BASICS
DESCRIPTION
- Complex regional pain syndrome (CRPS) is a pain syndrome that is seemingly disproportionate in time or degree to any known trauma or lesion.
- 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; reflex sympathetic dystrophy; posttraumatic neuralgia; sympathetically maintained pain
EPIDEMIOLOGY
- Incidence of 5.46/100,000 and prevalence of 20.57/1,000,000 in United States
- Peak age 50 to 70 years
- Predominant gender: female > male (3:1, 60-81%); favoring postmenopausal
- Recent studies found 3.8% occurrence after wrist fracture and 7% occurrence after intra-articular ankle fracture-both independent high risk for CPRS (1)[B].
- More prevalent in patients that report higher than usual expected pain in early phases of trauma (1)[B].
ETIOLOGY AND PATHOPHYSIOLOGY
- Poorly understood activation of abnormal sympathetic reflex that lowers pain threshold.
- Increased excitability of nociceptive neurons in the spinal cord; "central sensitization"¯
- Exaggerated responses to normally nonpainful stimuli (hyperalgesia, allodynia)
- Other than known nerve injury (type II or causalgia), no known definitive pathogenesis
Genetics
No known genetic pattern
RISK FACTORS
- Minor or severe trauma (upper extremity fracture noted in 44%)
- Surgery (particularly carpal tunnel release)
- Lacerations
- Burns
- Frostbite
- Casting/immobilization after extremity injury
- Penetrating injury
- Polymyalgia rheumatica
- Myocardial infarction (MI)
- Cerebral vascular accident
GENERAL PREVENTION
- Early mobilization after fracture, stroke, and MI has proven benefit in reducing incidence of CRPS.
- One study of wrist fractures found that addition of 500 mg/day of vitamin C lowered 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.
- Pain occurs in dermatomes as a sequela of herpes zoster.
DIAGNOSIS
Unprovoked pain is the hallmark of the condition, and the diagnosis of CRPS is excluded by the existence of conditions that would otherwise account for the degree of symptoms. Clinical diagnostic criteria (2):
HISTORY
- Continuing pain which is disproportionate to any inciting event.
- One reported symptom in 3 of the 4 following categories:
- Sensory: hyperalgesia and/or allodynia
- Vasomotor: skin, temperature, color asymmetry
- Sudomotor/edema: edema, sweating changes, or sweating asymmetry
- Motor/trophic: decreased range of motion or motor dysfunction and/or trophic changes (hair, nail, skin) (1)
PHYSICAL EXAM
At least one sign at evaluation in 2 of the following:
- Sensory: hyperalgesia (to pinprick) or allodynia (to light touch, pressure, or joint movement)
- Vasomotor: evidence of temperature, skin, color asymmetry
- Sudomotor/edema: evidence of edema or sweating changes or asymmetry
- Motor/trophic: decreased range of motion, motor dysfunction, or trophic changes in hair, nails, skin (1)
DIFFERENTIAL DIAGNOSIS
- Infection
- Hypertrophic scar
- Bone fragments
- Neuroma
- CNS tumor or syrinx
- Deep vein thrombosis or thrombophlebitis
- Thoracic outlet syndrome
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- CBC
- Erythrocyte sedimentation rate (ESR)
- Plain radiographs may show patchy demineralization within 3 to 6 weeks of onset of CRPS that are more pronounced than would be see from disuse alone.
- 3-phase bone scanning has varying sensitivity but is most accurate for support of the diagnosis when there is diffuse activity (especially on phase 3).
- Bone density
Diagnostic Procedures/Other
- Electromyelography (EMG) shows nerve injury with type II CRPS.
- Sudomotor function testing (resting sweat testing, resting skin temperature, quantitative sudomotor axon reflex testing-all related to increased autonomic activity of the affected limb)
Test Interpretation
- Partial or complete damage to afferent nerve pathways and probably reorganized central pain pathways
- Nerves most commonly involved are median and sciatic.
- Atrophy in affected muscles
- Incomplete nerve plexus lesion
TREATMENT
GENERAL MEASURES
Discourage maladaptive behaviors (pain medication seeking, secondary gain). Principle of functional restoration is a stepwise and multidisciplinary approach.
MEDICATION
First Line
- NSAIDS recommended early in course but mixed support in literature
- The following have literature support of either limited or suggestive benefit in treatment of CRPS-I:
- Corticosteroids (prednisone 30 mg/day for 2 to 12 weeks with taper) are the only class of drugs that have direct clinical trial support early in the course.
- Gabapentin 600 to 1,800 mg/day for 8 weeks following diagnosis
- 50% DMSO cream applied to affected extremity up to 5 times daily
- N-acetylcysteine 600 mg TID
- Bisphosphonates (alendronate) at 40 mg/day (however, optimal dose uncertain)
- Nifedipine 20 mg/day showed benefit early in the course of the condition.
- Although many have advocated the use of tricyclic antidepressants in the treatment of CRPS, there is no credible evidence of improvement of pain. They may be helpful in controlling depressive symptoms that develop with disease progression (2).
ISSUES FOR REFERRAL
- After 2 months of the illness, psychological evaluation is generally indicated to identify and treat any comorbid conditions.
- Identifying local resources and early referral for expert management give increased likelihood of long-term success in controlling condition.
ADDITIONAL THERAPIES
Type I
- Physical and occupational therapy (beneficial to the overall prognosis for recovery)
- Should be started early
- "Mirror therapy"¯ has shown good results.
- Transcutaneous nerve stimulation
- Psychotherapy
- Use of subdissociative (0.2 to 0.5 mg/kg) infusions of ketamine has shown some promise but effects seem to be time limited (3)[B].
SURGERY/OTHER PROCEDURES
- Type II responds more favorably to nerve-directed treatment
- Sympathetic blocks
- Cervicothoracic or lumbar sympathectomies have little data to support their use and should be used judiciously and after all other therapies have failed (4)[A].
- Anesthetic blockade (chemical or surgical) of sympathetic nerve function
- Transient relief suggests that chemical or surgical sympathectomy will be helpful.
- Little in the way of quality clinical trials exist to support local sympathetic blockage as the gold standard of therapy.
- IV regional sympathetic block with guanethidine or reserpine by pain specialist or anesthetist
- Transcutaneous electric nerve stimulation (controversial)
- Inject myofascial painful trigger points
- Spinal cord stimulation (quality of life improved only with implanted system)
- Intrathecal analgesia
- Amputation as a last resort in severe cases, with patients reporting improved quality of life
COMPLEMENTARY & ALTERNATIVE MEDICINE
- Vitamin C (500 mg/day) may help to prevent CRPS in those with wrist fracture.
- Briskly rub the affected part several times per day
- Acupuncture
- Hypnosis can be suggested.
- Relaxation training (alternate muscle relaxing and contracting)
- Biofeedback
- Whirlpool baths
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Only for proposed surgical therapy
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Weekly, to monitor progress and initiate additional modalities as needed
PATIENT EDUCATION
- Stress need to remain active physically
- Instruct carefully about any prescribed medications.
- Reflex Sympathetic Dystrophy Syndrome Association, http://rsds.org/, 203-877-3790
- American RSD Hope Group, www.rsdhope.org, 207-583-4589
PROGNOSIS
Most improve with early treatment, but symptoms may be lifelong if there is limited response to initial treatments.
COMPLICATIONS
- Depression
- Disability
- Opioid dependence
REFERENCES
11 Pons T, Shipton EA, Williman J, et al. Potential risk factors for the onset of complex regional pain syndrome type 1: a systematic literature review. Anesthesiol Res Pract. 2015;2015:956539.22 Harden RN, Oaklander AL, Burton AW, et al. Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edition. Pain Med. 2013;14(2):180-229.33 Azari P, Lindsay DR, Briones D, et al. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012;26(3):215-228.44 Straube S, Derry S, Moore RA, et al. Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome. Cochrane Database Syst Rev. 2013;(9):CD002918.
ADDITIONAL READING
- Goebel A. Complex regional pain syndrome in adults. Rheumatology (Oxford). 2011;50(10):1739-1750.
- Perez RS, Zollinger PE, Dijkstra PU, et al. Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol. 2010;10:20.
CODES
ICD10
- G90.50 Complex regional pain syndrome I, unspecified
- G90.519 Complex regional pain syndrome I of unspecified upper limb
- G90.529 Complex regional pain syndrome I of unspecified lower limb
- G56.40 Causalgia of unspecified upper limb
- G90.511 Complex regional pain syndrome I of right upper limb
- G90.521 Complex regional pain syndrome I of right lower limb
- G90.523 Complex regional pain syndrome I of lower limb, bilateral
- G90.59 Complex regional pain syndrome I of other specified site
- G90.522 Complex regional pain syndrome I of left lower limb
- G57.70 Causalgia of unspecified lower limb
- G90.512 Complex regional pain syndrome I of left upper limb
- G90.513 Complex regional pain syndrome I of upper limb, bilateral
ICD9
- 337.20 Reflex sympathetic dystrophy, unspecified
- 337.21 Reflex sympathetic dystrophy of the upper limb
- 337.22 Reflex sympathetic dystrophy of the lower limb
- 337.29 Reflex sympathetic dystrophy of other specified site
- 355.9 Mononeuritis of unspecified site
SNOMED
- 128200000 complex regional pain syndrome (disorder)
- 50642008 Algodystrophy (disorder)
- 408751001 Complex regional pain syndrome, type II
- 408749000 Complex regional pain syndrome, type II, lower limb
- 2103002 reflex sympathetic dystrophy of upper extremity (disorder)
- 408662006 reflex sympathetic dystrophy of lower extremity (disorder)
- 408750000 Complex regional pain syndrome, type II, upper limb
CLINICAL PEARLS
- A pain syndrome disproportioned to injury
- Pain control and early mobility are the key to recovery.
- Avoid use of opiate analgesics.
- Use a multidisciplinary approach.