Reflex Sympathetic Dystrophy
- Author: Don R Revis, Jr, MD; Chief Editor: Herbert S Diamond, MD more...
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 RSD; RSD in a hemiplegic upper limb after stroke is often termed shoulder-hand syndrome. RSD may also develop in the absence of an identifiable precipitating event.
Newer taxonomy categorizes RSD as type 1 complex regional pain syndrome (CRPS), which occurs in the absence of definable nerve injury. 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.
RSD is largely a clinical diagnosis (see Presentation and DDx). Two major approaches to the treatment of early RSD are sympathetic blockade and anti-inflammatory therapy. Surgical sympathectomy may be considered in patients with refractory RSD that had initially responded to sympathetic blockade. Spinal cord stimulation is another surgical option. (See Treatment and Medication.)
The pathogenesis of RSD is unknown. Three conditions are deemed important in the development of RSD: 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, 3, 4] 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.
Numerous studies have reported altered brain function in RDS. Researchers have also documented structural alterations in the brain. Pleger et al reported that magnetic resonance imaging (MRI) in patients with type 1 complex regional pain syndrome (RDS) 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.
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.
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.
RSD is usually posttraumatic or postsurgical; however, it can occur in a previously healthy extremity with no known trigger.
Penetrating wounds that can lead to RSD include the following:
Intramuscular injection of medication or illicit drugs
Other traumatic causes of RSD include the following:
Crush injuries and blunt trauma
Neck or shoulder injuries
Acute traumatic carpal tunnel syndrome
Sprain, fracture, or dislocation
Postsurgery RSD has been reported after the following procedures:
Carpal tunnel release
Cervical rib resection
Fracture repair (Colles fracture)
Local disorders associated with RSD include the following:
Nerve compression syndromes
Systemic disorders associated with RSD include the following:
Race-, Sex-, and Age-related Demographics
No racial predilection exists for RSD. Sexual distribution is equal. Although RSD can occur in children, the age of onset in most patients RSD is 30-60 years, and the mean age is 49 years.
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.
Stanton-Hicks M, Janig W, Hassenbusch S, et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995 Oct. 63(1):127-33. [Medline].
Kemler MA, van de Vusse AC, van den Berg-Loonen EM, et al. HLA-DQ1 associated with reflex sympathetic dystrophy. Neurology. 1999 Oct 12. 53(6):1350-1. [Medline].
Sebastin SJ. Complex regional pain syndrome. Indian J Plast Surg. 2011 May. 44(2):298-307. [Medline]. [Full Text].
Coderre TJ, Bennett GJ. A hypothesis for the cause of complex regional pain syndrome-type I (reflex sympathetic dystrophy): pain due to deep-tissue microvascular pathology. Pain Med. 2010 Aug. 11(8):1224-38. [Medline].
Pleger B, Draganski B, Schwenkreis P, Lenz M, Nicolas V, Maier C, et al. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex. PLoS One. 2014. 9(1):e85372. [Medline]. [Full Text].
Barad MJ, Ueno T, Younger J, Chatterjee N, Mackey S. Complex regional pain syndrome is associated with structural abnormalities in pain-related regions of the human brain. J Pain. 2014 Feb. 15(2):197-203. [Medline].
Lee DH, Lee KJ, Cho KI, Noh EC, Jang JH, Kim YC, et al. Brain alterations and neurocognitive dysfunction in patients with complex regional pain syndrome. J Pain. 2015 Jun. 16 (6):580-6. [Medline].
Goebel A. Complex regional pain syndrome in adults. Rheumatology (Oxford). 2011 Oct. 50(10):1739-50. [Medline].
Introduction and Diagnostic Considerations. Harden RN. Complex Regional Pain Syndrome: Treatment Guidelines. Milford, CT: Reflex Sympathetic Dystrophy Association; 2006. 1-11. [Full Text].
O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Apr 30. 4:CD009416. [Medline].
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. 2000 Aug 31. 343(9):625-30. [Medline].
Gobelet C, Waldburger M, Meier JL. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain. 1992 Feb. 48(2):171-5. [Medline].
Littlejohn G. Therapy: Bisphosphonates for early complex regional pain syndrome. Nat Rev Rheumatol. 2013 Apr. 9(4):199-200. [Medline].
Varenna M, Adami S, Rossini M, Gatti D, Idolazzi L, Zucchi F, et al. Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study. Rheumatology (Oxford). 2013 Mar. 52(3):534-42. [Medline].
Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors. Eur J Pain. 2006 Feb. 10(2):91-101. [Medline].
Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. 2000 Aug 31. 343(9):618-24. [Medline].
[Guideline] National Institute for Health and Care Excellence. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin. NICE. Available at http://www.nice.org.uk/guidance/ta159. Accessed: September 26, 2014.
Cimaz R, Matucci-Cerinic M, Zulian F, Falcini F. Reflex sympathetic dystrophy in children. J Child Neurol. 1999 Jun. 14(6):363-7. [Medline].
Badri T, Ben Jennet S, Fenniche S, Benmously R, Mokhtar I, Hammami H. Reflex sympathetic dystrophy syndrome in a child. Acta Dermatovenerol Alp Panonica Adriat. 2011 Jun. 20(2):77-9. [Medline].
Bean DJ, Johnson MH, Heiss-Dunlop W, Lee AC, Kydd RR. Do psychological factors influence recovery from Complex Regional Pain Syndrome Type-1? A Prospective Study. Pain. 2015 Jul 1. [Medline].
Stanton TR, Wand BM, Carr DB, Birklein F, Wasner GL, O'Connell NE. Local anaesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Aug 19. 8:CD004598. [Medline].
Azari P, Lindsay DR, Briones D, Clarke C, Buchheit T, Pyati S. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012 Mar 1. 26(3):215-28. [Medline].