今日の臨床サポート

浮腫

著者: 仲里信彦 沖縄県立南部医療センター・こども医療センター

監修: 徳田安春 一般社団法人 群星沖縄臨床研修センター

著者校正/監修レビュー済:2021/05/19
患者向け説明資料

概要・推奨   

  1. 両側性下腿浮腫の原因として多いのは、うっ血性心不全、慢性下肢静脈不全、肺高血圧症、蛋白尿を伴った腎炎、薬剤性が多いとされる片側性下腿浮腫の原因としては、急性はDVT、慢性は下肢静脈不全が多かった。したがって、分布、経時的変化をきちんと聞いたうえで診断を考えることが推奨される(推奨度1)
  1. 両下腿浮腫が見られ、頚静脈圧波が胸骨角から3cm以上上昇している所見を有する患者は右心側の拡張期圧の上昇が疑われ、左心不全、肺性心、肺高血圧症、循環血液量過多の存在を疑い、精査を行うことが推奨される(推奨度2
  1. 発症3カ月以内の圧痕性浮腫の圧痕の回復時間(pit-recovery time)が40秒未満の場合、低アルブミン血症(3~2.5g/dL以下)を疑い血中アルブミンの検査を行うことが奨められる(推奨度2)
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲 覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約 が必要となります 。閲覧 にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご 契約が必要となり ます。 閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
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:
仲里信彦 : 特に申告事項無し[2021年]
監修:徳田安春 : 特に申告事項無し[2021年]

改訂のポイント
  1. 定期レビューを行った(変更なし)。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 浮腫とは、3rdスペースと呼ばれる組織間質への過剰な体液の貯留のことであり、多様な原因によって生じるとされる。アレルギー性の局所浮腫を除くと、一般的には間質への体液貯留が2.5~3Lになると浮腫として観察される。
  1. 両側性(全身性)浮腫と片側性(局所性)浮腫に大別される。しかし、検査・画像所見のみで診断することは困難である。
  1. 原因疾患は多岐にわたるが、以下のように病態生理的に考えるとよい。
  1. ①毛細血管内の静水圧の上昇
  1. ②膠質浸透圧の低下
  1. ③毛細血管の透過性の亢進
  1. 静水圧のバランス異常は、静脈圧の増大による毛細血管内圧の上昇が起こり、間質へ水分が移動して浮腫となる。深部静脈血栓症などの片側性浮腫、うっ血性心不全などの両側性浮腫がある。
  1. 膠質浸透圧のバランス異常は、低アルブミン血症による血管内の膠質浸透圧の低下が起こり、血管内に水分を保てず、間質へ水が貯留する。両側性の浮腫がみられる。
  1. 腎臓でのNa・水の再吸収の亢進が、両側性浮腫に影響する。ネフローゼ症候群や肝硬変でも低アルブミン血症に伴うunderfillingだけではなく、腎での一次性のNa貯留によるoverfillingが関与している。
  1. 毛細血管の血管透過性亢進により間質に水分が漏れ出る。局所の炎症、アレルギー反応による血管浮腫が局所や全身性に起こる。
  1. リンパ管閉塞では、間質からのリンパ還流を妨げ、局所的なリンパ浮腫を来す。
 
浮腫の病態生理

浮腫を形成する要因には間質および血管内の静水圧と膠質浸透圧が主に関与している。さらに炎症ではサイトカインの放出により、毛細血管の透過性が亢進する。また、リンパ管の閉塞によりリンパ浮腫が起こる。

出典

img1:  Peripheral edema.
 
 Am J Med. 2002 Nov;113(7):580-6.
 
  1. 鑑別疾患は多様であるが、まず心疾患、肝疾患、腎炎を考え、重篤かつ緊急の治療が必要な疾患を除外する必要がある。プライマリーケア医を受診する患者における両側下腿浮腫の原因として主なものは、うっ血性心不全、慢性下肢静脈不全、肺高血圧症(睡眠時無呼吸症候群[sleep apnea syndrome、SAS]を含む)、蛋白尿を伴った腎炎、薬剤性である。片側性浮腫の主な原因は、急性では深部静脈血栓症(DVT)、慢性では下肢静脈不全が多いとされる。
 
  1. 両側性下腿浮腫の原因として多いのは、うっ血性心不全、慢性下肢静脈不全、肺高血圧症、蛋白尿を伴った腎炎、薬剤性であった。片側性下腿浮腫の原因としては、急性はDVT、慢性は下肢静脈不全が多かった。したがって、分布、経時的変化をきちんと聞いたうえで診断を考えることが推奨される(推奨度1)
  1. 米国の観察研究において、両側下腿浮腫の原因として、うっ血性心不全、慢性下肢静脈不全、肺高血圧症、1~3g/日の蛋白尿を伴った腎炎、薬剤性が多くみられた。うっ血性心不全は意外にも過小評価され見逃されていた。心疾患や肺高血圧症に伴う浮腫のほとんどの患者は45歳以上であった。蛋白尿を原因とする両側性浮腫のうち、ネフローゼ症候群の定義を満たすものは少なかった。薬剤性浮腫はNSAIDs、カルシウム拮抗薬を原因とするものが多かった[1][2]
  1. 片側性浮腫の原因は、急性の場合はDVTによるもの、慢性では下肢静脈不全が多くみられた[2]
 
鑑別疾患表
圧痕性浮腫
静脈圧の上昇:
  1. 局所性静脈疾患
  1. 慢性静脈不全(静脈弁不全、不全穿通枝による)(片側性浮腫、両側性浮腫)
  1. ほかの静脈不全(腫瘍や腫瘤、解剖学的な原因よる物理的圧迫)(主に片側性浮腫)
  1. 上大静脈症候群(腫瘍などによる上大静脈の閉塞)
  1.  May-Thurner 症候群 (右総腸骨動脈による左腸骨静脈の圧迫)
  1. その他の局所における静脈圧迫および閉塞
  1.  深部静脈血栓症 (片側性浮腫)
  1.  バッド・キアリ症候群 (両側性浮腫)
  1. 全身性の静脈圧上昇(両側性浮腫)
  1. うっ血性心不全( 心臓弁膜症 、 虚血性心疾患 、 心筋症 、不整脈
  1. 肺性心
  1.  収縮性心膜炎 
  1. 心タンポナーデ
  1.  急性糸球体腎炎 
  1.  急性腎不全 
  1.  慢性腎不全 
  1. ネフローゼ症候群
  1. 肝硬変
  1.  特発性浮腫 (月経がある女性で、心疾患・肝疾患・腎炎が除外されていること)
  1.  子癇 
  1. 妊娠
 
 低アルブミン血症 (両側性浮腫)
  1. 栄養障害
  1. 食事性
  1.  吸収不良症候群 
  1. 広範な熱傷からの蛋白漏出
  1. 肝硬変
  1. ネフローゼ症候群
 
血管透過性の亢進
  1. 炎症性(片側性浮腫)
  1. 熱傷
  1. 蜂巣炎
  1.  外傷 
  1. アレルギーおよびアナフィラキシー(両側性浮腫)
  1.  Stevens-Johnson 症候群 
  1.  アレルギー性血管性浮腫 
  1.  薬剤性浮腫 
  1. カルシウム拮抗薬(主にジヒドロピリジン系薬)
  1. アンジオテンシン変換酵素阻害薬
  1. NSAIDs
  1. 抗精神病薬
  1. インスリン感受性改善薬(ピオグリタゾン塩酸塩 など)
  1. その他
  1. 複合性局所疼痛症候群(complex regional pain syndrome 、CRPS)(片側性浮腫)
  1.  POEMS 症候群 (両側性浮腫)
  1. 血管性浮腫(アレルギー性を除く)(両側性浮腫)
  1. 遺伝性血管性浮腫
  1.  後天性血管性浮腫 
  1.  好酸球増多性血管性浮腫 
  1.  RS3PE症候群 (remitting seronegative symmetrical synovitis with pitting edema)(両側性浮腫)
  1.  パルボウイルス B19感染症 (両側性浮腫)
非圧痕性浮腫
  1.  粘液水腫 (両側性浮腫)
  1.  リンパ管閉塞 (片側性浮腫がほとんど)
  1. リンパ節郭清後
  1. リンパ節への放射線治療後
  1. フィラリア感染後遺症
問診・診察のポイント  
  1. 浮腫の診察のポイントは、やはり病歴聴取と身体診察である。循環器系および呼吸器系の症状を伴っているときには、急性心不全、腎不全、アナフィラキシー、肝硬変に合併した浮腫の可能性が高いため、それらをまず考えての診察・治療を並行して行う。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: R P Blankfield, R S Finkelhor, J J Alexander, S A Flocke, J Maiocco, M Goodwin, S J Zyzanski
雑誌名: Am J Med. 1998 Sep;105(3):192-7.
Abstract/Text PURPOSE: To identify the causes of bilateral leg edema in a primary care setting, and to determine the ability of primary care providers to arrive at the correct diagnosis using the information available at the initial clinical encounter.
PATIENTS AND METHODS: Fifty-eight ambulatory adult patients with bilateral leg edema were enrolled at an inner city family practice during a 3-year period. Historical information, physical examination findings, and clinical impressions of primary care providers were compared with the results of laboratory evaluations consisting of echocardiograms, venous duplex ultrasound leg scans, serum albumin levels, and when appropriate, 24-hour urinalyses.
RESULTS: Forty-five patients (78%) completed the study. The initial clinical impression was venous insufficiency in 32 (71%) patients and congestive heart failure in 8 (18%) patients. In actuality, 15 (33%) patients had a cardiac condition as a cause of their leg edema, and 19 (42%) had pulmonary hypertension. All of the patients with heart disease, and almost all of those with pulmonary hypertension, were age 45 years or older. Only 10 (22%) of the subjects had venous insufficiency. Renal conditions, medication use, and hypoalbuminemia were less common.
CONCLUSIONS: Utilizing clinical information only, many patients with cardiopulmonary pathology were incorrectly diagnosed as having more benign conditions, most commonly venous insufficiency. Echocardiographic evaluation, including an estimation of pulmonary artery pressure, may be advisable in many patients with bilateral leg edema, especially if they are at least 45 years old.

PMID 9753021  Am J Med. 1998 Sep;105(3):192-7.
著者: John W Ely, Jerome A Osheroff, M Lee Chambliss, Mark H Ebell
雑誌名: J Am Board Fam Med. 2006 Mar-Apr;19(2):148-60.
Abstract/Text A common challenge for primary care physicians is to determine the cause and find an effective treatment for leg edema of unclear etiology. We were unable to find existing practice guidelines that address this problem in a comprehensive manner. This article provides clinically oriented recommendations for the management of leg edema in adults. We searched on-line resources, textbooks, and MEDLINE (using the MeSH term, "edema") to find clinically relevant articles on leg edema. We then expanded the search by reviewing articles cited in the initial sources. Our goal was to write a brief, focused review that would answer questions about the management of leg edema. We organized the information to make it rapidly accessible to busy clinicians. The most common cause of leg edema in older adults is venous insufficiency. The most common cause in women between menarche and menopause is idiopathic edema, formerly known as "cyclic" edema. A common but under-recognized cause of edema is pulmonary hypertension, which is often associated with sleep apnea. Venous insufficiency is treated with leg elevation, compressive stockings, and sometimes diuretics. The initial treatment of idiopathic edema is spironolactone. Patients who have findings consistent with sleep apnea, such as daytime somnolence, loud [corrected] snoring, or neck circumference >17 inches, should be evaluated for pulmonary hypertension with an echocardiogram. If time is limited, the physician must decide whether the evaluation can be delayed until a later appointment (eg, an asymptomatic patient with chronic bilateral edema) or must be completed at the current visit (eg, a patient with dyspnea or a patient with acute edema [<72 hours]). If the evaluation should be conducted at the current visit, the algorithm shown in Figure 1 could be used as a guide. If the full evaluation could wait for a subsequent visit, the patient should be examined briefly to rule out an obvious systemic cause and basic laboratory tests should be ordered for later review (complete blood count, urinalysis, electrolytes, creatinine, blood sugar, thyroid stimulating hormone, and albumin).

PMID 16513903  J Am Board Fam Med. 2006 Mar-Apr;19(2):148-60.
著者: Roberto Chiesa, Enrico Maria Marone, Costanzo Limoni, Marina Volontè, Orlando Petrini
雑誌名: J Vasc Surg. 2007 Aug;46(2):322-30. doi: 10.1016/j.jvs.2007.04.030. Epub 2007 Jun 27.
Abstract/Text BACKGROUND: The aim of this study was to investigate the frequency of chronic venous disorders (CVD) in different demographic groups in Italy and to provide correlations between patterns of valve incompetence and clinical feature of disease severity.
METHODS: Advertisements in television and newspapers in 53 Italian cities were used to solicit 16,251 subjects (13,826 women, mean age 50.4 years; 2,425 men, mean age 59.1 years). They underwent a clinical examination of the lower limbs, including presence and severity of visible signs (CEAP classification), and assessment of functional disease by color-coded duplex ultrasound imaging.
RESULTS: Varicose veins and telangiectases were the most common objective signs in both men and women. Older people were more severely affected. Telangiectases were more frequent in women, and men had a higher incidence of trunk varices, trophic changes, and venous reflux. Frequency of both visible and functional venous disease increased with family history and body mass index. Presence of reflux correlated positively with increasing CEAP grade of visible disease (Pfor trend < .0001 for all superficial venous segments). A large number of subjects, especially women, complained of subjective symptoms in the legs, and the presence of symptoms correlated almost always positively with both worsening of visible findings (P for trend < .001) and presence of hemodynamic change in both genders.
CONCLUSIONS: The frequency of reflux increased with the severity of visible signs of disease as described by the CEAP classification. In men, the occurrence of subjective symptoms was mostly correlated with functional disorders.

PMID 17600668  J Vasc Surg. 2007 Aug;46(2):322-30. doi: 10.1016/j.jvs.・・・
著者: D J Cook, D L Simel
雑誌名: JAMA. 1996 Feb 28;275(8):630-4.
Abstract/Text
PMID 8594245  JAMA. 1996 Feb 28;275(8):630-4.
著者: J A Henry, P Altmann
雑誌名: Br Med J. 1978 Apr 8;1(6117):890-1.
Abstract/Text
PMID 638510  Br Med J. 1978 Apr 8;1(6117):890-1.
著者: Cochrane Injuries Group Albumin Reviewers
雑誌名: BMJ. 1998 Jul 25;317(7153):235-40.
Abstract/Text OBJECTIVE: To quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients.
DESIGN: Systematic review of randomised controlled trials comparing administration of albumin or plasma protein fraction with no administration or with administration of crystalloid solution in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia.
SUBJECTS: 30 randomised controlled trials including 1419 randomised patients.
MAIN OUTCOME MEASURE: Mortality from all causes at end of follow up for each trial.
RESULTS: For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death after albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia it was 1.69 (1.07 to 2.67). Pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Pooled difference in the risk of death with albumin was 6% (95% confidence interval 3% to 9%) with a fixed effects model. These data suggest that for every 17 critically ill patients treated with albumin there is one additional death.
CONCLUSIONS: There is no evidence that albumin administration reduces mortality in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia and a strong suggestion that it may increase mortality. These data suggest that use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of rigorously conducted, randomised controlled trials.

PMID 9677209  BMJ. 1998 Jul 25;317(7153):235-40.
著者: Jean-Louis Vincent, Marc-Jacques Dubois, Roberta J Navickis, Mahlon M Wilkes
雑誌名: Ann Surg. 2003 Mar;237(3):319-34. doi: 10.1097/01.SLA.0000055547.93484.87.
Abstract/Text OBJECTIVE: To determine whether hypoalbuminemia is an independent risk factor for poor outcome in the acutely ill, and to assess the potential of exogenous albumin administration for improving outcomes in hypoalbuminemic patients.
SUMMARY BACKGROUND DATA: Hypoalbuminemia is associated with poor outcomes in acutely ill patients, but whether this association is causal has remained unclear. Trials investigating albumin therapy to correct hypoalbuminemia have proven inconclusive.
METHODS: A meta-analysis was conducted of 90 cohort studies with 291,433 total patients evaluating hypoalbuminemia as an outcome predictor by multivariate analysis and, separately, of nine prospective controlled trials with 535 total patients on correcting hypoalbuminemia.
RESULTS: Hypoalbuminemia was a potent, dose-dependent independent predictor of poor outcome. Each 10-g/L decline in serum albumin concentration significantly raised the odds of mortality by 137%, morbidity by 89%, prolonged intensive care unit and hospital stay respectively by 28% and 71%, and increased resource utilization by 66%. The association between hypoalbuminemia and poor outcome appeared to be independent of both nutritional status and inflammation. Analysis of dose-dependency in controlled trials of albumin therapy suggested that complication rates may be reduced when the serum albumin level attained during albumin administration exceeds 30 g/L.
CONCLUSIONS: Hypoalbuminemia is strongly associated with poor clinical outcomes. Further well-designed trials are needed to characterize the effects of albumin therapy in hypoalbuminemic patients. In the interim, there is no compelling basis to withhold albumin therapy if it is judged clinically appropriate.

PMID 12616115  Ann Surg. 2003 Mar;237(3):319-34. doi: 10.1097/01.SLA.0・・・
著者: S P Allison, D N Lobo
雑誌名: Crit Care. 2000;4(3):147-50. doi: 10.1186/cc687.
Abstract/Text The recent Cochrane report on albumin administration is analysed and criticised on the grounds of clinical methodology, content and interpretation. Although it is naïve and illogical to treat hypoalbuminaemia with albumin infusions, a more balanced view on the use of albumin for resuscitation in acute hypovolaemia is necessary. Once the acute phase of critical illness is past, interstitial volume is often expanded causing oedema, with a low plasma volume. We argue for the use of salt-poor albumin solutions in this situation and conclude that, on current evidence, the assertion that albumin should be avoided in all situations is irrational and untenable.

PMID 11211855  Crit Care. 2000;4(3):147-50. doi: 10.1186/cc687.
著者: Charlie S Wang, J Mark FitzGerald, Michael Schulzer, Edwin Mak, Najib T Ayas
雑誌名: JAMA. 2005 Oct 19;294(15):1944-56. doi: 10.1001/jama.294.15.1944.
Abstract/Text CONTEXT: Dyspnea is a common complaint in the emergency department where physicians must accurately make a rapid diagnosis.
OBJECTIVE: To assess the usefulness of history, symptoms, and signs along with routine diagnostic studies (chest radiograph, electrocardiogram, and serum B-type natriuretic peptide [BNP]) that differentiate heart failure from other causes of dyspnea in the emergency department.
DATA SOURCES: We searched MEDLINE (1966-July 2005) and the reference lists from retrieved articles, previous reviews, and physical examination textbooks.
STUDY SELECTION: We retained 22 studies of various findings for diagnosing heart failure in adult patients presenting with dyspnea to the emergency department.
DATA EXTRACTION: Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality.
DATA SYNTHESIS: Many features increased the probability of heart failure, with the best feature for each category being the presence of (1) past history of heart failure (positive LR = 5.8; 95% confidence interval [CI], 4.1-8.0); (2) the symptom of paroxysmal nocturnal dyspnea (positive LR = 2.6; 95% CI, 1.5-4.5); (3) the sign of the third heart sound (S(3)) gallop (positive LR = 11; 95% CI, 4.9-25.0); (4) the chest radiograph showing pulmonary venous congestion (positive LR = 12.0; 95% CI, 6.8-21.0); and (5) electrocardiogram showing atrial fibrillation (positive LR = 3.8; 95% CI, 1.7-8.8). The features that best decreased the probability of heart failure were the absence of (1) past history of heart failure (negative LR = 0.45; 95% CI, 0.38-0.53); (2) the symptom of dyspnea on exertion (negative LR = 0.48; 95% CI, 0.35-0.67); (3) rales (negative LR = 0.51; 95% CI, 0.37-0.70); (4) the chest radiograph showing cardiomegaly (negative LR = 0.33; 95% CI, 0.23-0.48); and (5) any electrocardiogram abnormality (negative LR = 0.64; 95% CI, 0.47-0.88). A low serum BNP proved to be the most useful test (serum B-type natriuretic peptide <100 pg/mL; negative LR = 0.11; 95% CI, 0.07-0.16).
CONCLUSIONS: For dyspneic adult emergency department patients, a directed history, physical examination, chest radiograph, and electrocardiography should be performed. If the suspicion of heart failure remains, obtaining a serum BNP level may be helpful, especially for excluding heart failure.

PMID 16234501  JAMA. 2005 Oct 19;294(15):1944-56. doi: 10.1001/jama.29・・・
著者: Pramote Porapakkham, Pornwalee Porapakkham, Hendrik Zimmet, Baki Billah, Henry Krum
雑誌名: Arch Intern Med. 2010 Mar 22;170(6):507-14. doi: 10.1001/archinternmed.2010.35.
Abstract/Text BACKGROUND: The use of plasma levels of B-type natriuretic peptides (BNPs) to guide treatment of patients with chronic heart failure (HF) has been investigated in a number of randomized controlled trials (RCTs). However, the benefits of this treatment approach have been uncertain. We therefore performed a meta-analysis to examine the overall effect of BNP-guided drug therapy on cardiovascular outcomes in patients with chronic HF.
METHODS: We identified RCTs by systematic search of manuscripts, abstracts, and databases. Eligible RCTs were those that enrolled more than 20 patients and involved comparison of BNP-guided drug therapy vs usual clinical care of the patient with chronic HF in an outpatient setting.
RESULTS: Eight RCTs with a total of 1726 patients and with a mean duration of 16 months (range, 3-24 months) were included in the meta-analysis. Overall, there was a significantly lower risk of all-cause mortality (relative risk [RR], 0.76; 95% confidence interval [CI], 0.63-0.91; P = .003) in the BNP-guided therapy group compared with the control group. In the subgroup of patients younger than 75 years, all-cause mortality was also significantly lower in the BNP-guided group (RR, 0.52; 95% CI, 0.33-0.82; P = .005). However, there was no reduction in mortality with BNP-guided therapy in patients 75 years or older (RR, 0.94; 95% CI, 0.71-1.25; P = .70). The risk of all-cause hospitalization and survival free of any hospitalization was not significantly different between groups (RR, 0.82; 95% CI, 0.64-1.05; P = .12 and RR, 1.07; 95% CI, 0.85-1.34; P = .58, respectively). The additional percentage of patients achieving target doses of angiotensin-converting enzyme inhibitors and beta-blockers during the course of these trials averaged 21% and 22% in the BNP group and 11.7% and 12.5% in the control group, respectively.
CONCLUSIONS: B-type natriuretic peptide-guided therapy reduces all-cause mortality in patients with chronic HF compared with usual clinical care, especially in patients younger than 75 years. A component of this survival benefit may be due to increased use of agents proven to decrease mortality in chronic HF. However, there does not seem to be a reduction in all-cause hospitalization or an increase in survival free of hospitalization using this approach.

PMID 20308637  Arch Intern Med. 2010 Mar 22;170(6):507-14. doi: 10.100・・・
著者: R Indra, S S Patil, R Joshi, M Pai, S P Kalantri
雑誌名: J Postgrad Med. 2004 Jan-Mar;50(1):7-11; discussion 11.
Abstract/Text BACKGROUND: Hypothyroidism is a common, potentially treatable endocrine disorder. Since hypothyroidism is not always associated with the signs and symptoms typically attributed to it, the diagnosis is often missed. Conversely, patients with typical signs and symptoms may not have the disease when laboratory tests are performed.
AIMS: We aimed to determine the accuracy of physical examination in the diagnosis of hypothyroidism.
SETTING AND DESIGN: Prospective, hospital-based, cross-sectional diagnostic study.
MATERIAL AND METHODS: Consecutive outpatients from the medicine department were screened and an independent comparison of physical signs (coarse skin, puffy face, slow movements, bradycardia, pretibial oedema and ankle reflex) against thyroid hormone assay (TSH and FT4) was performed.
STATISTICAL ANALYSIS: Diagnostic accuracy was measured as sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and positive and negative predictive values.
RESULTS: Of the 1450 patients screened, 130 patients (102 women and 28 men) underwent both clinical examination and thyroid function tests. Twenty-three patients (18%) were diagnosed to have hypothyroidism by thyroid hormone assays. No single sign could easily discriminate a euthyroid from a hypothyroid patient (range of positive likelihood ratio (LR+) 1.0 to 3.88; range of negative likelihood ratio (LR-): 0.42 to 1.0). No physical sign generated a likelihood ratio large enough to increase the post-test probability significantly. The combination of signs that had the highest likelihood ratios (coarse skin, bradycardia and delayed ankle reflex) was associated with modest accuracy (LR+ 3.75; LR- 0.48).
CONCLUSION: Clinicians cannot rely exclusively on physical examination to confirm or rule out hypothyroidism. Patients with suspected hypothyroidism require a diagnostic workup that includes thyroid hormone assays.

PMID 15047991  J Postgrad Med. 2004 Jan-Mar;50(1):7-11; discussion 11.・・・
著者: P S Wells, D R Anderson, J Bormanis, F Guy, M Mitchell, L Gray, C Clement, K S Robinson, B Lewandowski
雑誌名: Lancet. 1997 Dec 20-27;350(9094):1795-8. doi: 10.1016/S0140-6736(97)08140-3.
Abstract/Text BACKGROUND: When ultrasonography is used to investigate deep-vein thrombosis, serial testing is recommended for those who test negative initially. Serial testing is inconvenient for patients and costly. We aimed to assess whether the calculation of pretest probability of deep-vein thrombosis, with a simple clinical model, could be used to improve the management of patients who present with suspected deep-vein thrombosis.
METHODS: Consecutive outpatients with suspected deep-vein thrombosis had their pretest probability calculated with a clinical model. They then underwent compression ultrasound imaging of proximal veins of the legs. Patients at low pretest probability underwent a single ultrasound test. A negative ultrasound excluded the diagnosis of deep-vein thrombosis whereas a positive ultrasound was confirmed by venography. Patients at moderate pretest probability with a positive ultrasound were treated for deep-vein thrombosis whereas patients with an initial negative ultrasound underwent a single follow-up ultrasound 1 week later. Patients at high pretest probability with a positive ultrasound were treated whereas those with negative ultrasound underwent venography. All patients were followed up for 3 months for thromboembolic complications.
FINDINGS: 95 (16.0%) of all 593 patients had deep-vein thrombosis; 3%, 17%, and 75% of the patients with low, moderate, and high pretest probability, respectively, had deep-vein thrombosis. Ten of 329 patients with low pretest probability had the diagnosis confirmed, nine at initial testing and one at follow-up. 32 of 193 patients with moderate pretest probability had deep-vein thrombosis, three diagnosed by the serial (1 week) test, and two during follow-up. 53 of 71 patients with high pretest probability had deep-vein thrombosis (49 by the initial ultrasound and four by venography). Only three (0.6%) of all 501 (95% CI 0.1-1.8) patients diagnosed as not having deep-vein thrombosis had events during the 3-month follow-up. Overall only 33 (5.6%) of 593 patients required venography and serial testing was limited to 166 (28%) of 593 patients.
INTERPRETATION: Management of patients with suspected deep-vein thrombosis based on clinical probability and ultrasound of the proximal deep veins is safe and feasible. Our strategy reduced the need for serial ultrasound testing and reduced the rate of false-negative or false-positive ultrasound studies.

PMID 9428249  Lancet. 1997 Dec 20-27;350(9094):1795-8. doi: 10.1016/S・・・
著者: Philip S Wells, David R Anderson, Marc Rodger, Melissa Forgie, Clive Kearon, Jonathan Dreyer, George Kovacs, Michael Mitchell, Bernard Lewandowski, Michael J Kovacs
雑誌名: N Engl J Med. 2003 Sep 25;349(13):1227-35. doi: 10.1056/NEJMoa023153.
Abstract/Text BACKGROUND: Several diagnostic strategies using ultrasound imaging, measurement of D-dimer, and assessment of clinical probability of disease have proved safe in patients with suspected deep-vein thrombosis, but they have not been compared in randomized trials.
METHODS: Outpatients presenting with suspected lower-extremity deep-vein thrombosis were potentially eligible. Using a clinical model, physicians evaluated the patients and categorized them as likely or unlikely to have deep-vein thrombosis. The patients were then randomly assigned to undergo ultrasound imaging alone (control group) or to undergo D-dimer testing (D-dimer group) followed by ultrasound imaging unless the D-dimer test was negative and the patient was considered clinically unlikely to have deep-vein thrombosis, in which case ultrasound imaging was not performed.
RESULTS: Five hundred thirty patients were randomly assigned to the control group, and 566 to the D-dimer group. The overall prevalence of deep-vein thrombosis or pulmonary embolism was 15.7 percent. Among patients for whom deep-vein thrombosis had been ruled out by the initial diagnostic strategy, there were two confirmed venous thromboembolic events in the D-dimer group (0.4 percent; 95 percent confidence interval, 0.05 to 1.5 percent) and six events in the control group (1.4 percent; 95 percent confidence interval, 0.5 to 2.9 percent; P=0.16) during three months of follow-up. The use of D-dimer testing resulted in a significant reduction in the use of ultrasonography, from a mean of 1.34 tests per patient in the control group to 0.78 in the D-dimer group (P=0.008). Two hundred eighteen patients (39 percent) in the D-dimer group did not require ultrasound imaging.
CONCLUSIONS: Deep-vein thrombosis can be ruled out in a patient who is judged clinically unlikely to have deep-vein thrombosis and who has a negative D-dimer test. Ultrasound testing can be safely omitted in such patients.

Copyright 2003 Massachusetts Medical Society
PMID 14507948  N Engl J Med. 2003 Sep 25;349(13):1227-35. doi: 10.1056・・・
著者: Philip S Wells, Carolyn Owen, Steve Doucette, Dean Fergusson, Huyen Tran
雑誌名: JAMA. 2006 Jan 11;295(2):199-207. doi: 10.1001/jama.295.2.199.
Abstract/Text CONTEXT: Outpatients with suspected deep vein thrombosis (DVT) have nonspecific signs and symptoms. Missed DVT diagnosis may result in fatal pulmonary embolism. Since many patients may have DVT, a selective and efficient diagnostic process is needed.
OBJECTIVE: To systematically review trials that determined the prevalence of DVT using clinical prediction rules either with or without D-dimer, for the diagnosis of DVT.
DATA SOURCES: English- and French-language studies were identified from MEDLINE from 1990 to July 2004 and supplemented by a review of all relevant bibliographies.
STUDY SELECTION: We included studies that prospectively enrolled consecutive, unselected outpatients with suspected DVT and applied clinical prediction rules before D-dimer testing or diagnostic imaging. All studies included sufficient information to allow the calculation of the prevalence of DVT for at least 1 of the 3 clinical probability estimates (low, moderate, or high). We required that patients be followed up for a minimum 3-month period. Unless the clinical model incorporated prior DVT, studies were excluded if patients with a history of prior DVT were enrolled.
DATA EXTRACTION: Two reviewers independently reviewed and abstracted data for estimating the prevalence of DVT, sensitivity, specificity, and likelihood ratios (LRs) of D-dimer in each of the 3 clinical probability estimates. Data for the D-dimer in all studies were pooled and analyzed as high-sensitivity/low-specificity test or a moderate-sensitivity/moderate-specificity test.
DATA SYNTHESIS: Fourteen studies involving more than 8000 patients used 1 clinical prediction rule for diagnosing DVT, of which 11 incorporated D-dimer testing in the diagnostic algorithm. The prevalence of DVT in the low, moderate, and high clinical probability groups was 5.0% (95% CI, 4.0%-8.0%), 17% (95% CI, 13%-23%), and 53% (95% CI, 44%-61%), respectively. The overall prevalence of DVT was 19% (95% CI, 16%-23%). Pooling all studies, the sensitivity, specificity, and negative LRs of D-dimer testing in the low probability group were 88% (95% CI, 81%-92%), 72% (95% CI, 65%-78%), and 0.18% (95% CI, 0.12-0.18); in the moderate probability group: 90% (95% CI, 80%-95%), 58% (95% CI, 49%-67%), and 0.19% (95% CI, 0.11-0.32); and in the high probability group: 92% (95% CI, 85%-96%), 45% (95% CI, 37%-52%), and 0.16% (95% CI, 0.09-0.30). The LRs for a normal result on a high or moderately sensitive D-dimer assay among patients with: (1) low clinical suspicion were 0.10 (95% CI, 0.03-0.37) and 0.20 (95% CI, 0.12-0.31); (2) moderate clinical suspicion were 0.05 (95% CI, 0.01-0.21) and 0.23 (95% CI, 0.13-0.39); and (3) high clinical suspicion were 0.07 (95% CI, 0.03-0.18) and 0.15 (95% CI, 0.10-0.38).
CONCLUSIONS: Diagnostic accuracy for DVT improves when clinical probability is estimated before diagnostic tests. Patients with low clinical probability on the predictive rule have prevalence of DVT of less than 5%. In low-probability patients with negative D-dimer results, diagnosis of DVT can be excluded without ultrasound; in patients with high clinical suspicion for DVT, results should not affect clinical decisions.

PMID 16403932  JAMA. 2006 Jan 11;295(2):199-207. doi: 10.1001/jama.295・・・
著者: K Arima, T Origuchi, M Tamai, N Iwanaga, Y Izumi, M Huang, F Tanaka, M Kamachi, K Aratake, H Nakamura, H Ida, M Uetani, A Kawakami, K Eguchi
雑誌名: Ann Rheum Dis. 2005 Nov;64(11):1653-5. doi: 10.1136/ard.2004.032995.
Abstract/Text OBJECTIVES: To characterise serum concentrations of various cytokines and detection by magnetic resonance imaging (MRI) of synovial hypervascularity in patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome before and after corticosteroid treatment.
METHODS: Vascular endothelial growth factor(165) (VEGF(165)), tumour necrosis factor alpha (TNFalpha), and interleukin 1beta (IL1beta) were measured by enzyme linked immunosorbent assay (ELISA) in serum samples from three patients with RS3PE syndrome. As controls, serum samples from 26 healthy volunteers, 12 patients with rheumatoid arthritis, 10 patients with systemic lupus erythematosus, 13 patients with polymyositis/dermatomyositis, 13 patients with vasculitis syndrome, and 6 patients with mixed connective tissue disease were also analysed. Synovial hypervascularity of patients with RS3PE syndrome was estimated by rate of enhancement (E-rate) in a dynamic MRI study.
RESULTS: Serum concentrations of VEGF(165) (mean (SD) 2223.3 (156.3) pg/ml) were significantly higher in patients with active RS3PE syndrome than in controls before corticosteroid treatment. TNFalpha and IL1beta levels were similar in patients and controls. Synovial hypervascularity in affected joints and subcutaneous oedema decreased during corticosteroid treatment, in parallel with the fall in serum VEGF(165).
CONCLUSIONS: VEGF promotes synovial inflammation and vascular permeability in patients with RS3PE syndrome, suggesting that RS3PE can be classified as a VEGF associated disorder.

PMID 16227418  Ann Rheum Dis. 2005 Nov;64(11):1653-5. doi: 10.1136/ard・・・
著者: G W Thorn
雑誌名: JAMA. 1968 Oct 7;206(2):333-8.
Abstract/Text
PMID 5695605  JAMA. 1968 Oct 7;206(2):333-8.
著者: G J Gleich, A L Schroeter, J P Marcoux, M I Sachs, E J O'Connell, P F Kohler
雑誌名: N Engl J Med. 1984 Jun 21;310(25):1621-6. doi: 10.1056/NEJM198406213102501.
Abstract/Text We studied four patients with recurrent attacks of angioedema, urticaria, and fever. During attacks, body weights increased up to 18 per cent, and leukocyte counts reached 108,000 per microliter (88 per cent eosinophils). The disease did not appear to threaten the function of vital organs. The two children received prednisone intermittently; the adults did not require treatment or were given alternate-day prednisone. Glucocorticoid therapy caused defervescence and diuresis and decreased total leukocyte and eosinophil counts. No patient had evidence of cardiac involvement (follow-up, 2 to 17 years). One patient remained in spontaneous remission for 20 years before symptoms recurred. Histologic studies showed that eosinophils localized and degranulated in the dermis, and they appeared to induce edema. Although this syndrome might be classified as a variant of the hypereosinophilic syndrome, we believe it is a separate entity because of its distinctive characteristics and its benign course.

PMID 6727934  N Engl J Med. 1984 Jun 21;310(25):1621-6. doi: 10.1056/・・・
著者: R Chikama, M Hosokawa, T Miyazawa, R Miura, T Suzuki, H Tagami
雑誌名: Dermatology. 1998;197(4):321-5.
Abstract/Text BACKGROUND: In 1984, Gleich et al. described 4 patients with episodic angioedema associated with eosinophilia (EAE), which was characterized by recurrent episodes of angioedema and urticaria, eosinophilia, elevated serum IgM, fever, increased body weight and a benign course without involvement of the internal organs demonstrating that it was a clinical entity distinct from the hypereosinophilic syndrome. Thereafter, 37 cases of EAE have been reported in Japan, 33 cases of which, although similar, had a different evolution from classical EAE.
OBJECTIVE: To describe 4 cases and review the cases of angioedema associated with eosinophilia reported in Japan.
RESULTS: Four Japanese female patients had persistent angioedema mainly involving the hands and lower legs, and eosinophilia which resolved within a few months. The review of the 37 cases of EAE in the Japanese literature demonstrated that in 33 cases, there were common characteristics which differed from EAE. These included: (1) the absence of recurrent attacks; (2) the predominance of young females (20-37 years, with a mean of 26 years); (3) the localization of the angioedema to the extremities; (4) the absence of increase in the serum IgM level, and (5) the effectiveness of low-dose prednisone or even the occurrence of spontaneous remission.
CONCLUSION: We propose that persistent angioedema with eosinophilia can be classified into 2 types, i.e. one being an episodic (recurrent) type as reported by Gleich and a nonepisodic type as our 4 cases and others found in the Japanese literature.

PMID 9873168  Dermatology. 1998;197(4):321-5.
著者: D J McCarty, J D O'Duffy, L Pearson, J B Hunter
雑誌名: JAMA. 1985 Nov 15;254(19):2763-7.
Abstract/Text Eight elderly men and two elderly women presented with symmetrical polysynovitis of acute onset involving most of their appendicular joints and flexor digitorum tendons associated with pitting edema of the dorsum of both hands and both feet. Onset of seven of the ten cases could be pinpointed almost to the hour. Rheumatoid factors were absent from serum samples in all, and no radiologically evident erosions developed. Clinical and laboratory signs of inflammation and the edema disappeared gradually in each case. Treatment consisted of aspirin or other nonsteroidal anti-inflammatory drugs. Hydroxychloroquine, 200 to 400 mg/day, was given in six and gold therapy in two cases. Painless limitation of motion of the wrists and/or fingers persisted in all, although the patients were both unaware of and unhampered by this abnormality. Six of eight cases where typing was possible were positive for HLA-B7, CW7, and DQW2 (relative risk for B7, 9.5). Three cases of this syndrome were found in a consecutive series of 52 men diagnosed as having definite "rheumatoid arthritis," and thus represent a distinctive condition with an excellent prognosis.

PMID 4057484  JAMA. 1985 Nov 15;254(19):2763-7.
著者: Makiko Kimura, Yasuharu Tokuda, Hideto Oshiawa, Kazuki Yoshida, Masako Utsunomiya, Tatsuo Kobayashi, Gautam A Deshpande, Kazuo Matsui, Mitsumasa Kishimoto
雑誌名: J Rheumatol. 2012 Jan;39(1):148-53. doi: 10.3899/jrheum.110558. Epub 2011 Dec 15.
Abstract/Text OBJECTIVE: To compare clinical features of patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) and patients with polymyalgia rheumatica (PMR) and to explore the purported association between RS3PE and malignancy.
METHODS: We did a retrospective chart review of patients with RS3PE and PMR treated in a community-based hospital between January 2000 and December 2009. Outcomes assessed were clinical course of disease and associated malignancies.
RESULTS: We identified 28 patients with RS3PE and 123 with pure PMR. All patients with RS3PE fulfilled PMR criteria as well. Age, comorbidity, erythrocyte sedimentation rate, duration and progression of symptoms, treatment response to initial low-dose steroids, and steroid complication rates were similar in both groups. Patients with RS3PE were more likely to be male (79% vs 41%; p = 0.001) and to have a history of smoking (39% vs 15%; p = 0.008) and a higher rate of depression (11% vs 2%; p = 0.044) at diagnosis. Among those with RS3PE, hip pain was less common (39% vs 74%; p = 0.001) than in the PMR group. No patients with RS3PE and 6 patients with pure PMR (4.9%) developed another rheumatological disease during followup. Seven of 9 patients (78%) with concurrent cancer presented slightly more frequently with systemic symptoms compared to patients without cancer (48%; p = 0.098), especially with fatigue (56% vs 22%; p = 0.037) and anorexia (33% vs 9.0%; p = 0.047). Despite rigorous cancer screening in patients with RS3PE, however, the rate of associated malignancy was not statistically different from that of patients with pure PMR [2 (7%) vs 7 (6%), respectively; p = 0.673].
CONCLUSION: Despite evidence that RS3PE is clinically distinct from PMR, we observed characteristics, treatment response, and outcomes like those expected in pure PMR. Compared to patients with pure PMR, patients with RS3PE are more likely to be male, to be depressed, and to smoke. Contrary to earlier studies, no clear association of RS3PE with malignancy was found despite rigorous cancer screening, although clinicians should be aware that patients with concurrent cancer may manifest more systemic signs and symptoms, as well as steroid resistance.

PMID 22174210  J Rheumatol. 2012 Jan;39(1):148-53. doi: 10.3899/jrheum・・・
著者: Angela Dispenzieri
雑誌名: Blood Rev. 2007 Nov;21(6):285-99. doi: 10.1016/j.blre.2007.07.004. Epub 2007 Sep 11.
Abstract/Text POEMS syndrome is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Recognition of the complex of a combination of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes, papilledema, extravascular volume overload (peripheral edema, pleural effusions, ascites), sclerotic bone lesions, thrombocytosis, Castleman disease is the first step in effectively managing the disease. A rise in the blood levels of vascular endothelial growth factor is usually confirmatory. More than 95% of patients will have monoclonal lambda sclerotic plasmacytoma(s) or bone marrow infiltration. In patients with a dominant sclerotic plasmacytoma, first line therapy should include radiation to the lesion. Retrospective analysis and personal experience would dictate that systemic therapy be considered for patients with diffuse sclerotic lesions or absence of any bone lesion and for those who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation therapy. For those patients with diffuse disease, systemic therapy is indicated. Useful approaches include therapy with corticosteroids, low dose alkylator therapy, and high dose chemotherapy with peripheral blood stem cell transplant. Until the pathogenesis is fully understood, these are the mainstays of treatment for patients with POEMS syndrome. The role of anti-VEGF therapies, immune modulatory drugs, and proteasome inhibitors has not yet been defined, but drugs with known high rates of treatment related neuropathy should not be considered as first line therapy.

PMID 17850941  Blood Rev. 2007 Nov;21(6):285-99. doi: 10.1016/j.blre.2・・・
著者: P H Veldman, H M Reynen, I E Arntz, R J Goris
雑誌名: Lancet. 1993 Oct 23;342(8878):1012-6.
Abstract/Text The pathogenesis of reflex sympathetic dystrophy--variously known as Sudeck's atrophy, causalgia, algodystrophy, and peripheral trophoneurosis--is not yet understood, and diagnosing and treating patients is difficult. We have prospectively studied 829 patients, paying particular attention to early signs and symptoms. In its early phase, reflex sympathetic dystrophy is characterised by regional inflammation, which increases after muscular exercise. Pain was present in 93% of patients, and hypoaesthesia and hyperpathy were present in 69% and 75% respectively. With time, tissue atrophy may occur as well as involuntary movements, muscle spasms, or pseudoparalysis. Tremor was found in 49% and muscular incoordination in 54% of patients. Sympathetic signs such as hyperhidrosis are infrequent and therefore have no diagnostic value. We found no evidence consistent with the presence of three consecutive phases of the disease. Early symptoms are those of an inflammatory reaction and not of a disturbance of the sympathetic nervous system. These data support the concept of an exaggerated regional inflammatory response to injury or operation in reflex sympathetic dystrophy.

PMID 8105263  Lancet. 1993 Oct 23;342(8878):1012-6.
著者: A J Pelosi, R A Sykes, J R Lough, W J Muir, M G Dunnigan
雑誌名: Lancet. 1986 Nov 1;2(8514):999-1002.
Abstract/Text Twenty-five women with idiopathic oedema and twenty-five women attending gynaecology clinics were assessed by means of a standardised psychiatric interview, an interview on dietary habits, and a specially designed interview on current health. The patients with idiopathic oedema were significantly more depressed and anxious, with a trend towards widespread neurotic symptoms. There was no evidence that diuretic or laxative abuse is an important aetiological factor. In many patients with idiopathic oedema excessive fluid retention may be related to the neuroendocrine abnormalities associated with psychiatric illness.

PMID 2877220  Lancet. 1986 Nov 1;2(8514):999-1002.

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから