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慢性疲労症候群

著者: 德永健一郎 熊本赤十字病院 リウマチ・膠原病内科

監修: 岸本暢将 杏林大学医学部 腎臓・リウマチ膠原病内科

著者校正/監修レビュー済:2018/01/31
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. 慢性疲労症候群(chronic fatigue syndrome、CFS)は全身性労作不耐性疾患(systemic excertion intolerance disease、SEID)としても知られ、ほかの疾患で説明できず、持続・反復する強い倦怠感を呈する疾患である。
 
診断:
  1. 特定の診察所見や検査結果で診断が確定できず難しい。
  1. 問診、診察、検査でほかの疾患を除外することが肝要である。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
德永健一郎 : 特に申告事項無し[2021年]
監修:岸本暢将 : 講演料(中外製薬,日本イーライリリー,ノバルティス,ヤンセンファーマ,ユーシービージャパン,田辺三菱製薬,アッヴィ合同会社,エーザイ(株),ブリストル・マイヤーズスクイブ(株),ギリアド・サイエンシズ(株))[2021年]

病態・疫学・診察

疾患(疫学・病態)のまとめ  
  1. 慢性疲労症候群(chronic fatigue syndrome、CFS)は全身性労作不耐性疾患(systemic excertion intolerance disease、SEID)としても知られ、ほかの疾患で説明できず、持続・反復する強い倦怠感を呈する疾患である。
  1. 病態は複雑ではっきりせず議論の余地がある疾患である。
  1. 慢性の倦怠感の訴えは日常診療においてよく遭遇する。CFSはその中のごく一部にすぎない。
  1. 疾患定義によっても有病率はまちまちであり疫学も不明である。
  1. 若年から中年成人に好発するが、小児例や高齢例もある。多くの報告において、男性に比べて女性が2倍。
  1. 疾患定義は複数あるが、2015年にthe Institute of Medicineから提唱されている。
  1. 米国医学研究所による慢性疲労症候群(chronic fatigue syndrome、CFS)/全身性労作不耐性疾患の診断基準、2015年: >詳細情報 
問診・診察のポイント  
  1. 倦怠感の発症は比較的急性であり、上気道炎や伝染性単核球症が契機であることがしばしばある。

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文献 

著者: W J Katon, D S Buchwald, G E Simon, J E Russo, P J Mease
雑誌名: J Gen Intern Med. 1991 Jul-Aug;6(4):277-85.
Abstract/Text OBJECTIVES: To identify psychiatric differences between patients with chronic fatigue and those with rheumatoid arthritis and to investigate whether patients meeting Centers for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS) can be differentiated from patients with chronic fatigue on measures of disability and psychosocial distress.
DESIGN: Cross-sectional study comparing 98 patients with chronic fatigue with 31 patients with rheumatoid arthritis on structured psychiatric interviews and patient questionnaires. Nineteen patients meeting CDC criteria for CFS were compared with 79 patients with chronic fatigue not meeting CDC criteria on questionnaires measuring disability and psychosocial distress.
SETTING: Consecutive patients with chronic fatigue were selected from a chronic fatigue clinic at the University of Washington, and 31 consecutive patients with rheumatoid arthritis were sampled from a private rheumatology practice.
MAIN RESULTS: Patients with chronic fatigue had a significantly higher prevalence of lifetime major depression and somatization disorder than did patients with rheumatoid arthritis. Patients with chronic fatigue also had a significantly higher prevalence of current and lifetime psychiatric diagnoses. Only 19 of 98 patients with chronic fatigue met CDC criteria for CFS. Patients meeting CDC criteria for CFS could not be differentiated from the larger group of patients with chronic fatigue on any study variable.
CONCLUSIONS: Patients with chronic fatigue have a significantly higher burden of psychiatric illness than do patients with rheumatoid arthritis. The psychiatric illness preceded the development of chronic fatigue in over half the patients. Centers for Disease Control criteria for CFS did not select a subset of chronic fatigue patients who could be differentiated on disability or psychosocial parameters from patients with chronic fatigue who did not meet CDC criteria.

PMID 1890495  J Gen Intern Med. 1991 Jul-Aug;6(4):277-85.
著者: T J Lane, P Manu, D A Matthews
雑誌名: Am J Med. 1991 Oct;91(4):335-44.
Abstract/Text PURPOSE: To report the prevalence, clinical features, and diagnostic associations of the proposed chronic fatigue syndrome (CFS) in a cohort of patients with chronic fatigue and to assess the usefulness of a structured psychiatric interview for detecting previously unrecognized psychiatric morbidity in patients with CFS.
PATIENTS AND METHODS: A consecutive sample of 200 adult patients with a chief complaint of chronic fatigue was prospectively evaluated in a referral-based clinic within a university general medicine practice. All patients received a thorough medical history, physical examination, diagnostic laboratory testing, and portions of the Diagnostic Interview Schedule, version III-A. The criteria for CFS were applied, and patients with CFS were compared with matched control subjects from the inception cohort.
RESULTS: The 60 patients with CFS had similar likelihoods of current psychiatric disorders (78% versus 82%), active mood disorders (73% versus 77%), and preexisting psychiatric disorders (42% versus 43%) when compared with fatigued control subjects. Patients with CFS were more likely to have somatization disorder (p less than 0.001) and to attribute their illness to a physical cause (p less than 0.005) than fatigued controls. Patients with CFS also displayed functional symptoms, often lifelong, which are not part of the case definition of CFS. Depressive features in patients with CFS were similar to those of control subjects, but a trend toward suicidal behavior was noted.
CONCLUSIONS: Patients with CFS have a high prevalence of unrecognized, current psychiatric disorders, which often predate their fatigue syndrome. Assessment of patients with CFS should include a structured psychiatric evaluation.

PMID 1951377  Am J Med. 1991 Oct;91(4):335-44.
著者: L A Aaron, M M Burke, D Buchwald
雑誌名: Arch Intern Med. 2000 Jan 24;160(2):221-7.
Abstract/Text BACKGROUND: Patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), and temporomandibular disorder (TMD) share many clinical illness features such as myalgia, fatigue, sleep disturbances, and impairment in ability to perform activities of daily living as a consequence of these symptoms. A growing literature suggests that a variety of comorbid illnesses also may commonly coexist in these patients, including irritable bowel syndrome, chronic tension-type headache, and interstitial cystitis.
OBJECTIVE: To describe the frequency of 10 clinical conditions among patients with CFS, FM, and TMD compared with healthy controls with respect to past diagnoses, degree to which they manifested symptoms for each condition as determined by expert-based criteria, and published diagnostic criteria.
METHODS: Patients diagnosed as having CFS, FM, and TMD by their physicians were recruited from hospital-based clinics. Healthy control subjects from a dermatology clinic were enrolled as a comparison group. All subjects completed a 138-item symptom checklist and underwent a brief physical examination performed by the project physicians.
RESULTS: With little exception, patients reported few past diagnoses of the 10 clinical conditions beyond their referring diagnosis of CFS, FM, or TMD. In contrast, patients were more likely than controls to meet lifetime symptom and diagnostic criteria for many of the conditions, including CFS, FM, irritable bowel syndrome, multiple chemical sensitivities, and headache. Lifetime rates of irritable bowel syndrome were particularly striking in the patient groups (CFS, 92%; FM, 77%; TMD, 64%) compared with controls (18%) (P<.001). Individual symptom analysis revealed that patients with CFS, FM, and TMD share common symptoms, including generalized pain sensitivity, sleep and concentration difficulties, bowel complaints, and headache. However, several symptoms also distinguished the patient groups.
CONCLUSIONS: This study provides preliminary evidence that patients with CFS, FM, and TMD share key symptoms. It also is apparent that other localized and systemic conditions may frequently co-occur with CFS, FM, and TMD. Future research that seeks to identify the temporal relationships and other pathophysiologic mechanism(s) linking CFS, FM, and TMD will likely advance our understanding and treatment of these chronic, recurrent conditions.

PMID 10647761  Arch Intern Med. 2000 Jan 24;160(2):221-7.
著者: D Buchwald, D Garrity
雑誌名: Arch Intern Med. 1994 Sep 26;154(18):2049-53.
Abstract/Text BACKGROUND: Chronic fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivities (MCS) are conditions associated with fatigue and a variety of other symptoms that appear to share many clinical and demographic features. Our objectives were to describe the similarities and differences among patients with CFS, FM, and MCS. Additional objectives were to determine how frequently patients with MCS and FM met the criteria for CFS and if they differed in their health locus of control.
METHODS: Demographic, clinical, and psychosocial measures were prospectively collected in 90 patients, 30 each with CFS, FM, and MCS. Patients were recruited from a university-based referral clinic devoted to the evaluation and treatment of chronic fatigue and three private practices. Variables included demographic features, symptoms characteristic of each condition, psychological complaints, a measure of health locus of control, and information on health care use.
RESULTS: Overall, the three patient groups were remarkably similar in demographic characteristics and the presence of specific symptoms. Patients with CFS and FM frequently reported symptoms compatible with MCS. Likewise, 70% of patients with FM and 30% of those with MCS met the criteria for CFS. Health care use was substantial among patients with CFS, FM, and MCS, with an average of 22.1, 39.7, and 23.3 visits, respectively, to a medical provider during the prior year. Health locus of control did not differ among the three populations.
CONCLUSIONS: In general, demographic and clinical factors and health locus of control do not clearly distinguish patients with CFS, FM, and MCS. Symptoms typical of each disorder are prevalent in the other two conditions.

PMID 8092909  Arch Intern Med. 1994 Sep 26;154(18):2049-53.
著者: P D White, K A Goldsmith, A L Johnson, L Potts, R Walwyn, J C DeCesare, H L Baber, M Burgess, L V Clark, D L Cox, J Bavinton, B J Angus, G Murphy, M Murphy, H O'Dowd, D Wilks, P McCrone, T Chalder, M Sharpe, PACE trial management group
雑誌名: Lancet. 2011 Mar 5;377(9768):823-36. doi: 10.1016/S0140-6736(11)60096-2. Epub 2011 Feb 18.
Abstract/Text BACKGROUND: Trial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients' organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments.
METHODS: In our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094.
FINDINGS: We recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p = 0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p = 0·0003), but did not differ for APT (0·7 [-0·9 to 2·3] points lower; p = 0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p = 0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p = 0·0005), but did not differ for APT (3·4 [-1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p = 0·0027; GET p = 0·0059) and better physical function (CBT p=0·0002; GET p<0·0001). Subgroup analysis of 427 participants meeting international criteria for chronic fatigue syndrome and 329 participants meeting London criteria for myalgic encephalomyelitis yielded equivalent results. Serious adverse reactions were recorded in two (1%) of 159 participants in the APT group, three (2%) of 161 in the CBT group, two (1%) of 160 in the GET group, and two (1%) of 160 in the SMC-alone group.
INTERPRETATION: CBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.
FUNDING: UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21334061  Lancet. 2011 Mar 5;377(9768):823-36. doi: 10.1016/S0140・・・
著者: Lillebeth Larun, Kjetil G Brurberg, Jan Odgaard-Jensen, Jonathan R Price
雑誌名: Cochrane Database Syst Rev. 2016 Feb 7;2:CD003200. doi: 10.1002/14651858.CD003200.pub4. Epub 2016 Feb 7.
Abstract/Text BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004.
OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone).
SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies
SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy.
DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome.
MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions.
AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

PMID 26852189  Cochrane Database Syst Rev. 2016 Feb 7;2:CD003200. doi:・・・

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