Curriculum Vitae

Isti Suharjanti, dr. SpS(K)

Pendidikan :
Lulus dokter : 1989
Lulus Spesialis : 2001
Konsultan : 2009
Pekerjaan:
Staf Dept./SMF Ilmu Penyakit Saraf FK.UNAIR/RSUD
Dr.Soetomo
Keanggotaan :
Association Member of International Headache
Society (IHS)
Kegiatan Profesi:
Ketua Pokdi Nassional Nyeri Kepala PERDOSSI
Wakil Sekjen PP PERDOSSI
Ketua Bidang Organisasi & Pengembangan Profesi Perdossi
Cabang Surabaya
Ketua Pokdi Nyeri Kepala Perdossi Cabamg Surabaya
Sekretas Indonesia Pain Society Surabaya Chapter

IS 4 June 2011 1
 Fibromyalgia: Nyeri Kronik
Widespread Neurologic

Isti Suharjanti, dr. SpS(K)

RSUD dr. Sutomo/Dept. Neurologi FK.Unair

2
 What is Fibromyalgia?

Pathogenesis of Fibromyalgia
Gambaran klinis dan Diagnosis
Fibromyalgia
Managemen Fibromyalgia
Ringkasan

3
3
 Kategori kondisi Nyeri
Central Pain
Nociceptive Pain Neuropathic Pain Inflammatory Pain Amplification

(ie, Burn) (ie, Herpes zoster) (ie, Rheumatoid arthritis) (ie, Fibromyalgia)

Noxious stimuli Neuronal damage Inflammation Abnormal pain

processing by
CNS

Acute Pain Chronic Pain

4
Courtesy of Woolf C. Ann Intern Med. 2004;140:441-451.
 Fibromyalgia (FM): Kronik
Widespread Nyeri Neurologi
FM adalah kondisi neurologi disertai nyeri kronik
widespread pain (CWP) dan tenderness1
Kriteri diagnosis American College of Rheumatology
(ACR)
of FM:2
Nyeri kronik widespread
Nyeri 3 bulan
Nyeri diatas dan dibawah pinggang
Nyeri di kanan dan kiri badan dan kerangka axialand
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. 5
2. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
 Epidemiologi FM
FM salah satu kondisi tersering CWP 1
Prevalensi di United States mencapai 2%-5%
population dewasa1

FM underdiagnosis cukup tinggi2

hanya 1 in 5 terdiagnosis
Terdiiagnosis rata-rata 5 tahun

Dampat pada pasien cukup besar2

Usia 25 - 60 tahun
Women > laki-laki

1. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28.

2. Weir PT, et al. J Clin Rheumatol. 2006;12:124-128. 6
3. National Pain Foundation. Available at: http://nationalpainfoundation.org/articles/849/facts-and-statistics. Accessed July 21, 2009.
 Factors Resiko FM
Genetic factors1
Relatives of FM patients are at higher risk for FM

Environmental factors2
Trauma fisik
Infeksi (Lyme disease, hepatitis C)
Stresor lain(eg, work, family, perubahan hidup)

Gender3
Laki > laki-laki

1. Arnold LM, et al. Arthritis Rheum. 2004;50(3):944-952.

2. Mease PJ. J Rheumatol. 2005;32(suppl 75):6-21. 7
3. Arnold LM, et al. Arthritis Rheum. 2004;50(9):2974-2984.
 Pathogenesis

8
8
 Jalur Proses Nyeri Normal
4. The descending tract carries
3. A signal is sent via
the ascending tract
Pain modulating impulses back to
to the brain, and Perceived the dorsal horn
perceived as pain

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
Substance P
(ie, skin)

1. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98. 9

2. Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
 Central Sensitization: teori Nyeri
Neurologi yg meyakinkan FM
Central sensitization dipercaya sebagai dasar perception nyeri
yg menghasilkan disfungsi CNS1
o Hal ini yg menjelaskan gambaran umum sensitif nyeri2
Hyperalgesia respon nyeri berlebihan
Allodynia nyeri timbul karena stimulus normal
Theory of central sensitization diduga:
o Peningkatan neurotransmitters nyeri3,4
Glutamate
Substance P
Data fMRI menunjukkan low intensity stimuli pada pasien FM
dibanding kontrol high intensity stimuli5
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. Vaery H, et al. Pain. 1988;32:21-26. 10
5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343. fMRI = functional magnetic resonance imaging
 Central Sensitization Produces
Abnormal Pain Signaling
After nerve injury, increased input to the dorsal
Perceived pain horn can induce central sensitization

Nerve dysfunction
Ascending Descending
input 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. 11
2. Woolf CJ. Ann Intern Med. 2004;140:441-451.
 FM: An Amplified Pain Response

10 Pain in FM
Normal pain
Subjective pain intensity

8 response
Hyperalgesia Pain
amplification
(when a pinprick causes an response
6 intense stabbing sensation)

4 Allodynia
(hugs that feel painful)

0
Stimulus intensity
12
Adapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1986.
 fMRI Study Supports the Amplification of
Normal Pain Response in Patients With FM
14

12
Pain intensity

10

0
1.5 2.5 3.5 4.5
Red: Activation at low intensity stimulus in patients with FM
Stimulus intensity (kg/cm2)

Patients with FM experienced high Green: Activated only at high intensity stimulus in controls
pain with low grade stimuli
Yellow: Area of overlap (ie, area activated at high
FM (n=16) intensity stimuli in control patients was activated by low
Subjective pain control intensity stimuli in patients with FM)
(n=16)
Stimulus pressure control

fMRI = functional magnetic resonance imaging 13

Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
 Pasien dg FM terjadi Neurotransmitter
Nyeri: Substance P di CSF
In 3 separate clinical studies, substance P, a pain
neurotransmitter, was elevated in FM patients1-3

50
Substance P concentration

P<0.001 P<0.001
FM patients
40
42.8 43 Healthy control subjects
(fmoles/mL)

30

P<0.03
20
19.26
16.3 17
10 12.83

0
*1 *2 *3
Russell 1994 Russell 1995 Bradley
n=32 n=24 n=14
n=30 n=24 n=10

CSF = cerebrospinal fluid

*CSF 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,15
TX.
3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109.
 Pasien FM terjadi Neurotransmitter
Glutamate di CSF
CSF Levels of Glutamate
2.5 Sarchielli et al measured CSF
CSF level of glutamate (g/mL)

P<0.003 FM patient levels of glutamate in 20 FM

Control
2.0 patients and 20 age-matched
controls
1.5 Significantly higher levels of
glutamate were found in FM
1.0 patients compared with
controls
0.5

0
FM patient Control

CSF = cerebrospinal fluid 16

Sarchielli P, et al. J Pain. 2007;8:737-745.
 Ringkasan Patofisiologi FM
Teori Central sensitization mendasari
patofiologi FM 1
neurotransmitter nyeri di CSF pasien FM2-4
Beberapa studi menunjukkan glutamate and substance P
Pengkatan tersebut diduga mendasari timbulnya nyeri
Data fMRI meyakinkan FM adalah suatu
gangguan nyeri sentral central5
Stimulus intensitas tinggi pada pasien kontrol
Stimulus intensitas rendah pada pasien FM

CSF = cerebrospinal fluid

fMRI = functional magnetic resonance imaging 3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109.
1. Staud R and Rodriguez ME. Nat Clin Pract Rheum. 2006;2:90-98. 4. Sarchielli P, et al. J Pain. 2007;8:737-745. 17
2. Russell IJ, et al. Arthritis Rheum. 1994;37:1593-1601. 5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
Gambaran Klinis
 Gambaran Klinis 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
Neurologic symptoms
Other Nondermatomal paresthesias
Symptoms 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. 4. Staud R. Arthritis Res Ther. 2006;8(3):208-214. 19
3. Roizenblatt S, et al. Arthritis Rheum. 2001;44:222-230. 5. Harding SM. Am J Med Sci. 1998;315:367-376.
19
Status Kesehatan yg berkaitan dg QoL pd pasien FM

Fibromyalgia berkaitan dg triad of pain:6

Pain Sleep disturbance Fatigue

CONCOMITANT SYMPTOMS AND PROBLEMS ASSOCIATED WITH FIBROMYALGIA7

Muscle pain, fatigue and insomnia are

present in 86% of bromyalgia patients

Fibromyalgia has a profound negative impact on patients professional lives:8

Up to 71% of employed patients missed at least 10 days of work in the past year due to their condition
Up to 29% of patients report that they have been unable to work due to their condition
Only 20% of patients with bromyalgia meet the Diagnostic criteria for major depressive
disorder.2
 Fibromyalgia berkaitan dg Pain TRIAD

Pain

Functional
impairment

Fatigue Sleep
disturbances

Nicholson and Verma. Pain Med. 2004;5 (suppl. 1):S9-S27

 Widespread Pain and Tenderness
sebagai gambaran FM
Pasien dg FM, nyeri mengenai beberapa area melebihi
kondisi nyeri kronik lain
* Chronic Pain Controls
98 FM patients
100
*
* 85
* 79
80
72
69
% of patients

60
51
46

40

24
20

0
Widespread pain Thoracic pain Lumbar pain Cervical pain
*P<0.001
22
Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
Diagnosis
 Diagnosis Fibromyalgia
Anamnesis Fibromyalgia berkaitan dg
kondisi:
o Riwayat Personal
o Riwayat keluarga
Pemeriksaan Fisik
o Tetapkan kriteria diagnosis
o Tevaluasi ender-point
Differential diagnosis
o Pemeriksaan laboratorium untuk mwnyingkirkan:
Osteoarthritis, rheumatoid arthritis,
hypothyroidism, lupus, and Sjgrens syndrome
Mease. J Rheumatol. 2005;32:6-21. Wolfe et al. Arthritis Rheum. 1990;33:160-172.
 Pasien FM:
Global Pain Disorder
Kriteria Klasifikasi ACR
difokuskan pd 18 titik
tender points1
Nyeri tergambar dg area
merah di badan yg terasa
nyeri
Tampak gambaran nyeri
FM widespread1

ACR = American College of Rheumatology Back Front

1. Wolfe F, et al. Arthritis Rheum. 1990:33:160-172. 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 25
Syndromes. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2005:309-319.
American College of Rheumatology criteria for fibromyalgia6
(1990)
TENDER POINTS FROM THE AMERICAN COLLEGE OF
RHEUMATOLOGY CRITERIA FOR DIAGNOSIS OF FIBROMYALGIA

Tender points are evaluated via palpation with the pulp of the thumb or the rst
2 or 3 ngers at a pressure of ~4 kg, which should just cause the nail to blanch3,6

ACR criteria6
History of chronic widespread pain for months
Patients must exhibit 11 of 18 tender points
Widespread pain was found in 97.6% of patients with Fm, compared with 69.1% in controls
FM can be identified from among other rheumatologic conditions with use of ACR criteria
American College of Rheumatology criteria for Fibromyalgia23
(2010)
Criteria based on 3 conditions:

1. Widespread pain index (WPI) 7 and symptom severity (SS) scale score 5 or
WPI 36 and SS scale score 9
2. Symptoms have been present at a similar level for at least 3 months
3. The patient does not have a disorder that would otherwise explain the pain

WPI IS THE TOTAL NUMBER OF PAIN AREAS

(SCORE BETWEEN 0-19) EXPERIENCED OVER THE PAST WEEK
 ACR-Recommended Manual Tender Point
Survey* for the Diagnosis of FM
TRAPEZIUS
LOW CERVICAL Upper border of trapezius,
Anterior aspects of C5, C7 midportion
OCCIPUT
intertransverse spaces At nuchal muscle
insertion

FOREHEAD
SUPRASPINATUS
SECOND RIB SPACE
about 3 cm lateral to sternal At attachment to medial
border border of scapula

ELBOW RIGHT FOREARM

Muscle attachments to
Lateral Epicondyle
GLUTEAL
Upper outer quadrant of
gluteal muscles
KNEE
Medial fat pad of knee GREATER
proximal to joint line LEFT TROCHANTER
THUMB Muscle attachments just
posterior to GT

Manual Tender Points Survey:

Presence of 11 tender points on palpation to a maximum of 4 kg Control Points
of pressure (just enough to blanch examiners thumbnail) Tender Points
*Based on 1990 ACR FM Criteria
1. Adapted from Chakrabarty S and Zoorob R. Am Fam Physician. 2007;76(2);247-254. 28
 Pasien FM are disertai dg kondisi Nyeri
Kronik
Associations of pain-related conditions among patients diagnosed with
FM in the DMBA database between 1997 and 2002
7 Female Male
6 FM Patients
Female n=906 Baseline
5
Risk ratio

Male n=1689
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. 29

2. Wolfe F and Rasker JJ. Fibromyalgia. In: Firestein, ed. Kellys Textbook of Rheumatology, 8th Edition. St. Louis, MO: WB Saunders Co; 2008.
American College of Rheumatology criteria for Fibromyalgia23
(2010)
SS scale score (between 0-12) the sum of severity of the 3 following
symptoms* plus somatic symptoms in general over the past week

0 = no problem
*3 symptoms
1 = slight or mild problems, generally mild or intermittent
Fatigue 2 = moderate, considerable problems, often present and/
Waking unrefreshed or at a moderate level
Cognitive symptoms 3 = severe: pervasive, continuous, life-disturbing problems

0= no symptoms
1= few symptoms
Somatic symptoms 2= a moderate number of symptoms
3= a great deal of symptoms

Somatic symptoms that might be considered: muscle pain, irritable bowel syndrome, fatigue/tiredness, thinking or remembering problem, muscle weakness,
headache, pain/cramps in the abdomen, numbness/tingling, dizziness, insomnia, depression, constipation, pain in the upper abdomen, nausea, nervousness, chest
pain, blurred vision, fever, diarrhea, dry mouth, itching, wheezing, Raynauds phenomenon, hives/welts, ringing in ears, vomiting, heartburn, oral ulcers, loss of/change
in taste, seizures, dry eyes, shortness of breath, loss of appetite, rash, sun sensitivity, hearing difficulties, easy bruising, hair loss, frequent urination, painful urination,
and bladder spasms.
 Somatic symptoms that might be considered
in reaching a diagnosis of fibromyalgia

Muscle pain/ Fever Loss of appetite

weakness
Fatigue/tiredness Diarrhoea Rash
Cognitive problems Dry mouth Sun sensitivity
Headache Itching Hearing difficulties
Abdominal pain/ Wheezing Easily bruised
cramps Raynauds Hair loss
Numbness/tingling phenomenon Frequent urination
Dizziness Hives/welts Painful urination
Insomnia Ringing in ears Bladder spasms
Depression Vomiting Loss of taste
Constipation Heartburn Change in taste
Nausea Oral ulcers Blurred vision
Nervousness Seizures Shortness of
Chest pain Dry eyes breath

Wolfe et al. Arthritis Care Res 2010;62:600-610

 Summary of ACR 2010 criteria

WPI 7 AND SS 5
OR
WPI 36 AND SS 9

This case definition of fibromyalgia correctly classifies

88% of cases classified by existing ACR 1990 classification
criteria, but does not require a tender point examination

32
Wolfe F, et al. Arthritis Care Res (Hoboken) 2010;62:600-610.
Managemen Fibromyalgia

33
 The Future of Fibromyalgia:
A Comprehensive, Stepwise Management Approach
Confirm diagnosis

Identify important symptom domains, their

severity, and level of patient function

Evaluate for comorbid medical and psychiatric

disorders
Assess psychosocial stressors, level of May require referral to a specialist
fitness, and barriers to treatment for full evaluation
Provide education about Fibromyalgia

Review treatment options

As a first-line approach for patients with moderate to

severe pain, trial with evidence-based medications
Provide additional treatment for comorbid
conditions
Adjunctive cognitive-behavioral therapy for patients with
prominent psychosocial stressors, and/or difficulty coping,
and/or difficulty functioning

Encourage exercise according to fitness level

34
Arnold. Arthritis Res Ther. 2006;8:212.
 Nonpharmacological Treatments With
Demonstrated Efficacy Currently in Use
Cognitive-behavioral therapy
o Positive effects on coping with and control over pain
Not proven to improve pain
o Proven to improve physical function
Aerobic exercise
o Demonstrated short-term improvements in
cardiovascular fitness and decreased tenderness
o Did not significantly decrease pain
Patient education
o Shown to improve pain, sleep, fatigue, and quality of life

Vlaeyen JW, Teeken-Gruben NJ, Goossens ME, et al. Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. I: clinical effects. J Rheumatol. 1996;23:1237-1245.
Nicassio PM, Radojevic V, Weisman MH, et al. A comparison of behavioral and educational interventions for fibromyalgia. J Rheumatol. 1997;24:2000-2007.
Williams DA, Cary MA, Groner KH, et al. Improving physical functional status in patients with fibromyalgia: a brief cognitive behavioral intervention. J Rheumatol. 2002;29:1280-1286.
Busch et al. Cochrane Database Syst Rev. 2006.
Harris RE, Jeter J, Chan P, et al. Using acupressure to modify alertness in the classroom: a single-blinded, randomized, cross-over trial. J Altern Complement Med. 2005;11:673-679.
Assefi NP, Sherman KJ, Jacobsen C, Goldberg J, Smith WR, Buchwald D. A randomized clinical trial of acupuncture compared with sham acupuncture in fibromyalgia. Ann Intern Med. 2005;143:10-19.
 Summary
FM is one of the most common chronic widespread neurologic
pain conditions1
o Associated with hyperalgesia and allodynia2
o Central sensitization is a leading theory to explain FM3
o 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
o History of CWP 3 months
o Pain in 4 quadrants and axial skeleton
o WPI 7 dan SS 5 atau WPI 3-6 dan SS = 9
FM diagnosis is a key to successful management6
1. Wolfe F, et al. Arthritis Rheum. 1995;38(1):19-28. 4. Weir PT, et al. J Clin Rheumatol. 2006;12(3):124-128.
2. Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984. 5. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. 39
3. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98. 6. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
40