LEFT
THUMB
Manual Tender Points Survey:
• Presence of 11 tender points on palpation to a maximum of 4 kg
of pressure (just enough to blanch examiners thumbnail)
*Based on 1990 ACR FM Criteria
1. Adapted from Chakrabarty S and Zoorob R. Am Fam Physician. 2007;76(2);247-254.
GREATER
TROCHANTER –
Muscle attachments just
posterior to GT
Control Points
Tender Points
20
Patients With FM are More Likely to Have
Concomitant Chronic Pain Conditions
Associations of pain-related conditions among patients diagnosed
with FM in the DMBA database between 1997 and 2002
Female
Risk ratio ‡
7
Male
6
FM Patients
5
Female n=906
Male n=1689
Baseline†
4
3
2
1
0
SLE
RA
IBS
Headache*
• 20% of patients with SLE, RA and OA have concomitant FM2
• Because patients with FM are often diagnosed with other pain-related conditions, FM may go undetected
DMBA = Deseret Mutual Benefits Administration
SLE = Systemic lupus erythematosus; RA = Rheumatoid Arthritis; IBS = Irritable Bowel Syndrome
*Headache = headache, tension headache, migraine
†Baseline from 52,698 females and 52,232 males without FM
‡Risk ratio = The probability of each condition occurring as compared to a normal, healthy control group (baseline=1)
1. Weir PT, et al. J Clin Rheumatology. 2006;12(3):124-128.
2. Wolfe F and Rasker JJ. Fibromyalgia. In: Firestein, ed. Kelly’s Textbook of Rheumatology, 8th Edition. St. Louis, MO: WB Saunders Co; 2008.
21
Diagnosis of FM Improves
Health Satisfaction
Patient health dissatisfaction
4
3
Lower number
indicates improved
patient satisfaction
3
*
2.2
2
1
0
Baseline
Post-diagnosis
*Statistically significant versus baseline (P value not provided) as a change in the 5-point Likert scale
1. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
2. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
3. Adapted from White KP, et al. Arthritis Rheum. 2002;47:260-265.
22
• What is Fibromyalgia?
• Pathogenesis of Fibromyalgia
• Clinical Features and Diagnosis
of Fibromyalgia
Summary
23
Summary
FM is one of the most common chronic widespread neurologic
pain conditions1
– Associated with hyperalgesia and allodynia2
– Central sensitization is a leading theory to explain FM3
– Demonstrated by excessive release of the pain neurotransmitters3
glutamate and substance P
FM is commonly seen with other chronic pain-related conditions4
ACR criteria for the diagnosis of FM are sensitive and specific5
– History of CWP ≥3 months
– Pain in 4 quadrants and axial skeleton
– ≥11 of 18 tender points
FM diagnosis is a key to successful management6
1. Wolfe F, et al. Arthritis Rheum. 1995;38(1):19-28.
2. Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
3. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.
4. Weir PT, et al. J Clin Rheumatol. 2006;12(3):124-128.
5. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
6. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
24