Complex Regional Pain Xd

PAIN

Complex Regional PainSyndromeDouglas Natusch

AbstractComplex Regional Pain Syndrome (CPRS) is a syndrome associated with

severe pain in a distal limb with associated peripheral sensory, vaso-

motor, sudomotor/oedema and motor/trophic changes. Current interna-

tionally accepted diagnostic criteria are know as the Budapest Criteria

which allow a clinical diagnosis to be made on the basis of a combination

of symptoms and signs seen in these four clinical categories. The

syndrome has also been called Reflex Sympathetic Dystrophy and Algo-

dystrophy in the past. CRPS involves a complex process where local

tissue changes and peripheral & central nervous system changes have

been reported in studies but the pathophysiology has not been fully

explained. Epidemiological studies report a variance in incidence rates

but a higher incidence in women, in the upper limb, after fracture and

also a pattern of recovery is seen. Vitamin C prophylaxis has been demon-

strated to reduce the incidence of CRPS post wrist fracture in a multicentre

study, graded as level 1 evidence. A multidisciplinary approach to

management is recommended.

Keywords Algodystrophy; Complex Regional Pain Syndrome; Reflex

Sympathetic Dystrophy

Introduction

Complex Regional Pain Syndrome (CRPS) is a condition which is

often first seen in Orthopaedic clinics and is a common reason for

referral to a pain team. This article will explore how to approach

diagnosis, and will discuss natural history, pathophysiology and

current approaches to management. It will also make some

recommendations about early management in an Orthopaedic

clinic.

Recognizing CRPS

From time to time you will meet a patient in clinic complaining of

severe pain in a limb, preventing them from using it normally

after a fracture or operation. It is usually unrelenting pain

keeping them awake at night and they may also describe

a number of features they have noticed in the limb such as

Douglas Natusch BSc MBChB FRCA MSc (Pain Management) FFPMRCA Consultant

in Anaesthetics and Pain Medicine, South Devon Healthcare NHS

Foundation Trust, Torbay Hospital, Torquay, UK. Conflicts of interest:

Some material used to write this article is available as an online

presentation provided, by and the copyright of Cardiff University.

“CRPS”, Dr Dougie Natusch, The Pain Community Centre library at

www.paincommunitycentre.org. Other material was presented at

a workshop for The British Elbow and Shoulder Society, Annual Meeting

2012. The author has no other declarations of interest.

ORTHOPAEDICS AND TRAUMA 26:6 405

swelling, temperature and colour change. They could have

noticed that even light touch provokes severe pain and be unable

to wear a sock or shoe, or hold a knife or fork. Their distal limb

can look dusky and poorly perfused or red and swollen. It may

feel either warmer or colder when compared to the other side.

Sometimes a clear peripheral nerve injury can be detected but the

symptoms and signs they report are usually seen in a more

extensive area than the territory of the identified nerve. They

may hold their limb protectively, avoid moving it or occasionally

they seem to neglect it. They can also describe strange or dis-

tressing neurological symptoms.1 Later, they can go on to

develop abnormal hair or nail growth on the affected limb and

radiographs may show patchy osteopoenia.2 They cannot always

function normally and may struggle to cope with social roles.

They can present as distressed, depressed or suffer from another

concurrent mental health disorder, such as post-traumatic stress

disorder, for example, if they suffered significant trauma at the

initiating event.

It is likely your patient has Complex Regional Pain Syndrome

(CRPS). The syndrome has been called a variety of other names

in the past: severe distal limb pain was described as a sequel to

limb injury during the American civil war. The terms Causalgia,

Reflex Sympathetic Dystrophy, Algodystrophy and Sudeck’s

Atrophy have all been used as labels for this condition.3 Ironi-

cally, by the time that you see your patient you may have already

missed the opportunity to use a simple therapy that could have

significantly reduced the likelihood of their developing CRPS

after, for example, as in wrist fracture. The treatment that can

abolish this complication if given early enough is a course of the

antioxidant Vitamin C, 500 mg a day for 50 days and costing as

little as five pounds sterling. This is one of the few examples of

level 1 evidence in the CRPS literature.4

How do I make a diagnosis of CRPS?

The current internationally accepted diagnostic criteria for CRPS

are called the ‘Budapest Criteria’ (Table 1).5 The Budapest

Criteria require a patient to have at least two signs and three

symptoms in four categories e sensory, vasomotor, sudomotor/

oedema and motor/trophic. While this does help to provide

clarity in communicating diagnosis, it introduces a categorical

cut off in patients with symptoms and signs that can vary over

time. The Budapest Criteria do not cover all the features that

have been described in CRPS. Symptoms and signs not encom-

passed by the criteria include the radiographic features described

by Sudeck and other “out of limb” neurological symptoms and

signs implying central nervous system involvement rather than

exclusively a peripheral process.2,6,7

Importantly, however, CRPS is a diagnosis of exclusion. The

Orthopaedic team must exclude pathological causes such as bone

or joint disruption, infection, thrombosis or peripheral vascular

disease if their patient develops a red, hot and swollen or cold and

poorly perfused limb after fracture, after surgery or after both.

What is likely to happen to your patient?

Your patient is likely either to make a complete or a partially

compete recovery over the next 12 months.8,9 One study that

can be used to illustrate recovery prospectively followed 274

patients with distal radial fractures. It reported that 28% of

� 2012 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.mporth.2012.10.001

www.paincommunitycentre.org

The Budapest Criteria, � IASP

C Continuing pain, which is disproportionate to any inciting event.

C Must have at least one symptom in three of the four following

categories:

Sensory: reports of hyperaesthesia and/or allodynia.

Vasomotor: reports of temperature asymmetry and/or skin

colour asymmetry.

Sudomotor/oedema: reports of oedema 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).

C 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

colour changes changes and/or asymmetry.

Sudomotor/oedema: evidence of oedema 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/nails/skin).

C There is no other diagnosis that better explains the symptoms

and signs.

Table 1

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patients had pain, swelling, stiffness and vascular instability

and in up to half of patients one of these features was present 2

weeks after coming out of plaster. At 12 months only around

2% still had all the features. Not all patients recovered

completely, with up to half reporting ongoing stiffness.10

Unfortunately a small minority of patients do go on to have

chronic distal limb pain and the literature describes symptoms

persisting for up to 8 years.11 This pattern of early rapid

recovery in some patients, followed by a pattern of recovery in

the majority of patients over the ensuing 12 months, can

perhaps be compared to the recovery profile of sciatica.

Epidemiological studies suggest a wide range in the incidence

of CRPS, from 5.4 per 100,000 in a US study to 16.3e26.6 per

100,000 in a Dutch study.8,12 Complaints of pain by patients

while still in plaster is associated with the development of CRPS

and should alert the clinician to the possibility that CRPS is

developing.4

What is known about the pathophysiology of CRPS?

Changes have been found both in local tissues and in the

peripheral and central nervous systems. Pro-inflammatory cyto-

kines can be isolated and small fibre axon damage has been

described, along with changes in the vasculature and the pres-

ence of tissue hypoxia.13e15 The damage to small nerve fibres

rather blurs the previous concept that there are two types of

CRPS, one with and one without nerve damage.16 More recently,


the possibility of antibodies to autonomic receptors points to

a more complex peripheral picture.17

CRPS is proposed to involve a process of ‘neurogenic

inflammation’, where the inflammatory process is driven largely

by the nervous system.18 In the brain a pattern of both structural

and functional changes has been reported, based on magnetic

resonance imaging studies.19,20

What therapies are used in CRPS?

Accepted guidance for the management of CRPS centres around

physical therapy-based approaches, focused on reactivation of

the affected limb alongside contextual medical and psychological

interventions.21 The recovery profile of CRPS, particularly in the

early stages, makes the interpretation of studies in acute CRPS

problematic if they are not controlled. Many commonly used

pain therapies have yet to be subject to adequately powered

multicentre studies in CRPS.

Immobilization e is it a helpful strategy?

It has been observed in the plaster room that some patients may

have features of CRPS when they first come out of plaster, such

as muscle wasting, skin colour changes and alterations to hair,

nails and joint stiffness. One study explored the idea that CRPS

may be related to immobilization. A group of 23 volunteers

agreed to wear a forearm cast for a month. It was found that all of

the individuals had at least one symptom or sign typical of CRPS

by the end of the study. Significant changes were also seen on

brain scanning using Positron Emission Tomography. This

implies that immobilization can affect not only the limb but the

brain as well.22 Accepted clinical guidance for CRPS recommends

a return to normal use of the affected limb rather than prolonged

immobilization as a means of achieving pain relief.21

There has been a suggestion that CRPS may be a psychiatric

condition, or a form of somatization disorder. This is because it

can be triggered by minor injury and patients can present with

significant emotional distress and sometimes with co-morbid

mental health problems. The fact that the syndrome is difficult

to diagnose, as there is no specific test for it, and patients tend to

recover over time when they return to normal activity, has

contributed to the debate.23 This view does seem difficult to

reconcile with pathophysiological findings, the fact that antioxi-

dant therapy with Vitamin C can reduce the incidence of the

condition post-fracture and the natural history and epidemio-

logical observations. In one study no link to prior psychiatric

morbidity was found in primary care data, although a systematic

review exploring psychological factors and CRPS found an

association with previous life events, but not other factors.24,25

Some patients with established CRPS have been observed to

have a phobic fear of movement and reinjury of the affected limb

impacting on their ability to engage with rehabilitation. This has

been addressed in selected patients using graded exposure

techniques in one study with positive results.26

Physical and occupational therapy approaches

Physical therapy techniques provide the mainstay for helping

patients return to normal activity. There is no specific evidence

supporting any modality of treatment and ‘Physiotherapy’ can be

used as a term encompassing a number of different approaches.



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Many Physiotherapists or Occupational Therapists will use

a strategy of engaging with their patients to encourage a return to

normal activity, using techniques such as pacing (activity

management) or desensitization, while supporting the patient

during the process. The word desensitization can be used in two

ways. It has been used to describe progressive exposure to touch

or other tactile modalities in the affected area. Alternatively it can

sometimes be used to describe a process involving psychological

desensitization approaches to feared movement(s) in a process of

rehabilitation.26

The changes seen on functional brain scanning and various

clues that the condition involves more than a single limb led to

development of novel neural retraining approaches used by

therapists. One author has described a process of Graded Motor

Imagery for CRPS27,28 and another approach aimed to restore

normal skin tactile discrimination.29

Graded Motor Imagery using a specific motor imagery pro-

gramme is worth discussing, as it is widely used. The programme

involves the patient working through an intensive process of

limb laterality recognition exercises, then imagined limb move-

ments and finally movement of the affected limb to a variety of

positions while it is hidden behind a mirror and moved to match

the reflection of the unaffected limb. It was developed after it was

reported in a pilot study that using mirror visual feedback in

CRPS showed benefit in patients with early, but not in long-

standing, CRPS.30 Neural retraining had been described before,

including using mirror visual feedback, in the management of

phantom limb pain.31 The two randomized trials of graded motor

imagery show improvements in a number of areas including pain

and the process only seems to work when done in the correct

sequence. However, how helpful the mirror component is in the

process has been called into question by the author and the

results of the studies have yet to be fully replicated in clinical

practice in UK centres.9,32

Medical therapies

Gabapentin has been shown to have a mild effect, possibly in

reducing sensory deficit.33 Many common analgesics, including

strong opioids and medications licenced for neuropathic pain,

have not been studied in CRPS. Isolated case reports exist, for

example for topical lidocaine plasters, but this is low-grade

evidence.34 There may be some benefit from a single parenteral

infusion of bisphosphonates.32 Oral steroids are shown to have

benefit in one randomized study, though methodological issues

would probably dictate its replication before steroids can be

recommended for general adoption.35 The anaesthetic agent

Ketamine has been shown in one study to be effective as a topical

10% formulation and medium-term pain relief has been shown

with parenteral ketamine infusions.36,37

Interventional therapies

The traditional ‘gold standard’ interventional therapy in CRPS is

the sympathectomy. It is undertaken on the rationale that in

neurogenic inflammation the peripheral symptoms are driven

partially through the sympathetic nervous system and the

process can be interrupted by applying local anaesthetics to

either the cervico-thoracic or lumbar sympathetic plexus. This

remains a common procedure, with widespread clinical support


in spite of being based on very little high quality evidence.38

Interrupting the sympathetic nervous system using intravenous

regional blocks containing Guanethidine is not supported by the

literature, but there is some evidence of the effectiveness of other

substances when used in intravenous regional blocks.39 Spinal

Cord Stimulation for CRPS has been shown to improve analgesia,

but not necessarily function, and its use in CRPS falls within the

framework of NICE Guidance for stimulation therapy in chronic

pain. It is recognized to be a therapy that will have a diminishing

effect over time.40

Psychological therapies

There are few studies looking purely at psychological therapy in

CRPS. Psychological therapies in chronic pain are generally

integrated with physiotherapy and occupational therapy tech-

niques and delivered in Pain Management Programmes. Some

evidence exists for group Cognitive Behavioural Therapy, CBT,

in children.41 As with most medical treatments, the psychological

approaches to patients with CRPS are usually those commonly

used in the management of patients with chronic pain.

In summary, an eclectic combination of medical, physical and

psychological therapies have some evidence of effectiveness in

CRPS, but no one single therapy is consistently effective in all

patients. Many common treatments have not been subjected to

any trials in CRPS specifically, and the general consensus is that

patients are best served by a multidisciplinary approach

involving combining medical, physical and psychological

therapies.

So back to my patient in clinic. What can I do?

� Explain to the patient what you think the problem is but

investigate to exclude other pathology that may present with

similar symptoms and signs.

� Reassure the patient that if they have CRPS they are

likely to see a degree of recovery with time. Be careful to

stress that in this situation ‘hurt’ does not equal ‘harm’

and that they are not damaging themselves by starting

to rehabilitate their limb. Importantly, they should not

have to wait for complete pain relief before starting the

process.

� Make an urgent referral to Physiotherapy or Occupational

therapy, depending on local arrangements, to start

a process of rehabilitation and activity management. The

therapist will need to spend some time finding out how the

patient is approaching activity and will need to explore

their thoughts and feelings during the process.

� Try to avoid further immobilization.

� Consider starting, or requesting that the patient’s General

Practitioner start, a combination of licenced analgesics and

medications for neuropathic pain.

� Consider making an early referral to your local multidis-

ciplinary pain service if the patient is not showing early

signs of recovery, is struggling to cope with severe pain or

is not showing signs of progress in physical therapy.

Finally, if you want to cut down the likelihood of seeing another

similar patient discuss with your colleagues about developing

a policy of either providing or recommending the use of

prophylactic Vitamin C therapy for patients with wrist fractures



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in your service and consider the advantages and disadvantages of

recommending this to patients with other types of limb fracture.

Summary

Patients who present with CRPS often have severe pain in a distal

limb after injury, with associated autonomic features and

neurological symptoms and signs. CRPS involves a complex

process of peripheral tissue changes and both peripheral and

central nervous system changes. The role of the Orthopaedic

surgeon is to recognize the condition and exclude any other

pathology that may produce the same symptoms and signs. Pain

experienced whilst still in a plaster cast can be a prodromal

symptom. Patients recognized with the syndrome should be

referred for urgent physical therapy to start a process of reha-

bilitation. They can be offered standard analgesics and medica-

tion for neuropathic pain, but should be advised not to wait for

complete pain relief before starting rehabilitation. Do not extin-

guish hope of recovery in the early stages of the condition, as this

is not borne out by the natural history. The majority of patients

with CRPS largely recover in the first 12 months. Evidence exists

for a variety of different medical, physical and psychological

therapies but the picture is clouded by an uneven and incomplete

evidence base and a multidisciplinary approach is recommended

to help the patient navigate their options. Seek early advice from

your local multidisciplinary pain service if your patient is not

improving or is struggling with severe pain. Consider introducing

or advising the use of Vitamin C prophylaxis in your service.A

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Complex Regional Pain Xd