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 (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. In 1864, Mitchell referred to this malady as causalgia, a Greek word meaning burning pain. Newer taxonomy refers to RSD as a type of complex regional pain syndrome (CRPS), which may develop after an initiating event such as trauma or surgery or may occur spontaneously.¹ Under this classification, causalgia is a type of CRPS that develops after nerve injury. In patients with either of these conditions, sympathetic mediation of the pain (ie, improvement with sympathetic blockade) may or may not be evident.

Pathophysiology

The pathogenesis of RSD is unknown. Three conditions are deemed important in the development of RSD, including a persistent painful lesion, a predisposition or susceptibility to developing RSD, and an abnormal sympathetic reflex. Susceptibility factors are unknown and may include genetic predisposition (HLA typing)² and, in some patients, a tendency toward increased sympathetic activity. This includes cold hands, hyperhidrosis, or a history of fainting.

Healthy individuals undergo 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 RSD, 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 RSD in some patients.

Frequency

United States

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

Mortality/Morbidity

RSD causes essentially no mortality.

Race

No racial predilection exists.

Sex

Sexual distribution is equal.

Age

• The age of onset in most patients with RSD is 30-60 years, and the mean age is 49 years.
• RSD affects children and carries a much better prognosis than in adults.³

CLINICAL

Section 3 of 10  

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

History

The 3 clinical stages of reflex sympathetic dystrophy (RSD) 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.

• RSD commonly involves only one extremity. It is bilateral in approximately 25% of cases but is usually more prominent on one side.
• Pain
• • 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
• • Hyperhidrosis
  • Cold hands
  • Fainting
• Prior trauma, which may be trivial 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

Perform a thorough physical examination followed by a focused examination of the involved extremity. Patients with RSD may present with suggestive physical findings that point to a presumptive diagnosis.

• Edema
• • 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
  • May be dusky, cyanotic, pale, or red and may eventually lead to skin hypopigmentation
  • 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
• Abnormal skin moisture
• • Hyperhidrosis (early)
  • Dry skin (late)
• 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).
• 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

Causes

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

• Trauma
• • Penetrating wounds
  • • Lacerations
    • Abrasions
    • Venipuncture
    • Intramuscular injection of medication or illicit drugs
    • Gunshot wounds
  • Crush injuries and blunt trauma
  • Neck or shoulder injuries
  • Acute traumatic carpal tunnel syndrome
  • Chest trauma
  • Sprain, fracture, or dislocation
• Postsurgery
• • Carpal tunnel release
  • Dental extractions
  • Cervical rib resection
  • Fracture repair (Colles fracture)
  • Postarthroscopy
• Local disease
• • Nerve compression syndromes
  • Arthritis
  • Tissue ischemia
  • Stenosing tenosynovitis
• Systemic disease
• • Myocardial infarction
  • Stroke
  • Pancoast tumor
  • Pancreatic cancer
  • Herpes zoster

DIFFERENTIALS

Section 4 of 10  

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

WORKUP

Section 5 of 10  

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

Lab Studies

• Levels of acute-phase reactants (ie, erythrocyte sedimentation rate [ESR], C-reactive protein) are generally within the reference range.

Imaging Studies

• Plain 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 3-phase bone scan are positive in 50-90% of patients, 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 reflex sympathetic dystrophy (RSD) but is supportive of that diagnosis in the appropriate clinical situation. In third-stage RSD, the bone scan findings may be normal, but the plain radiographs generally reveal profound demineralization of the affected extremity.

TREATMENT

Section 6 of 10  

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

Medical Care

The natural history of reflex sympathetic dystrophy (RSD) is variable and unpredictable, the pathogenesis is unknown, and few controlled treatment trials exist. Thus, evidence-based treatment guidelines do not exist, 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 RSD 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 RSD, physical and occupational therapy are key components of any therapeutic regimen.

Two major approaches to the medical treatment of early RSD 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 (upper extremity, stellate; lower extremity, lumbar)
• • Ensure that this is performed by a trained individual.
  • 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.
  • 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 the patient is adequately blocked, ensure their participation 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.
• Sympatholytic drugs
• • Sympatholytic drugs may be efficacious when used alone in early disease.
  • Sympatholytic drugs may be beneficial in combination with sympathetic block or sympathectomy in later stages of the disorder.
  • 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 performed in 2000 suggested that intrathecal baclofen, a GABA-receptor agonist, relieved the dystonia and, in some cases, the hand pain in patients with RSD.⁴ This suggests that GABA-ergic inhibitory pathways may also be important in the pathogenesis of RSD.
• Anti-inflammatory medications (corticosteroids, calcitonin)
• • Although nonsteroidal anti-inflammatory drugs (NSAIDs) may provide some symptomatic pain relief in patients with RSD, they are not effective in altering the skin changes or natural history of the process and thus play only a supportive role. On the other hand, 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 RSD (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 RSD, 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 calcitonin⁵ and oral bisphosphonates may also be effective in treating RSD.

Surgical Care

• Upper thoracic or lumbar sympathectomy
• • Consider this procedure if the relief achieved with sympathetic blockade and anti-inflammatory therapy has not permanently resolved the RSD 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.
  • Indications include disease duration of longer than 6 months and failure of permanent resolution after 5 percutaneous sympathetic blocks are performed.
  • The most significant improvement following surgical sympathectomy is pain relief, although circulation, range of motion, strength, and function are usually somewhat improved.
  • Choose sympathectomy early in the course of disease because, once joint fibrosis develops, minimal functional improvement occurs. Pain relief, however, is still significant in late disease.
  • 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
• • Inject phenol or alcohol 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: In 2000, a controlled trial demonstrated the efficacy of epidural implantation of a spinal cord stimulator in pain relief and functional improvement in RSD (hand or foot) compared with physical therapy alone.^{6, 7}

Consultations

• Multiple consultants are often needed in challenging RSD cases, including an anesthesiologist who specializes in pain management and who is capable of performing sympathetic blocks, an internist/rheumatologist capable of supervising anti-inflammatory regimens, and 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.

Activity

• Physical and occupational therapy
• • As discussed above, an aggressive range-of-motion exercise program is an essential part of RSD 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.
  • 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. Remove it 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

Section 7 of 10  

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

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.

Drug Category: Sympatholytics

These medications reduce the activity of the sympathetic nervous system.

Drug Category: Anti-inflammatory agents

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.

Drug Category: Endocrine agents

These agents may inhibit osteoclastic bone resorption.

FOLLOW-UP

Section 8 of 10  

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

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

Prognosis is better in younger patients and with institution of early treatment.

Patient Education

• Ensure that the patient understands this confusing disease entity.
• Encouragement and family support are important for maintaining the physical therapy program and treatment regimen.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Potential medicolegal pitfalls include misdiagnosis, delayed diagnosis, incorrect treatment, and failure to refer to appropriate specialists.

Special Concerns

• Some uncontrolled studies have reported encouraging results with transcutaneous nerve stimulation and acupuncture for pain reduction.

REFERENCES

Section 10 of 10

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

1. Stanton-Hicks M, Janig W, Hassenbusch S, et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. Oct 1995;63(1):127-33. [Medline].
2. Kemler MA, van de Vusse AC, van den Berg-Loonen EM, et al. HLA-DQ1 associated with reflex sympathetic dystrophy. Neurology. Oct 12 1999;53(6):1350-1. [Medline].
3. Cimaz R, Matucci-Cerinic M, Zulian F, Falcini F. Reflex sympathetic dystrophy in children. J Child Neurol. Jun 1999;14(6):363-7. [Medline].
4. van Hilten BJ, van de Beek WJ, Hoff JI, et al. Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. N Engl J Med. Aug 31 2000;343(9):625-30. [Medline].
5. Gobelet C, Waldburger M, Meier JL. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain. Feb 1992;48(2):171-5. [Medline].
6. Kemler MA, Barendse GA, Van Kleef M, et al. Electrical spinal cord stimulation in reflex sympathetic dystrophy: retrospective analysis of 23 patients. J Neurosurg. Jan 1999;90(1 Suppl):79-83. [Medline].
7. Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. Aug 31 2000;343(9):618-24. [Medline].
8. Driessens M, Dijs H, Verheyen G, Blockx P. What is reflex sympathetic dystrophy?. Acta Orthop Belg. Jun 1999;65(2):202-17. [Medline].
9. Johnson JP, Obasi C, Hahn MS, Glatleider P. Endoscopic thoracic sympathectomy. J Neurosurg. Jul 1999;91(1 Suppl):90-7. [Medline].
10. Lundborg C, Dahm P, Nitescu P, et al. Clinical experience using intrathecal (IT) bupivacaine infusion in three patients with complex regional pain syndrome type I (CRPS-I). Acta Anaesthesiol Scand. Jul 1999;43(6):667-78. [Medline].
11. Oerlemans HM, Perez RS, Oostendorp RA, Goris RJ. Objective and subjective assessments of temperature differences between the hands in reflex sympathetic dystrophy. Clin Rehabil. Oct 1999;13(5):430-8. [Medline].
12. Pandita D, Danielson BD, Potti A, et al. Complex regional pain syndrome type-1: a rare complication of arteriovenous graft placement. J Rheumatol. Oct 1999;26(10):2254-6. [Medline].
13. Poncelet C, Perdu M, Levy-Weil F, et al. Reflex sympathetic dystrophy in pregnancy: nine cases and a review of the literature. Eur J Obstet Gynecol Reprod Biol. Sep 1999;86(1):55-63. [Medline].
14. Reuben SS, Steinberg RB, Madabhushi L, Rosenthal E. Intravenous regional clonidine in the management of sympathetically maintained pain. Anesthesiology. Aug 1998;89(2):527-30. [Medline].
15. Schwartzman RJ. New treatments for reflex sympathetic dystrophy. N Engl J Med. Aug 31 2000;343(9):654-6. [Medline].
16. Schwartzman RJ, Maleki J. Postinjury neuropathic pain syndromes. Med Clin North Am. May 1999;83(3):597-626. [Medline].
17. Severens JL, Oerlemans HM, Weegels AJ, et al. Cost-effectiveness analysis of adjuvant physical or occupational therapy for patients with reflex sympathetic dystrophy. Arch Phys Med Rehabil. Sep 1999;80(9):1038-43. [Medline].
18. Viel E, Ripart J, Pelissier J, Eledjam JJ. Management of reflex sympathetic dystrophy. Ann Med Interne (Paris). Apr 1999;150(3):205-10. [Medline].
19. Wesselmann U, Srinivasa NR. Reflex sympathetic dystrophy and causalgia. Anesth Clin North Am. 1997;15:407-27.

Article Last Updated: Nov 30, 2007