COMPLEX REGIONAL PAIN SYNDROME -

ONE OF THE MOST DEVASTATING AND UNRECOGNIZED

PAINFUL CONDITIONS

 W. Scott Shaffer, M.D.

INTRODUCTION

Complex Regional Pain Syndrome (CRPS), formerly known as Reflex Sympathetic

Dystrophy (RSD), is a chronic, painful condition usually affecting the upper

or lower extremities and less commonly the trunk. While the exact cause is

unknown, the pattern of signs and symptoms along with a typical history of

injury to the affected area should lead the clinician to an early suspicion.

Unfortunately, CRPS/RSD remains poorly understood and often misdiagnosed.

When left untreated, this is a disabling disease that can lead to serious

physical and emotional debility that, many times, is not reversible.

Patient response to successful treatment is dependent upon early

detection/recognition, accurate diagnosis, and prompt, aggressive treatment.

A review of CRPS/RSD will assist the astute clinician in recognizing this

challenging pain syndrome.

DEFINITION

CRPS is part of a diverse group of neuropathic disorders and one of the most

painful diseases a person can acquire. It shares several distinctive

clinical features:

· Precipitation by either recent or remote trauma

· Persistent dysesthetic pains

· Autonomic dysregulation

· Local autonomic changes

CRPS is an all-inclusive term applied to a great variety of seemingly

unrelated disorders that have been described separately under many different

names in the past, i.e., minor causalgia, post-traumatic pain syndrome,

post-traumatic spreading neuralgia, post-traumatic vasomotor disorder,

post-traumatic painful arthritis, Sudeck's atrophy, sympathalgia,

shoulder-hand syndrome, chronic traumatic edema, post-traumatic edema, and

reflex dystrophy. The most common terminology used in the past decade to

describe these painful conditions has been reflex sympathetic dystrophy and

causalgia. Reflex sympathetic dystrophy was used when there was no

identifiable nerve damage associated with the trauma and causalgia was used

when there was identifiable nerve damage associated with the trauma. In

1993, complex regional pain syndrome, type I, replaced reflex sympathetic

dystrophy and complex regional pain syndrome, type II, replaced causalgia.

This change was brought about because we recognized that

sympathetically-mediated pain is a continuum of patient complaints and

physical findings and not just a distinct entity. Both types of CRPS are

characterized by an excessive or abnormal response of the sympathetic

nervous system to injury of the extremities in the majority of cases and, in

some cases, no history of trauma can be found.

INCIDENCES/PREVALENCE

The exact prevalence of CRPS is unknown; however, data suggests it is more

frequent than commonly believed. As many as five million people in the

United States suffer from CRPS, types I and II. By far, CRPS type I

patients outnumber the CRPS type II patients. Both sexes are affected but

the incidence appears to be higher in females.

ETIOLOGY OF CRPS

The etiology of CRPS continues to be controversial although an orthopedic

injury to an extremity appears to be the most common predisposing factor.

Some precipitating events can be identified in two-thirds of the cases with

the other one-third occurring "spontaneously." Both iatrogenic causes and

certain diseases have been implicated as well. Iatrogenic causes have

included complications of surgical or medical treatment including

amputations, excision of a ganglion or tumors, tight casts, myelography, and

injection of medications into major nerves. Medical conditions associated

with CRPS include myocardial infarction, diabetic neuropathy, spinal disc

disease, degenerative joint disease of the spine, cerebrovascular accidents,

poliomyelitis, and multiple sclerosis. Reflex autonomic changes have been

proposed as the pathological basis of the syndrome but other factors such as

alterations in central pain transmission and altered production, release, or

reuptake of neurotransmitters may be involved. The peripheral nervous

system appears to play a role of initiation and maintenance of the pain

state and may very well represent maladoptive neuronal plasticity.

Neuronal plasticity is the capability of the nervous system to adjust its

function, structure, and chemistry in response to changing inputs. Normally

these changes are adoptive and promote repair, regeneration, and restoration

of function. In certain circumstances, these modifications malfunction

producing tissue damage and pain. With any painful stimuli, a normal

sympathetic reflex arc is set into motion resulting in temporary

vasoconstriction of the arterial blood supply. However, if this normal

sympathetic response fails to shut down at an appropriate time, an abnormal

reflex may develop resulting in the development of this extremely painful

condition.

CLINICAL FEATURES OF CRPS

The main difference between CRPS type I (RSD) and CRPS type II (causalgia)

is that type II is caused by an injury to a major nerve. The symptoms of

both diseases are identical. The classic signs and symptoms of are pain,

hyperesthesia/allodynia and swelling of extremity; trophic skin and/or nail

changes in the affected limb, and a history of a precipitating event that

typically involves injury to a peripheral nerve. Onset can occur

immediately or within weeks of an injury. Because of the often minor nature

of the precipitating event, the cause of the patients' CRPS may be missed.

In some cases, the pain, edema, and autonomic changes can spread to the

contralateral or epsilateral extremity.

v PAIN: Pain is the first and primary complaint with CRPS. It is typically

described as severe, constant, and burning in nature. Some patients

describe the pain as a deep, aching sensation and others experience pain as

a paroxysmal nature that is exacerbated by different stimuli such as stages

in temperature, stress or anxiety. Even light stroking or gentle touching

of the affected extremity may elicit severe pain. The pain of CRPS is

typically out of proportion to the physical findings or severity of the

initiating injury and usually does not conform to known patterns of

segmental or peripheral nerve distribution.

v EDEMA: Pitting or non-pitting edema is usually localized to the painful

area or limb.

v OTHER CHANGES: Skin atrophy/thinning, tissue atrophy, dryness, scaling,

increased hair growth or loss and nail changes all occur frequently and are

called the sudomotor changes. While these changes occur primarily in the

affected limb, they may progress to other areas over time.

v VASOMOTOR INSTABILITY: Vasomotor changes range from cool-pallid, mottled

changes from vasoconstriction to warm erythematous changes of

vasodilitations. Hyperhydrosis of the affected extremity is a very common

finding in the early onset of this disease. Temperature differences between

the affected and unaffected limbs may vary from 5-10E C. in the early stages

of the disorder.

v DIMINISHED MOTOR FUNCTION: Limitation of movement with eventual dystrophy

and/or atrophy often develop leading to severe loss of the range of motion

in the joints of the affected limb if not treated.

v MUSCLE SPASMS: Moderate to severe spasms occur in the affected limb and

associated musculature. These spasms may become debilitating and add

significantly to the patient's pain levels.

v BONE CHANGES: In early stages, increased vascularity and increased

osteoclastic activity can be identified. In latter stages, significant

diffuse osteoporosis can develop.

STAGING OF CRPS

The following is a list of the major characteristics of the three stages of

CRPS. The later the stage this condition is diagnosed, the poorer the

overall prognosis for salvage of the affected extremities in regard to

reduction of the pain and improvement of the function of the extremity.

STAGE I:

A. Onset of severe, burning pain limited to the injury site.

B. Hyperesthesia of the same distribution.

C. Localized edema.

D. Isolated muscle spasms of the involved limb.

E. Stiffness and limited mobility.

F. Vasospasms (Starts with vasodilatory symptoms progressing to

vasoconstrictive patterns)

G. Hyperhydrosis.

STAGE II:

A. Pain becomes more severe and diffuse.

B. Edema spreads and becomes more pitting in nature.

C. Hair becomes scant, nails become brittle, cracked, and heavily grooved.

D. Osteoporosis appears in a spotty pattern then potentially becoming more

severe and diffuse.

E. Joint spaces increase in thickness.

F. Muscle wasting develops.

STAGE III:

A. Marked trophic changes that eventually become irreversible.

B. The pain may become intractable and may involve the entire limb,

contralateral limb, or epsilateral limb.

C. Muscular atrophy.

D. Extreme weakness of interphalangeal and other joints of the hand or foot

with limited motion and finally ankylosis.

E. Flexor or extensor tendon contractures.

F. Bone deossification is marked and diffuse.

G. Severe, chronic changes occur in about 1% of patients and may include

chronic edema, ulcers, infection and in some cases the need for amputation.

A striking feature of CRPS is that while all cases show the typical pattern

of symptoms with one sign or symptom frequently being out of proportion to

the others. There may be severe pain with little or no vasomotor

disturbance and in others, there may be little pain but intense vasomotor

response. Some may have marked edema with varying vasomotor response and

pain levels. Some patients will progress very rapidly through all the stages

within several weeks to months but others may have no progression beyond the

early stages.

DIAGNOSIS

A high degree of suspicion is a "must" in being able to accurately

recognize, diagnose, and treat the extremely painful and disabling disease.

As stated above, the pain is usually a constant burning type of pain in an

extremity with or without a history of trauma and vasomotor and/or sudomotor

findings may be present. One of the most characteristic complaints is pain

out of proportion to the physical findings. If the above occur, it is

imperative that a referral to a Pain Management Specialist competent in the

management of this disease be made. After the evaluation, the patient will

typically undergo regional sympathetic blockade to either "rule in" or "rule

out" this condition. There is a conspicuous absence of abnormal laboratory

findings in patients with CRPS. Plain films may reveal osteopenia in the

mid- to latter stages of this disease. One of the most helpful diagnostic

studies is a triphasic bone scan which has been shown to have a 96%

sensitivity and 97% specificity in diagnosing CRPS with 99% predictability

in excluding the diagnosis. However, one of the most important diagnostic

tools is relief of pain and modification of the vasomotor and/or sudomotor

signs with regional sympathetic blockade.

TREATMENT

The principal goal in the treatment of CRPS is the restoration of normal

function of the involved limb and reduction of pain. The treatment of this

disease is typically multi-disciplinary due to the fact that no one

treatment alone is uniformly successful. The typical team will involve the

primary or referring physician, Pain Management physician, Physical and/or

Occupational Therapist, and Psychologist and/or Psychiatrist, but not all

cases require the treatment of the entire team. However, this treatment

cannot begin until the disease is recognized or suspected by the Primary

Care Physician, Internist, Orthopedist, Spinal Surgeon, etc. and referred to

a physician who knows how to treat this condition. The general strategies

in the management of patients with CRPS are as follows:

1. Identify the underlying pain generator that precipitated the CRPS

symptoms and treat accordingly.

2. Determine whether the predominant component of the pain is

sympathetically mediated or sympathetically independent. In cases where the

pain is sympathetically mediated, sympathetic blockade should be pursued

aggressively.

3. Functional rehabilitations with aggressive, active and passive

physiotherapy.

4. Psychological management including behavioral modification and active

treatment of associated depression when present.

Once the diagnosis of CRPS is suspected, the Pain Management Physician will

then proceed with diagnostic sympathetic blockade followed by therapeutic

sympathetic blockade if the diagnostic block provided pain relief and

improvement of the vasomotor and/or sudomotor signs. The sympathetic blocks

will typically continue until the symptoms are minimal or until improvement

ceases. At that point, continuous sympathetic block via a catheter placed

in the cervical or lumbar epidural space for 14-21 days with a continuous

infusion of a local anesthetic with narcotics can be quite helpful.

At the same time, aggressive physical and/or occupational therapy needs to

be instituted. Typically, pain relief through the use of sympathetic

blockade is required before more aggressive forms of therapy can be

tolerated by the patient. Oral medications are also beneficial and used as

adjustments in CRPS management. These often include oral analgesics,

antidepressants, anticonvulsants (i.e. Neurontin), muscle relaxants, and

calcium channel blockers. To help reduce the edema, lymphedema management

with compressive dressings can be helpful.

In cases where the above treatments are not effective in controlling the

pain, patients can be effectively managed with advanced pain therapy devices

including spinally administered medications via an implantable pump and/or

spinal cord stimulator. In other cases, surgical sympathetectomy is an

option.

PROGNOSIS

Once the diagnosis of CRPS has been given to an individual patient, the

patient needs to understand that this is a life-long illness and that it is

never "cured". However, significant improvement of the function of the

affected extremity and reduction of the severe pain are obtainable clinical

outcomes. This favorable outcome depends on early recognition followed by

aggressive treatment with a combination of regional sympathetic blockade,

physical therapy, and psychological techniques/modalities. It is important

to stress once again that regional sympathetic blockade is used in

conjunction with the other modalities in order to fully maximize the patient

's chances for a favorable outcome. Studies indicate that the patient's

prognosis is significantly improved if this disease is diagnosed less than

six months from the onset of the disease.

SUMMARY

CRPS is characterized by an abnormal or excessive response of the

sympathetic nervous system to an injury of an extremity however, in a

smaller percentage of patients, no identifiable trauma can be found.

Because this remains a commonly unrecognized and misunderstood condition

which affects millions of people in this country, clinicians need to be

aware of the unrelenting pain and loss of function a patient with complex

regional pain syndrome can suffer. This is one disease that depends on

early recognition and treatment for a favorable outcome.