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  1. 1. Complex regional pain syndrome CRPS, RSD(Reflex sympathetic dystrophy) 13年9月21日土曜日
  2. 2. CRPS • CRPS; 外傷後に生じる神経性 痛を呈する病態の総称. • Causalgia, Sudeck atrophy, Reflex sympathetic dystrophy,Algodystrophy,  Post-traumatic dystrophy, Shoulder-hand syndromeといった病態を含む. • 手術治療後に多く, 末梢の 痛, 浮腫, 発汗低下, 血管調節障害,  運動障害を呈し, しばしば社会復帰を障害させる. • 痛が主だが, 筋萎縮や感覚障害もあり.   痛は末梢, 局所的であることが多く, 間欠的で誘因無く出現する. • また, 明確な診断Criteria, 特異的な検査所見, 治療も無く, 臨床的に問題となり易い. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  3. 3. • CRPSの頻度は<2%と稀. 報告によっては5.5-26.2/100000との報告もある. • 40歳台の女性例が76%を占める. • 部位は上肢が下肢の2倍を占め, 骨折がトリガーとして最多(46%) 10-26%は明らかなトリガーが認められない. 喫煙や飲酒, 糖尿病との関連性は無し. • 外傷後の発症頻度は母集団が不明瞭であり分かっていない. Dupuytren拘縮に対する筋膜切除術の4.5-40%, 手根管症候群の術後 2-5% 橈骨遠位骨折の22-39%で合併する報告あり. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  4. 4. CRPSの原因 • 大半の患者で外傷や虚血, 神経圧迫のトリガーがあるが, なぜ一部の患者でCRPSを発症するかは不明瞭な部分が多い. • 多因子が影響している可能性が高く, 皮膚神経の障害, 末梢, 中枢の感受性の障害, 交感神経の機能障害, カテコラミン循環の低下, 局所の炎症性サイトカインの上昇, 局所の抗炎症サイトカインの低下, 遺伝的問題, 神経的問題が挙げられる. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. Neurology 2013;80:106–117 13年9月21日土曜日
  5. 5. CRPSの3 stage • Stage I (Acute stage 0-3m); 痛と感覚障害で特徴づけられる.  Hyperalgesia, allodynia等. 血管調節障害, 浮腫や発汗障害を来す. • Stage II (Dystrophic stage 3-9m); より 痛, 感覚障害が増強し,  血管調節障害が持続性となり, 筋萎縮も出現する • Stage III (Atrophic stage: 9-18m); 痛, 感覚障害は減弱するが,  血管調節障害は持続し, 筋萎縮が著明となる. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  6. 6. CRPSの診断 • CRPSの診断は病歴と身体所見による臨床的診断が基本. • IASPの診断criteria(1994)は感度99%だが, 特異度は41% • (1) トリガーとなり得る損傷, 体動不能な原因がある (2) 誘発の程度に見合わない 痛, 異痛症, 痛過敏がある. (3) 痛部位に浮腫, 皮膚の血流変化, 発汗異常がある (4) 他に考えられる病態が無い. 診断には2,3,4が必須. 1はどちらでもよい. “Major nerve damage”が無い場合 CRPS I, ある場合 CRPS IIと呼称. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  7. 7. • Budapest criteria(2003)は, 感度99%, 特異度68% • 以下の4項目から3項目以上において, 1つ以上の症状を認め, 同様に2項目以上において1つ以上の所見が認められる.  感覚,  血管運動,  発汗/浮腫  運動/筋萎縮 • 他の診断が除外される. • 神経損傷を伴うCRPSをCRPS type II, 損傷を伴わないものをCRPS type Iと呼び, 更にIASPを満たすがBudapestを満たさないものをCRPS-NOSと呼ぶ Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  8. 8. A study testing the ability of these proposed criteria to differentiate between CRPS and non-CRPS neuropathic pain groups suggested that a modification of the Orlando IASP/CRPS diagnostic criteria could improve overall diag- nostic accuracy [21–23]. Results showed that employing a decision rule requiring two of four sign categories and four of four symptom categories for a positive diagnosis resulted in a sensitivity of 0.70 and a specificity of 0.94. Of all those tested, this decision rule resulted in the highest Table 5 Clinical diagnostic criteria for complex regional pain syndrome 1) Continuing pain, which is disproportionate to any inciting event 2) Must report at least one symptom in three of the four following categories Sensory: Reports of hyperalgesia and/or allodynia Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry Sudomotor/Edema: Reports of edema and/or sweating changes and/or sweating asymmetry Motor/Trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin) 3) Must display at least one sign* at time of evaluation in two or more of the following categories Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement) Vasomotor: Evidence of temperature asymmetry and/or skin color changes and/or asymmetry Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin) 4) There is no other diagnosis that better explains the signs and symptoms * A sign is counted only if it is observed at time of diagnosis. Pain Medicine 2013; 14: 180–229 症状が4/4, 所見が2/4を満たす場合は, 感度70%, 特異度94% samples (minimizing false-positives) vs identification of the highest number of CRPS patients possible (minimizing false-negatives). The Budapest consensus panel therefore implemented a different set of decision rules for proposed clinical criteria (see Table 5), requiring two of four sign categories and three of four symptom categories to be positive [27]. This ostensibly minor adjustment (merely requiring three rather than four symptoms) resulted in a sensitivity of 0.85 and a specificity of 0.69, which repre- sented a good compromise in identifying as many patients as possible at an acceptably accurate rate in the clinical context (see Table 5; for a summary of the sensitivity and specificity of the two criteria, see Table 7). Recently, the Committee for Classification of Chronic Pain of the IASP has accepted and codified the “Budapest” criteria for clinical and research diagnosis (Table 3). In response to the consensus group’s concern with the approximately 15% of patients previously diagnosed with CRPS, a third diagnostic subtype called CRPS-not otherwise specified CRPS Stages? CRPS Subtypes? Is CRPS a uniform phenomenon across individuals, or are there distinct subtypes and/or stages of the syndrome? This issue addressing whether or not patient presenta- tions (i.e., the overall pattern of CRPS signs and symp- toms) tend to be similar across individuals requires validation. Historically, three progressive stages of CRPS have been cited as important in identifying and treating the syndrome (e.g., [4,28,29]), but the existence of such sequential stages is a clinical lore, an unsubstantiated theory based on certain authors’ experience rather than an outcome of specific scientific study (level 4). This hypothesized staging can be tested by using cluster analysis to bracket CRPS patients into three subgroups delineated according to similarity of signs and symptoms. If the theorized stages exist, the subsequent statistically derived patient subgroups should vary considerably with regard to pain duration (i.e., predictable progress of CRPS through the three stages should take place); furthermore, the clinical presentation within the three subgroups should correspond to the three assumed stages of CRPS (best described in Bonica [4]). One hundred and thirteen patients meeting IASP criteria for CRPS went through standardized history and physical examinations designed to evaluate CRPS signs and Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin) 4) There is no other diagnosis that better explains the signs and symptoms * A sign is counted only if observed at time of diagnosis. Table 7 Summary of sensitivity and specificity of the clinical and research criteria Criterion Type Symptom Categories Required for Diagnosis Sign Categories Required for Diagnosis Sensitivity Specificity Clinical Ն3 Ն2 0.85 0.69 Research =4 Ն2 0.70 0.96 13年9月21日土曜日
  9. 9. Clinical diagnostic criteria for CRPS – Budapest Criteria (2003) Table 3 Common clinical characteristics of CRPS Figure 2 * Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  10. 10. A 45-year-old lady with Madelung deformity of both wrists presented with bilateral pain greater in the right wrist in May 2010. Her pre-operative visual analogue scale (VAS) pain score was 2/10. She underwent excision of the distal ulna (Darrach procedure) for the right wrist in June 2010. Post-operatively (July 2010), she continued to have severe pain (VAS: 9/10) and swelling in the wrist and hand. She described the pain as burning in nature. She also complained of numbness of all fingers, frequent colour changes in her hand (purplish hue), and a subjective feeling of objects feeling colder to touch with her right hand compared to the left 13年9月21日土曜日
  11. 11. On examination, the right hand appeared pale, swollen, and with limited range of motion at all joints of the hand and wrist. Her motor power at the wrist and fingers (extension/ flexion) was diminished (grade 3) and skin temperature recordings showed the right side to be 34.2 °C and the left hand to be 33.6 °C. Nerve conduction studies were reported as normal. Patient was diagnosed to have CRPS I and started on gabapentin and oxycodone. On follow-up in August 2010, she did not report any improvement in symptoms and a diagnostic stellate ganglion block was done. She did not have any improvement following the sympathetic block 13年9月21日土曜日
  12. 12. CRPSの検査所見 • 単純XP; 初期では正常像でも, 時間の経過と伴に  関節周囲や斑状の骨萎縮を伴うことがある. • 発症2wk後から認められ始めることがある. • 骨シンチ;Tc99m bisphosphonateが最も高感度. • blood-pool phase(I層), blood phase(II層), scan phase(III層)で評価し, I, II層では斑な造影 (血管運動障害) III層では取り込み増強が認められる. III層にけるMCP, IP関節周囲のバンド形成状の集積はCRPSに特異的. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  13. 13. with a duration of less than 3 months. In our study, TBPS was also particularly helpful when it was performed in the first 6 months. Figure 2 shows the TBPS images in a partial form. Taking all these results together, the role of TBPS in the diagnosis of CRPS is still uncertain. It is certainly not a screening tool for diagnosis of CRPS in which clinical find- ings remain the gold standard. Nevertheless, we believe that TBPS should be only recommended in the first months of the disease progression for unclear situations which do not fully meet the Budapest criteria [29,30]. Based on the pre- sent knowledge, we have proposed a diagnosis flow chart (Figure 3) on the application of the Budapest criteria and of radiology in cases of partial CRPS. The disease course, reported briefly in the literature, is described as favourable in the majority of cases (see Table 1), was modest. Nearly half of our patients (47%) reported im- provement of at least 30% in pain, which is considered the smallest clinically significant change that could be detected [31]. The patients’ perception of global improvement was more than 50 mm and can be defined as clinically signifi- cant change (i.e. more than 30 mm) in 80% of patients. This more global parameter probably reflects patient satisfaction with the whole interdisciplinary rehabilitation process. Re- garding return to work, in our series, 50% of patients didn’t return to work with a follow up of 4 to 9 years. We cannot explain this long lasting sick leave but none of our patients had an invalidity pension related to CRPS. The literature is not very precise, especially concerning return to work, and to date our study is the first to use detailed insurance data. Hence, it could happen that old studies may have been Figure 2 Three-phase bone scintigraphy: early phase (a) and delayed phase (b) Same patient as Figure 1. Staged early and delayed hyperfixation on 4th and 5th fingers suggesting CRPS stage 1. BMC Neurology 2013, 13:28 13年9月21日土曜日
  14. 14. • Thermography; 両側の同じ部位で皮膚温を測定し,  0.5度の差があれば陽性. 1.0度の差は著明な左右差ありと判断 • 発汗テスト; Indicator-starch powderを罹患部位に塗り,  発汗によるPowderの変色を捉える.  他の発汗試験も可で, CRPSの臨床所見との相関が認められる. • 交感神経ブロック; 交感神経由来の 痛と非由来の 痛の鑑別は,  Phentolamine(α1, 2-R阻害薬)のIVにて鑑別が可能. • 交感神経由来の 痛(SMP)では投与後短期間 痛が改善. • また, ブロックも有用で, 上肢ならば星状神経節ブロック, 下肢ならば傍腰椎ブロックで 痛, 症状が改善する. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  15. 15. CRPSの治療 • 治療の目標は 痛コントロールと四肢機能の改善. • どの治療が優れているか, 有用かを評価したStudyは少なく, ほぼEmpilicalな治療となる. • 早期発見, 介入が予後に重要であり, 疑いの時点でペインクリニックへの紹介も1つの手段となる. また, 精神面の対応も必要. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  16. 16. • Physical therapy; 1st lineとなる治療で, 効果も期待できる • 患肢の固定と牽引から始め, マッサージ, 挙上, 緩徐なROM運動, 等張性運動を行ってゆく. • 痛が改善してくればその分強度を増やすが, 痛が増強する様なPhysical therapyは行ってはダメ. • 風呂や電気療法も効果が期待できる. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  17. 17. • 薬物治療; 痛を緩和する目的での投薬 • NSAID, COX-2阻害薬, Opioidが緩和に有用. 他にはGabapentin, Carbamazepine, Ca-modulating drugs(nifidipine, amlodipine, calcitonin, bisphosphonate)が効果が期待できる. • ステロイドは急性のCRPS症例では効果が証明されている. 急性例では炎症性サイトカインが多い病態であり, サイトカインが少ない慢性例で効果があるかどうかは不明. PSL 30mg/d 2-12wkの投与が推奨される. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. Pain Medicine 2013; 14: 180–229 13年9月21日土曜日
  18. 18. • Bisphosphonate(alendronate, pamidronate, clodronate)は Placeboと比較して有意に 痛緩和効果が示された薬剤.  3日間のAlendronate IV, もしくはAlendronateの経口投与は,  CRPS患者の 痛, 浮腫, ROMを有意に改善させたRCTあり.  Meta-analysisでもBisphosphonateの効果は認められている. (Can J Anesth/J Can Anesth (2010) 57:149–166) • また, NACやDimethylsulfoxide,Vit Cといったfree radical scavengersも 効果が期待できるかもしれない.  Vit CはCRPS Iを対象としたRCTで効果が証明されている. • 抗うつ薬も鎮痛作用と精神面への効果が期待できるため,良い選択となる Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. Pain Medicine 2013; 14: 180–229 13年9月21日土曜日
  19. 19. • Regional anaesthesia techniques; 運動療法, 薬物でも反応不良な例. • 2つの方法がある; 交感神経ブロックと交感神経, 体性神経ブロック. 交感神経ブロックは, 診断的ブロックにて著明に改善した例で選択され, 交感, 体性神経ブロックは著明に改善しなかった例で選択される. • ブロック後は速やかに運動療法を開始. 連日のブロック, もしくは隔日のブロック+鎮痛剤使用は大体3wk程度継続 され, 運動療法が進めばブロックの効果が認められたと判断. 効果が無い場合は長期の鎮痛剤使用を考慮する必要がある. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  20. 20. • 手術治療; 外科的, 科学的交感神経切除術 • Controlled trialが無い点, 合併症が多い点からこの治療は推奨されない. Indian J Plast Surg. 2011 May-Aug; 44(2): 298–307. 13年9月21日土曜日
  21. 21. the emerging trend of state-by-state legalization of medical marijuana improves the feasibility of such a trial. Botulinum toxin type A used for years to weaken specific muscles in movement disorders and spasticity works by available in generic formulation [216]. It may have efficacy in some local or focal CRPS phenomena such as allodynia (level 4 evidence) [217]. Capsaicin, the vanilloid compound in chili peppers, is a highly selective agonist for the tran- sient receptor potential channel, vanilloid-receptor type 1 Table 9 Pharmacotherapy guide. The following strategies are suggested for patients who have been diagnosed with CRPS but who cannot begin or progress in the functional restoration algorithm Reason for Inability to Begin or Progress Action Mild-to-moderate pain Simple analgesics and/or blocks (see interventional therapy section) Excruciating, intractable pain Opioids and/or blocks or later, more experimental interventions (see interventional therapy section) Inflammation/swelling and edema Steroids, systemic or targeted (acutely) or NSAIDs (chronically); immune modulators Depression, anxiety, insomnia Sedative, analgesic antidepressant/anxiolytics and/or psychotherapy (see pharmacotherapy section) Significant allodynia/hyperalgesia Anticonvulsants and/or other sodium channel blockers and/or NMDA receptor antagonists Significant osteopenia, immobility and trophic changes* Calcitonin or bisphosphonates Profound vasomotor disturbance Calcium channel blockers, sympatholytics, and/or blocks (see interventional therapy section) It is important to remember that these suggestions are overruled by individual patient presentation. * It is also important to note that certain drugs, such as calcitonin, may be associated with analgesia as well as the more primary action. CRPS = complex regional pain syndrome; NMDA = N-methyl-D-aspartate; NSAID = nonsteroidal anti-inflammatory drug. CRPS Diagnostic and Treatment Guidelines Pain Medicine 2013; 14: 180–229 13年9月21日土曜日
  22. 22. Table 5 Randomized controlled trials comparing treatment with control Therapeutic modality Total number of RCTs comparing treatment with control Number of RCTs with positive findings* Biphosphonates 4 4 DMSO 1 1 Steroids (in CRPS patients with cerebral infarct) 1 1 Steroids (in CRPS patients without cerebral infarct) 1 1 Epidural clonidine 1 1 Intrathecal baclofen 1 1 Motor imagery program 1 1 Spinal cord stimulation 1 1} Calcitonin 4 1 Sympatholytic IVRB (lidocaine/methylprednisolone, guanethidine, reserpine, bretylium, droperidol) 5 0 Neuromodulative IVRB (atropine, ketanserin) 2 0 Vasodilator (tadalafil, sarpogrelate) 2 0 Stellate ganglion/lumbar sympathetic block 1 0 Mannitol 1 0 Gabapentin 1 0 Physical therapy 1 0 Occupational therapy 1 0 * A RCT with positive findings is defined as a trial comparing treatment with control that demonstrates improved primary outcomes in the treatment group. RCTs comparing different therapeutic modalities are not included in this table } Beneficial effects were observed from zero to two years but not from two to five years RCT = randomized controlled trial; DMSO = dimethyl sulfoxide; CRPS = complex regional pain syndrome; IVRB = intravenous regional blockade Can J Anesth/J Can Anesth (2010) 57:149–166 13年9月21日土曜日
  23. 23. • 具体的なリハビリ内容, 治療内容についてはガイドライン参照 SPECIAL ARTICLE Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 4th Edition R. Norman Harden, MD,*§¶ Ann Louise Oaklander, MD, PhD,** Allen W. Burton, MD,†† Roberto S. G. M. Perez, RPT, PhD,*** Kathryn Richardson, MOTR,† Melanie Swan, OTR/L,‡‡ Jennifer Barthel, MS, CRC,‡ Brienne Costa, CTRS/R,§§ Joseph R. Graciosa, BA,* and Stephen Bruehl, PhD¶¶ *Center for Pain Studies, Disclosures: This work was sponsored by the Reflex Sympathetic Dystrophy Syndrome Association (RSDSA), on which Dr. Harden currently serves as the Chairman of the Research Committee and is on the Board of Directors. Dr. Bruehl serves on the RSDSA Scientific Advisory Board. Dr. Burton consults for Medtronic, Inc. and Boston Scientific. Dr. Perez has received consultancy fees and an unrestricted research grant from the Dutch Alliance for Improvement of Paincare (DALI), which is funded by bs_bs_banner Pain Medicine 2013; 14: 180–229 Wiley Periodicals, Inc. Pain Medicine 2013; 14: 180–229 13年9月21日土曜日
  24. 24. 予後因子 • CRPS Iの予後因子はMeta-analysisで精査されているものの, その分野のEvidenceが少なく, 未だ明らかなものは無い. • 一応挙げられているものとして, 229Prognostic factors in complex regional pain syndrome 1 Table IV. Prognostic factors grouped within 7 clinical clusters Cluster Positive prognostic factors Negative prognostic factors Gender (n=3) Female (17) Male (10, 16) Age (n=3) Age at onset <40 years (10) Median age at onset 35 years (17) Age at onset <16 years (16) Diagnosis (n=1) Delayed diagnosis (>2 months after initiating event) (10) Initiating event (n=5) Fracture (7) Spontaneous onset CRPS (10) Polytrauma (11) Initiating event other than fracture (12) Severe initial injury (15) Localization (n=4) Distal articular location (11, 15) Upper extremity (12) Lower extremity (17) Clinical features (n=19) Absence of sensory changes (7) Swelling (7) Disease duration (16) Exercise-induced pain (14) Sensory disturbances (15, 18, 19) Initially cold skin temperature (17) Cold skin temperature (10, 12, 14, 17, 18) Complications (infection, ulcers, chronic oedema, dystonia, myoclonus) (17, 18) Clinical algodystrophy score >7 (7) Low score on general health in SF-36 (16) Disease duration >1 year (20) Coexistence of misdiagnosed nerve injury or compression (20) Contextual factors (n=2) Comorbidities (e.g. alcoholism) (11) Psychological background in non-traumatic CRPS (13) CRPS: complex regional pain syndrome. J Rehabil Med 2013; 45: 225–231 13年9月21日土曜日
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