Complex regional pain syndrome (CRPS) is characterized by persistent pain that occurs after trauma and is disproportionate to the inciting event. It involves pain, swelling, sweating changes, and motor dysfunction localized to limbs, often impairing social reintegration. CRPS is diagnosed clinically based on symptoms in 3 of 4 categories (sensory, vasomotor, sudomotor/edema, motor/trophic) and signs in 2 categories. While diagnostic criteria lack sensitivity and specificity, the Budapest criteria improved accuracy with 2 symptom and 2 sign categories required. CRPS may involve 3 stages defined by increasing pain, dysfunction and trophic changes, though distinct stages are not validated.

1. Complex regional pain syndrome
CRPS, RSD(Reflex sympathetic dystrophy)
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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.
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13年9月21日土曜日

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.
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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. 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.
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13年9月21日土曜日

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.
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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
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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
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9. Clinical diagnostic criteria for CRPS – Budapest Criteria (2003)
Table 3
Common clinical characteristics of CRPS
Figure 2
*
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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
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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
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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. 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. • 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.
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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.
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13年9月21日土曜日

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.
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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.
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13年9月21日土曜日

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
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13年9月21日土曜日

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.
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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.
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13年9月21日土曜日

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
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13年9月21日土曜日

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. • 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. 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
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