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ment procedure leads to escalation of pain, this
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Guide to Pain Management in Low-Resource Settings
arthrogenic pain
(particularly during
physical examination),
oral glucocorticoids are Chapter 33
indicat- Complex Regional Pain Syndrome
ed (prednisolone in
decreasing doses of Andreas Schwarzer and Christoph Maier
90/60/30/10/5
mg for 14 days).

In 1865, the neurologist Silas Weir Mitchell reported single nerve, e.g., the whole hand is affected following
about soldiers complaining of strong burning pain, pro- fracture of the radius; (3) usually both joints and nerves
nounced hyperesthesia, edema, and reduction of motor are affected; (4) patients often present with psychological
function of the limb following injuries of the upper or disturbances. There are no clinical differences between
lower extremity. Mitchell named these disturbances “cau- CRPS type I and type II; except for the nerve damage.
salgia." In the following years, these symptoms were de-
scribed again and again after extremity injuries but were What is the incidence of CRPS, and
labeled differently (algodystrophy, reflex sympathetic dys-
are there specific triggers?
trophy, Morbus Sudecl<). Currently, this disease pattern is
referred to as complex regional pain syndrome (CRPS). CRPS is a rare disease. Approximately 1% of patients de-
Two types are recognized: CRPS type I without nerve in- velop CRPS following a fracture or nerve injury. How-
jury and CRPS type II associated with major nerve injury. ever, exact data on prevalence do not exist. In a current
study from the Netherlands, the incidence was esti-
What are the main characteristics mated 26/100,000 persons per year, with females being
affected at least three times more often than males. In
of patients with CRPS?
another population-based study from the United States,
As a general rule, the symptoms of CRPS manifest the incidence was estimated at 5.5/ 100,000 persons per
themselves in the distal extremity (usually in the upper year. The upper extremity is more often affected, and a
limb, and less often in the lower limb). Almost all pa- fracture is the most common trigger (60%).
tients (90—95%) suffer from pain, which is described as
burning and drilling and is felt deep in the tissue. Fur- What is the explanation for
thermore, an edema of the affected extremity, with an
development of CRPS?
emphasis on the dorsal areas (dorsum of the hand or
foot) can be observed in almost all patients. Pain and In almost all of the patients (90—95%) there is an ini-
edema increase when the limb is hanging down. Further tiating noxious event (trauma) in the clinical history.
essential disease features are the following: (1) patients The reason why only some patients develop CRPS is
suffer from sensory, motor, and autonomic impairment; still unclear. There is also no comprehensive theory
(2) the symptoms spread beyond the area of the primary that can explain the diversity and the heterogeneity
damage and cannot be assigned to the supply area of one of the symptoms (edema, central nervous symptoms,
Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. This material may be used for educational
and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property
as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the
medical sciences, the publisher recommends that there should be independent verification of diagnoses and drug dosages. The mention of specific pharmaceutical products and any
medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text.
250
joint involvement, etc.). Current attempts explain sin-
gle symptoms, but not the overall picture. An essential
hypothesis about the main pathomechanism for de-
veloping CRPS includes inflammatory processes. This
point of view is supported by the fact that the classic
inflammatory signs (edema, redness, hyperthermia,
and impaired function) are prominent, especially in the
early stages of the disease, and that these symptoms are
positively influenced by the use of corticosteroids.
What is the prognosis of patients
who have developed CRPS?
The number of favorable cases that heal up spontane-
ously or following adequate treatment (and avoidance
of mistreatment), are unknown. Prognosis regarding the
full recovery of function of the affected limb is unfavor-
able, and only 25—30% of all patients fully recover, ac-
cording to the degree of severity and their comorbidity.
The extent of the effects of osteoporotic changes on the
prognosis is still unclear. The following symptoms point
to an unfavorable course of the disease: a tendency to
stiff joints, contracture in the early stages, pronounced
motor symptoms (dystonia, tremor, and spasticity), ede-
ma, and psychological comorbidity.
Which treatment strategies play an
important role in the management
of CRPS?
Treatment should take place in three steps: in the begin-
ning, treatment of pain at rest and treatment of edema
have utmost priority. Next to pharmacological treat-
ment, rest and immobilization are most important. In
the second stage, the therapy should include treatment
of the pain during movement as well as during physi-
cal and occupational therapy. Pain treatment takes a
back seat in the third stage, when the emphasis is on
the treatment of functional orthopedic disorders as well
as on psychosocial reintegration. The intensification of
physical therapy can be limited due to reoccurrence of
pain or edema. The main rule is that the treatment must
not cause any pain.
Case report
Etta, a 58-year-old olfice worker, had bad luck when
she left her house on a rainy day andfell on the slip-
pery steps ofherfront porch. Afracture ofthe left distal
Andreas Schwarzer and Christoph Maier
radius was diagnosed in the hospital. Everything seemed
fine after the fracture was treated by osteosynthesis and
cast, but within afew days after discharge shefelt an in-
creasing constant burning pain in herforearm, and her
fingers got swollen. When visiting her surgeon, she com-
plained about the pain, and the cast was removed.
Are the symptoms a “normal”
consequence of her fracture?
After the application of a looser cast and the prescription
of pain medication, the pain was tolerable, even though
herfingers remained swollen. Six weeks later the cast was
removed, and physiotherapy commenced. A few days lat-
en Etta reported an increase in swelling after the removal
of the cast and said shefelt a stinging, partly burning pain
circularly around the wrist, radiating to the fingers. Fur-
thermore, the movement of her fingers was reduced; the
hand was shiny, swollen, and blueish-reddish.
Once again, is this a “normal”
consequence of her fracture?
Dr. ]ones, the attending physician, recommended inten-
sifying the physical treatment and increasing the doses
of the pain medication. During intensification of physi-
cal therapy, Etta’s fingers were trained forcefully, which
was very painful. With exercise, the pain and swelling
increased, and the hand was still bluish-reddish colored
and shiny. Moreover; Etta noticed an increased growth
of herfinger nails and the hair on the dorsum of her left
hand. Although physical therapy was intensified, the lack
of mobility of the fingers worsened, the hand was con-
stantly swollen, and the pain was burning and almost
unbearable, at rest as well as during movement. Etta be-
came desperate, and Dr. [ones was at the limit ofhis wis-
dom on how to help her.
What should be done?
Why has Dr. Iones’ therapy failed?
Six weeks passed, and Dr. fones referred Etta to a pain
management center. She was still complaining about
the pain, which at that point was radiating to the fore-
arm and elbow as well. Additionally, she reported strong
functional deficits in the hand (it was not possible to
make a fist, and the finger-palm distance was 10 cm).
In the past few days, she had also noticed a restriction
in the shoulder movements (especially abduction). Dr.
Ndungu, the attending doctor from the pain center rec-
ognized the problem and recommended an appropriate
treatment; Etta was lucky.
Complex Regional Pain Syndrome
What are Dr. Ndungu’s options
for further diagnostic procedures?
Based on the diagnostic criteria defined by IASP (see
below) and the course of the disease, Dr. Ndungu diag-
nosed a complex regional pain syndrome. Llpon start of
the treatment at the pain center, he explained to Etta
the disease pattern and the principles of therapy, which
require her active cooperation, understanding, and pa-
tience because progress may be slow, with relapses and
periods of stagnation. He prescribed Etta a splint and
recommended that she position the hand and the fore-
arm higher than the heart, until the edema is reduced.
Coxibs (celecoxib) and anticonvulsants (gabapentin)
were prescribed as pain medications. Physical and occu-
pational therapy was started one week after the decrease
ofthe edema and the pain at rest.
Are there any other therapeutic options?
What are the main rules for therapy?
At the beginning of physical therapy, focus was put on
the shoulder and 2 weeks later normal mobility was re-
gained. The progress of improvement in hand function
was much slower. As soon as Etta exercised too strongly
with her hand or used it for household tasks, the edema
developed again and the pain became stronger. After ap-
proximately 3 months, with physical and occupational
therapy, Etta was able to achieve an improvement in
hand function and a reduction in pain. It took 6 more
months before she was able to return to her olfice and op-
erate her computer with her lefi‘ hand.
Was this a typical course of CRPS?
This case exemplifies a typical course of CRPS with re-
spect to sex, age, injury, and symptoms. However, espe-
cially in the early stages of the disease, it is often diffi-
cult to differentiate between the symptoms of CRPS and
the normal or slightly delayed fracture healing. The di-
agnosis of CRPS is possible only after the development
of typical symptoms, such as an impairment of sensory,
vasomotor, motor, and sudomotor function. In Etta's
case, attention should be focused on two typical clini-
cal phenomena: first, the negative influence of forced
physical exercises on the further course of the disease,
and second, the commonly observed involvement of the
shoulder during the course of the disease. The mobility
of the elbow joint is mostly unaffected, whereas abduc-
tion and rotation of the shoulder joint are often dis-
abled. Patience and individually adjusted physical activ-
ity are essential requirements for patients.
251
What are the clinical
symptoms of CRPS?
The clinical pattern of CRPS is characterized by sen-
sory, motor, and autonomic impairment. Additionally,
patients with CRPS often feel as if the hand or the foot
does not belong to them anymore or as if it is not per-
ceptible or controllable; movements can only be per-
formed under direct visual control (“neglect-like syn-
drome"). Furthermore, the following features occur in
almost all cases:
» The impairment due to CRPS is disproportionate
to the inciting event.
» There is a tendency for a distal generalization
for all symptoms, i.e., not a single finger, but the
whole hand is affected, and the hand is more
strongly affected than the forearm.
» The joint and soft tissue structures are also affect-
ed, with according mobility impairment.
» An edema, depending on position and physi-
cal activity, usually occurs, especially in the early
stages of the disease.
Sensory impairment: Spontaneous pain and hy-
peralgesia in the hand or foot, which is not restricted to
the supply area of a single peripheral nerve, are main
characteristics of the clinical pattern of CRPS. The pain
is described as burning and is felt in the deep tissues;
additionally, sudden pain attacks, described like electri-
cal shocks, are often present. A periarticular pressure
pain of the finger joints is almost always present. As a
rule, strong hypersensitivity to mild painful stimuli (hy-
peralgesia) or pain following usually nonpainful stimuli
(allodynia) can be observed.
Motor impairment: In 90% of all cases, the vol-
untary motor function of all distal muscles is impaired.
Complex movements, such as fist closure or finger-
thumb opposition, are restricted. These movements are
only possible under visual control. Approximately 50%
of patients with involvement of the upper limb develop
a tremor; dystonia or spasticity is seldom found.
Autonomic impairment: Skin temperature dif-
ferences of more than 2°C between the affected and
the unaffected extremity are often present (the affected
side is warmer in about 75% of cases), and they corre-
spond to an altered skin blood flow. About 60% of pa-
tients have hyperhidrosis, and 20% have hypohidrosis.
In the early stages, hair and nail growth on the affected
extremity is often increased, in the further course of the
disease it is often decreased. Dystrophic symptoms (i.e.,
252 Andreas Schwarzer and Christoph Maier

skin and muscle atrophy, connective tissue fibrosis) are
typical for the later stages of the disease; however, they
are not always found.
What are the diagnostic
criteria for CRPS?
CRPS is a clinical diagnosis. There are no laboratory
parameters that confirm the presence or absence of the
disease. Patchy demineralization especially in the peri-
articular regions appears in the radiography some weeks
or months after the disease begins, but it can be seen in
less than 50% of patients with CRPS. CT and MRI ex-
aminations are not specific for the diagnosis of CRPS.
However, triple-phase bone scintigraphy plays an im-
portant role for the diagnosis of CRPS during the first
year after trauma. Band-shaped increased radionuclide
accumulation in the metacarpophalangeal and interpha-
langeal joints of the affected extremity during the min-
eralization phase is a very specific diagnostic criterion.
The current diagnostic criteria are listed below
according to Harden and Bruehl [3]. Aside from differ-
entiation between sensory, vasomotor, sudomotor, and
motor impairment, the physician should discriminate
between anamnestic hints (symptoms) and current clin-
ical signs during the physical examination.
What is the differential
diagnosis for CRPS?
In the clinical routine, it is most essential to differenti-
ate between CRPS and a delayed healing of a trauma
or complaints after long-term immobilization. In the
case of CRPS, not only an increase in pain intensity,
but also a change in the characteristics of pain usually
occurs. Differential diagnosis is nerve or plexus injury,
especially after an operation to treat nerve entrapment
syndromes (carpal tunnel syndrome). However, in these
cases, the symptoms are limited to the area supplied
by the injured nerve. Autonomic impairment does not
prove the diagnosis of CRPS. Furthermore, self-injuri-
ous behavior is another differential diagnosis to CRPS.
What are the treatment
options for CRPS?
The treatment of CRPS should be based on a multidisci-
plinary approach. Next to pain treatment, the recovery
of limb function should play an important role.
Pharmacological options: Traditional NSAIDs
(ibuprofen 3 >< 600 mg) or COX-2 inhibitors (celecox-
ib 2 >< 200 mg) can be taken temporarily for treatment
of CRPS pain. Additionally, metamizol (4 >< 1000 mg)

Table 1
Diagnostic criteria for CRPS (according to Harden and Bruehl [3])
1 Persistent pain, which is disproportionate to any known inciting event
2 The patient must report at least one symptom in three of the following categories (anamnestic hints):
2.1 Sensory Reports of hyperesthesia and/or allodynia
2.2 Vasomotor Reports of temperature asymmetry and/ or skin color changes and/or skin
color asymmetry
2.3 Sudomotor/edema Reports of edema and/or sweating changes and/or sweating asymmetry
2.4 Motor/trophic Reports of decreased range of motion and/or motor dysfunction (weakness,
tremor, dystonia) and/or trophic changes (hair, nails, skin)
3 The patient must display at least one sign in two or more of the following categories during the current
physical examination:
3.1 Sensory Evidence of hyperesthesia and/or allodynia
3.2 Vasomotor Evidence of temperature asymmetry and/or skin color changes and/or skin
color asymmetry
3.3 Sudomotor/edema Evidence of edema and/or sweating changes and/or sweating asymmetry
3.4 Motor/trophic Evidence of decreased range of motion and/or motor dysfunction (weakness,
tremor, dystonia) and/or trophic changes (hair, nails, skin)
4 There is no other diagnosis that would otherwise account for the signs and symptoms and the degree of
pain and dysfunction.
 Complex Regional Pain Syndrome
and opioids (controlled-release) can be prescribed. The
most important adjuvants for the treatment of neuro-
pathic pain are tricyclic antidepressants (amitriptyline)
and anticonvulsive drugs (gabapentin). After taking into
consideration their possible contraindications and their
anticholinergic effects, the physician should increase
the dose slowly. Furthermore, the dose should be high
enough before its eflicacy is evaluated. The dose of ami-
triptyline should be initially 25 mg in the evening (alter-
natively 10 mg). The dose can be increased every seven
days in 25-mg steps up to a maximal dose of 75 mg. The
starting dose of gabapentin is 3 >< 100 mg, and the dose
should be increased in 300-mg steps every three days.
A dose of at least 1800 mg/d should be achieved. Espe-
cially in cases of arthrogenic pain (particularly during
physical examination), oral glucocorticoids are indicat-
ed (prednisolone in decreasing doses of 90/60/30/ 10/5
mg for 14 days).
Invasive therapies: The sympathetic nervous
system can be blocked either by unilateral anesthetic
or blockades of the lower cervical sympathetic ganglion
blocks (stellate ganglion) (10—15 mL bupivacaine 0,5%) or by
lumbar blocks of the lumbar or thoracic sympathetic chain (5
mL bupivacaine 0.5%). Intravenous regional anesthe-
sympat sia blocks are seldom performed because of poor effect
hetic and painful procedures. The indication for a sympa-
chain thetic block is pain at rest despite immobilization and/
or pronounced allodynia. Sympathetic blocks not only
reduce the pain, but can often also improve the motor
and autonomic impairment. However, it is important to
prove that the sympatholysis was technically successful
by noting a significant skin temperature increase in the
supplying area.
Nonpharmacological options: As long as pain
at rest prevails, therapy should be restricted to consis-
tent immobilization of the affected extremity in a po-
sition higher than the heart, supported by a splint and
by lymphatic drainage. After a distinct decrease of the
pain, physical and occupational therapy come to the
fore. Initially, the proximal joints of the affected and the
contralateral extremity should be treated. Especially in
cases of sensory impairment and allodynia, desensitiza-
tion exercises are indicated. The main treatment prin-
ciple should start with stimulus adaptation, followed by
exercises aiming at pain-free mobility and improvement
of fine motor skills, and ultimately movements against
strong resistance.
Therapy for CRPS, with regard to the use of medi-
cal and nonmedical treatment, does not require any
253
particular setting and meets the standards of a com-
munity or primary care level. The application of nerve
block techniques should be reserved for specialized pain
management centers (“referral hospital level”). The ad-
vantage of treatment in specialized pain management
centers is, besides the reliability of making the diagnosis
of CRPS and the use of sympathetic blocks, the greater
experience in dosing the physical and the occupational
treatment—finally, it is perhaps the most essential issue
for the function recovery of the affected extremity.
What are today's insights about
the pathophysiology of CRPS?
Currently, there is no global pathophysiological concept
that explains all the symptoms in CRPS. There are sev-
eral possible explanations. Next to hints for a genetic
predisposition, inflammation seems to play an impor-
tant role. In the context of a neurogenic inflammation,
C fibers and some receptors may release neuropeptides,
inducing clinical signs such as vasodilatation and ede-
ma. Additionally, experts are discussing the concept of a
disease of the central nervous system, in which changes
of the afferent neurons, such as pathological connec-
tions with the sympathetic nervous system, may cause
spontaneous and evoked pain. The pattern of symptom
spread resembles that of diseases of the central nervous
system. The central nervous dysregulation is assumed
to result in maladaptation, for example a change in the
ambient temperature induces an inadequate reaction of
skin blood flow and sudomotor function. Furthermore,
cortical reorganization processes seem to play an im-
portant role, wherein the degree of the reorganization
correlates positively with the spread of the mechanical
hyperalgesia and the pain, which in turn is reversible us-
ing the appropriate treatment.
Pearls of wisdom
~ Three important aspects account for the diag-
nosis of CRPS: pain or functional impairment,
which is disproportionate to the inciting event;
hints of sensory, vasomotor, sudomotor, or motor
impairment in the past; and current findings of
sensory, vasomotor, sudomotor, or motor impair-
ment in the clinical examination
» The treatment must not induce pain. If a treat-
ment procedure leads to escalation of pain, this
procedure must be given up. The following three
insurer

therapeutic steps should be followed: first, treat-
ment of the pain and edema; second, treatment
of the pain, allowing movement; and third, treat-
ment of the functional orthopedic impairment.
» The intensity of physiotherapy must be reduced if
pain increases again or after a new physical trau-
ma.
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Andreas Schwarzer and Christoph Maier
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Websites
http://www.mayoclinic.com/health/complex-regional-pain-syndrome/
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