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Transcript of 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.
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
PAIN
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,
ORTHOPAEDICS AND TRAUMA 26:6 406
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.
� 2012 Elsevier Ltd. All rights reserved.
PAIN
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
ORTHOPAEDICS AND TRAUMA 26:6 407
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
� 2012 Elsevier Ltd. All rights reserved.
PAIN
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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