eMedicine Specialties > Neurology > Headache and Pain

Reflex Sympathetic Dystrophy

Author: Eugenia-Daniela Hord, MD, Instructor, Departments of Anesthesia and Neurology, Massachusetts General Hospital Pain Center, Harvard Medical School
Coauthor(s): Sajjad Mueed, MD, Consulting Staff, Department of Medicine, Division of Neurology, Carle Clinic Association
Contributor Information and Disclosures

Updated: Apr 18, 2006

Introduction

Background

In 1994, the International Association for the Study of Pain (IASP), after development of consensus by a group of pain medicine experts, suggested that the term complex regional pain syndrome (CRPS) should replace reflex sympathetic dystrophy (RSD) and causalgia—CRPS type 1 for RSD, and CRPS type 2 for causalgia. However, the IASP diagnostic criteria were never fully validated, and several pain specialists raised concerns about their clinical and scientific value. The criteria have poor diagnostic specificity and may result in overdiagnosis of CRPS.

RSD is a descriptive term meaning a complex disorder or a group of disorders that may develop as a consequence of trauma affecting the limbs, with or without an obvious nerve lesion. RSD also may develop after visceral diseases or CNS lesions or, rarely, without an obvious antecedent event. It consists of pain and related sensory abnormalities, abnormal blood flow and sweating, abnormalities in the motor system, and changes in structure of both superficial and deep tissues ("trophic" changes). Not all components need be present.

The term "reflex sympathetic dystrophy" is intended to be used in a descriptive sense and does not imply specific underlying mechanisms. Most of the definition of RSD can be applied equally well to causalgia; however, CRPS type 1 (ie, RSD) occurs without a definable nerve lesion, while type 2 (ie, causalgia) refers to cases in which a definable nerve lesion is present.

Evans described RSD as a syndrome with the following manifestations:

• Pain and swelling at a site remote from the inciting injury
• No obvious local tissue damage
• Altered skin color
• Altered sweat production

On the basis of the description by Veldman et al, diagnosis of RSD can be made if the following clinical grounds are met:

• At least 4 of the following 5 symptoms/signs are present: unexplained diffuse pain, altered skin color, altered skin temperature, edema, reduced active range of motion
• Symptoms aggravated by activity of the extremity
• Symptoms present in an area much larger than and also distal to the primary injury

IASP diagnostic criteria for CRPS are the following:

• The presence of an initiating noxious event, or a cause for immobilization
• Continuing pain, allodynia, or hyperalgesia that is disproportionate to any inciting event in severity
• Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain
• Exclusion of conditions that would otherwise account for the degree of pain and dysfunction. The distinction between CRPS with (type 2) and without (type 1) nerve injury is based on findings on electromyography (EMG) and nerve conduction studies (NCS). The clinical validation of these criteria still is being debated.

Associated signs and symptoms of CRPS listed in IASP taxonomy but not used for diagnosis are as follows:

• Atrophy of hair, nails, and other soft tissues
• Alterations of hair growth
• Loss of joint mobility
• Impairment of motor function, including weakness, tremor, and dystonia
• Sympathetically maintained pain - May be present

Staging has no clinical value, but for historical interest the authors would like to mention that the course commonly was divided into the following 3 stages:

• Acute or hyperemic
• Dystrophic or ischemic
• Atrophic

Pathophysiology

No consensus exists regarding the pathogenic mechanisms involved in RSD. Hypotheses include (1) sympathetic nervous system (SNS) dysfunction leading to sympathetically maintained pain (SMP), (2) peripheral dysfunction, (3) central dysfunction, and (4) inflammatory process.

SNS involvement in the mechanism of RSD/CRPS type 1 is supported clinically by the presence of abnormal temperature and color of the skin as well as altered sweat excretion in the affected extremities. Surgical and chemical sympathectomy can relieve pain in some cases. The prevailing hypothesis is that posttraumatic sympathetic-afferent interaction can be established, so that sympathetic efferents can enhance primary afferent nociceptor activity. The coupling of sympathetic and afferent neurons can occur peripherally or at the level of dorsal root ganglia. Experimental studies have demonstrated that within 2 weeks of a nerve lesion that spares a significant number of axons, electrical stimulation of the sympathetic trunk and injections of catecholamines can activate or sensitize C-nociceptors.

The peripheral dysfunction is related to peripheral denervation and/or sympathetic denervation. Initially, vasodilatation is present in the denervated area. Later, the vasculature may develop increased sensitivity to circulating catecholamines due to up-regulation of adrenoreceptors.

The central dysfunction may be related to the effect of high levels of discharge originating in sensory fibers within the affected extremity. These discharges may induce changes in the autonomic CNS and subsequently an alteration in central autonomic control. Clinically, hyperhidrosis is found in many patients with RSD but cannot be explained by a peripheral mechanism, because unlike blood vessels, sweat glands do not develop denervation hypersensitivity.

Early RSD/CRPS type 1 has an inflammatory component. Substance P and other neuropeptides are considered to be the cardinal mediators of neurogenic inflammation. Analyses of joint fluid and synovial biopsies in patients with RSD have shown an increase in protein concentration, synovial hypervascularity, and neutrophil infiltration. Response of RSD/CRPS type 1 to steroids further supports the notion of an inflammatory process.

Frequency

United States

Surveys of veterans suggest that the incidence of causalgia following injury to a peripheral nerve is 1-5%. Little is known about the epidemiology of CRPS type 1 in the United States or internationally. The reported incidence of CRPS type 1/RSD is 1-2% after various fractures, 2-5% after peripheral nerve injury, and 7-35% in prospective studies of Colles fracture. The likelihood of developing CRPS/RSD is higher if the lesion is distal or if the sciatic nerve is affected.

Mortality/Morbidity

• Despite treatment, many patients are left with varying degrees of chronic pain, atrophic changes, and disability. Pain is the most important factor leading to disability.
• Some have suggested that aggressive treatment of pain in an acute setting could reduce the incidence of CRPS type 1/RSD, although further studies are needed to support this observation. Remissions followed by relapse also have been described.
• The frequency of the HLA-DQ1 antigen appears to be higher in patients with CRPS type 1 than in controls. However, no genetic marker is known for CRPS type 1/RSD.

Race

RSD affects all races; no racial predilection is observed.

Sex

A female predominance exists; female-to-male ratio is 2:1.

Age

• Mean age of patients at their initial evaluation in pain centers is approximately 40-42 years.
• The highest incidence of the disease appears to be in adults aged 40-49 years; it appears frequently in almost every age group except children. RSD/CRPS type 1 has been described in children, but the incidence is much lower than in adults.

Clinical

History

Often symptoms of CRPS type 1 begin immediately, days or weeks after an injury, usually in a distal extremity. Rarely, the onset can be months after the injury. Usually one limb is involved, but rarely the involvement can be bilateral (4-5%), and very rarely 3 or 4 extremities can be affected. CRPS type 1 can be acute (first 2 months) or chronic (after 2 months). Approximately half of patients with CRPS type 1 report it to be related to an on-the-job injury.

• Clinical features of CRPS type 1/RSD are influenced by the following:
  • Duration: As many as 80% of patients with initial symptoms of CRPS type 1/RSD are cured within 18 months from onset, spontaneously or with treatment. Greater duration of CRPS is related to significantly greater likelihood of abnormalities of sensation and less likelihood of sweating abnormalities or edema.
  • Location: The pain and other symptoms can be located virtually located anywhere in the body. Extremities are involved most often, although locations such as external genitalia or nose may be involved. Patients may have pain at the ulnar styloid process after Colles fracture or at the lateral malleolus after a sprain. Frozen shoulder and/or tendinitis of biceps often accompany CRPS type 1/RSD in the hand.
• Symptoms of CRPS type 1 include the following:
  • Spontaneous pain: Pain that is not limited to the territory of a single peripheral nerve is the cardinal feature of CRPS. The character of pain can be burning (most often), aching, throbbing, or tingling. The pain is aggravated by activity of the extremity, and its severity is typically disproportionate to the inciting event.
  • Difficulty/inability in using the affected extremity
  • Neglect-like symptoms: These include "cognitive neglect" in which the limb may feel foreign and "motor neglect" in which directed mental and visual attention are needed to move the limb.
  • Altered skin temperature: This often is noted as a difference in skin temperature between the affected and unaffected limbs. At onset, the affected extremity is warmer in two thirds of cases and colder in one third. Many patients give a history of warmer extremities at onset and colder extremities later in the evolution of the disease. Some authors describe "primarily cold RSD" and "primarily warm RSD."
  • Rapid fatigability: This is almost invariably present in late stages.

Physical

• The impairment of motor function is present in about 80-90% of patients at some point in the disease and consists of paresis or pseudoparalysis or clumsiness.
• Range of motion often is limited secondary to motor deficit and/or pain.
• Tremor of the affected limb is present in about half of the patients in late stages.
• Dystonia of the affected foot or hand is described in 10% of patients in late stages.
• Muscle spasms are present in 25% of patients in CRPS type 1/RSD of longer duration.
• Hypoesthesia is described in about 70% of patients and most often is present in a glovelike or stockinglike distribution. Hemihypoesthesia also is described; hypothermesthesia and loss of proprioception are described in some cases.
• Anesthesia dolorosa is sometimes present; this means the sensitivity to touch is absent while severe pain is present in that area.
• Allodynia (ie, pain to touch) is described in 70-80% of patients.
• Hyperpathy (ie, exaggerated response to painful stimuli) is present in 70-80% of patients.
• Abnormal sweating is a sign of autonomic dysfunction. About half of the patients have hyperhidrosis.
• Edema is secondary to autonomic dysfunction. Sometimes persistent edema is caused by infection of the atrophic soft tissues.
• Altered skin color is related to vasomotor changes. Skin discoloration and atrophy can occur later. Brown-gray scaly pigmentation of the skin in the affected limb is described in some studies.
• Atrophy of soft tissue, muscles, and bones also can occur. The trophic changes are not included in the IASP criteria because so far the pathophysiology is unknown and they might result from simple disuse of the extremity.
• Altered skin temperature reflects vasomotor instability and leads to "primarily cold RSD," "primarily warm RSD," or "secondarily cold RSD." At the time of assessment by a physician, approximately 5-10% do not have a significant difference in skin temperature, about 40-45% have a warmer affected extremity, and 40-45% have a colder affected extremity.
• Hypotrichoses often is noticed in the affected area. Sometimes hypertrichosis is present, and this is considered a sign of sympathetic dysfunction. However, hypotrichosis or hypertrichoses is irrelevant for establishing the diagnosis.
• Altered nail growth is also a sign of sympathetic dysfunction; however, it is not reliable for diagnostic purposes.

Causes

Most often CRPS type 1 is initiated by trauma to an extremity. Such injuries account for more than 90% of patients with RSD/CRPS type 1.

• Injuries precipitating the development of CRPS in decreasing order of frequency are as follows: (1) sprain/strain, (2) surgical wounds, (3) fractures, (4) contusion/crush injury, and (5) rarely, other injuries such as venipuncture, lacerations, burns, inflammatory processes, electric shock, and spinal cord injuries.
• Spontaneous cases/unknown causes account for approximately 5% of patients and often may be explained by minor injuries that have been forgotten.
• Unusual precipitating events supposedly accounting for RSD/CRPS type 1 include visceral lesions, CNS lesions (eg, stroke, tumors, brain injury, amyotrophic lateral sclerosis, meningitis, syringomyelia), peripheral vascular bypass procedures, arteriovenous graft for hemodialysis, carpal tunnel surgery, and spinal cord injury.

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