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1 개원의와함께하는임상강좌 2011 꾀병으로오해받는외로운통증 경희대학교의과대학류마티스내과학교실 이연아 Fibromyalgia Fibromyalgia is real disease entity? Spend too much time in clinical practice Frequent failure of controlling symptoms of FMS Symptom based approach should be needed to control diverse spectrum of FMS Definition and diagnostic criteria 개원의와함께하는임상강좌

2 길라잡이 What is fibromyalgia (FM)? * M79.7 Fibromyalgia 섬유근육통 Chronic widespread pain ( 만성적, 전신적통증 ) Diffuse tender points ( 다발성압통 ) Often occurring with multiple symptoms & associated with high psychosocial stress Diagnosis of FM 명확한해부학적병변과관련없는만성근골격계통증에서는의심을... 병력 + 이학적검사 >> diagnostic tests 3개월이상지속되는전신통증 몸의좌우모두 허리위, 아래모두 척추부위통증도있어야 압통점 : 18군데중 11군데이상 Arthritis Rheum 1990;33: ACR 1990 Classification Criteria for FM History of widespread pain >3 months Pain in 11 of 18 tender point sites on digital palpation (4kg) Wolfe F, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum 1990;33: 개원의와함께하는임상강좌 2011

이연아 : 꾀병으로오해받는외로운통증 Tender points in FM 후두 경추하부 Tender points 눌러서국소적으로통증이 삼각근중앙엉덩이바깥쪽 상완외과 견갑골내측 제 2 늑연골관절 느껴지는부위 특히목, 등, 어깨, 엉덩이 대전자부 부위에많음 Definite FM 무릎안쪽 18 군데중 11 이상 Trigger points vs.

of MPS J Manipulative Physiol Ther 1995;18:398-406 Tender-point examination Thumb pressure is applied to 18 standardized areas until nail bed is starting to blanch (~ 4 kg of pressure) Use of these

3 이연아 : 꾀병으로오해받는외로운통증 Tender points in FM 후두 경추하부 Tender points 눌러서국소적으로통증이 삼각근중앙엉덩이바깥쪽 상완외과 견갑골내측 제 2 늑연골관절 느껴지는부위 특히목, 등, 어깨, 엉덩이 대전자부 부위에많음 Definite FM 무릎안쪽 18 군데중 11 이상 Trigger points vs. Tender points Trigger points of MPS taut band 에위치자극시 referred pain 자극시 muscle twitching nodular texture Tender points of FMS 대개 insertion site에위치자극시 pain은국한됨자극시 twitching은없음주변과구별되는특징없음 Trigger points of MPS J Manipulative Physiol Ther 1995;18: Tender-point examination Thumb pressure is applied to 18 standardized areas until nail bed is starting to blanch (~ 4 kg of pressure) Use of these criteria for diagnosing FM 88.4% sensitivity, 81.1% specificity Controversies regarding tender-point exam Subjective May not be necessary for diagnostic studies What about fewer than 11 of 18 tender points? 개원의와함께하는임상강좌

4 길라잡이 ACR 2010 FM Diagnostic Criteria 다음 3가지기준을모두만족할때 1) Widespread pain index (WPI) 7 and symptom severity (SS) scale score 5 or WPI 3-6 and SS scale score 9 2) 증상이 3개월이상비슷한수준으로지속 3) 통증을설명할수있는다른질환이없어야함 SS scale score (0-12) = severity of 3 symptoms (0-9)+ extent of somatic symptoms (0-3) 3 symptoms: fatigue, awakening unfreshed, cognitive dysfunction Somatic symtoms : IBS, muscle pain, weakness, numbness, headache, dizziness, insomnia, depression, diarrhea, dry mouth, oral ulcer, dry eye, frequent urination Widespread pain index (WPI) Please indicate any areas of pain in the past 7 days Areas Yes No Areas Yes No Jaw (left) Upper arm (left) Jaw (right) Upper arm (right) Chest Upper back Abdomen Hip (left) Forearm (left) Hip (right) Forearm (right) Shoulder (left) Upper leg (left) Shoulder (right) Upper leg (right) Neck Lower leg (left) Low back Lower leg (right) 2010 Fibromyalgia Diagnostic Criteria Arthritis Care & Research 2010;62: 개원의와함께하는임상강좌 2011

5 이연아 : 꾀병으로오해받는외로운통증 Modified ACR2010 FM Diagnostic Criteria FDC: A & B must be true: A. Item 4 (yes) B. Item 5 (no) Either C or D must be true: C. WPI>= 7 & SS>= 5 D. WPI 3-6 & SS>= 9 Fibromyalgia-ness: WPI+SS >= 13 cutpoint Adapted from Wolfe et al. Arth Care & Res (2010), 62: Etiology & Pathogenesis Environmental factors Biologic stressors Etiology Genetic factors 1,2 Familial aggregation>8 odds ratio for first-degree relatives Genetic polymorphisms associated with higher risk of FM 5-HT 2A receptor polymorphism T/T phenotype Serotonin transporter Dopamine 4 receptor exon III repeat polymorphism COMT (catecholamine o-methyl transferase) Involved in metabolism of monoamines; human stress response 1. Buskila D. Arthritis Res Ther 2006;8: Kato K. Arthritis Rheum 2006;54: 개원의와함께하는임상강좌

6 길라잡이 Stressors triggering FM Peripheral pain syndromes Infections (eg, parvovirus, EBV, Lyme disease, Q fever) Physical trauma (automobile accidents) Psychological stress/distress Hormonal alterations (eg, hypothyroidism) Drugs Vaccines Certain catastrophic events (war, but not natural disasters) Semin Arthritis Rheum. 2007;36(6): Acute pain vs. Chronic pain A time based definition (6 months) Acute pain 방어적알람기능 질환의증상 조직손상치유시해소됨 정신과적문제동반거의없음 원인치료 소염진통제, 마약성진통제 Chronic pain 생리적이점없음 만성통증자체가질환 질병기간이후에도지속 불면, 우울, 피로, 불안등동반 통증자체치료필요 소염진통제, 마약성진통제 항경련제, 항우울제 Pathogenesis of FM Central pain augmentation : Substance P, glutamate / NE, serotonin in CSF from FM patients (Harris RE. Curr Pain Headache Rep 2006;10:403-7) Autonomic/neuroendocrine dysfunction : Abnormal HPA function, decreased GH level (McBeth J. Arthritis Rheum 2007;56:360-71) Immune dysfunction : Increased pro-inflammatory cytokines (Wang H. J Rheumatol 2008;35: ) Structural changes : Accelerated brain gray matter loss (Kuchinad A. J Neurosci 2007;27:4004-7) 34 개원의와함께하는임상강좌 2011

이연아 : 꾀병으로오해받는외로운통증 Central pain augumentation Serotonin and NE : implicated in the mediation of analgesic mechanisms via descending inhibitory pain pathway Serotonin : 척수에서말초자극에반응하여 substance P

증가된 CSF Substance P 를감소시킴 Low levels of NE and its metabolite, 3-methoxy, 4-hydroxy phenylglycol (MHPG) in FMS CSF Descending influences on nociceptive processing Facilitation Substance P Glutamate

sensitization 3. Finally, a pain signal is sent to the brain from the dorsal horn 2.

7 이연아 : 꾀병으로오해받는외로운통증 Central pain augumentation Serotonin and NE : implicated in the mediation of analgesic mechanisms via descending inhibitory pain pathway Serotonin : 척수에서말초자극에반응하여 substance P 가분비되는것을억제 < Serotonin in FMS> Low serum concentration of serotonin (5HT 1a ) and its precursor, L-tryptophan Lower level of principal metabolite, 5-HIAA (metabolite product) in CSF Norepinephrine : 증가된 CSF Substance P 를감소시킴 Low levels of NE and its metabolite, 3-methoxy, 4-hydroxy phenylglycol (MHPG) in FMS CSF Descending influences on nociceptive processing Facilitation Substance P Glutamate and EAA Serotonin (5HT 2a, 3a ) Neurotensin Nerve growth factor CCK + Inhibition Descending anti-nociceptive pathways Norepinephrine-serotonin (5HT 1a,b ) Opioids GABA Cannabanoids Role of central sensitization 3. Finally, a pain signal is sent to the brain from the dorsal horn 2. Then, extracellular Ca 2+ and nitric oxide diffuse into neurons and cause exaggerated release of substance P and glutamate; this results in neuronal hyperexcitability 1. First, impulses from afferents depolarize dorsal horn neurons In FM, dorsal horn neurons become hyperresponsive to nociceptive and nonnociceptive somatic stimulation This is known as central sensitization and is thought to result in hyperalgesia and allodynia Despite extensive research, the pathogenesis of pain in FM is not clearly understood. However, central sensitization has emerged as a leading theory of disease mechanism. Staud. Arthritis Res Ther [serial online]. 2006;8:208; Henriksson. J Rehabil Med. 2003;41(suppl 41): 개원의와함께하는임상강좌

8 길라잡이 Central sensitivity syndrome Neuroendocrine dysfunction Plasma Total Cortisol (mg/l) TSST onset Controls CPP FM Decreased cortisol response in FMS CPP=chronic pelvic pain; TSST=Tier Social Stress Test. Wingenfeld K, et al. Psychosom Med. 2008;70:65-72 Immune dysfunction 1000 n=45 n=43* n=19* n=18 IL-8 (pg/ml) *P < Controls with depression with anxiety without psychiatric illness Elevated inflammatory cytokines in FMS patients Bazzichi et al. Clin Exp Rheum. 2008;25: 개원의와함께하는임상강좌 2011

9 이연아 : 꾀병으로오해받는외로운통증 Structural changes Accelerated brain gray matter loss in FMS patients Kuchinad A, et al. J Neurosci 2007;27: Epidemiology Prevalence of FM Chronic widespread pain (CWP) US study 10.6% (95% CI; ) UK study 11% FMS : 전인구의 2-4% 로추정 Wolfe et al 2.0% (95% CI ) Finland study 0.8% 대부분중년여성 between the ages of 35 and 60 years Female dominant x 10 times 개원의와함께하는임상강좌

10 길라잡이 Prevalence in Korea 경상북도포항, 울진 1028 명, 2004년 Prevalence of chronic widespread pain 144/1028 cases (14.0%) F:M = 130:14 연령증가에따른증가경향 Prevalence of fibromyalgia 23/1028 cases (2.2%) F:M = 21:2 연령증가에따른증가경향 Kim SH JKRA 2006;13(1):1-8 Clinical Manifestations & Differential Diagnosis FM-associated symptoms 만성피로감 (fatigue) - 80% 수면장애 (sleep disturbance) - 75% 두통 (tension headache, migraine) - 50% 조조강직 (Morning stiffness) - 77%, 류마티스관절염으로오인되기도주관적인관절부종 (Subjective joint swelling) 손발저림 (Parethesia) - 62% 불안 48%, 우울한기분 32% 등생리통 40%, 빈뇨, 여성요도증후군과민성대장증후군30% 38 개원의와함께하는임상강좌 2011

11 이연아 : 꾀병으로오해받는외로운통증 Conditions that simulate FM Sleep apnea syndrome Drugs Statins and fibrates Antimalarials Endocrinopathies Hypothyroidism Hyperparathyroidism Cushing s syndrome Diabetes mellitus Multiple sclerosis Myasthenia gravis Malignancy Infections Hepatitis C HIV Rheumatologic diseases Rheumatoid arthritis Systemic lupus erythematosus Sjögren s syndrome Ankylosing spondylitis Polymyalgia rheumatica Metabolic myopathy Inflammatory myositis Polymyositis Dermatomyositis Connective tissue disease Osteomalacia Regional pain syndrome MPS Hypermobility syndrome Pearls to differentiate FM History and Physical Sx, onset, progression, distribution Sleep history (sleep apnea, restless legs syndrome) Detail medications and family history Probe for red flags (e.g. cancer history, fevers, unexplained weight loss, synovitis, myoglobinuria) Complete neurological and musculoskeletal exam Lab work : ESR, CRP, CBC, Chemistry panel, TSH, ± CK, Urinalysis Screening serologic testing : not necessary (ANA, RF) Imaging work-up: 필요시 X-rays, EMG, NCV, CT scans, nuclear scans or MRI Muscle biopsy : only if clinical evidence of inflammatory or metabolic myopathy 개원의와함께하는임상강좌

12 길라잡이 Chronic Fatigue Syndrome (ICD-10 G93.3 Postviral fatigue syndrome) CDC Criteria 1. Fatigue unexplained, persisting (lasting six months or longer), "not due to ongoing exertion," and not substantially reduced by rest. must have experienced a significant reduction in activity levels. 2. Four or more of the following symptoms: Impaired memory or concentration Post-exertional malaise, where physical or mental exertions bring on "extreme, prolonged exhaustion and sickness" Unrefreshing sleep Muscle pain (myalgia) Pain in multiple joints (arthralgia) Headaches of a new kind or greater severity Sore throat, frequent or recurring Tender lymph nodes (cervical or axillary) Treatment 40 개원의와함께하는임상강좌 2011

13 이연아 : 꾀병으로오해받는외로운통증 Non-pharmacologic treatment Strong evidence 환자교육 (Education), Self management 유산소운동 (Aerobic exercise) 인지행동치료 (Cognitive behavioral therapy, CBT) Moderate evidence Strength training, Acupuncture Hypnotherapy, Balneotherap (medicinal bathing) EMG biofeedback, Transcranial electrical stimulation Goldenberg DL, et al. JAMA. 2004;292: ; Williams DA, et al. J Rheumatol. 2002;29: ; Busch AJ, et al. Cochrane Database Syst Rev Excercise 약물치료수개월뒤시작 Graded aerobic exercise 유산소운동 : 걷기, 수중운동, 자전거타기운동의강도 (Low- to moderate-intensity) : 하루 5분부터조금씩천천히시작, 차츰늘려가도록 Stretching, strengthening excercise는근거미약 Tai-chi exercise (N Engl J Med 2010 Aug;363:743-54) Cognitive Behavioral Therapy A program designed to teach patients techniques to reduce their symptoms, to increase coping strategies, and to identify and eliminate maladaptive illness behaviors Shown to be effective for nearly any chronic medical illness Not all CBT is created equally; very dependent on therapist and program 개원의와함께하는임상강좌

14 길라잡이 Pharmacological treatment Strong evidence Dual reuptake inhibitors such as tricyclic antidepressant, TCAs (amitriptyline, cyclobenzaprine) SNRIs and NSRIs (milnacipran, duloxetine) Anticonvulsants (e.g. gabapentin, pregabalin) Modest evidence Tramadol Selective serotonin reuptake inhibitors, SSRIs (paroxetine, fluoxetine) Gamma hydroxybutyrate Dopamine agonists No evidence Opioids Corticosteroids, Nonsteroidal anti-inflammatory drugs Benzodiazepine and nonbenzodiazepine hypnotics, guanifenesin Modified from: Goldenberg et al. JAMA 2004;292: Medications for FM symptoms Traditional Medication Muscle relaxant Analgesics Sedative Hypnotics TCA SSRI SNRI FDA-approved New Drugs Milnacipran (Ixel, Savella) Duloxetin (Cymbalta) Pregabalin (Lyrica) Antidepressant Increase serotonin- and NE- mediated neurotransmission effective in other chronic pain conditions Inhibitition of both the serotonin and NE reuptake : more effective than inhibition of either alone. Since many patients do not tolerate TCA, SSRI (fluoxetine, paroxetine, sertraline) or SNRI (venlafaxine, duloxetine, milnacipran) may be preferable as first line. 42 개원의와함께하는임상강좌 2011

이연아 : 꾀병으로오해받는외로운통증 Tricyclic antidepressant (TCA) 우울증용량보다훨씬적은용량우울증의호전시기보다훨씬빠른 2주이내에효과개선효과 : 통증, 경직감, 우울, 피로, 수면장애부작용 : 구강건조, 변비, 체중증가, 집중력감소 Amitriptyline 25-50mg qd hs ( 상품명 : 에나폰, 에트라빌 )

15 이연아 : 꾀병으로오해받는외로운통증 Tricyclic antidepressant (TCA) 우울증용량보다훨씬적은용량우울증의호전시기보다훨씬빠른 2주이내에효과개선효과 : 통증, 경직감, 우울, 피로, 수면장애부작용 : 구강건조, 변비, 체중증가, 집중력감소 Amitriptyline 25-50mg qd hs ( 상품명 : 에나폰, 에트라빌 ) Cyclobenzaprine 10-30mg qd hs Tricyclic antidepressants (TCA) 7 studies (amitryptyline in 7 and nortryptyline in 1) No of studies Patients No Effect size (95% CI) Test for all effect P value Pain (-2.57 to -0.71) <0.01 Fatigue (-1.87 to -0.38) Sleep (-2.62 to -1.60) <0.001 Decreased mood (-4.53 to -3.33) 0.76 HRQOL (-0.60 to -0.01) 0.04 HRQOL: health-related quality of life Hauser W et al. JAMA 2009;301: Amitriptyline (25mg) References Carette et al Ginsberg et al Goldenberg et al Goldenberg et al Patient s global Assessment (VAS) (P < 0.05) (P < 0.001) (P < 0.001) (P = 0.02) Pain (VAS) (P < 0.05) (P < 0.001) ND (P = 0.02) Tender points (0 18 ACR) ND* (P < 0.001) ND ND Physician's global assessment (VAS) (P < 0.05) (P < 0.001) (P < 0.001) (P = 0.04) Sleep disturbance (VAS) (P < 0.05) (P=0.003) (P < 0.001) (P < 0.001) Hannonen et al ND ND ND ND ND ND Heymann et al (P = 0.009) NM ND NM NM NM ND*: no difference between group, NM : not measured Fatigue (VAS) (P < 0.05) (P < 0.001) (P < 0.001) ND Nishishinya B, et al. Rheumatology (Oxford). 2008;47: 개원의와함께하는임상강좌

길라잡이 Selective serotonin reuptake inhibitor (SSRI) 6 studies (Fluoxetine in 3, citalopram in 2, and paroxetine in 1) No of studies Patients No Effect size (95% CI) Test

10) 0.02 HRQOL 3 62-0.41(-0.78 to -0.05) 0.03 HRQOL: health-related quality of life Hauser W et al.

studies (duloxetine in 3, milnacipran in 1) No of studies Patients No Effect size (95% CI) Test for all effect P value Pain 3 804-0.36(-0.46 to -0.25) <0.

16 길라잡이 Selective serotonin reuptake inhibitor (SSRI) 6 studies (Fluoxetine in 3, citalopram in 2, and paroxetine in 1) No of studies Patients No Effect size (95% CI) Test for all effect P value Pain (-0.77 to -0.01) 0.04 Fatigue (-0.47 to 0.12) 0.25 Sleep (-0.56 to 0.10) 0.18 Decreased mood (-0.66 to 0.10) 0.02 HRQOL (-0.78 to -0.05) 0.03 HRQOL: health-related quality of life Hauser W et al. JAMA 2009;301: Selective serotonin reuptake inhibitor (SSRI) Fluoxetin ( 상품명 ; 프로작 ) 이대표적 불면을유발가능성으로가급적오전에복용 Serotonin norepinephrine reuptake inhibitors (SNRIs) 4 studies (duloxetine in 3, milnacipran in 1) No of studies Patients No Effect size (95% CI) Test for all effect P value Pain (-0.46 to -0.25) <0.001 Fatigue (-0.20 to 0.05) 0.23 Sleep (-0.47 to -0.14) <0.001 Decreased mood (-0.42 to -0.10) HRQOL (-0.44 to -0.17) <0.001 HRQOL: health-related quality of life Hauser W et al. JAMA 2009;301: 개원의와함께하는임상강좌 2011

17 이연아 : 꾀병으로오해받는외로운통증 SNRI : Duloxetin/milnacipran FM 치료제로 FDA 승인 First choice in FM with severe symptoms of depression Milnacipran > duloxetin for NE transporter : better for severe fatigue/cognitive dysfunction Duloxetin : 20 mg AM titrate up to 60 mg, 강직감, 압통점수감소 Milnacipran : 12.5 mg bid 50 mg bid, 피로감소 S/Ex: nausea, appetite ; good choice for obese patient, potential drug interaction (duloxetin); avoid in severe hepato-renal impairment, risk of bleeding/suicidal tendency (common to serotonin activating drug) Cyclobenzaprine 5-10 mg hs increase 10 mg 3-4 times/day anti-cholinergic AE: dry mouth, urinary retention, constipation Tofferi JK Arthritis Rheum. 2004;51:9-13. Differences between TCAs and SNRIs SNRI TCA Inhibition of 5-HT & norepinephrine reuptake Treatment of neuropathic pain receptor blockade Muscarinic receptor Histamine H1 receptor Blurred vision Xerostomia Urianry retention Constipation Narrow angle glaucoma Sedation Treatment of depressive mood disorders Alpha Adrenergic receptor Orthostatic hypotension Dizziness Reflex tachycardia 개원의와함께하는임상강좌

길라잡이 Anti-convulsants 신경말단에서칼슘유입차단 Pregabalin ( 상품명 : 리리카 ) Gabapetin ( 상품명 : 뉴론틴, 가바틴 ) Sodium oxybate (precursor of GABA) 통증, 피로, 수면,

Neurotransmitters Postsynaptic Postsynaptic Schematic representation of pregabalin s proposed mechanism of action Pregabalin selectively binds to α

substance P) Pharmacologic effect requires binding at this site in animal models The clinical significance of these observations in humans is

2007;73:137-150 Pregabalin (Lyrica) Decrease sleep latency/modify sleep architecture improving slowwave- sleep Especially good choice for FMS with

18 길라잡이 Anti-convulsants 신경말단에서칼슘유입차단 Pregabalin ( 상품명 : 리리카 ) Gabapetin ( 상품명 : 뉴론틴, 가바틴 ) Sodium oxybate (precursor of GABA) 통증, 피로, 수면, 삶의질모두를유의하게개선 Pregabalin (Lyrica) Pregabalin Presynaptic α 2 -δ subunit Presynaptic α 2 -δ subunit Ca 2+ channel Ca 2+ channel Neurotransmitters Neurotransmitters Postsynaptic Postsynaptic Schematic representation of pregabalin s proposed mechanism of action Pregabalin selectively binds to α 2 -δ subunit of voltage-gated Ca channels in CNS Modulates calcium influx in hyperexcited neurons Reduces neurotransmitter release (glutamate, substance P) Pharmacologic effect requires binding at this site in animal models The clinical significance of these observations in humans is currently unknown Taylor. Epilepsy Res. 2007;73: Pregabalin (Lyrica) Decrease sleep latency/modify sleep architecture improving slowwave- sleep Especially good choice for FMS with sleep complaints Side effects: dizziness, somnolence, weight gain, peripheral edema (with increasing the dose) Prescription tips: start at low doses at dinner (25-75 mg) weekly up-titration depending on the symptoms Should be monitored for worsening of fatigue 46 개원의와함께하는임상강좌 2011

19 이연아 : 꾀병으로오해받는외로운통증 Pregabalin 14-week fixed-dose FM trial : significant improvement in pain IMPROVEMENT LS mean change from baseline 0 Placebo (n=184) Pregabalin 300 mg (n=183) Pregabalin 450 mg (n=190) Pregabalin 600 mg (n=188)* EP Week P<0.01; P *600 mg/day of pregabalin is not an approved dose for FM. End point mean pain score based on modified baseline observation carried forward approach (mbocf). Baseline mean = 6.7 (moderate to severe pain). P value based LS means using MMRM ANCOVA. Scored 0-10, lower score represents improvement. Arnold LM et al. APS 2007; Data on file. Pfizer Inc, New York, NY. Continuous outcomes at the end of trials Outcome Placebo 300 mg/day Individual domains of SF mg/day 600 mg/day Physical functioning * 51.3 Physical role limitation Social functioning *** 60.6 Bodily pain * 41.0**** 39.7* Mental health ** 63.1* Emotional role limitation ** 63.1* Vitality ** 35.0*** 35.2** General health perception ** 52.0** 50.8 Mental component score ** 43.3* Physical component score *P<0.05; **P<0.01; ***P<0.001; ****P< Straube S et al. Rheumatology 2010;49: Adverse events of pregabalin Lyseng-Williamson KA et al. Drugs. 2008;68: 개원의와함께하는임상강좌

20 길라잡이 국내보험인정기준 -Pregabalin FM 진단 (1990, ACR 기준 ) 후최소 1 개월간근이완제나 TCA 를처방받음근이완제 : cyclobenzaprine ( 시클펜, 벤자민 ) 등 TCAs: amitriptyline ( 에트라빌, 에나폰 ), nortriptyline ( 센시발정 ) 등 117 제제 위의치료 1 개월후에도효과불충분 VAS 40mm, FIQ 40 점이상 13 주이후재평가기록첨부 Pregabalin 사용이후 VAS 가처음시작보다감소했음효과불충분시사용하지말것 섬유근통의보험청구코드는 M (79.9) 보건복지가족부고시제 호 Korean version of fibromyalgia impact questionnaire (FIQ) Sodium oxybate A Randomized, Double-Blind, Placebo-Controlled, 8 weeks, trial Russell IJ, et al Arthritis Rheum. 2009;60: 개원의와함께하는임상강좌 2011

21 이연아 : 꾀병으로오해받는외로운통증 Tramadol 약한오피오이드약제, 진통과수면유도효과 Dual mechanism of action Binding to μ-opioid receptor Inhibition of neuronal reuptake of serotonin and norepinephrine Efficacy shown in nociceptive pain & neuropathic pain Lower back pain and pain from OA Fibromyalgia diabetic neuropathy mg q 4-6 hrs, up to 400 mg daily in pts < 75 age without renal failure R. B. Raffa. Journal of Clinical Pharmacy and Therapeutics 2001, 26 Tramadol and acetaminophen combination tablets Base line Final visit Tramadol/ Aceamiophen (n=156) Placebo (n=157) Tramadol/ Aceamiophen (n=156) Placebo (n=157) P Value* Pain score (mm) 72 ± ± ± ± 29 <0.001 Pain relief score ± ± 1.3 <0.001 Number of tender points 16 ± ± ± ± Sleep Index 6 62 ± ± ± ± Sleep Index 9 62 ± ± ± ± * Comparison between final values based on analysis of covariance adjusting for clinical center and baseline values. Bennett RM, et al. Am J Med. 2003;114: Symptoms management by FIBRO a rapid strategy for assessment and management of fibromyalgia syndrome Fatigue Insomnia (sleep quality) Blues (depression and anxiety) Rigidity (stiffness) O Ow! (pain and work disability) 개원의와함께하는임상강좌

22 길라잡이 Symptom based management for FM Treat FMS symptoms: all patients PAIN Pregabalin(insomnia++), duloxetine(>>depression++) or milnacipran(fatigue++) Activity: daily stretching, low impact aerobic exercise Information: No narcotics: avoid narcotics, benzodiazepines and steroids Individualize Sx-based Tx using mvasfiq to treat FIBRO Re-evaluate using mvasfiq at each visit to monitor therapy Fatigue Modafinil Methylphenidate Insomnia Sleep hygiene Screening for OSA/RLS Pregabalin Zolpidem Sedating TCA Clonazepam (RLS) Blues Psychiatry referal SNRI SSRI (older) TCA Rigidity Cyclobenzaprine Tizanidine AAP/Tramadol Methocarbamol Metaxalone Ow (pain) Pregabalin Duloxetine Milnacipran AAP Tramadol Gabapentin Subgroups of FM Patients Group 1 Low depression/anxiety Not very tender Low catastrophizing Moderate control over pain Group 2 Tender High depression/anxiety Very high catastrophizing No control over pain Psychological factors neutral Psychological factors worsening symptoms Group 3 Extremely tender Low depression/anxiety Very low catastrophizing High control over pain Psychological factors improving symptoms 50 개원의와함께하는임상강좌 2011

23 이연아 : 꾀병으로오해받는외로운통증 Clinical case review Case 1. Chief Complaint : 손 O 옥, Female/ 46 years generalized ache and fatigue (onset: 4 months ago) Associated Symptoms: multiple joints pain-both wrists, knees & ankles, LBP both hand stiffness in the morning for 20 minutes Physical exam. and lab. findings distribution of painful joints complained of multiple joints pain and tenderness but, no other inflammatory signs such as swelling, local heating or redness Lab : ANA (-), RF(-), ESR 8mm/hr, CRP<0.5 mg/dl 개원의와함께하는임상강좌

24 길라잡이 Hand X-ray Bone scan Mild uptake on both shoulder joints Shoulder X-ray 52 개원의와함께하는임상강좌 2011

25 이연아 : 꾀병으로오해받는외로운통증 Physical examination Tender points : 14 of 18 points FIQ = ( ) Diagnosis: Fibromyalgia Medication Fluoxetine (SSRI) Ultracet (Tramadol & Acetaminophen) Amitriptyline (TCA) After medication for 2 weeks, FIQ was decreased 개원의와함께하는임상강좌

26 길라잡이 3 months later Flare up of polyarthralgia and whole body pain joint swelling and local heating both wrist, right 1 st PIP, left 2 nd PIP both ankles, both 2 nd, 3 rd MTP increased morning stiffness more than 4 hours Laboratory findings anti-ccp 1110 U/mL, ESR 31mm/hr, CRP 2.1 mg/dl Final diagnosis : Rheumatoid arthritis and fibromyalgia combination therapy of DMARDs Take home message 섬유근통증후군은유병률이 2.2% 인흔한질환현재의손상이나염증에근거해설명할수없는만성적인다발성통증을호소할때, 섬유근통증후군을먼저생각중추성민감화가주된기전감소된 Serotonin과 NE의균형을맞춰주는약물이효과 : SNRI 상승된 substance P 및 glutamate를낮춰주는약물이효과 : Pregabalin 처음엔증상을호전시킬수있는맞는약물의선택이필수증상의호전후비약물적인치료들이병행되어야 54 개원의와함께하는임상강좌 2011

27 이연아 : 꾀병으로오해받는외로운통증 Pain Treatment is the Responsibility of EVERY physician!! 개원의와함께하는임상강좌

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract