AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Reflex sympathetic dystrophy syndrome (RSDS) has been recognized since the Civil War when it was called causalgia, a name chosen to describe intense, burning extremity pain after an injury. Since then, RSDS has had a number of name changes. Bonica coined the term reflex sympathetic dystrophy in 1953. The American Association of Hand Surgery proposed changing the name to sympathetic maintained pain syndrome. A consensus expert panel recommended a change to complex regional pain syndrome (CRPS). However, although many clinicians still use the term RSDS, the terms currently in favor are complex regional pain syndrome I (the equivalent of RSD) and complex regional pain syndrome II, also known as causalgia.

CRPS/RSDS has readily identifiable signs and symptoms and is treatable if recognized early; however, the syndrome may become disabling if unrecognized. Emergency physicians are frequently in a position to identify the problem and may play a significant role in minimizing impact of this common entity.

Pathophysiology

No single hypothesis explains all features of RSDS. Schwartzmann stated that a common mechanism may be injury to central or peripheral neural tissue.¹ Roberts proposed that sympathetic pain results from tonic activity in myelinated mechanoreceptor afferents.² Input causes tonic firing in neurons that are part of a nociceptive pathway. Campbell et al propose a hypothesis that places the primary abnormality in the peripheral nervous system.³

Most agree that CRPS is a neurologic disorder affecting central and peripheral nervous systems.

Two new etiologic possibilities have been suggested. German research has noted the association between elevated levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) and enhanced tumor necrosis factor-alpha activity in patients with polyneuropathy with allodynia.⁴ Other German researchers have described autoantibodies in patients with CRPS, especially CRPS type 2.⁵

All agree that, regardless of the mechanism, the patient experiences intense, burning pain in one or more extremities.

Frequency

United States

RSDS occurs in approximately 1-15% of peripheral nerve injury cases. Schwartzmann states that CRPS usually occurs secondary to fractures, sprains, and trivial soft tissue injury.¹ The incidence after fractures and contusions ranges from 10-30%. While some cases are associated with an identifiable nerve injury, many are not. Even "microtrauma" as might occur with an immunization may be responsible. The upper extremities are more likely to be involved than the lower. Entities that have led to RSDS include the following:

• Head injury
• Stroke
• Polio
• Amyotrophic lateral sclerosis (ALS)
• Myocardial infarction
• Polymyalgia rheumatica
• Operative procedures (eg, carpal tunnel release)
• Brachial plexopathy
• Cast/splint immobilization
• Minor extremity injury
• Prolonged bedrest

Mortality/Morbidity

In and of itself, the disease is not fatal. Morbidity of RSDS is associated with disease progress through a series of stages (see Physical).

Race

No racial predilection is noted.

Sex

Stanton-Hicks⁶ and others note that women predominate in a range of 60-80% of cases.

Age

Persons of all ages are affected; however, CRPS is treated most effectively in pediatric patients.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The International Association for the Study of Pain (IASP) lists the diagnostic criteria for complex regional pain syndrome I (CRPS I) (RSDS) as follows:

1. The presence of an initiating noxious event or a cause of immobilization
2. Continuing pain, allodynia (perception of pain from a nonpainful stimulus), or hyperalgesia disproportionate to the inciting event
3. Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the area of pain
4. The diagnosis is excluded by the existence of any condition that would otherwise account for the degree of pain and dysfunction.

According to the IASP, CRPS II (also known as causalgia) is diagnosed as follows:

1. The presence of continuing pain, allodynia, or hyperalgesia after a nerve injury, not necessarily limited to the distribution of the injured nerve
2. Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain
3. The diagnosis is excluded by the existence of any condition that would otherwise account for the degree of pain and dysfunction.

Note that the primary difference between type I and type II is the identification of a definable nerve injury.

Older literature records cardinal and secondary signs. They are worth noting not because they are in common use as primary and secondary but rather because they expand on the constellation of signs and symptoms the ED physician may see in patients.

• Cardinal signs include pain, edema, stiffness, and discoloration.  
• • Pain that is intense and burning, out of proportion to the injury, and affects the entire extremity occurs with RSDS.
  • • Hyperpathia refers to pain that persists after the stimulus has been removed.
    • Allodynia refers to pain with light touch.
    • Movement frequently aggravates pain.
    • Patients describe exacerbations with cold. Many patients feel worse when a low-pressure weather front is arriving. Airplane ascent and descent can be painful.
  • Edema is usually one of the earliest findings.
  • Stiffness may occur.
  • Discoloration may vary from intensely erythematous to cyanotic, pale, purple, or gray.
• Lankford's secondary characteristics include the following:⁷  
• • Demineralization and osteoporosis are among the most classic (late) findings.
  • Sudomotor changes vary from hyperhidrosis to dryness.
  • Temperature difference between affected and unaffected extremities may be marked but is usually measurable at some point in time.
  • Vasomotor instability most commonly is manifested as decreased capillary refill.
  • Erythema may be a sign of increased capillary refill and should be compared with refill in unaffected extremity.
  • Skin may develop a glossy shiny appearance. In late stages, trophic changes may involve a decrease in subcutaneous tissue.
  • In RSDS of the hand, nodules and thickening of the palmar fascia may develop.
• Much RSDS literature notes a predisposing personality of depression. However, many other studies have demonstrated that, while most patients are depressed, they are depressed because of their pain.
• Many patients with CRPS/RSDS will exhibit some type of movement disorder ranging from strength reduction (78%) to tremor (25-60%) to myoclonus and dystonia. Although some authors believe these are pain-induced findings, others believe they are primary abnormalities.

Physical

Three stages have been classified. Although the consensus panel recommended that staging be eliminated, it is important for the emergency physician to have awareness of potential disease progress. Disease progress is very variable.

• Stage I or early RSDS: Pain is more severe than would be expected from the injury, and it has a burning or aching quality. It may be increased by dependency of the limb, physical contact, or emotional upset. The affected area becomes edematous, may be hyperthermic or hypothermic, and shows increased nail and hair growth. Radiographs may show early bony changes. Duration is usually 3 months from onset of symptoms. Some patients remain in one stage or another for many months or even years. They may never progress or they may progress quickly to late stage. Remember that physical findings may be minimal, especially in those who remain in stage I or progress slowly.
• Stage II or established RSDS: Edematous tissue becomes indurated. Skin becomes cool and hyperhidrotic with livedo reticularis or cyanosis. Hair may be lost, and nails become ridged, cracked, and brittle. Hand dryness becomes prominent, and atrophy of skin and subcutaneous tissues becomes noticeable. Pain remains the dominant feature. It usually is constant and is increased by any stimulus to the affected area. Stiffness develops at this stage. Radiographs may show diffuse osteoporosis. The 3-phase bone scan is usually positive. Duration is 3-12 months from onset.
• Stage III or late RSDS: Pain spreads proximally. Although it may diminish in intensity, pain remains a prominent feature. Flare-ups may occur spontaneously. Irreversible tissue damage occurs. Skin is thin and shiny. Edema is absent. Contractures may occur. Radiographs indicate marked demineralization.

Causes

Some authors believe that development of RSDS requires the following triad of conditions: an injury, an abnormal sympathetic response, and a predisposing personality. Others, however, dispute the need for an underlying personality disorder. In August 2000, Schwartzman stated, "There is no evidence that affected patients have a personality disorder, but the severity of pain and the disruption of the patient's life can lead to anxiety and depression."⁸

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Improperly placed splints or casts
Primary neurologic problems, such as carpal tunnel syndrome
Pain and/or edema from fractures or sprains

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• A single, reliable, sensitive, and specific diagnostic test for RSDS is not available.
• Quantitative sensory testing and quantitative sudomotor axon reflex test (QSART) may be performed to look for sensory and sweating abnormalities.

Imaging Studies

• A 3-phase bone scan and gadolinium magnetic resonance imaging (MRI) have been used to diagnose and stage the disease.
• Standard radiographs are normal in as many as 30% of patients. However, they may show osteoporosis as soon as 3-5 weeks of onset.
• Laser Doppler flow studies have been used to monitor background vasomotor control.
• A cold pressor test performed in conjunction with thermographic imaging observes vasoconstrictor response.
• Functional MRI (fMRI) has been used to demonstrate that allodynic stimulation produces objective findings.⁹

Procedures

• Many authors believe that the best diagnostic approach involves use of differential neural blockade. In those with sympathetically mediated pain (as opposed to those whose pain is sympathetically independent), response to neural blockade may help guide medical therapy.
• • For cases involving an upper extremity, a stellate ganglion block may be diagnostic and therapeutic. However, failure to relieve pain does not eliminate the diagnosis.
  • Differential blockade has been performed using Bier blocks with a variety of agents, including local anesthetics, bretylium, steroids, ketorolac, reserpine, and guanethidine.
  • The rationale for selective neural blockade is to interrupt stimulation to the sympathetic nervous system. Again, this is effective only in those whose pain is sympathetically dependent.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

There is nothing for prehospital providers to do except transport. Most state guidelines do not include chronic pain syndromes as an indication for narcotic administration.

Emergency Department Care

Definitive care is really beyond the purview of the ED physician. An emergency physician's primary role with patients who have CPRS/RSDS is to recognize the possibility of the diagnosis and refer such patients to colleagues who are capable of using available therapies. The 3 basic measures in therapy include pain management, rehabilitation (including physical therapy), and psychological therapy.

• Once the diagnosis is established, a number of treatment modalities that have been proven helpful are available. The most effective treatment involves differential neural blockade. 
• The anesthesia literature provides good evidence that spinal stimulation is effective.
• Most patients, especially children, can benefit from physical therapy.
• Tricyclic antidepressants have been used to decrease burning. Gabapentin (Neurontin) and systemic steroids have also been used with varying degrees of success. Other agents include the alpha-1 adrenoreceptor antagonists terazosin and phenoxybenzamine; the alpha-2 adrenoreceptor agonist clonidine; and the NDMA receptor antagonists ketamine, dextromethorphan, and calcitonin. When treatment reaches a plateau invasive interventions to be considered include tunneled epidural catheters and neuroaugmentation.
• In the ED, narcotics often are required to provide temporary relief while waiting for definitive treatment to begin. Patients with refractory disease may present to the ED with flare-ups that require narcotics. Although distinguishing between those who are truly in pain and those who are malingering is very difficult, the clinician must not assume that all who present without an obvious painful problem are drug seekers. Those with CRPS/RSDS may have a paucity of objective findings. Many are under the care of a knowledgeable pain expert and do not allow themselves to run out of analgesia.  
• Breaking through the pain cycle early precipitates a better outcome.
• For patients who cannot be seen in the ED or cannot be treated in an expeditious fashion with neural blockade, the primary care physician who knows the patient best should arrange for narcotic analgesia, recognizing that neuropathic pain may be very resistant to standard analgesics, even potent ones. Patients who fail neural blockade very well may have disease that has progressed to the sympathetic-independent stage, and they are likely to have a lifelong problem. In this group, treatment by specialists in pain management, who have access to more sophisticated and experimental therapies, is mandatory.
• Dadure et al recently described a series of pediatric patients with recurrent CRPS who benefited from continuous peripheral nerve blocks given at home.¹⁰
• Acupuncture has been reported to have some value, especially in children.^{11, 12} 
• In a randomized controlled trial of 84 currently pain-free patients with CRPS, Reuben et al used intravenous regional anesthesia with either lidocaine and saline or lidocaine and clonidine.¹³ All required surgery on the previously affected extremity. The recurrence rate of CRPS was significantly less in those who received the lidocaine and clonidine combination.

Consultations

• Consider consultation with an anesthesiologist regarding pain management.
• Consider consultation with physical medicine personnel regarding rehabilitation.
• Consider consultation with a hand surgeon.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Specialists in pain management (usually anesthesiologists) commonly perform neural blockade. Use of pain modifying agents, such as cyclic antidepressants and gabapentin, usually is left to the primary care physician or pain management team.

The ED physician's primary responsibilities are to recognize the disease and refer patients to an appropriate specialist. However, these patients experience severe pain and should be given sufficient analgesia to provide relief. Narcotics usually are required.

Discussion of available agents has been limited to morphine and hydromorphone. ED physicians choose the agent with which they are most familiar and comfortable. Clinicians who choose to use meperidine should remember that it provides some euphoria and also has an active metabolite that may build up.

Drug Category: Analgesics

Pain relief should be a high priority. Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties. Noted that controversy exists among authors about the appropriateness of chronic narcotic analgesia. Some are opposed.  Others note that when more specific measures fail, patients must have pain relief in order to live their lives. The latter believe that patients with CRPS have a true chronic pain syndrome.

Drug Name	Hydromorphone (Dilaudid)
Description	Used to manage moderate to severe pain. Available IV and PO.
Adult Dose	2 mg PO initial; 1 mg IV slow push initial
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; hypotension; potentially compromised airway with uncertain rapid airway control; hypotension; respiratory depression; nausea; emesis; constipation; urinary retention
Interactions	Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate adverse effects of morphine
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution in atrial flutter and other supraventricular tachycardias; has vagolytic actions and may increase ventricular response rate

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Although not FDA approved in the United States, in some countries, patients are hospitalized and placed on continuous intravenous infusions of medications such as lidocaine or ketamine. As a dissociative anesthetic, the latter is intended to "erase" the memory of dysfunctioning neurons. Results have been variable.

Further Outpatient Care

• It is in the best interest of patients with CRPS to have a physician knowledgeable about this entity orchestrate all care. Appropriate referral is important.

Deterrence/Prevention

• It has been well documented that those who are diagnosed earliest do the best. Once the disease is well established, it probably cannot be reversed.

Complications

• Once refractory to neural blockade, pain is probably lifelong and may be severe enough to be debilitating.

Prognosis

• Prognosis depends largely on timely diagnosis and use of early aggressive therapy.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Because many clinicians are not aware of CRPS, the possibility of misdiagnosis or late diagnosis with consequent poor outcome exists.
• Individuals with CRPS/RSDS may depend on potent analgesia to control pain. Do not assume that they are illegitimate drug seekers.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Apr 3, 2008