Description

• Complex regional pain syndrome (CRPS) is a pain syndrome that can be chronic and debilitating. It is divided into two subtypes and can result in significant physical and psychosocial short and long-term disability. Most cases are a result of a physical insult to an extremity such as trauma or surgery. The lack of a dermatomal distribution (i.e., the pain is regional) distinguishes CPRS from other pain syndromes.
  • Type I: no nerve injury (reflex sympathetic dystrophy [RSD])
  • Type II: associated with a demonstrable nerve injury (causalgia)
• Synonym(s): traumatic erythromelalgia; Weir Mitchell causalgia; causalgia; RSD; posttraumatic neuralgia; sympathetically maintained pain

Epidemiology

• Peak age: 50 to 70 years
• Predominant gender: female > male (3:1, 60–81%), with postmenopausal women affected disproportionally.
• Rarely seen in pediatrics—cases in this age group predominantly involve lower extremities in females.
• Recent studies found 3.8% occurrence after wrist fracture and 7% occurrence after intra-articular ankle fracture—both independent strong risk for CRPS. Fractures and sprains are associated in ~60% of cases, the remaining 40% have less precise or no recognized inciting event. Upper extremities are more commonly involved.
• CPRS is more prevalent in patients who report higher than commonly expected pain in early phases of trauma. Latency depends on normal injury recovery time—prolonged pain (> 2 months) after injury hints at diagnosis.

Incidence
Incidence of 5.46 to 26.2/100,000 for type I and 0.82/100,000 for type II in the United States

Etiology and Pathophysiology

• Poorly understood activation of abnormal sympathetic reflex that lowers pain threshold. The process is multifactorial and involves both central and peripheral nervous systems.
  • Increased excitability of nociceptive neurons in the spinal cord; “central sensitization”
  • Exaggerated responses to normally nonpainful stimuli (hyperalgesia, allodynia)
  • The exaggerated inflammatory response results in afferent neurons releasing increased amounts of neuropeptides (1).
• Type II is associated with physical injury to nerve. This represents a minority of cases.
• Emerging information reveals CNS changes (functional, anatomic, biochemical) in addition to spinal level changes. Increased levels of immunomodulators suggest autoimmune component. The lack of a definitive pathophysiologic mechanism has led to suggest that CRPS is a “functional neurologic syndrome.”

Genetics
No known genetic pattern

Risk Factors

• Minor or severe trauma (upper extremity fracture—particularly distal radius noted in a significant number of those with CRPS)
• Surgery (particularly carpal tunnel release)
• Lacerations, burns, frostbite
• Casting/immobilization after extremity injury
• Penetrating injury (case reports of CRPS developing after snakebites)
• Polymyalgia rheumatica
• Myocardial infarction, cerebral vascular accident
• Reports of CRPS development after “innocuous” events such as IV catheters and IM injections

General Prevention

• Early mobilization and avoiding prolonged immobilization has proven to benefit in reducing incidence of CRPS.
• One study of wrist fractures found that addition of 500 mg/day of vitamin C lowered the rates of CRPS.
• There is evidence that limiting use of tourniquets, liberal regional anesthetic use, and ensuring adequate perioperative analgesia can reduce the incidence of CRPS-I.

Commonly Associated Conditions

• Serious injury to bone and soft tissue
• Herpes zoster postherpetic neuralgia results from partial or complete damage to afferent nerve pathways that occurs in a dermatomal distribution.
• Signal exists for patients having comorbid painful conditions or psychiatric diagnosis at increased risk of developing CRPS.