안재영가톨릭대학교의과대학신경과교실 Diagnosis and Treatment of Fibromyalgia Jae Young An Department of Neurology, College of Medicine, The Catholic University of Korea, Suwon, Korea Fibromyalgia is characterized by chronic widespread pain and is often accompanied by one or more concomitant symptoms including fatigue, sleep disturbances, cognitive dysfunction, and mood disorder. Fibromyalgia is widely accepted as a true syndrome with pathogenesis centered in the nervous system and abnormalities shown in pain regulating mechanisms at various levels of the central and peripheral nervous systems. Fibromyalgia was recognized with the publication of the American College of Rheumatology classification criteria in 1990, which were remodeled in 2010. New diagnostic criteria do not require the presence of tender points. Ideal treatment is a multimodal approach combining nonpharmacologic and pharmacologic treatments, with the understanding that fibromyalgia symptoms fluctuate over time and seldom completely disappear. Key Words: Fibromyalgia; Pathogenesis; Diagnostic criteria; Treatment 서론 역학연구에따르면전체인구의 10% 정도에서만성통증을호소하고있으며, 1 섬유근육통환자는1990 년미국류마티스학회 (American College of Rheumatology, ACR) 의분류기준을적용한역학연구에서는 2% 정도로비교적흔한질환이다. 2 이질환은선진국에서더흔한질환이아니라, 후진국이나, 도시농촌간, 도시내에서도빈부에따른지역별유병율은차이가없는것으로알려져있다. 2-4 섬유근육통은 1904년 Gowers 에의해전신적인통증을근육과주위결합조직의염증에의한것으로 섬유조직염 (fibrositis) 이란용어로기술되면서의학적으로처음알려지게되었다. 5 하지만이후여러연구에서염증변화는없는것으로확인되었다. 6 1947년 Boland 는섬유근육통을불안과우울증이 Jae Young An Department of Neurology, College of Medicine, The Catholic University of Korea, St. Vincent s Hospital, 93-6 Ji-dong, Paldal-gu, Suwon 442-723, Korea TEL: +82-31-249-8316 FAX: +82-31-243-0306 E-mail: nrjyan@gmail.com 연관된심인성질환으로생각하고 psychogenic rheumatism 이란용어를사용하였다. 7 하지만섬유근육통이일부우울증환자에서발생할수있어도대부분정신적으로건강한환자에서발생하며, 만성전신통증에동반되어불안, 우울과같은정신증상이발생한다는사실과정신증상이없는섬유근육통환자들이더많다는사실을고려해볼때정신질환과구별되는하나의독립된질환으로보고, 섬유근육통이신체형장애의증상과서로중복될수도있다고보는것이적절하겠다. 8 섬유근육통에대해하나의통일된분류기준을제안하여연구에많은기여를한 1990 년 ACR 의분류기준이제시된지 20년만인 2010년 5월개정됨으로써진료와연구에새로운국면을맞이하고있다. 9,10 본종설에서는섬유근육통의병태생리, 임상증상및진단과치료에대해기술하고자한다. 본론 1. 병태생리 섬유근육통의증상과병태생리는과민대장증후군, 간질설 48 2014 년대한신경과학회제 33 차학술대회 - 강의록 -
방광염 / 방광통증증후군 (interstitial cystitis/painful bladder syndrome), 만성골반통 (chronic pelvic pain) 과악관절장애 (temporomandibular joint disorders) 와같은중추성통증또는기능성신체장애뿐아니라우울증과불안장애와같은정신질환과도공통점이있다. 11,12 1) 스트레스 섬유근육통은다양한스트레스에의해유발될수있으나연관관계는단순하지않다. 일부인구집단연구에서는상당한정신적인스트레스를받은사람이그다음해에만성전신통증이발생할확률은대략 2배라고하지만, 13,14 새로이진단된섬유근육통환자의상당수는이전에스트레스와관련된증상을가지고있지않다는점을볼때정신적인스트레스는상대적인위험은높지만절대적인위험도는낮다고볼수있다. 정신적인스트레스외에도생물학적스트레스도섬유근육통발생과연관성이있다. 특정감염 (Lyme disease, Epstein-Barr virus, parvovirus or Q fever) 에걸린환자의 5-10% 에서만성전신통증이발생하고, 수술적치료, 군복무중당한부상과교통사고에서입은신체손상에의해섬유근육통이나만성국소통증이발생한다는보고들이있다. 15-18 스트레스와섬유근육통발생관계로인해많은스트레스시스템에관한연구가이루어졌고, 연구마다결과는다르지만일반적으로시상하부-뇌하수체-부신축 (hypothalamic-pituitaryadrenal axis) 과교감신경계의이상이보고되고있다. 19,20 2) 중추통증전달기전및중추신경전달물질 현재가장확립된원인으로받아들여지고있는것은중추감작 (central sensitization) 과비정상적인감각처리과정에의해통증역치가저하되어나타나는것으로생각하고있다. 실제섬유근육통환자는거의모든종류의통증에대해과민반응을보이고, 청각과시각적인자극에있어서도더민감한반응을보이고있어통증처리과정의특정문제가아니라감각처리과정에서전반적인문제가있을것으로도생각되고있다. 21-23 광범위유해억제조절 (diffuse noxious inhibitory control, DNIC) 효과로정상인에서심한통증자극을주게되면자극부위에서떨어진신체부위에서도통증역치가증가하게되는데, DNIC 효과는섬유근육통환자와다른만성통증질환에서약화되어있다. 24 DNIC는뇌간에서척수로이어지는하행통증조절경로 (descending pain inhibitory pathway) 를통해서일어나며, 이시스템은앞띠다발피질 (anterior cingulate cortex), 편도 (amygdala), 전두극피질 (frontopolar cortex) 과같은다양한전뇌 (forebrain) 구조물에영향을받는다. 25 섬유근육통환자에서기능적 MRI를이용한연구에서도통증처리와부위에서증가된신경활성을보이고있어, 26,27 섬유근육통환자는전뇌에서구조적, 형태학적변화가일어나고있다는것을시사하고있다. 섬유근육통환자의뇌척수액에서통증전달을촉진시키는신경전달물질인 substance P, 글루탄산염, 신경성장인자 (nerve growth factor) 가증가되어있고, 통증을억제하는세로토닌, 노르에피네프린, 도파민은감소되어있었다. 28-30 역설적으로내인성아편유사물질인엔케팔린이섬유근육통환자에서증가되어있다. 31 이것은섬유근육통환자의대뇌측좌핵 (nucleus accumbens) 과띠이랑 (cingulate gyrus) 에서의뮤-아편유사제 (μopioid) 수용체의가용성이감소되어있는 PET 연구결과와연관성이있으며, 32 아편유사제수용체의기준점유율이증가되어있다는것을반영하고있다. 증가된엔케팔린은섬유근육통환자에서통증을조절하기위한과정의결과로추정되며, 섬유근육통환자에서마약성진통제의효과가적은원인중하나로생각된다. 3) 유전학적증거 섬유근육통의가족적소인은알려진현상이다. 섬유근육통환자의일촌관계가족에서는섬유근육통의발생위험이 8배나높은것으로보고되고있고다른종류의만성통증이나정신질환유병율도높은것으로보고되고있다. 33 쌍둥이연구에따르면유전적요소가섬유근육통의발생위험도에서 50% 정도는영향을끼치는것으로보고있다. 34 이러한유전적요소는 catecholamineo-methyl-transferase (COMT), GTP cyclohydroxylase, 다양한나트륨통로, 칼륨통로를부호화하는유전자들의다형태 (polymorphism) 가보고되고있다. 35-38 2. 임상증상 1) 만성전신통증 만성통증은침범부위에따라만성국소통증 (chronic regional pain) 과만성전신통증 (chronic widespread pain) 으로분류되는데만성전신통증은신체의좌, 우측부위와허리를기준으로상하부위에서 3개월이상지속되는통증을말한다. 8 통증은흔히옮겨다니기도하며, 통증의강도는기복 (wax and wane) 이있다. 이상감각또는감각이상이동반될수 2014 년대한신경과학회제 33 차학술대회 - 강의록 - 49
안재영 있으며, 무감각, 저림, 작열감과같은신경통증같은양상을보이기도한다. 39 그외에도섬유근육통환자는만성두통, 인후통, 내장통증을호소하기도하며, 밝은빛이나소리, 냄새에도과민반응을보이기도한다. 40 2) 피로감 / 수면장애 / 인지기능장애 피로감은통증과함께가장흔한증상중하나로보고되어있고, 수면장애도섬유근육통환자의 76-96% 에서나타나고있다. 10,41 잠을자도잔것같지않고항상피곤하거나상쾌하지않고, 잠에서일찍깬다고호소한다. 전체섬유근육통환자의 70-90% 에서인지기능장애를보인다. 작업기억, 언어 42 유창성, 삽화적기억에서두드러진저하가발견된다. 43 이런증상등은적절한섬유근육통치료로통증이호전됨에따라같이호전되는경우가많다. 40 3. 진단 섬유근육통은비교적흔한질환임에도진단에까지평균 5년이걸리고전체환자의 25% 만이진단되고있어진단그자체만으로도환자에게긍정적인효과를가져올수있다. 44 섬유근육통 이라는용어는 1976년 Hench 에의해만성통 증이있고다양한검사에서이상소견이없을때섬유근육통으로진단할수있다고하였다. 45 이것은일종의배제기준으로용인 (rule in) 기준으로서최초는 1977년 Smythe 와 Moldofsky 의진단기준이다. 만성통증, 수면장애, 조조강직, 피로와같은증상이있으면서 14군데압통점가운데 12 군데이상에서압통을호소할때진단할수있다. 46 여기에서언급된 14군데압통점은 1990년 ACR의분류기준에있는 18군데의압통점과거의일치하고수면장애를섬유근육통환자의주요증상으로인식해서진단기준에포함시켰다는점에의미가있다. Smythe 는 1979년에진단기준을수정하여 3개월이상지속되는통증을만성통증으로정의하였고, ESR, SGOT, RF, ANA, 근육효소검사와엉치엉덩이관절 X-ray 검사가정상이어야하는기준을추가하였다. 47 하지만이것은개발자의경험에의지하여만들어진진단기준으로이후 1981 년 Yunus 등이섬유근육통환자들과대조군을비교한진단기준이발표되었다. 50명의섬유근육통환자와나이, 성별이일치한 50명의정상대조군을비교하여통증, 피로, 수면장애, 압통점의빈도가환자군에서유의하게높고, 주관적인부종, 감각이상, 과민대장증후군, 긴장형두통, 편두통도환자군에서높은빈도를보인다고하였다. 48 Table 1. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia * 1. History of chronic widespread pain Definition. Pain is considered widespread when all of the following are present: pain in the left side of the body, pain in the right side of the body, pain above the waist, and pain below the waist. In addition, axial skeletal pain (cervical spine or anterior chest or thoracic spine or low back) must be present. In this definition, shoulder and buttock pain is considered as pain for each involved side. "Low back" pain is considered lower segment pain. 2. Pain in 11 of 18 tender point sites on digital palpation Definition. Pain, on digital palpation, must be present in at least 11 of the following 18 sites: 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 the second costochondral junctions, just lateral to the junctions on upper surfaces. 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. Digital palpation should be performed with an approximate force of 4 kg. For a tender point to be considered "positive" the subject must state that the palpation was painful. "Tender is not to be considered "painful." * For classification purposes, patients are considered to have fibromyalgia if both criteria are satisfied. Widespread pain must have been present for at least 3 months. The presence of a second clinical disorder does not exclude the diagnosis of fibromyalgia (Arthritis Rheum 1995;38:19-28). 50 2014 년대한신경과학회제 33 차학술대회 - 강의록 -
1990년 ACR 분류기준이나오기전까지가장널리사용된진단기준이었다. 48 섬유근육통은 ACR에서 1990년새로운분류기준 (Table 1) 을제시하면서섬유근육통의역학, 병태생리, 치료전반에걸친연구가비약적인발전을하게되었다. 이분류기준은 293명의섬유근육통환자와나이, 성별이일치하면서다양 한류마티스질환을가진 265명의대조군을대상으로개발된것으로 3개월이상지속되는만성전신통증이있으면서 18군데의압통점중 11곳이상에서압통을호소할때진단할수있으며, 88.4% 의민감도와 81.1% 의특이도를보였다. 10 하지만이분류기준은진단기준이아니라는것과만성전신통증이있는환자중심한상태의환자를섬유근육 Table 2. The 2010 American College of Rheumatology diagnostic criteria Criteria A patient satisfies diagnostic criteria for fibromyalgia if the following 3 conditions are met: 1. Widespread pain index (WPI) 7 and symptom severity (SS) scale score 5 or WPI 3-6 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. Ascertainment 1. WPI: note the number areas in which the patient has had pain over the last week. In how many areas has the patient had pain? Score will be between 0 and 19. Shoulder girdle, left; Hip (buttock, trochanter), left; Jaw, left; Upper back Shoulder girdle, right; Hip (buttock, trochanter), right; Jaw, right; Lower back Upper arm, left; Upper leg, left; Chest; Neck Upper arm, right; Upper leg, right; Abdomen Lower arm, left; Lower leg, left Lower arm, right; Lower leg, right 2. SS scale score: Fatigue Waking unrefreshed Cognitive symptoms For the each of the 3 symptoms above, indicate the level of severity over the past week using the following scale: 0=no problem 1=slight or mild problems, generally mild or intermittent 2=moderate, considerable problems, often present and/or at a moderate level 3=severe: pervasive, continuous, life-disturbing problems Considering somatic symptoms in general, indicate whether the patient has: * 0=no symptoms 1=few symptoms 2=a moderate number of symptoms 3=a great deal of symptoms The SS scale score is the sum of the severity of the 3 symptoms (fatigue, waking unrefreshed, cognitive symptoms) plus the extent (severity) of somatic symptoms in general. The final score is between 0 and 12. * Somatic symptoms that may be considered include muscle pain, irritable bowel syndrome, fatigue/tiredness, thinking or remembering problems, 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, Raynaud s 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 (Arthritis Care & Research 2010; 62:600-610). 2014 년대한신경과학회제 33 차학술대회 - 강의록 - 51
안재영 통으로분류하였다는것, 나머지만성전신통증환자에대해서는어떻게접근을해야하는지구체적인지침이없다는점에서문제가제기되고있었다. 특히압통점검사는근육자체에문제가있어섬유근육통이발생하는것처럼비쳐질수있다는점에서압통점검사의필요성에대해서의문이제기되어왔다. 현실적으로일차진료에서거의시행되지않고더욱이일차진료의사들이압통점검사하는방법을잘모른다는데에문제점이있다. 그리고 1990년진단기준에서는수면장애, 피로, 인지문제와신체증상의중요성이빠져있다. 이런문제점들을개선시키기위해 2010년새로운진단기준을발표하였다 (Table 2). 49 새로운진단기준은최소한 3개월동안통증과신체증상이지속되고이러한통증을설명할만한다른질환이없는경우전신통증지수 (widespread pain index, WPI) 와증상중증도척도 (symptom severity scale) 를통해진단이이루어져압통점검사없이설문만으로도진단이가능하게되고다양한임상증상들을진단기준에포함시키게됨에따라상당수의만성전신통증환자들을섬유근육통으로진단할수있게되었다. WPI는신체를 19 군데로구분하여통증부위를수치로계산하는것이고, 증상중증도척도점수는피로, 상쾌하지않은각성 (waking unrefreshed), 인지증상, 그리고일반적인신체증상의정도를 3 점척도로평가해서 WPI와증상중증도의최대점수는각각 19점과 12점이다. WPI는직접면담을통해표시하는것이가장바람직하며, 여의치않을경우환자에게체크리스트또는그림을통해표시하도록하고증상중증도척도는설문지가아니라직접면담을한후평가한다. 섬유근육통으로진단하기위해서는 WPI가 7점이상이면서증상중증도가 5 점이상이거나 WPI가 3-6점사이인경우에는증상중등도가 9점이상이어야한다. 이새로운기준은개발자가강조한대로 1990년분류기준을대체하기위한것이아니라일차진료의사들이쉽게섬유근육통을진단할수있게위해만든것이어서몇가지문제점들을가지고있다. 8 첫째, 여전히통증역치를객관적으로평가할수있는압통점검사의필요성을제기하는의견이있고, 50 환자의증상에초점을맞추었기때문에질환의상태 (state) 보다는특성 (trait) 을충분히반영했다고보기어렵다. 둘째로이전 1990년기준의소요시간이 1분이내에비해최소 5분에서 10분이상걸린다는점이다. 셋째, 전신성홍반성루푸스, 류마티스관절염, 특히근막통증증후군과의감별이어렵다. 더욱이이전 1990년기준과달리일정점수이상의 WPI와증상중증도가있으면서다른질환이없어야섬유근육통을진단할수있는데다 른류마티스질환과동반되어있으면서치료에있어원발성과차이가없는이차성섬유근육통을진단할수없는경우가생겨동반질환이있는경우진단을어렵게하는단점이있다. 넷째, 2010년진단기준으로많게는 9.1% 의유병율을나타내는것으로보고되어이전분류기준에비해 4배이상의증가를보인다. 이것은진단기준에따라다른환자군이정의되고여기에따른임상증상, 치료, 예후에대한결과가달라질가능성이높다. 4. 검사섬유근육통증후군진단에많은검사실검사나영상검사가필요하지않다. 검사는섬유근육통을유발하는다른질환을감별하기위해전혈구계산 (complete blood count), 적혈구침강속도 (erythrocyte sedimentation rate), C 반응단백질 (C-reactive protein) 을우선확인한다. 갑상선질환이나염증근육질환이의심되는환자에서갑상선기능검사와크레아틴키나제 (creatine kinse) 검사가각각필요하며비타민 D 수치검사는일부환자에서는도움이될수도있다. 하지만자가항체와같은혈청검사는병력과신체검사에서자가면역질환이의심될경우에시행한다. 항핵항체 (antineuclear antibody) 나류마티스인자 (rheumatoid factor) 와같은경우정상인에서도양성을보일수있기때문이다. 51 섬유근육통이있는모든환자는자세한병력을통해일차수면장애나정동장애가동반되어있는지확인할필요가있다. 섬유근육통환자중최소 1/3에서진단당시에정동장애가있으므로우울증과불안증증상에대한문진이꼭필요하다. 또한수면무호흡과수면중주기사지운동장애가있는지알아보고의심되면수면다원검사를고려할수있다. 섬유근육통증후군환자에서자율신경계장애가알려져있으나혈압과심박확인이외에다른적당한선별검사가없으며자율신경계장애가의심되는환자는틸트테이블검사 (Tilt-table test) 와같은객관적인검사가필요하다. 5. 치료섬유근육통치료는증상을완화시키는것이주목적으로약물치료와비약물치료로나뉘고, 특히환자스스로적극적으로치료에협조적이지않다면단순한약물치료만으로는의미있는증상개선이어렵다. 먼저환자에게섬유근육통에대한이해를시키는교육이중요하다. 다른류마티스질환과달리관절이변형되거나진행하지않는다는사실을주지시키고잘못된소문이나인터넷의내용을따라잘못된치 52 2014 년대한신경과학회제 33 차학술대회 - 강의록 -
료를하지않도록해야한다. 특히정신적인요인이섬유근육통의발생과관련이있을수있고우울과불안이동반될수있지만정신질환은아니라는사실을알려줄필요가있다. 8 6. 약물적치료 섬유근육통에서통증을억제하는신경전달물질인세로토닌과노르에피네프린이감소되어있고, 통증전달물질인 substance P가뇌척수액에서증가되어있어, 28-30 약물치료도이런발병기전에맞춰약제를사용한다. 세로토닌과노르에피네프린의농도를증가시키는약제들은항우울제로사용하고있는약물로삼환계약물 (tricyclic agents), 선택적세로토닌재흡수억제제 (selective serotonin reuptake inhibitor, SSRI), 세로토닌-노르에피네프린재흡수억제제 (serotonin-norepinephrine reuptake inhibitor, SNRI) 가있다. SSRI로는 fluoxetine, citalopram, paroxetine 등이있고이들약제가운데가장효과적인것은 fluoxetine 이다. 52 효과에서 SSRI 제제들사이에차이가나는이유로는세로토닌이시냅스후신경말단에서는통증을억제시키지만시냅스전신경말단에서는오히려통증을유발시키기때문에 SSRI 가운데노르에피네프린에전혀영향을미치지않는 citalopram 보다는어느정도노르에피네프린을증가시켜주는 fluoxetine 이더효과적이라고할수있다. SSRI는저녁에복용을하는경우불면증을일으킬수있기때문에가급적오전에복용을해야한다. SSRI에효과가충분치않는경우에는 duloxetine, milnacipran, venlafaxine과같은 SNRI로교체할수있다. SNRI 가운데 duloxetine, milnacipran 이환자-대조군연구에서섬유근육통증상이의미있게호전되어각각 2008년, 2009년에 FDA 승인을받았다. 이런항우울제약물들은항우울증작용을통한간접적인효과가아니라통증전달경로에직접작용하여통증이조절되었다는연구결과를보이고있다. 53,54 SSRI, SNRI 약제이외아편유사작용제인 tramadol도세로토닌과노르에피네프린의재흡수를억제하는효과를가지고있어이중맹검교차시험과무작위대조시험에서도통증완화효과가보고되었고, 55 acetaminophen과 tramadol을병합한제제도위약에비해섬유근육통의여러증상들을의미있게개선시켰다. 56 tramadol은삼환계항우울제, SSRI, SNRI 등에조절되지않는통증이있는경우이들약제에추가해서사용해볼수있다. Substance P와같은통증전달물질들을억제시켜통증을 개선시키는약제로 2007년 FDA 승인을받은 pregabalin 이있다. Pregabalin 은 α2-δ ligand 로칼슘전압작동통로 (voltagegated calcium channel) 의보조단백인 α2-δ에결합하여신경말단에서칼슘의유입을차단해서 substance P와글루탐산염같은통증을유발하는신경전달물질의분비가억제되고이러한기전에의해진통, 항경련작용을나타내는것으로알려져있다. 다기관무작위대조시험에서 pregabalin 이위약에비해통증을유의하게감소시키고피로, 수면등을현저하게개선시키는것으로나타났다. 57,58 섬유근육통환자에서통증이외의다른증상들을개선시키기위해여러가지약제들을추가적으로사용해볼수있다. 심한피로를호소하는경우에는 modafinil 과 methylphenidate 가도움이될수있고불면증에서는 zolpidem 과 zopiclone 이, 뻣뻣함에는 cyclobenzaprine 과 tizanidine, 두근거림, 기립성저혈압과같은자율신경기능장애가있는경우에는저용량의베타차단제가효과적일수있다. 하지만글루코코르티코이드와아편성진통제의사용은결코바람직하지않다. 7. 비약물치료 효과가가장입증된비약물치료는교육, 인지행동치료, 운동이다. 이세가지모두섬유근육통치료효과에서있어서 level 1A 근거수준을가진다. 40 경우에따라비약물치료의효과는약물치료보다더효과적일수있다. 운동은수중운동과육상운동모두효과적이고저강도또는중등도의강도로일주일에 2-3회최소 4주이상지속해야효과가있다. 이것은운동을중단하게되면통증감소효과는바로사라지기때문이다. 운동이섬유근육통의치료에도움이된다고해서환자의상태를고려하지않고처음부터운동을하도록하는것은오히려해가될수있기때문에환자의상태를고려하여통증이심한경우에는약물치료로증상을어느정도호전시킨후에시작할수있도록한다. 인지행동치료는조작조건화와관찰학습을통해행동을바꾸게하는기법으로우울감과자기효능감을의미있게개선시킨다. 59 하지만통증, 피로, 수면, 삶의질과같은섬유근육통의주된증상들은개선시키지를못하기때문에주된치료방법으로활용하기에는한계가있다. 보완의학적인치료방법가운데메타분석이가능할정도로충분히연구가이루어진것들로는침술, 지압요법, 동종요법, 수치료, 마사지가있다. 60 이가운데지압요법은메타분석에서효과가없는것으로되어있고나머지침술, 동종요법, 수치료, 마사지는효과가미미하고잘짜인무작위대 2014 년대한신경과학회제 33 차학술대회 - 강의록 - 53
안재영 조군연구가많지않아적극적으로권장하기에는어려움이있다. 결론 섬유근육통은여러가지증상으로이루어진다증상증후군의일종으로유전적소인과통증조절기전의문제로발생하는질병으로여겨지고있다. 광범위한검사나특별한전문과의진료없이도자세한병력과신체검진으로진단할수있다. 그리고진단자체와질병의경과에대한설명만으로도환자의삶의질이개선되고불필요한의료비용을감소시킬수있다. 섬유근육통진단에있어서 1990년 ACR 분류기준은역학, 병태생리, 치료전반에많은영향을끼쳤지만제한점이있어개선하기위해새로이개정된 2010년진단기준은압통점검사없이설문만으로도진단할수있어만성전신통증을호소하는상당수의환자를진단할수있게되어큰의미가있다. 하지만여전히문제점들을가지고있어추가적인연구가필요하겠다. 치료에있어서약물치료만으로는효과가제한적이기때문에동시에비약물치료에도환자가적극적으로참여할수있도록해야효과가지속적이고극대화할수있다. References 1. Croft P, Rigby AS, Boswell R, Schollum J, Silman A. The prevalence of chronic widespread pain in the general population. J Rheumatol 1993;20:710-713. 2. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995;38:19-28. 3. Haq SA, Darmawan J, Islam MN, Uddin MZ, Das BB, Rahman F, et al. Prevalence of rheumatic diseases and associated outcomes in rural and urban communities in Bangladesh: a COPCORD study. J Rheumatol 2005;32:348-353. 4. Vincent A, Lahr BD, Wolfe F, Clauw DJ, Whipple MO, Oh TH, et al. Prevalence of fibromyalgia: a population-based study in Olmsted County, Minnesota, utilizing the Rochester Epidemiology Project. Arthritis Care Res (Hoboken) 2013;65:786-792. 5.Gowers WR. A Lecture on Lumbago: Its Lessons and Analogues: Delivered at the National Hospital for the Paralysed and Epileptic. Br Med J 1904;1:117-121. 6. Williams DA, Clauw DJ. Understanding fibromyalgia: lessons from the broader pain research community. J Pain 2009;10:777-791. 7. Boland EW. Psychogenic rheumatism; the musculoskeletal expression of psychoneurosis. Ann Rheum Dis 1947;6:195-203. 8. Lee S. Diagnosis and treatment of fibromyalgia syndrome. Korean J Med 2013;84:650-658. 9.Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010;62:600-610. 10. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, 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. 11. Dadabhoy D, Clauw DJ. Therapy Insight: fibromyalgia-a different type of pain needing a different type of treatment. Nat Clin Pract Rheumatol 2006;2:364-372. 12.Hauser W, Turp JC, Lempa M, Wesselmann U, Derra C. [Functional somatic pain syndromes-nomenclature]. Schmerz 2004;18:98-103. 13. McBeth J, Macfarlane GJ, Benjamin S, Morris S, Silman AJ. The association between tender points, psychological distress, and adverse childhood experiences: a community-based study. Arthritis Rheum 1999;42:1397-1404. 14. Papageorgiou AC, Silman AJ, Macfarlane GJ. Chronic widespread pain in the population: a seven year follow up study. Ann Rheum Dis 2002;61:1071-1074. 15. Clauw D. The health consequences of the first Gulf war. Bmj 2003;327:1357-1358. 16. Clauw DJ, Engel CC, Jr., Aronowitz R, Jones E, Kipen HM, Kroenke K, et al. Unexplained symptoms after terrorism and war: an expert consensus statement. J Occup Environ Med 2003;45:1040-1048. 17. Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. Bmj 2006;333:575. 18. White PD, Thomas JM, Amess J, Crawford DH, Grover SA, Kangro HO, et al. Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. Br J Psychiatry 1998;173:475-481. 19. Crofford LJ, Pillemer SR, Kalogeras KT, Cash JM, Michelson D, Kling MA, et al. Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. Arthritis Rheum 1994;37:1583-1592. 20. Adler GK, Kinsley BT, Hurwitz S, Mossey CJ, Goldenberg DL. Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome. Am J Med 1999;106:534-543. 21. Geisser ME, Casey KL, Brucksch CB, Ribbens CM, Appleton BB, Crofford LJ. Perception of noxious and innocuous heat stimulation among healthy women and women with fibromyalgia: association with mood, somatic focus, and catastrophizing. Pain 2003;102:243-250. 54 2014 년대한신경과학회제 33 차학술대회 - 강의록 -
22. Geisser ME, Glass JM, Rajcevska LD, Clauw DJ, Williams DA, Kileny PR, et al. A psychophysical study of auditory and pressure sensitivity in patients with fibromyalgia and healthy controls. J Pain 2008;9:417-422. 23. Giesecke T, Gracely RH, Grant MA, Nachemson A, Petzke F, Williams DA, et al. Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum 2004;50:613-623. 24. Lautenbacher S, Rollman GB. Possible deficiencies of pain modulation in fibromyalgia. Clin J Pain 1997;13:189-196. 25. Bingel U, Lorenz J, Schoell E, Weiller C, Buchel C. Mechanisms of placebo analgesia: racc recruitment of a subcortical antinociceptive network. Pain 2006;120:8-15. 26. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 2002;46:1333-1343. 27.Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH. Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol 2004;31:364-378. 28. Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum 1992;35: 550-556. 29. Giovengo SL, Russell IJ, Larson AA. Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia. J Rheumatol 1999;26:1564-1569. 30. Sarchielli P, Di Filippo M, Nardi K, Calabresi P. Sensitization, glutamate, and the link between migraine and fibromyalgia. Curr Pain Headache Rep 2007;11:343-351. 31. Baraniuk JN, Whalen G, Cunningham J, Clauw DJ. Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain. BMC Musculoskelet Disord 2004; 5:48. 32. Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci 2007;27:10000-10006. 33. Arnold LM, Hudson JI, Hess EV, Ware AE, Fritz DA, Auchenbach MB, et al. Family study of fibromyalgia. Arthritis Rheum 2004;50:944-952. 34. Kato K, Sullivan PF, Evengard B, Pedersen NL. A population-based twin study of functional somatic syndromes. Psychol Med 2009;39:497-505. 35. Amaya F, Wang H, Costigan M, Allchorne AJ, Hatcher JP, Egerton J, et al. The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci 2006;26:12852-12860. 36. Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, et al. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 2006;12:1269-1277. 37. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 2003;299: 1240-1243. 38. Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, et al. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron 2006;52:767-774. 39. Sumpton JE, Moulin DE. Fibromyalgia. Handb Clin Neurol 2014;119:513-527. 40. Clauw DJ. Fibromyalgia: a clinical review. Jama 2014;311: 1547-1555. 41. Bigatti SM, Hernandez AM, Cronan TA, Rand KL. Sleep disturbances in fibromyalgia syndrome: relationship to pain and depression. Arthritis Rheum 2008;59:961-967. 42. Katz RS, Heard AR, Mills M, Leavitt F. The prevalence and clinical impact of reported cognitive difficulties (fibrofog) in patients with rheumatic disease with and without fibromyalgia. J Clin Rheumatol 2004;10:53-58. 43. Park DC, Glass JM, Minear M, Crofford LJ. Cognitive function in fibromyalgia patients. Arthritis Rheum 2001;44:2125-2133. 44. White KP, Nielson WR, Harth M, Ostbye T, Speechley M. Does the label "fibromyalgia" alter health status, function, and health service utilization? A prospective, within-group comparison in a community cohort of adults with chronic widespread pain. Arthritis Rheum 2002;47:260-265. 45. PK H. Twenty-second rheumatism review. Review of the American and English literature for the years 1973 and 1974. Arthritis Rheum 1976;19:973-1223. 46. Smythe HA, Moldofsky H. Two contributions to understanding of the "fibrositis" syndrome. Bull Rheum Dis 1977; 28:928-931. 47.Smythe HA. Nonarticular rheumatism and the fibrositis syndrome. In: Hollander JL, McCarthy DJ, eds. Arthritis and Allied Conditions. 9th ed. Philadelphia: Lea & Febiger. 1979. 48. Yunus M, Masi AT, Calabro JJ, Miller KA, Feigenbaum SL. Primary fibromyalgia (fibrositis): clinical study of 50 patients with matched normal controls. Semin Arthritis Rheum 1981;11:151-171. 49. Fitzcharles MA, Boulos P. Inaccuracy in the diagnosis of fibromyalgia syndrome: analysis of referrals. Rheumatology (Oxford) 2003;42:263-267. 50. Vanderschueren S, Van Wambeke P, Morlion B. Fibromyalgia: do not give up the tender point count too easily: comment on the article by Wolfe et al. Arthritis Care Res (Hoboken) 2010;62:1675; author reply 1676-1678. 51. Tan EM, Feltkamp TE, Smolen JS, Butcher B, Dawkins R, Fritzler MJ, et al. Range of antinuclear antibodies in "healthy" individuals. Arthritis Rheum 1997;40:1601-1611. 52. Arnold LM, Hess EV, Hudson JI, Welge JA, Berno SE, Keck PE, Jr. A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia. Am J Med 2002;112:191-197. 53.Arnold LM, Lu Y, Crofford LJ, Wohlreich M, Detke MJ, 2014 년대한신경과학회제 33 차학술대회 - 강의록 - 55
안재영 Iyengar S, et al. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum 2004;50:2974-2984. 54. Vitton O, Gendreau M, Gendreau J, Kranzler J, Rao SG. A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia. Hum Psychopharmacol 2004;19 Suppl 1:S27-35. 55. Russell IJ, Kamin M, Bennett RM, Schnitzer TJ, Green JA, Katz WA. Efficacy of tramadol in treatment of pain in fibromyalgia. J Clin Rheumatol 2000;6:250-257. 56. Bennett RM, Kamin M, Karim R, Rosenthal N. Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Am J Med 2003;114:537-545. 57. Crofford LJ, Rowbotham MC, Mease PJ, Russell IJ, Dworkin RH, Corbin AE, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, doubleblind, placebo-controlled trial. Arthritis Rheum 2005;52: 1264-1273. 58. Arnold LM, Russell IJ, Diri EW, Duan WR, Young JP, Jr., Sharma U, et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain 2008;9:792-805. 59. Bernardy K, Fuber N, Kollner V, Hauser W. Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome - a systematic review and metaanalysis of randomized controlled trials. J Rheumatol 2010;37:1991-2005. 60. Terry R, Perry R, Ernst E. An overview of systematic reviews of complementary and alternative medicine for fibromyalgia. Clin Rheumatol 2012;31:55-66. 56 2014 년대한신경과학회제 33 차학술대회 - 강의록 -