Terminology describing the complex regional pain syndromes has evolved over the last century. The term causalgia was first coined by Weir Mitchell in the 1870s for severe progressive distal limb pain with major nerve injury. In 1946, Evans introduced the term reflex sympathetic dystrophy (RSD). It was late defined by the International Association for Study of Pain (IASP) as “continuous pain in a portion of an extremity after trauma, which may include fracture but does not involve a major nerve, associated with sympathetic hyperactivity”. In 1994, the IASP introduced the term Complex Regional Pain Syndrome (CRPS), describing a painful condition that includes regional pain, sensory changes (e.g. allodynia), abnormalities of temperature, abnormal sudomotor activity, edema and abnormal skin color changes that occur after an initiating noxious event such as trauma. Two types of CRPS have been recognized: CRPS I corresponds to RSD, in which no definable nerve lesion is found. CRPS II refers to a case with a definable nerve lesion and corresponds to the earlier term of causalgia.
The mean age of CRPS patients ranges from 36-46 years with women predominating (60-81%). It is caused typically by an injury, such as a fracture (16-46%), strain or sprain (10-29%), post-surgery (3-24%), and contusion or crush injury (8-18%). Clinical features of CRPS often include pain, edema, autonomic dysfunction such as change in temperature, color in the involved limbs, motor dysfunction and psychological abnormalities such as depression. Schwartzman and Maleki reported the pattern of spreading of CRPS in three stages. In the early stage, CRPS often involves only one limb with pain, minor edema and increased skin temperature. CRPS may spread from one limb to the others. In the later stage, CRPS could involve the full body and the four extremities with severe pain, edema, cold and cyanotic limbs, joint contracture, and atrophy of muscles and bones.
Excruciating pain is the cardinal feature of CRPS. Pain is often described as burning, aching, pricking or shooting. Severity of pain is not proportional to the initial injury and pain is not limited to the area of the injury or a specific nerve distribution. Patients may feel severe pain to minor pain stimulation such as a safety-pin prick (hyperalgesia). A light touch to skin (innocuous stimulation) may cause severe long-lasting pain (mechanical allodynia). A cooling stimulus such as a drop of alcohol may be perceived as painful (thermal allodynia). Decreased temperature and pinprick sensations in the affected limb are common.
Edema of the affected limb is present in the majority of patients. It could be very mild in the early stage of CRPS, mimicking mild cellulitis. However, in the late stage, edema may be so severe that a Doppler test is needed to rule out the possibility of deep vein thrombosis.
Autonomic dysfunction may be manifested by changes of skin color and temperature, as well as sweating abnormalities. The affected area may be reddish at one time and then become blue, purple or pale over a course of minutes to hours. Livedo reticularis is common in CRPS. Livedo is a descriptive term used to describe the red, non-blanchable (i.e. it does not turn white when pressed) network-pattern (reticulated) in the skin. About 60 % of patients may report excessive sweating in the affected limbs. Temperature asymmetry between the affected and unaffected sides may exceed 1 °C .
Motor dysfunctions in CRPS include mild weakness, decreased range of motion, tremor, dystonia and myoclonus. Dystrophic manifestations are seen in the form of increased or decreased nail and hair growth in the affected extremity, hyperkeratosis or thin, glossy skin, and osteoporosis of the underlying bones.
Diagnosis of CRPS
Diagnosis of CRPS is clinical. According to IASP (1994), if a patient has the above-mentioned features, a diagnosis of CRPS may be made if other clinical conditions, such as infection or DVT, are ruled out. EMV/NCV tests are not sensitive to CRPS and frequently cause severe pain to patients. A triple-phase bone scan may reveal abnormal absorption in the affected limbs (increased or decreased), though it is not a primary diagnostic procedure for CRPS.
The pathophysiology of CRPS is not completely understood. Multiple mechanisms are considered in the generation and maintenance of CRPS. Increased systemic calcitonin gene-related peptide (CRGP) levels may contribute to neurogenic inflammation, edema, vasodilatation and increased sweating. Elevated neuropeptide concentrations may lead to pain and hyperalgesia. Immunological mechanisms (such as altered expressions of HLA, substance P, cytokines, and interleukins) are believed to contribute to the pathogenesis of clinical symptoms, such as edema. Up-regulation of adrenergic receptors and functional coupling between sympathetic efferent and sensory afferent fibers may provide the basis of the sympathetic nervous system abnormalities in the pathogenesis of CRPS. The central mechanisms in CRPS may include central sensitization in the spinal cord, brainstem or thalamus, cortical reorganization in the primary somatosensory cortex, as well as disinhibition of the motor cortex.
The goals of treatment for CRPS are pain relief, functional recovery and psychological improvement. However, treatment of CRPS remains a challenge. There is little, if any, evidence for the efficacy of any treatment modality. In the early stages of CRPS treatment, occupational and physical therapies are often used. Occupational and physical therapies are supported by anecdotal data, and have not been validated by randomized prospective trials.
Patients diagnosed with CRPS for over 2 months should also receive a psychological evaluation, which includes psychometric testing, to identify and treat psychological disorders, such as anxiety, depression, or personality disorders. Counseling, behavioral modification, biofeedback, relaxation therapy, group therapy, and self-hypnosis should be considered. The goal of psychotherapy is to improve patient motivation and coping skills.
Tricyclic antidepressants, antiepileptics, and narcotics such as methadone are commonly used empirically for CRPS, even though clinical controlled studies have not proven their efficacy. Corticosteroids have proven to be effective analgesics in several trials with early CRPS patients. However, this is not widely used, possibly due to the side effects of corticosteroids. Subcutaneous calcitonin and intravenous phentolamine studies have had conflicting results. NMDA receptor modulation is a major interest of current research. A recent study indicated that sub-anesthetic infusions of ketamine might offer a promising therapeutic option in the treatment of appropriately selected patients with intractable CRPS. However, more studies are needed to further establish the safety and efficacy of this novel approach.
Minimally invasive techniques have been used extensively for the treatment of CRPS. These techniques include sympathetic block, intravenous regional block (IVRB), somatic nerve block, epidural drug administration, intrathecal drug delivery, and neurostimulation. A stellate ganglion block in the early stage CRPS may significantly decrease pain and hasten clinical recovery. It may also prevent the recurrence of CRPS after re-operation of the affected extremity. In a double blind study, IVRB with bretylium provided significantly longer analgesia than lidocaine. Epidural delivery of clonidine and ketamine, intrathecal baclofen and morphine have reported to provide good pain relief. A randomized trial, with a two-year follow-up of 36 patients, suggested that spinal cord stimulation results in a long-term pain reduction and improvement in health-related qualities of life.