Complex Regional Pain Syndrome (CRPS)
(Reflex Sympathetic Dystrophy and Causalgia)
Complex regional pain syndrome (CRPS) is chronic neuropathic pain that follows soft-tissue or bone injury (type I) or nerve injury (type II) and lasts longer and is more severe than expected for the original tissue damage. Other manifestations include autonomic changes (eg, sweating, vasomotor abnormalities), motor changes (eg, weakness, dystonia), and trophic changes (eg, skin or bone atrophy, hair loss, joint contractures). Diagnosis is clinical. Treatment includes drugs, physical therapy, and sympathetic blockade.
CRPS type I was previously known as reflex sympathetic dystrophy (see also the Clinical practice guideline [fourth edition] for the diagnosis, treatment, and management of reflex sympathetic dystrophy/complex regional pain syndrome [RSD/CRPS] from the Reflex Sympathetic Dystrophy Syndrome Association), and type II was known as causalgia. Both types occur most often in young adults and are 2 or 3 times more common among women.
CRPS type I typically follows an injury (usually of a hand or foot), most commonly after crush injuries, especially in a lower limb. It may follow amputation, acute MI, stroke, or cancer (eg, lung, breast, ovary, CNS); no precipitant is apparent in about 10% of patients. CRPS type II is similar to type I but involves overt damage to a peripheral nerve.
Pathophysiology is unclear, but peripheral nociceptor and central sensitization and release of neuropeptides (substance P, calcitonin gene-related peptide) help maintain pain and inflammation. The sympathetic nervous system is more involved in CRPS than in other neuropathic pain syndromes: Central sympathetic activity is increased, and peripheral nociceptors are sensitized to norepinephrine (a sympathetic neurotransmitter); these changes may lead to sweating abnormalities and poor blood flow due to vasoconstriction. Nonetheless, only some patients respond to sympathetic manipulation (ie, central or peripheral sympathetic blockade).
Symptoms vary greatly and do not follow a pattern; they include sensory, focal autonomic (vasomotor or sudomotor), and motor abnormalities.
Pain—burning or aching—is common. It does not follow the distribution of a single peripheral nerve; it may worsen with changes in environment or emotional stress. Allodynia and hyperalgesia may occur. Pain often causes patients to limit use of an extremity.
Cutaneous vasomotor changes (eg, red, mottled, or ashen color; increased or decreased temperature) and sudomotor abnormalities (dry or hyperhidrotic skin) may be present. Edema may be considerable and locally confined. Other symptoms include trophic abnormalities (eg, shiny, atrophic skin; cracking or excess growth of nails; bone atrophy; hair loss) and motor abnormalities (weakness, tremors, spasm, dystonia with fingers fixed in flexion or equinovarus position of foot). Range of motion is often limited, sometimes leading to joint contractures. Symptoms may interfere with fitting a prosthesis after amputation.
Psychologic distress (eg, depression, anxiety, anger) is common, fostered by the poorly understood cause, lack of effective therapy, and prolonged course.
The following clinical criteria must be present to establish the diagnosis of CRPS:
If another disorder is present, CRPS should be considered possible or probable.
Other symptoms and findings may support the diagnosis: edema, trophic abnormalities, or a change in temperature of the affected area. Thermography may be used to document the temperature change if clinical evaluation is equivocal and if this finding would help establish the diagnosis. Bone changes (eg, demineralization on x-ray, increased uptake on a triple-phase radionuclide bone scan) may be detected and are usually evaluated only if the diagnosis is equivocal. However, imaging tests may also be abnormal after trauma in patients without CRPS.
Sympathetic nerve block (cervical stellate ganglion or lumbar) can be used for diagnosis and treatment. However, false-positive and false-negative results are common because not all CRPS pain is sympathetically maintained and nerve block may also affect nonsympathetic fibers. In another test of sympathetic involvement, a patient is given IV infusions of saline (placebo) or phentolamine 1 mg/kg over 10 min while pain scores are recorded; a decrease in pain after phentolamine but not placebo indicates sympathetically maintained pain.
Treatment is complex and often unsatisfactory, particularly if begun late. It includes drugs, physical therapy, sympathetic blockade, psychologic treatments, and neuromodulation. Few controlled trials have been done.
Many of the drugs used for neuropathic pain, including tricyclic antidepressants, anticonvulsants, and corticosteroids (see Table: Drugs for Neuropathic Pain), may be tried; none is known to be superior. Long-term treatment with opioid analgesics may be useful for selected patients.
In some patients with sympathetically maintained pain, regional sympathetic blockade relieves pain, making physical therapy possible. Oral analgesics (NSAIDs, opioids, and various adjuvant analgesics) may also relieve pain sufficiently to allow rehabilitation.
For neuromodulation, implanted spinal cord stimulators are being increasingly used. Transcutaneous electrical nerve stimulation (TENS), applied at multiple locations with different stimulation parameters, should be given a long trial. Implanted stimulation systems targeting peripheral nerves (eg, occipital nerve stimulation for some headache syndromes) may be beneficial. Other methods of neuromodulation include brisk rubbing of the affected part (counterirritation) and acupuncture. No one form of neuromodulation is known to be more effective than another, and a poor response to one form does not mean a poor response to another.
Neuraxial infusion with opioids, anesthetics, and clonidine may help, and intrathecal baclofen has reduced dystonia in a few patients.
Physical therapy is essential. Goals include strengthening, increased range of motion, and vocational rehabilitation.
Mirror therapy has been reported to benefit patients with CRPS type 1 due to phantom limb pain or stroke. Patients straddle a large mirror between their legs. The mirror reflects the image of the unaffected limb and hides the affected (painful or missing) limb, giving patients the impression that they have 2 normal limbs. Patients are instructed to move their painful or missing limb while viewing the reflected image of their normal limb attempting the same movement. Most patients who do this exercise for 30 min/day for 4 wk report a substantial reduction in pain.
CRPS may follow injury (to soft tissue, bone, or nerve), amputation, acute MI, stroke, or cancer or have no apparent precipitant.
Diagnose CRPS if patients have neuropathic pain, allodynia or hyperalgesia, and focal autonomic dysregulation when no other cause is identified.
Prognosis is unpredictable, and treatment is often unsatisfactory.
Treat as early as possible using multiple modalities (eg, drugs used for neuropathic pain, physical therapy, sympathetic blockade, psychologic treatments, neuromodulation, mirror therapy).