Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy) 

Updated: Sep 09, 2018
Author: T P Sudha Rao, MD; Chief Editor: Herbert S Diamond, MD 

Overview

Practice Essentials

Type 1 complex regional pain syndrome (CRPS 1), formerly known as reflex sympathetic dystrophy (RSD), is a clinical syndrome of variable course and unknown cause characterized by pain, swelling, and vasomotor dysfunction of an extremity. This condition is often the result of trauma or surgery. Limb immobility may lead to CRPS 1; in a hemiplegic upper limb after stroke, the syndrome is often termed shoulder-hand syndrome. CRPS 1 may also develop in the absence of an identifiable precipitating event.

Current taxonomy categorizes CRPS 1 as occurring in the absence of definable nerve injury.[1] Type 2 CRPS, causalgia, develops after nerve injury; the term causalgia was coined by Mitchell in 1864 and derives from the Greek for burning pain. In patients with either type 1 or type 2 CRPS, sympathetic mediation of the pain (ie, improvement with sympathetic blockade) may or may not be evident.

CRPS 1 is largely a clinical diagnosis (see Presentation and DDx). Two major approaches to the treatment of early CRPS 1 are sympathetic blockade and anti-inflammatory therapy. Surgical sympathectomy may be considered in patients with refractory CRPS 1 that had initially responded to sympathetic blockade. Spinal cord stimulation is another surgical option. (See Treatment and Medication.)

For discussion of all types of CRPS, see Complex Regional Pain Syndromes. 

Pathophysiology

The pathogenesis of CRPS 1 is unknown. Three conditions are deemed important in the development of CRPS 1, as follows:

  • A persistent painful lesion
  • A predisposition or susceptibility to developing the syndrome
  • An abnormal sympathetic reflex

Susceptibility factors are unknown and may include genetic predisposition (HLA typing)[2, 3, 4] and, in some patients, a tendency toward increased sympathetic activity. This includes cold hands, hyperhidrosis, or a history of fainting.

Healthy individuals have a sympathetic response to injury, with vasoconstriction designed to prevent blood loss and swelling. This initial response soon subsides and gives way to vasodilatation and increased capillary permeability, allowing tissue repair.

In patients with CRPS 1, this sympathetic response continues unabated. The reasons for the perpetuation of the response are unknown but may be related to central dysregulation of nociceptive impulses. This dysregulation may be mediated by wide dynamic range neurons in the spinal cord.

Prolonged ischemia caused by the vasoconstriction produces more pain, establishing a reflex arc that promotes further sympathetic discharge and vasospasm. This is compounded by the local response to trauma, with liberation of substantial amounts of proinflammatory mediators, such as histamine, serotonin, and bradykinin.

The result is a swollen, painful, stiff, nonfunctioning extremity. At least partial sympathetic mediation of this phenomenon is likely because of the ability of sympathetic nerve blockade to relieve pain and other features of CRPS 1 in some patients.

Numerous studies have reported altered brain function in CRPS 1. Researchers have also documented structural alterations in the brain. Pleger et al reported that magnetic resonance imaging (MRI) in patients with CRPS 1 showed altered gray matter structure in dorsomedial prefrontal cortex, as well as increases in gray matter density in the motor cortex contralateral to the affected limb, which were inversely related to decreased white matter density of the internal capsule within that brain hemisphere.[5]

A study by Barad that used structural MRI found that compared with controls, patients with complex regional pain syndrome had decreased gray matter volume in several pain-affect regions (including the dorsal insula, left orbitofrontal cortex, and several aspects of the cingulate cortex) and increased gray matter volume in the bilateral dorsal putamen and right hypothalamus.[6]

Lee et al found that the right dorsolateral prefrontal cortex and left ventromedial prefrontal cortex were significantly thinner in patients with CRPS than in healthy controls. In addition, CRPS patients had longer stop-signal task reaction times and made more perseveration errors on the Wisconsin Card Sorting Test.[7]

Etiology

CRPS 1 is usually posttraumatic or postsurgical; however, it can occur in a previously healthy extremity with no known trigger.

Penetrating wounds that can lead to CRPS 1 include the following:

  • Lacerations

  • Abrasions

  • Venipuncture

  • Intramuscular injection of medication or illicit drugs

  • Gunshot wounds

Other traumatic causes of CRPS 1 include the following:

  • Crush injuries and blunt trauma

  • Neck or shoulder injuries

  • Acute traumatic carpal tunnel syndrome

  • Chest trauma

  • Sprain, fracture, or dislocation

Postsurgery CRPS 1 has been reported after the following procedures:

  • Carpal tunnel release

  • Dental extractions

  • Cervical rib resection

  • Fracture repair (Colles fracture)

  • Arthroscopy

Local disorders associated with CRPS 1 include the following:

  • Nerve compression syndromes

  • Arthritis

  • Tissue ischemia

  • Stenosing tenosynovitis

Systemic disorders associated with CRPS 1 include the following:

  • Myocardial infarction

  • Stroke

  • Pancoast tumor

  • Pancreatic cancer

  • Herpes zoster

Epidemiology

Frequency

In the United States, an estimated 5% of patients who experience trauma to the upper extremity develop CRPS 1, although this figure is not known with certainty because of confusion over the diagnosis. Extremity immobilization can trigger CRPS 1. Without prophylactic measures (active physical therapy), CRPS 1 can develop in 12-20% of people who experience a hemiplegic stroke.

Race-, Sex-, and Age-related Demographics

No racial predilection exists for CRPS 1. Sexual distribution is equal. Although CRPS 1 can occur in children, the age of onset in most patients CRPS 1 is 30-60 years, and the mean age is 49 years.[8]

A Scottish study estimated that the incidence of CRPS in children 5-15 years of age is 1.2 per 100,000. Girls constituted 73% of patients. Most cases involed a single site, with legs often affected than arms and the right side more often affected than the left. Clear trauma had occurred at the onset of the illness in most cases. Diagnosis was made a median of 2 months (range, 1-12) after the onset of symptoms.[9]

 

Presentation

History

The three clinical stages of type 1 complex regional pain syndrome (CRPS 1) are acute, subacute, and chronic. The acute form lasts approximately 3 months. Pain, often burning in nature, is one of the first symptoms that initially limits function. Swelling, redness with vasomotor instability that worsens with dependency, hyperhidrosis, and coolness to the touch are common physical findings. Demineralization of the underlying bony skeleton begins because of disuse.

If the process is not arrested or reversed in the acute phase, the condition may progress to the subacute stage, which can last for up to 9 months. The patient develops persistent severe pain in the extremity and fixed edema that would have been reversible with elevation during the acute phase. The redness of the acute stage gives way to cyanosis or pallor and hyperhidrosis to dry skin. Loss of function progresses, both because of increased pain and fibrosis of the joints caused by chronic inflammation. In the hand, this leads to flexion deformity of the fingers. The skin and subcutaneous tissues begin to atrophy. Demineralization of the underlying bony skeleton becomes pronounced.

If the process continues, the chronic phase may develop approximately 1 year after disease onset. This stage may last for many years or can be permanent. Pain is more variable during this period. It may continue undiminished or abate. Edema tends to subside over time, leaving fibrosis around the involved joints. The skin is dry, pale, cool, and shiny. Flexion and extension creases are absent. Loss of function and stiffness are marked, and osteoporosis is extreme. In the upper extremity, this can manifest as a frozen shoulder and claw hand.

A thorough general history is strongly suggested. Maintaining a high index of suspicion is important because proper treatment requires rapid diagnosis and prompt therapy.

CRPS 1 commonly involves only one extremity. It is bilateral in approximately 25% of cases, but in those cases it is usually more prominent on one side.

Pain in CRPS 1 has the following characteristics:

  • Usually constant and disproportionate to the precipitant injury

  • May be exacerbated by ambient factors such as loud noises and emotional factors (eg, stress, light touch, active motion, passive motion)

  • May be described as burning, cutting, searing, pressure, or tearing

  • Usually begins locally but may progress to involve the entire extremity

Possible evidence of prior increased sympathetic activity includes the following:

  • Hyperhidrosis

  • Cold hands

  • Fainting

Precipitating factors may include any of the following:

  • Prior trauma, which may be trivial (eg, venipuncture) or significant (eg, Colles fracture), with or without diagnosable nerve injury

  • Prior surgery

  • Recent limb immobilization due to hemiplegic stroke, myocardial infarction

  • Systemic disease such as diabetes

Physical Examination

Perform a thorough physical examination followed by a focused examination of the involved extremity. Patients with CRPS 1 may present with suggestive physical findings that point to a presumptive diagnosis (eg, edema, stiffness, discoloration, abnormal skin moisture, tenderness).

Edema is the most consistent physical finding and is always disproportionate to the severity of the precipitant injury or event. Pain, swelling, and color change may be more prominent with dependency in the early stages. Edema worsens rather than improves and extends beyond the region of initial concern. It evolves into a brawny, nonpitting edema that may progress to an intense fibrosis in all the joints of the extremity.

Stiffness is more severe than expected and may be very distressing to the patient.

Discoloration varies depending on the stage of disease. It may be dusky, cyanotic, pale, or red and may eventually lead to skin hypopigmentation. In the hand, discoloration begins as redness over the metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joint flexion creases early in the disease and progresses as a streak across the palm.

Early in the course of CRPS 1, abnormal skin moisture consists of hyperhidrosis. Late in the course, it consists of dry skin.

Tenderness is initially localized but may progress to generalized tenderness. Exquisite tenderness, both periarticular and interarticular, is often present. Patients may exhibit allodynia (ie, pain with nonnoxious stimuli) and hyperpathia (ie, persistent pain after light pressure).

Other physical findings may include the following:

  • Atrophy of the skin and subcutaneous fat pads

  • Fibrosis of the palmar fascia

  • Absence of extensor and flexor creases over joints

  • Frozen shoulder, flexion deformities of the fingers, claw hand

 

DDx

Diagnostic Considerations

The International Association for the Study of Pain (IASP) has developed criteria (also known as the Budapest criteria) for the clinical diagnosis of complex regional pain syndrome and continues to update these criteria.[10] Current IASP criteria are presented below.

A clinical diagnosis can be made when four criteria are met. The first is continuing pain that is disproportionate to any inciting event.

Second, the patient must report at least one symptom in at least three of the following categories:

  • Sensory: Hyperalgesia, allodynia

  • Vasomotor: Temperature asymmetry, skin color changes, skin color asymmetry

  • Sudomotor/edema: Edema, sweating changes, sweating asymmetry

  • Motor/trophic: Decreased range of motion, motor dysfunction (eg, weakness, tremor, dystonia), trophic changes (eg, hair, nail, skin)

Third, at time of evaluation the clinician must observe at least one sign in at least two of the following categories:

  • Sensory: Evidence of hyperalgesia (to pinprick), allodynia (to light touch, temperature sensation, deep somatic pressure,  joint movement)

  • Vasomotor: Evidence of temperature asymmetry (> 1° C), skin color changes or asymmetry

  • Sudomotor/edema: Evidence of edema, sweating changes, or sweating asymmetry

  • Motor/trophic: Evidence of decreased range of motion, motor dysfunction (eg, weakness, tremor, dystonia), trophic changes (eg, hair, nail, skin)

Fourth, there must be no other diagnosis that better explains the signs and symptoms

Differential diagnosis

Differential diagnostic considerations include the following[11] :

  • Infection (of bone, soft tissue, joint, or skin)
  • Orthopedic malfixation
  • Joint instability
  • Arthritis or arthrosis
  • Bone or soft tissue injury (eg, stress fracture, instability, ligament damage)
  • Compartment syndrome
  • Neural injury (peripheral nerve damage, including compression or entrapment, or central nervous system or spinal lesions), or neuropathy (such as from diabetes mellitus or alcohol misuse)
  • Thoracic outlet syndrome (due to nerve or vascular compression)
  • Arterial insufficiency (usually after preceding trauma, atherosclerosis in older people, or thrombangiitis obliterans [Burger disease])
  • Raynaud syndrome
  • Lymphatic or venous obstruction
  • Gardner–Diamond syndrome
  • Brachial neuritis or plexitis (Parsonage-Turner syndrome or neuralgic amyotrophy)
  • Erythromelalgia (may include all limbs)
  • Self-harm

Differential Diagnoses

 

Workup

Laboratory Studies

Laboratory studies are not useful for the diagnosis of complex regional pain syndrome (CRPS). Levels of acute-phase reactants (ie, erythrocyte sedimentation rate [ESR], C-reactive protein) are generally within the reference range.

Radiography

Plain radiographs usually demonstrate pronounced demineralization in the underlying bony skeleton of the involved extremity (ie, Sudeck atrophy) that may become more severe with disease progression. No joint erosions are present. Demineralization begins at the ends of the bones and progresses to become homogeneous.

Radionuclide Imaging

Findings on three-phase radionuclide bone scans are positive in 50-90% of patients with CRPS, and this study is most useful in early disease. Findings on the delayed image (ie, third phase) are generally abnormal, with increased uptake in the articular and periarticular structures of the involved extremity. Of course, this finding is not specific for CRPS) but is supportive of that diagnosis in the appropriate clinical situation. In chronic CRPS, the bone scan findings may be normal, but the plain radiographs generally reveal profound demineralization of the affected extremity. For more information, see Reflex Sympathetic Dystrophy Imaging.

 

Treatment

Approach Considerations

United Kingdom guidelines on complex regional pain syndrome (CRPS) list four ‘pillars’ of CRPS care: education, pain relief (medication and procedures), physical rehabilitation, and psychological intervention. All four are of equal importance, and addressing them may require involvement of a range of specialties, such as physiotherapy, pain medicine, rheumatology, neurology, and surgery.[11]

International guidelines for the management of CRP, sponsored by the Reflex Sympathetic Dystrophy Syndrome Association (RSDSA) and most recently updated in 2014, acknowledge the paucity of high-level studies, and thus base the recommendations on literature review supplemented with clinical expertise. The guidelines include a treatment algorithm focused on functional restoration provided by an interdisciplinary team (eg, occupational, physical, recreational therapist; vocational rehabilitation counselor).[10]  

In addition, the guidelines recommend providing access to medications, psychotherapy, and/or injections from the start of treatment, if needed and appropriate. If the patient cannot begin treatment or fails to progress with treatment at any step or in any regard, consideration should be given to starting or adding more or stronger medication, more intensive psychotherapies, and/or different interventions.

The functional restoration algorithm has four parts. Initial measures include the following:

  • Mirror visual feedback
  • Graded motor imagery
  • Reactivation
  • Contrast baths
  • Desensitization
  • Exposure therapy

The second phase of therapy includes the following:

  • Edema control
  • Flexibility (active)
  • Isometric strengthening
  • Correction of postural abnormalities
  • Diagnosis and treatment of secondary myofascial pain

The third phase of therapy includes the following:

  • Stress loading
  • Isotonic strengthening
  • Range of motion (gentle, passive)
  • General aerobic conditioning
  • Postural normalization and balanced use

The fourth phase of therapy includes the following:

  • Ergonomics
  • Movement therapies
  • Normalization of use
  • Vocational/functional rehabilitation

Indications for pharmacotherapy and suggested choices include the following[10] :

  • Mild-to-moderate pain – Simple analgesics and/or blocks
  • Excruciating, intractable pain – Opioids and/or blocks or later, more experimental interventions
  • Inflammation/swelling and edema – Steroids, systemic or targeted (for acute treatment) or nonsteroidal anti-inflammatory drugs (for long-term treatment); immune modulators
  • Depression, anxiety, insomnia – Sedative, analgesic antidepressant/anxiolytics (and/or psychotherapy)
  • Significant allodynia/hyperalgesia – Anticonvulsants and/or other sodium channel blockers and/or N-methyl-D-aspartate (NMDA) receptor antagonists (eg, ketamine)
  • Significant osteopenia, immobility and trophic changes – Calcitonin or bisphosphonates
  • Profound vasomotor disturbance – Calcium channel blockers, sympatholytics, and/or blocks

Virtual reality is increasingly under study for treatment of CRPS. This approach expands on principles of mirror therapy, and appears to provide reduction in pain and increase in function.[12, 13]

For information on physical medicine approaches to CRPS, see Physical Medicine and Rehabilitation for Complex Regional Pain Syndromes. 

Medical Care

The natural history of type 1 CRPS is variable and unpredictable, the pathogenesis is unknown, and few controlled treatment trials exist. Thus, published recommendations rely heavily on expert opinion, and the approach depends largely on the specialty of the treating physician. Even if a disturbance in sympathetic nervous system function is important in the development of the clinical syndrome, not all patients respond to sympatholytic medications or to chemical or surgical sympathectomy.

Clinical experience teaches that early recognition and treatment are necessary to avoid permanent disability and that the effectiveness of treatment is limited once the patient has reached the chronic fibrotic stage. Certainly, the incidence and severity of CRPS can be greatly reduced by initiating prophylactic measures in situations that are known to be triggers (eg, hemiplegic stroke, Colles fracture). These measures include immediate and aggressive mobilization of the involved extremity with passive and then active range-of-motion exercises. Similarly, in patients with established CRPS, physical and occupational therapy are key components of any therapeutic regimen.

Two major approaches to the medical treatment of early CRPS 1 exist: sympathetic blockade and anti-inflammatory therapy. Although these are not mutually exclusive, the order of usage is generally specialty-dependent, with anesthesiologists/surgeons starting with the former and internists/rheumatologists starting with the latter.

Sympathetic block

For CRPS affecting an upper extremity, inject a local anesthetic into the stellate and upper dorsal sympathetic ganglia to block the efferent sympathetic impulses from the involved extremity. Lidocaine or bupivacaine, with or without epinephrine, is usually used. Guanethidine has been used, but was found to be no more effective than placebo, and was associated with significant adverse effects.[14]

This procedure warms the skin, inhibits sweating, and causes flushing. A successful blockade is indicated by the development of ipsilateral Horner syndrome, ie, ptosis, miosis, and enophthalmos.

Symptoms usually abate within 30 minutes, confirming the diagnosis. Once adequate blockade has been achieved, ensure that the patient participates in hand therapy. Although the interruption lasts only a few hours, the benefits may persist for several days.

Use 1-2 blocks per week. An average of 4-5 blocks is required to permanently relieve symptoms. For symptoms that are not adequately relieved after 4-5 blocks, institute a continuous stellate blockade via a subcutaneously placed catheter or conduct an operative sympathectomy.

For lower-extremity CRPS, a lumbar block is used.

A systematic review found insufficient evidence to draw firm conclusions regarding the efficacy or safety of sympathetic blockade with local anesthetic, but determined that the limited data available do not suggest the technique is effective for reducing pain in CRPS.[15]

Sympatholytic drugs

Sympatholytic drugs alone may be effective in early disease. In later stages of the disorder, sympatholytic drugs may be beneficial in combination with sympathetic block or sympathectomy.

Regional intravenous sympathetic blockade with sympatholytic drugs, such as phenoxybenzamine, using a Bier block–like procedure may be helpful, but results have varied. This is most useful in early disease.

A randomized study suggested that intrathecal baclofen, a GABA-receptor agonist, relieved the dystonia and, in some cases, the hand pain in patients with CRPS.[16] This suggests that GABA-ergic inhibitory pathways may also be important in the pathogenesis of CRPS.

Other medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) may provide some pain relief in patients with CRPS. However, they are not effective in altering the skin changes or natural history of the process and thus play only a supportive role.

A course of high-dose corticosteroids (eg, prednisone 30-40 mg/d tapering over 2-4 weeks) can dramatically reduce pain, swelling, and stiffness. This enables the institution of an aggressive physical-therapy program. In general, corticosteroids are of most value in early CRPS (acute and subacute) when the bone scan shows increased uptake in the involved extremity.

Calcitonin is not an anti-inflammatory medication per se but has been reported to reverse the inflammatory changes and reduce pain in early CRPS, especially in patients with hyperdynamic blood flow. Subcutaneous injections of 100-160 units are administered daily for 4-8 weeks, then every other day for 3-6 weeks. A few reports suggest that intranasal calcitonin[17] may also be effective in treating RSD.

Oral and intravenous bisphosphonates (eg, alendronate) have demonstrated benefit in early CRPS.[18] In a randomized, double-blind, placebo-controlled trial, the aminobisphosphonate neridronate, administered intravenously, provided significant and persistent benefit in patients with CRPS.[19] Neridronate has received orphan drug designation by the US Food and Drug Administration for treatment of CRPS.

The anesthetic agent ketamine has shown promise in the treatment of CRPS. Intravenous administration of subanesthetic doses and topical application have been studied. However, the optimum dose and the route and timing of administration remain to be determined.[20]

Surgical Care

Surgical procedures used for CRPS include the following:

  • Upper thoracic or lumbar sympathectomy
  • Chemical sympathectomy
  • Spinal cord stimulator implantation
  • Amputation

For more information, see Surgery for Reflex Sympathetic Dystrophy (Complex Regional Pain Syndrome Type 1).

Upper thoracic or lumbar sympathectomy 

Consider surgical sympathectomy if the relief achieved with sympathetic blockade and anti-inflammatory therapy has not permanently resolved the CRPS and relapse has occurred despite continuing treatment. These procedures are reserved for patients who have had an initial response to sympathetic blockade and are thus likely have a sympathetically mediated process. Choose sympathectomy early in the course of disease because once joint fibrosis develops, minimal functional improvement occurs. Pain relief, however, remains significant in late disease.

Considerations include the following:

  • Indications include disease duration of longer than 6 months and failure of permanent resolution despite five percutaneous sympathetic blocks.

  • The most significant improvement following surgical sympathectomy is pain relief, although circulation, range of motion, strength, and function usually improve somewhat

  • If surgery of the involved extremity is required, perform it after the sympathectomy

  • Ensure that a surgical sympathectomy is performed by an adequately trained individual

Chemical sympathectomy

For chemical sympathectomy, phenol or alcohol in injected to ablate the sympathetic chain. Perform this only if the patient is at a very high surgical risk for hoarseness from a recurrent laryngeal nerve injury, lung injury, or permanent Horner syndrome.

Spinal cord stimulation

Epidural implantation of a spinal cord stimulator has been shown to provide significant, prolonged pain relief and functional improvement in CRPS (hand or foot).[21, 22] In the United Kingdom, the National Institute for Health and Care Excellence (NICE) recommends spinal cord stimulation as a possible treatment for adults with chronic pain of neuropathic origin, including CRPS, who have had chronic pain for at least 6 months despite standard treatments and have had a successful trial of spinal cord stimulation as part of an assessment by a specialist team.[23]

Amputation

Amputation is sometimes performed in patients with severe complications of CRPS type 1 who have severe, untreatable inflammation with the threat of sepsis or severe functional impairment. Patients who are in despair may request amputation as a last resort.[24, 20]

Two evidence-based guidelines found insufficient evidence that amputation makes a positive contribution to the treatment of CRPS 1.[24, 20] A more recent study that compared pain, function, depression, and quality of life in 19 patients with intractable CRPS who underwent amputation, and 19 patients in whom amputation was considered but not performed, reported consistently better results in the amputation group and recommended considering amputation for patients with intractable CRPS.[25]

Consultations

Multiple consultants are often needed in challenging CRPS cases, including the following:

  • An anesthesiologist who specializes in pain management and who is capable of performing sympathetic blocks
  • An internist/rheumatologist capable of supervising anti-inflammatory regimens
  • A surgeon who is capable of performing surgical sympathectomy

Consultation with a physical therapist and occupational therapist (hand therapist) is important to institute aggressive exercise programs.

Physical and Occupational Therapy

As discussed above, an aggressive range-of-motion exercise program is an essential part of CRPS management. However, especially after sympathetic block or sympathectomy, this may have to be a graduated regimen, with patient-directed passive range of motion to tolerance and, later, active range of motion. When appropriate (eg, in patients with hemiplegia), the entire extremity requires attention.

Following the stellate block or sympathectomy, hand therapy may proceed without causing further pain. Ensure that the therapist does not cause pain, usually by avoiding application of passive motion. Patients can safely apply passive motion because they know when motion becomes painful.

Other features of physical therapy include the following:

  • Massage of the involved extremity is an important component of therapy

  • The patient requires close follow-up, education, and encouragement to maintain an exercise routine

  • Heat therapy relaxes muscle spasms, improves motion, and relieves pain

  • Judicious use of splinting with Thermoplast and Velcro straps in the balanced hand position may help to prevent shortening of the collateral ligaments of involved joints and may provide intermittent pain relief; the splint must be comfortably fit, and needs to be removed frequently throughout the day for exercise and massage

  • Record routine measurements of the patient's strength and range of motion; this provides encouragement to the patient and facilitates communication between the therapist and the treating physician

 

Medication

Medication Summary

Several drugs, either alone or in combination with sympathetic blockade, may be efficacious in prolonging the duration of symptomatic relief. Some of these drugs reduce the activity of the sympathetic nervous system, whereas others are primarily anti-inflammatory.

Sympatholytics

Class Summary

These medications reduce the activity of the sympathetic nervous system.

Clonidine (Catapres)

Stimulates alpha2-adrenoreceptors in brain stem, activating an inhibitory neuron, which in turn results in reduced sympathetic outflow. These effects result in a decrease in vasomotor tone and heart rate.

Phenoxybenzamine (Dibenzyline)

Produces a long-lasting blockade of alpha-adrenergic receptors in smooth muscle and exocrine glands. Blocks epinephrine-induced and norepinephrine-induced vasoconstriction.

Prazosin (Minipress)

Dilates both arteries and veins by blocking postsynaptic alpha1-adrenergic receptors.

Anti-inflammatory agents

Class Summary

Although little evidence exists for systemic inflammation in reflex sympathetic dystrophy (RSD), prominent local inflammation with pain, tenderness, swelling, redness, and loss of function is present.

Prednisone (Deltasone, Meticorten, Orasone)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Endocrine agents

Class Summary

These agents may inhibit osteoclastic bone resorption.

Calcitonin (Miacalcin, Osteocalcin)

Lowers elevated serum calcium levels in patients with multiple myeloma, carcinoma, or primary hyperparathyroidism. Can expect a higher response when serum calcium levels are high. Onset of action is approximately 2 h following injection, and activity lasts for 6-8 h. May lower calcium levels for 5-8 d by about 9% if administered q12h. IM route is preferred at multiple injection sites with dose >2 mL. It can also be administered via intranasal spray.

Calcitonin is also an effective agent to treat metabolic bone disease such as osteoporosis. Through some unknown mechanism, it appears to have an analgesic effect on bone pain, such as occurs with osteoporotic vertebral collapse. The mechanism by which calcitonin relieves the symptoms of RSD is unknown.

 

Follow-up

Deterrence/Prevention

Knowing the triggers for reflex sympathetic dystrophy (RSD), especially extremity immobilization for any cause, and recognizing the disease process early and instituting prompt therapy are the most important aspects of prevention.

Complications

Disease progression may lead to an unusable stiff extremity that is constantly painful. This leads some patients to commit suicide.

Prognosis

RSD is rare in children, but it carries a much better prognosis in children than in adults.[26, 27]   Prognosis is also better with early institution of treatment.

A study by Bean and colleagues suggests that psychological factors may influence recovery from CRPS. In a prospective study of 66 patients with type 1 CRPS, those patients with lower anxiety and pain-related fear at baseline had the lowest pain intensity over the 12-month study period. These researchers proposed that those psychological variables could be considered as targets for early treatment.[28]

Royal College of Physicians guidelines list the following psychosocial risk factors (so-called yellow flags), which may be present initially or may develop during the course of treatment, and which may guide referral for more comprehensive care[11] :

  • Iatrogenic factors (ie previous negative experiences with health professionals)
  • Poor coping strategies (eg ongoing ‘guarding’ of the limb despite education)
  • Involvement in litigation/securing benefits (note that this may affect progress with treatment in some patients, but there must be no assumption that this applies in every patient)
  • Overuse of appliances
  • Distress
  • Anxiety/depression
  • Unwillingness to set goals
  • Passivity in treatment sessions
  • Inaccurate beliefs despite education
  • Fear avoidance
  • Negative family influences

Patient Education

The clinician should ensure that the patient understands this confusing disease entity. Patient education information on RSD is available from the National Institutes of Heatlh at Complex Regional Pain Syndrome. In addition, encouragement and family support are important for maintaining the physical therapy program and treatment regimen.

 

Questions & Answers

Overview

What is the clinical background of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Which conditions are relevant in the development of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the pathophysiology of complex regional pain syndrome type 1 (CRPS 1)?

What types of penetrating wounds can lead to complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What are the traumatic causes of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Which procedures are implicated in the development of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Which local disorders are associated with complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Which systemic disorders are associated with complex regional pain syndrome type 1 (CRPS 1) (RSD)?

How common is complex regional pain syndrome type 1 (CRPS 1) (RSD) in the US?

What are the demographics of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Presentation

What is the clinical history of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

How is pain in complex regional pain syndrome type 1 (CRPS 1) (RSD) characterized?

What are the symptoms of increased sympathetic activity in complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What precipitating factors may lead to complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What are the physical findings in complex regional pain syndrome type 1 (CRPS 1) (RSD)?

DDX

What are the IASP criteria for diagnosis of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What are the differential diagnoses for Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy)?

Workup

Which lab studies are indicated in the workup of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of radiography in the workup of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of radionuclide imaging in the workup of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Treatment

What are the treatment guidelines for complex regional pain syndrome (CRPS 1) (RSD)?

How is the functional restoration algorithm for complex regional pain syndrome type 1 (CRPS 1) (RSD) implemented?

Which medications are used in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the medical treatment for complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of sympathetic block in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of sympatholytic drugs in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Which medications are indicated in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What are the surgical options for the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of upper thoracic or lumbar sympathectomy in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What are the considerations in upper thoracic or lumbar sympathectomy for the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of chemical sympathectomy in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of spinal cord stimulation in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of amputation in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Which specialist consultations are indicated in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the role of physical and occupational therapy in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

How is physical therapy used in the treatment of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Medications

How do medications treat complex regional pain syndrome type 1 (CRPS 1) (RSD)?

Which medications in the drug class Endocrine agents are used in the treatment of Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy)?

Which medications in the drug class Anti-inflammatory agents are used in the treatment of Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy)?

Which medications in the drug class Sympatholytics are used in the treatment of Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy)?

Follow-up

How is complex regional pain syndrome type 1 (CRPS 1) (RSD) prevented?

What are the complications of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What is the prognosis of complex regional pain syndrome type 1 (CRPS 1) (RSD)?

What should patients with complex regional pain syndrome type 1 (CRPS 1) (RSD) be educated about?