Company LOGO Fibromyalgia & Soft Tissue Rheumatism Shin-Seok Lee, M.D. Chonnam National University Medical School Musculoskeletal Disorder Articular Inflammatory Noninflammatory Monarticular Septic arthritis Gout Pseudogout Viral arthritis Juvenile arthritis Sarcoid Fungal Trauma Osteonecrosis Osteoarthritis Charcot joint Hemarthrosis PVNS Foreign body Polyarticular Rheumatoid arthritis SpA SLE Rheumatic fever Juvenile arthritis Scleroderma Lyme Osteoarthritis Sickle cell Hemarthrosis Hemochromatosis Hypertrophic osteoarthropathy Periarticular Inflammatory Noninflammatory Localized Bursitis Tendinitis Tenosynovitis Epicondylitis Periostitis Costochondritis Carpal tunnel Sickle cell Multiple myeloma Osteoid Osteoma Reflex sympathetic dystrophy Systemic PMR Polymyositis Periostitis Enthesitis Eosinophilic fasciitis Myasthenia gravis Polychondritis Fibromyalgia Multiple myeloma Myxedema Osteoporosis Pagets 섬유근통 증후군에 관한 설명 중 틀린 설명은? 1. 80-90%가 여성이며, 호발 연령은 25-55세이다. 2. 만성 근골격계의 증후군으로 미만성 통증과 압통점이 특징적이며 이럴 경우 NSAID와 steroid가 도움이 된다. 3. stage 4(non-REM) sleep 장애, serotonin의 결핍, 우울증 등이 이 질환과 관계 있다. 4. 주요 압통 부위는 thumbnail, forehead, distal dorsal forearm 등이 있다. 가. 1,2,3 나. 1,3 다. 2,4 라. 4 마. 1,2,3,4 Chronic Widespread Pain and Fibromyalgia www.themegalllery.com Prevalence of chronic widespread pain Prevalence of chronic widespread pain 1. US study – 10.6%, 95% CI (9.5, 12) 2. UK study – 11% 25 Prevalence (%) 20 female male 15 10 5 0 18-29 30-39 40-49 50-59 60-69 70-79 >80 Prevalence of fibromyalgia 1. Wolfe et al – 2.0% 95% CI (1.4, 2.7) 2. Finland study – 0.8% Age-group (years) COMPANY LOGO Prevalence of CWP and FM in Korea www.themegalllery.com Uljin and Pohang, Kyongsangbuk-do 1028 participants in 2004 Prevalence of chronic widespread pain 144/1028 cases (14.0%) F:M = 103:14 Increasing trend in older age Prevalence of fibromyalgia 23/1028 cases (2.2%) F:M = 21:2 Increasing trend in older age Kim S, et al. JKRA 2005;12:S71 COMPANY LOGO Chronic Widespread Pain and Fibromyalgia www.themegalllery.com Percentile Prevalence of fibromyalgia Individuals with fibromyalgia Rheumatology clinics 20% Internal medicine clinics 6% Family practice clinics 2% General medicine inpatients (UK) 5% General population 1% Tenderness COMPANY LOGO What is Fibromyalgia? Pressure pain threshold (kg) www.themegalllery.com Fibromyalgia Healthy control 4kg Allodynia Hyperalgesia COMPANY LOGO 1990 ACR Classification Criteria www.themegalllery.com I. History of chronic widespread pain involving all 4 quadrants of the body II. Pain in 11 of 18 tender points on digital palpation 1. 2. 3. 4. 5. 6. 7. 8. 9. Occiput: bilateral, at the suboccipital muscle insertions. Low cervical: bilateral, at the anterior aspects of the intertransverse spaces at C5-C7. Trapezius: bilateral, at the midpoint of the upper border. Supraspinatus: bilateral, at origins, above the scapula spine near the medial border. Second rib: bilateral, at 2nd costochondral junctions. Lateral epicondyle: bilateral, 2 cm distal to the epicondyles. Gluteal: bilateral, in upper outer quadrants of buttocks in anterior fold of muscle. Greater trochanter: bilateral, posterior to the trochanteric prominence. Knee: bilateral, at the medial fat pad proximal to the joint line. 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;33:160-172. COMPANY LOGO Tender Point www.themegalllery.com COMPANY LOGO Tender Point www.themegalllery.com Control anatomic sites Thumbnail, mid forearm, forehead Processus styloideus on the right side In the middle of os sacrum Fold of the skin on the dorsal side of the right antebrachium Fold of the skin over m. gluteus maximum on the right side COMPANY LOGO What is Fibromyalgia? www.themegalllery.com Definition of fibromyalgia Chronic widespread pain with a reduced threshold for pain, generally identified by an increased sensitivity to pressure at particular points on the body Associated subjective symptoms such as fatigue, sleep disturbance, headache, migraine, variable bowel habits, diffuse abdominal pain, and urinary frequency. One third of patients experience significant minor depression or anxiety. COMPANY LOGO What is Fibromyalgia? www.themegalllery.com Tension/migraine headache Temporomandibular joint syndrome Regional musculoskeletal pain (e.g. chronic cervical or lumbar pain, “tendinosis”, repetitive strain syndrome, myofascial pain syndrome) Irritable bowel syndrome Chronic sinusitis Sicca symptoms, vasomotor rhinitis Non-cardiac chest pain, “Syndrome X”, costochondritis Biliary dyskinesia, postcholecystectomy syndrome Interstitial cystitis, female urethral syndrome, vulvar vestibulitis, vulvodynia COMPANY LOGO Pathogenesis www.themegalllery.com Increased nociception Deficiency of stage II/IV sleep – Alpha EEG NREM sleep anomaly Aberrant CNS function – Abnormalities in sensory processing – Hypothalamic-pituitary axis dysfunction – Autonomic dysfunction – Psychobehavioral factor Cytokines COMPANY LOGO The pain–brain–pain loop www.themegalllery.com OA, RA, Inflammation, Neuropathies, Injuries, Disc disorders, Visceral pain, Chronic headaches, TMJ, Spinal stenosis, Repetitive strain, Endometriosis, Myofascial pain peripheral tissues pain generators central spinal cord and brain sensitization COMPANY LOGO Altered central pain processing www.themegalllery.com Lower rCBF in the Thalamus and the Caudate Nucleus by SPECT Normal Control Fibromyalgia Mountz JM, et al, Arthritis Rheum 1995;38:926-38 COMPANY LOGO Altered central pain processing www.themegalllery.com fMRI Imaging Evidence of Augmented Pain Processing in Fibromyalgia Gracely RH, et al. Arthritis Rheum 2002;46:1333-43 COMPANY LOGO Altered central pain processing www.themegalllery.com Mean CSF levels of substance P in fibromyalgia 50 Normal FMS fmole/ml 40 Threefold higher concentrations of substance P in CSF of FM patients Low levels of norepinephrine and its metabolite, 3-methoy-4-hydroxy phenethylene, in CSF of FM patients 30 Low levels of serotonin and its precursor, 20 L-tryptophan, in the serum and low levels of the principal metabolite, 5-hydroxy 10 indoleacetic acid in CSF 0 Vaeroy Russell Welin Bradley COMPANY LOGO 섬유근통 증후군에 관한 설명 중 틀린 설명은? 1. 80-90%가 여성이며, 호발 연령은 25-55세이다. 2. 만성 근골격계의 증후군으로 미만성 통증과 압통점이 특징적이며 이럴 경우 NSAID와 steroid가 도움이 된다. 3. stage 4(non-REM) sleep 장애, serotonin의 결핍, 우울증 등이 이 질환과 관계 있다. 4. 주요 압통 부위는 thumbnail, forehead, distal dorsal forearm 등이 있다. 가. 1,2,3 나. 1,3 다. 2,4 라. 4 마. 1,2,3,4 58세 여자환자로 6개월 전부터 지속된 쇠약감과 전신적인 근육통을 주소로 내원하였다. 승모근, 늑골, 늑역골 관절, 내측 무릎 등에 대칭 적인 통점을 가지고 있었다. 환자는 류마티스 인자 및 항핵항체는 음 성이었고 적혈구 침강속도도 정상이었으며 기타 신경학적 검사에서 이상소견은 없었다. 상기 환자에 대한 설명 중 옳은 것은? 1. 주로 여자에게서 발생하며 대부분 연령은30-50대 이다. 2. 대부분의 환자들이 활동성의 정신의학적 질환을 가지고 있다. 3. 류마티스 관절염에 병발할 수 있다. 4. 특징적인 REM sleep의 장애를 동반한다. 가. 1,2,3 나. 1,3 다. 2,4 라. 4 마. 1,2,3,4 45세 여자가 수 년간 지속되는 전신 통증으로 왔다. 관절 의 압통과 종창은 없었고, 전신 근육에 압통점이 뚜렷하게 있었다. 류마티스 인자, 항핵항체는 음성이었고 갑상선 기 능검사는 정상이었으며 다른 특이소견은 없었다. 치료로 적절한 것은? 1. amitriptyline 2. 유산소운동 3. tramadol 4. prednisolone 가. 1,2,3 나. 1,3 다. 2,4 라. 4 마. 1,2,3,4 Management www.themegalllery.com Education Nonprogressive condition that is not causing damage or inflammation Not focusing on symptoms. All symptoms are from the same underlying condition. Existential crisis from denial, searching for ‘the cure’, to eventual acceptance Pharmacologic therapy Antidepressants (TCA, SSRI, SNRI, MAOI) Analgesics, sedative hypnotics, muscle relaxant Nonpharmacologic therapy Exercise, cognitive behavioral therapy COMPANY LOGO Pharmacologic therapy www.themegalllery.com Antidepressant: summary of randomized, controlled trials Class Compound(s) TCA Amitriptyline Clomipramine Doxepin SSRI SNRI MAOI Pharmacology 5-HT/NE reuptake inhibitor Cation channel blocker NMDA antagonist Anticholinergic Antihistaminergic Fluoxetine 5-HT reuptake inhibitor Citalopram 5-HT reuptake inhibitor Sertraline 5-HT reuptake inhibitor Venlafaxine 5-HT > NE reuptake inhibitor Milnacipran NE > 5-HT reuptake inhibitor NMDA antagonist MoclobemideReversible, MAO inhibitor Pirlindole Reversible, MAO inhibitor Pain Sleep Fatigue Mood Treating other FSS + + + - IBS TMJD CLBP? CTTH prophylaxis + + + + + - + + + + + CTTH prophylaxis CTTH prophylaxis CTTH prophylaxis CTTH prophylaxis + + + - + + CTTH prophylaxis, CFS CTTH prophylaxis COMPANY LOGO Pharmacologic therapy www.themegalllery.com Summary of randomized, controlled trials Class Compound(s) Muscle relaxant Cyclobenzaprine 5-HT2 antagonist + Anticholinergic Antihistaminergic Pregabalin Ca channel blocker + Zopiclone BZ receptor agonist Zolpidem Ibuprofen Nonspecific COX inhibitor Naproxen Morphine (IV) Mu agonist Tramadol Mu agonist + 5-HT/NE reuptake inhibitor Tropisetron 5-HT3 antagonist + Growth hormone Growth hormone + Anti-epileptics Sedative Hypnotics NSAIDs Opiates Other Pharmacology Pain Sleep Fatigue Mood + +/- + + + - - - - - + + Other FSS IBS CLBP TMJD CTTH CLBP IBS? + COMPANY LOGO Pharmacologic therapy www.themegalllery.com Antidepressant – rationale Alpha-delta NREM sleep abnormality mediated by an abnormality in central serotonergic neurotransmission Personal and family history of depression in FM patients TCA studies on chronic pain syndromes Antidepressant – mechanism Increase neurotransmission mediated by the monoamine neurotransmitters, particularly serotonin (5-HT) and/or norepinephrine (NE) COMPANY LOGO Pharmacologic therapy www.themegalllery.com Treatment of Fibromyalgia with Tricyclic Antidepressants: A Meta-Analysis 9% 11.6 10.6 rating scale 12 treatment mean* placebo mean* 10 8 6 5.0 23% 6.5 26% 14% 5.8 5.8 4.3 4 5.0 18% 6.5 5.2 2 0 fatigue trigger points pain symptoms sleep wellbeing O’Malley PG, et al. J Gen Intern Med 2000;15:659 COMPANY LOGO Pharmacologic therapy www.themegalllery.com Effect Size (Standard Deviations) TCA Treatment of Fibromyalgia: A Meta-Analysis 1.5 1.0 0.5 0.0 -0.5 Patient M.D. Global Global AssessmentAssessment Pain Fatigue Sleep Tenderness Stiffness Outcome Measure Arnold LM, et al. Psychosomatics 2000;41:104 COMPANY LOGO Pharmacologic therapy www.themegalllery.com Recommendations 1. Start with amitriptyline at a dose 5 mg 1-2h before bedtime. The dose can be gradually increased to a maximum of 50 mg/day 2. If these are ineffective, institute trials of SSRI such as fluoxetine. 3. Consider the combination of SSRI and low dose TCA. 4. If ineffective, substitute SNRI such as venlafaxine for SSRI. 5. For insomnia in patients intolerant of TCA, bedtime doses of zolpidem and zopiclone may be of benefit. 6. For pain control, use the tramadol. Limit the use of antiinflammatory agents, narcotic analgesics, and muscle relaxants. COMPANY LOGO 45세 여자가 수 년간 지속되는 전신 통증으로 왔다. 관절 의 압통과 종창은 없었고, 전신 근육에 압통점이 뚜렷하게 있었다. 류마티스 인자, 항핵항체는 음성이었고 갑상선 기 능검사는 정상이었으며 다른 특이소견은 없었다. 치료로 적절한 것은? 1. amitriptyline 2. 유산소운동 3. tramadol 4. prednisolone 가. 1,2,3 나. 1,3 다. 2,4 라. 4 마. 1,2,3,4 35세 여자 환자가 전신통증과 피로감을 주소로 내원하였다. 평소 에 만성 근육통과 수면장애가 있었다. 목, 어깨, 하지에 걸치는 전 신적인 통증이 있었고 약간의 움직임에도 악화되었다. 신체검사 에서 뒷목, 양어깨, 허리, 무릎에 대칭적인 압통점이 있었으나 방 사선 검사에서 이상소견은 관찰되지 않았다. 항핵항체와 류마티 스 인자는 음성이었고 ESR은 10 mm/hr였다. 이 환자에서 적절하 지 않은 치료는? 1. 2. 3. 4. 5. 유산소운동 cyclobenzaprine prednisolone tricyclic antidepressants zolpidem 삼환계 항우울제와 플루옥세틴(fluoxetine)으로 증상이 조 절되지 않는 섬유근통 환자에서 다음 단계로 투여해 볼 수 있는 약제로 옳은 것은? 1. 플루옥세틴 대신 벤라팍신(venlafaxine)을 투여한다. 2. 트라마돌(tramadol)을 추가한다. 3. 플루옥세틴을 둘록세틴(duloxetine)으로 교체한다. 4. 저용량의 프레드니솔론을 추가한다. 가. 1,2,3 나. 1,3 다. 2,4 라. 4 마. 1,2,3,4 손목굴증후군 (carpal tunnel syndrome)을 진단하기 위한 신 체검사 두 가지는? 답) Tinel's sign과 Phalen's sign Tinel’s sign percussion of median nerve at the flexor retinaculum (just radial to the palmaris longus tendon at the distal wrist crease) produces paresthesia in the median nerve distribution: thumb, index and middle fingers and the radial half of the ring finger Phalen’s sign sustained palmar flexion of the wrist for 30-60 seconds induces finger paresthesia 다음 사진에서 보이는 검사는 어떤 질병을 진단하기 위한 것인가? 답) de Quervain's tenosynovitis de Quervain’s stenosing tenosynovitis tenosynovitis of abductor pollicis longus and extensor pollicis brevis Finkelstein test passive ulnar deviation of the wrist with the fingers flexed over the thumb placed in the palm 50세 여자가 왼쪽 어깨관절의 통증을 주소로 내원하였다. 환자는 3개월 전부터 왼쪽 어깨의 통증을 느끼기 시작했 으며 최근 들어서는 왼쪽으로는 누워 자기가 힘들 정도로 통증이 심하다고 하였다. 과거력상 당뇨는 없었고 신체검 사에서 왼쪽 어깨의 수동 능동 운동 모두에 제한이 있었고 X선 촬영에서 뚜렷한 이상 소견은 발견되지 않았다. 상기 환자의 가능한 진단은? 답) 유착관절낭염 (adhesive capsulitis) Differential Diagnosis of Shoulder Pain Diagnosis Age Type of Location Night Active onset of pain pain ROM Passive Impinge Radia Pares- Weak- InstaRadio- Special ROM ment -tion thesia ness bility graphic features sign changes Rotator cuff Any Acute or Deltoid + ↓↓ Normal +++ Only due Look for In chronic Painful arc of tendinitis chronic region guarding to pain cases abduction Rototor cuff Over Often Deltoid ++ ↓↓↓ Normal ++ ++ + Wasting of tears (chronic) 40 yr chronic region cuff muscles Bicipital Any Overuse Anterior ↓ Normal + Only due Look for None Speed test ± tendinitis guarding to pain Yergason test Calcific tendinitis 30- Acute Point of ++ ↓↓↓ Normal +++ Only due ++ Tenderness 60 yr shoulder guarding to pain ++ Adhesive Over Insidious Deep in ++ ↓↓ ↓↓ + Global ROM↓ capsulitis 40 yr shoulder Acromioclavicular Any Acute or Over Lying ↓full Normal In chronic Local joint chronic joint on elevation cases tenderness side Osteoarthritis of Over Insidious Deep in ++ ↓↓ ↓↓ May have +++ Crepitus glenohumoral jt. 40 yr shoulder mild Glenohumoral <25 Episodic Ant. or Only Only Possible + with + with +++ Often Stress test instability yr post. appre- appreacute acute hension hension episode episode Cervical Over Insidious Supra- Often Normal Normal ++ +++ + Cervical Pain with spondylosis 40 yr scapular spine neck movement Thoracic outlet Any Usually Neck Normal Normal ++ ++ ++ syndrome with shoulder activity arm 55세 여자가 6개월 전부터 서서히 진행하는 우측 어깨의 통증과 운동 장애를 주소로 내원하였다. 신체검사에서 부종이나 종창, 발 적은 동반되지 않았으나 환자 스스로 우측 어깨를 모든 방향으로 움직일 수 없었으며 검사자의 도움으로도 비슷한 정도의 운동 장 애를 보였다. 방사선 촬영에서는 우측 어깨 관절 주위의 골감소 이 외에 특이 소견은 없었다. 이 환자에 맞는 소견은? 1. 관절의 진행성 미란을 동반한다. 2. 당뇨병, 갑상선 질환, 폐질환에 동반되기도 한다. 3. 진단을 위해 관절경 검사가 필수적이다. 4. 관절강내 코르티코스테로이드 주사가 증상 개선에 도움이 된다. 가. 1,2,3 나. 1,3 다. 2,4 라. 4 마. 1,2,3,4