eMedicine Specialties > Emergency Medicine > Neurology

Complex Regional Pain Syndrome

Author: Steven J Parrillo, DO, FACOEP, FACEP, Associate Professor, Emergency Medicine, Jefferson Medical College and Philadelphia College of Osteopathic Medicine; Medical Director, Department of Emergency Medicine, Einstein Elkins Park; Chair, Emergency Management Committee, Albert Einstein Healthcare Network; Medical Director, Disaster Medicine and Management Masters Program, Philadelphia University
Contributor Information and Disclosures

Updated: Oct 26, 2009

Introduction

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 reflex sympathetic dystrophy syndrome (RSDS). Schwartzman 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. 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.2

Most agree that complex regional pain syndrome (CRPS) is a neurologic disorder affecting central and peripheral nervous systems.3

Other 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

Harvard researchers Oaklander and Fields have proposed that distal degeneration of small-diameter peripheral axons may be responsible for the pain, vasomotor instability, edema, osteopenia, and skin hypersensitivity of CRPS-1.6

The recent association between the use of ACE inhibitors and CRPS have caused some to consider a neuroinflammatory pathogenesis.7

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

Frequency

United States

Reflex sympathetic dystrophy syndrome (RSDS) occurs in approximately 1-15% of peripheral nerve injury cases. Schwartzman states that complex regional pain syndrome (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:

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).

Schwartzman et al recently reviewed questionnaires from 656 patients with CRPS. Once patients had experienced symptoms for more than one year, the majority of signs and symptoms were developed. No one reported spontaneous remission of symptoms.8

Race

The 2009 questionnaire review by Schwartzman et al showed that, in the population he studied, the overwhelming majority (96%) were white and 80% were female.8

Sex

Stanton-Hicks and others note that women predominate in a range of 60-80% of cases.9

Age

Persons of all ages are affected; however, complex regional pain syndrome (CRPS) is treated most effectively in pediatric patients.10

An Israeli group suggested that CRPS in children and adolescents is underdiagnosed. They emphasize the importance of early recognition and multidisciplinary treatment.11

Clinical

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:12

  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.13 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:13
    • 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 of the 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. (See Causes below).
  • 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.14

Physical

Three stages have been classified. Although a 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

Older literature suggested that development of complex regional pain syndrome (CRPS) required a triad of conditions: an injury, an abnormal sympathetic response, and a predisposing personality. Most current literature disputes 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."15 Beerthuizen et al reviewed 31 articles that addressed an association between psychiatric illness and CRPS-1. Almost all the studies showed no causal relationship.16

Peterlin et al suggested that migraine may be a risk factor for the development of CRPS, but theirs is the only paper of its type.17

ACE inhibitors have recently been suggested as a possible cause for the development of CRPS.7,18

More on Complex Regional Pain Syndrome

Overview: Complex Regional Pain Syndrome
Differential Diagnoses & Workup: Complex Regional Pain Syndrome
Treatment & Medication: Complex Regional Pain Syndrome
Follow-up: Complex Regional Pain Syndrome
References
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References

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  2. Campbell JN, Meyer RA, Raja SN. Is nociceptor activation by alpha-1 adrenoreceptors the culprit in sympathetically mediated pain?. Am Pain Soc J. 1992;1:3-11.

  3. [Guideline] Reflex Sympathetic Dystrophy Syndrome Association (RSDSA). Complex regional pain syndrome: treatment guidelines. Jun 2006;[Full Text].

  4. Maihofner C, Handwerker HO, Neundorfer B, Birklein F. Mechanical hyperalgesia in complex regional pain syndrome: a role for TNF-alpha?. Neurology. Jul 26 2005;65(2):311-3. [Medline].

  5. Blaes F, Schmitz K, Tschernatsch M, et al. Autoimmune etiology of complex regional pain syndrome (M. Sudeck). Neurology. Nov 9 2004;63(9):1734-6. [Medline].

  6. Oaklander AL, Fields HL. Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy?. Ann Neurol. Jun 2009;65(6):629-38. [Medline].

  7. de Mos M, Huygen FJ, Stricker BH, Dieleman JP, Sturkenboom MC. The association between ACE inhibitors and the complex regional pain syndrome: Suggestions for a neuro-inflammatory pathogenesis of CRPS. Pain. Apr 2009;142(3):218-24. [Medline].

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  10. Tong HC, Nelson VS. Recurrent and migratory reflex sympathetic dystrophy in children. Pediatr Rehabil. Apr-Jun 2000;4(2):87-9. [Medline].

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  14. van Hilten JJ, van de Beek WJ, Vein AA, van Dijk JG, Middelkoop HA. Clinical aspects of multifocal or generalized tonic dystonia in reflex sympathetic dystrophy. Neurology. Jun 26 2001;56(12):1762-5. [Medline].

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  31. Sigtermans MJ, van Hilten JJ, Bauer MC, Arbous MS, Marinus J, Sarton EY, et al. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. Oct 2009;145(3):304-11. [Medline].

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Further Reading

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Keywords

complex regional pain syndrome symptoms, complex regional pain syndrome treatment, RSDS, RSD, reflex sympathetic dystrophy syndrome, causalgia, sympathetic maintained pain syndrome, complex regional pain syndrome, CRPS, CRPS I, CRPS II, peripheral nerve injury

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Contributor Information and Disclosures

Author

Steven J Parrillo, DO, FACOEP, FACEP, Associate Professor, Emergency Medicine, Jefferson Medical College and Philadelphia College of Osteopathic Medicine; Medical Director, Department of Emergency Medicine, Einstein Elkins Park; Chair, Emergency Management Committee, Albert Einstein Healthcare Network; Medical Director, Disaster Medicine and Management Masters Program, Philadelphia University
Steven J Parrillo, DO, FACOEP, FACEP is a member of the following medical societies: American College of Emergency Physicians, American College of Osteopathic Emergency Physicians, American Osteopathic Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Joseph A Salomone III, MD, EMS Medical Director, Kansas City, Missouri; Associate Professor and Staff Physician, Truman Medical Centers/UMKC School of Medicine
Joseph A Salomone III, MD is a member of the following medical societies: American Academy of Emergency Medicine, National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Robert E O'Connor, MD, MPH, Professor and Chair, Department of Emergency Medicine, University of Virginia Health System
Robert E O'Connor, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physician Executives, American Heart Association, American Medical Association, Medical Society of Delaware, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

 
 
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