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FibromyalgiaWRAP Principles and Practice Strategies for Fibromyalgia


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Title: FibromyalgiaWRAP Principles and Practice Strategies for Fibromyalgia

FibromyalgiaWRAP Principles and Practice
Strategies for Fibromyalgia
Fibromyalgia Controversies
  • Is it real?
  • What is the relationship with other functional
    somatic syndromes?
  • Can it be reliably diagnosed?
  • Is it physical or psychological?
  • Is there any effective treatment?
  • Is a diagnosis helpful or harmful?
  • What is role of rheumatology?

Primary Care and Functional Illnesses
  • Account for 30-50 of office visits
  • Medical classification FM, IBS, irritable
    bladder, vulvodynia, non-cardiac chest pain, TMJ,
    multiple chemical sensitivity, tension headaches
  • Psychiatric classification Somatization
    disorder, hypochondriasis, conversion disorder,
  • Commonest primary care problem
  • Specialty referral based on most distressing

Chronic Pain/Suffering Syndromes
  • FM is the prototype for a fundamentally different
    type of pain syndrome where pain is
  • Not due to damage or inflammation of peripheral
  • Frequently accompanied by a variety of other
    somatic symptoms and syndromes
  • There are many different labels that one can
    legitimately use for an individual with this type
    of pain (if one decides to use any label)
  • There is no agreed upon, all encompassing term to
    describe this entire spectrum of illness
  • No medical specialty has accepted ownership of
    these patients

American College of Rheumatology (ACR) Diagnostic
Criteria for FM
  • ACR diagnostic criteria
  • History of chronic widespread pain 3 months
  • Patients must exhibit 11 of 18 tender points
  • FM can be identified from among other
    rheumatologic conditions with use of ACR criteria
    with good sensitivity (88.4) and specificity

FM Diagnosis is Very Physician Dependent
  • History of chronic, widespread pain for 3 months

History of chronic, widespread pain for 3 months
  • Rule out other conditions that may present with
    chronic widespread pain (Operator dependent)

Rule out other conditions that may present with
chronic widespread pain Depending on physician
Mental health evaluation, sleep evaluation
  • General physical exam, neurologic exam, selected
    laboratory testing (ESR, thyroid tests avoid
    screening serologic tests)

General physical exam, neurologic exam, selected
laboratory testing (ESR, thyroid tests avoid
screening serologic tests)
  • Confirm presence of tender points
  • (Fibromyalgia may be present, even if lt11 of 18)

Confirm presence of tender points (Fibromyalgia
may be present, even if lt11 of 18)
  • Confirm diagnosis of fibromyalgia

Confirm diagnosis of fibromyalgia
  • 6

Modified from Goldenberg JAMA 2004
Problems in Defining Fibromyalgia
  • Real if no clear pathophysiologic basis?
  • Gold standard is expert opinion
  • Tender points, symptoms are subjective
  • Fewer than 11 tender points?
  • Symptoms are not dichotomous
  • Same diagnostic criteria and dilemma for any
    illness lacking objective biologic markers
    (depression, migraine, IBS, CFS)

Earlier Diagnosis of Fibromyalgia
  • Long delay in diagnosis adversely affects outcome
  • Characteristic symptoms speed diagnosis
  • I hurt all over
  • It feels like I always have the flu
  • Fatigue, Sleep and Mood disturbances
  • IBS, Irritable bladder, multiple other somatic
  • Exclusion of structural or systemic disease
  • Not a fishing expedition
  • Avoid screening rheumatology tests
  • Early subspecialty referral

Structured Interview for Fibromyalgia
A. Widespread pain (axial upper and lower L
and R sides)
C. At least 4 of generalized fatigue, headache,
sleep disturbance, neuropsych complaints,
numbness/tingling, IBS
B. 11 of 18 reproducible tender points
Explained by no other condition
  • A. Generalized, chronic pain ( 3 months)
    affecting the axial, plus upper and lower
    segments, plus left and right sides of the body
  • C. At least 4 of the following symptoms
  • 1. Generalized fatigue
  • 2. Headaches
  • 3. Sleep disturbance
  • 4. Neuropsychiatric complaints
  • 5. Numbness, tingling sensations
  • 6. Irritable bowel symptoms

Pope HG Jr, Hudson JI. Int J Psychiatry Med
Why Do A Tender Point Exam?
  • Confirm Dx impression
  • Proxy for pain sensitivity
  • Compare to joint tenderness
  • Potential prognostic factor

Who Gets Fibromyalgia?
  • No concurrent medical illness
  • Any age, but peak age 40-60
  • 60-90 female in clinic, although less gender
    difference in population-based studies
  • Concurrent medical illness (e.g., SLE, RA, OA,
    hypothyroidism, hepatitis). Important to consider
    in patients with rheumatic or chronic pain
  • Prior medical illness (e.g., Lyme disease, viral
  • Medications (steroid taper)

Medically Unexplained Illnesses Concurrent With
  • Chronic fatigue syndrome
  • Irritable bowel syndrome
  • Muscle, migraine headaches
  • Irritable bladder syndrome
  • Mood disturbances
  • Vulvodynia
  • Temporomandibular joint (TMJ) disorder
  • IN EACH OF THESE Diagnosis dependent on
  • Exclusion of disease
  • Symptoms rather than signs
  • No reproducible laboratory findings
  • Gold standard is expert opinion

Is FM Physical or Psychological?
  • Is it a psychiatric illness?
  • What is the interaction with depression?
  • Is it a maladaptive psychosocial response?
  • Is it somatization?
  • What is the role of stress?

FM and Mood Disorders
  • At the time of FM diagnosis, mood disorders are
    present in 30-50, primarily depression.
  • Increased prevalence of mood disorders is
    primarily in tertiary-referral patients.
  • Increased lifetime and family history of mood
    disorders in FM vs RA (Odds 2.0).
  • Fibromyalgia co-aggregates with major mood
    disorder in families (OR 1.8 95 CI 1.1, 2.9),

Arnold LM et al. J Clin Psychiatry
20066712191225, Arnold, et al. Arthritis Rheum
200 50944-952
Is Fibromyalgia a Medical or Psychiatric Illness?
  • Harmful and unproductive argument
  • Fruitless quandary to work out what came first
  • For all patients, symptoms are real and can be
  • Need a dual treatment approach targeting both
    physical and psychological symptoms

FM and Fragmented Sleep
  • Some patients with FM have fragmented sleep,
    which is associated with involuntary
    sleep-related periodic disturbances during the
    night. These disturbances include
  • Periodic limb movements (PLMs)
  • Restless leg syndrome (RLS)
  • Sleep apnea
  • An underlying periodic arousal disturbance in the
    sleep EEG known as sleep related periodic K-alpha
    or frequent cyclic alternating EEG sleep pattern

Al-Alarvi A at al. J Clin Sleep Med.
20062281-287. Jennum P et al. J Rheumatol.
EEG, electroencephalogram. CAP, cyclic
alternating pattern.
Shared Features of FM and Depression Clues to
  • Both have strong genetic predisposition and
    similar co-morbidity
  • Similar sleep disturbances
  • Similar cognitive disturbances
  • Orthostatic features, ANS dysfunction
  • Childhood abuse, stress
  • Catastrophizing
  • Imaging studies
  • Neuroendocrine studies

FM Pathophysiologic Pathways
  • Genetic factors
  • Fibromyalgia is strongly familial (the odds ratio
    is 8.5 for first-degree relatives)
  • No single candidate gene identified
  • Central pain augmentation
  • CSF substance P
  • Neuroimaging studies
  • Autonomic/neuroendocrine dysfunction
  • Immune dysfunction?
  • Structural changes?

Genetics of Fibromyalgia
  • Familial predisposition
  • Most recent work by Arnold, et al suggests gt8
    odds ratio (OR) for first-degree relatives, and
    much less familial aggregation (OR 2) with major
    mood disorders, much stronger with bipolarity,
    obsessive compulsive disorder1
  • Genes that may be involved
  • 5-HT2A receptor polymorphism T/T phenotype2
  • Serotonin transporter3
  • Dopamine D4 receptor exon III repeat
  • COMT (catecholamine o-methyl transferase)5

1. Arnold LM, et al. Arthritis Rheum.
200450944-952. 2. Bondy B, et al. Neurobiol
Dis. 19996433-439. 3. Offenbaecher M, et al.
Arthritis Rheum. 1999422482-2488. 4. Buskila D,
et al. Mol Psychiatry. 20049730-731. 6. Gürsoy
S, et al. Rheumatol Int. 200323104-107.
Pain Matrix Pain is Processed in at Least
Three Domains in CNS
  • Sensory - Where it is and how much it hurts
  • Primary and secondary somatosensory cortices
  • Thalamus
  • Posterior insula
  • Affective Emotional valence of pain
  • Anterior cingulate cortex
  • Anterior insula
  • Amygdala
  • Cognitive Similar to affective plus pre-frontal

Melzack et al. Science. 1965150971-979. Casey
et al. Headache. 19698141-153.
Specific Underlying Mechanisms in Fibromyalgia
  • Global problem with sensory processing (i.e.
  • FM patients equally sensitive to loudness of
    auditory tones1
  • Insular hyper-reactivity consistently seen2-4
  • H-MRS studies of glutamate levels in posterior

1. Geisser et. al. J. Pain (2008) 2. Gracely
et. al. Arthritis Rheum. 46, 1333-1343 (2002)
3. Giesecke et. al. Arthritis Rheum. 50, 613-623
(2004) 4. Cook J Rheumatol. 31, 364-378 (2004)
5. Harris et. al. Arthritis Rheum. 58, 903-907
Neuroimaging in Fibromyalgia
  • Hypoperfusion of thalamus and head of the caudate
  • fMRI of cortical response to pain consistent with
    augmentated pain perception
  • In FM, levels of depression did not modulate the
    sensory aspects of pain but correlated with the
    magnitude of brain activation in the medial
    region of the brain.
  • Castrophizing correlated with pain response in
    these medial brain regions.
  • Changes in posterior insula glutamate in PET scans

Gracely et al. Arthritis Rheum.
2002461333-1343. Giesecke, et al Arthritis
Rheum 2005 521577 Harris, et al Arthritis Rheum
2008 58, 903-907
Alterations in Descending Analgesic Activity in
  • Opioids
  • Normal or high levels of CSF enkephalins1
  • Never administered in RCT, but most feel that
    opioids are ineffective or marginally effective
  • Harris recently used PET to show decreased
    mu-opioid receptor binding in fibromyalgia2
  • Noradrenergic/Serotonergic
  • Elevated levels of substance P in CSF in
  • Nearly any class of drug that raises both
    serotonin and norepinephrine levels has
    demonstrated efficacy in fibromyalgia

CSFcerebrospinal fluid PETpositron emission
tomography. 1. Baraniuk JN et al. BMC
Musculoskelet Disord. 2004548 2. Harris JA et
al. J Neurosci. 2007277136-7140 3. Russell IJ
et al. Arthritis Rheum. 199235550-556.
Is There Any Effective Management of Fibromyalgia?
  • All patients
  • Reassurance re diagnosis
  • Give explanation, including, but not solely,
    psychological factors
  • Promote return to normal activity, exercise
  • Most patients
  • Medication trial (esp antidepressants,
  • Cognitive behavior therapy, counseling
  • Physical rehabilitation

Initial Treatment of Fibromyalgia
May require referral to a specialist for full
evaluation for example To psychiatry, sleep
Assess psychosocial stressors, level of fitness,
and barriers to treatment
Provide education about fibromyalgia
Modified from Arnold LM. Arthritis Res Ther
FM From Mechanism to Treatment
  • Treatments aimed at the periphery (ie, drugs,
    injections) are not very efficacious
  • There will be sub-groups of FM needing different
  • Drugs that raise norepinephrine and serotonin, or
    lower levels of excitatory neurotransmitters,
    will be efficacious in some
  • Exercise, sleep hygiene, and other behavioral
    interventions are effective therapies for
    biological reasons
  • Cognitive therapies are effective in FM and have
    a biological substrate
  • This is primarily a neural disease and central
    factors play a critical role
  • This is a polygenic disorder
  • There is a deficiency of noradrenergic-serotonerg
    ic activity and/or excess levels of excitatory
  • Lack of sleep or exercise increases pain and
    other somatic sx, even in normals
  • How FM patients think about their pain
    (cognitions) may directly influence pain levels

Rationale for the Use of Central Nervous System
Active Medications in FM
  • No evidence for muscle pathology
  • Current research supports role of augmented
    central pain mechanisms
  • Genetic predisposition
  • 5-HT2A receptor polymorphism
  • ? Pain severity in FM patients with T/T genotype
  • ? Frequency of S/S genotype in FM patients
    compared with healthy controls
  • ? Incidence of COMT polymorphism in FM patients
  • Substance P increased in CSF
  • 5-HT and NE serum levels decreased in some
  • Imaging studies
  • Elevated lifetime rates of mood disorders in
    patients with FM
  • Elevated rates of mood disorders in first-degree
    relatives of FM patients
  • Sleep disturbances

Russell IJ et al. Arthritis Rheum.
199235550-556 Bondy B et al. Neurobiol Dis.
19996433-439 Offenbaecher M et al. Arthritis
Rheum. 1999422482-2488. Arnold LM, et al.
Arthritis Rheum. 200450944-52. Moldofsky H. Adv
Neuroimmunol. 1995539-56. Buskila D,
Sarzi-Puttini P. Arthritis Res Ther.
20068(5)218 Harris RE, et al. Arthritis Rheum.
200858903-907. .
Medications in FMS
  • Strong evidence for efficacy
  • Amitriptyline, 25-50 mg at bedtime
  • Cyclobenzaprine, 10-30 mgs at bedtime
  • Pregabalin, 300-450 mg/day
  • Gabepentin, 1600-2400 mg/day
  • Duloxetine, 60-120 mg/day
  • Milnacipran, 100-200 mg/day
  • Modest evidence for efficacy
  • Tramadol, 200-300 mg/day
  • SSRIs (fluoxetine, sertraline)
  • Weak evidence for efficacy pramipexole, gamma
    hydroxybutyrate, growth hormone,
    5-hydroxytryptamine, tropisetron,
  • No evidence opioids, NSAIDS, benzodiazepene and
    nonbenzodiazepene hypnotics, melatonin,
    magnesium, DHEA, thyroid hormone, OTC including
  • Modified from Goldenberg, et al Management of
    fibromyalgia syndrome. JAMA 2004 2922388-95.

Tricylics in Fibromyalgia
  • Four placebo-controlled trials
  • Goldenberg,1985
  • Carette,1986
  • Carette,1994
  • Dose 25 50 mg
  • Duration 6-26 weeks
  • All showed modest efficacy
  • Four placebo-controlled trials
  • Quimby, 1989
  • Carette, 1994
  • Reynolds,1991
  • Dose 10 40 mg
  • Duration 4 12 weeks
  • 2 showed efficacy

Arnold L et al. Psychosomatics 200041104-113.
Pregabalin in Fibromyalgia
Patient Global Impression of Change
p lt 0.01 vs PBO
p lt 0.01 vs PBO
Treatment Group (mg/day)
Crofford L, et al. Arth Rheum 2005 52 1264-1273
Improvement in Average Pain Severity with
Phase III Study Female Patients (N354)
Duloxetine 60 mg QD
Duloxetine 60 mg BID
Plt.05 P.001 vs placebo

LS Mean Change from Baseline



Arnold LM, et al. Pain 2005 1195-15.
(J Rheumatol 200532197585)
Milnacipran (31) Not currently available in US.
Hlife 8 h, no liver metab
Milnacipran Phase III (3 months,)
Number 1196 Parallel, PL controlled, double
blind Randomized to M 100 or 200 mg or placebo
for 3 months Completers 810 (68) Pain
composite VAS - 30 very much or much impr on
PGIC FM composite pain composite 6 pt impr on
PCS of SF36 Secondary PGIC, SF36 (PCS and MCS)
and FIQ total Baseline observation carried
forward (BOCF) at 3 mnths 39,46 achieved Pain
composite, v 25 PL (0.011, 0.015) 25,26
achieved FM composite, v 13 PL (0.025,
0.004) Generally well tolerated
(discontinuations 34,35 v 28 PL) Common AEs
nausea M 37, PL -20 (both studies)
headache M 18, PL -14
constipation M 16, PL -4
hyperhidrosis M 9, PL - 2 NB no sig
hypertension or wt gain
Milnacipran Phase III (6 months)
Number 888 Randomized to M 100 or 200 mg or
placebo for 6 months Completers 511 (58) Pain
composite - VAS, 30 very much or much impr on
PGIC FM composite pain composite 6 pt impr on
PCS of SF36 Secondary PGIC, SF36 (PCS and MCS)
and FIQ total Baseline observation carried
forward (BOCF) at 6 mnths 44,45 achieved Pain
composite, v 28 PL (0.056, 0.032) 33,32
achieved FM composite, v 19 PL (0.028,
Nonpharmacologic Strategies Evidence of Efficacy

Strong Evidence Exercise Physical and
psychological benefits May increase aerobic
performance and tender point pain pressure
threshold, and improve pain Efficacy not
maintained if exercise stops Cognitive-behavioral
therapy Improvements in pain, fatigue, mood, and
physical function Improvement often sustained for
months Patient education/self-management Improves
pain, sleep, fatigue, and quality of life
Combination (multidisciplinary therapy)
Goldenberg DL, et al. JAMA. 20042922388-2395
Williams DA, et al. J Rheumatol.
2002291280-1286 Busch AJ, et al. Cochrane
Database Syst Rev. 2002
FM and Prognosis
  • Children and individuals treated in primary care
    settings and those with recent onset of symptoms
    generally have a better prognosis
  • Longer-term studies with larger study populations
    are needed to define risk factors for prognosis
    and to determine outcome relative to those risk

Modified from Horizon A and Weisman MH. In
Fibromyalgia and Other Pain Related Syndromes.
2006, p. 401.
Patient, Family Education
  • Primary care or specialist setting.
  • Core set of information should always be
  • Pathophysiology best based on biopsychological
    illness model.
  • Anticipate common patient questions and concerns.
  • Recognize the wealth of patient misinformation.
  • Encourage patient participation.

Who Should Treat Fibromyalgia?
  • More than 50 of visits are to primary care
  • Currently, 16 of FM visits are to
  • The American College of Rheumatology suggest that
    rheumatologists serve as consultants (tertiary
  • Other specialists should include mental health
    professionals, physiatrists and pain management

Multidisciplinary FM Treatment
  • Physical medicine/rehabilitation
  • Avoiding inactivity
  • Analgesic advice and non-pharmacologic treatment
    (trigger point injections)
  • Cardiovascular fitness
  • Stretching, strengthening
  • OT, work rehab, ergonomics
  • Mental health professional
  • Psychopharmacology
  • Counseling
  • CBT

Fibromyalgia Controversies
  • Does the diagnostic label promote helplessness
    and disability?
  • Only one controlled study it didnt
  • Diagnosis should be reassuring and end doctor
  • Only if diagnosis is coupled with education

Fibromyalgia Controversies
  • Does the diagnosis promote litigation?
  • Not because of the diagnosis but rather
    medico-legal misconceptions
  • This can lead to symptom amplification and
    rehabilitation difficulties
  • Problems with causation
  • Use headache or fatigue models

Total Rate of Diagnostic Tests Performed on FM
Cases and on Matched Controls (N2,260)
Positive Impact of Fibromyalgia Diagnosis in
Clinical Practice
  • 200

95 CI
  • 150

Rate per 100 person-years
The vertical line at 0 indicates the date of
fibromyalgia diagnosis
Years relative to index date
Decrease in diagnostic testing and visit rates
following diagnosis
Hughes G, et al. Arthritis Rheum. 200654177-183.
Initial Medication and Non-pharmacologic
Treatment of Fibromyalgia
As a first-line approach for patients with
moderate to severe pain, trial with
evidence-based medications for example Trial
with low-dose tricyclic antidepressants, SSRI,
SNRI, antiseizure medication
Provide additional treatment for comorbid
Stress management techniques
Encourage exercise according to fitness level
Modified From Arnold LM. Arthritis Res Ther
Further Medication and Non-pharmacologic
Treatment of Fibromyalgia Often with
Specialists Input
Polypharmacy for example, trial of SSRI in AM
and tricyclic in PM, SNRI in AM and anti-seizure
drug in PM
Trial of additional analgesics such as tramadol
Structured rehabilitation program Formal mental
health program, such as CBT for patients with
prominent psychosocial stressors, and/or
difficulty coping, and/or difficulty functioning
Comprehensive pain management program
Modified from Arnold LM. Arthritis Res Ther
Explaining the Typical Outcome in Fibromyalgia
  • FM does not herald the onset of a systemic
  • There is no progressive, structural or organ
  • Most patients in specialty practice have
    chronic, persistent symptoms
  • Primary care patients more commonly report
    complete remission of symptoms
  • Most patients continue to work, but 10-15 are
  • There is often adverse impact on work and leisure
  • Most patients quality of life improves with
    medical management

Granges G, Zilko P, Littlejohn GO.Fibromyalgia
syndrome assessment of the severity of the
condition 2 years after diagnosis. J Rheumatol
21523-529, 1994 Felson DT, Goldenberg DL. The
natural history of fibromyalgia. Arthritis Rheum.
Interdisciplinary Pain Management
Integrated Coordinated