Dolores, a 20-year-old student, simply tripped while hurrying to her classroom and fell and landed on the books she was holding. By early evening, her right wrist was swollen and very painful. By the next morning, despite ice, elevation, and acetaminophen, the pain persisted and her wrist remained swollen, red, and warm to the touch. She stayed out of school to visit her family physician. After normal X-ray findings, Dolores started a course of analgesics. Despite treatment, she still suffered from symptoms of swelling and extreme pain that now extended up her right arm from the affected area. She was unable to go to school, use her dominant upper extremity or type on the computer effectively.

After no improvement through the second week, Dolores’ physician sent her to a neurologist, who diagnosed her with CRPS type I. A thermogram demonstrated asymmetric color variations consistent with abnormal sympathetic nervous function in her right forearm, wrist and hand. Dolores received a series of nerve blocks with guanethidine, which relieved up to 90% of her pain, followed by therapy. Her therapist started by using The Canadian Occupational Performance Measure, a measure of occupational performance, and a Visual Analogue Scale, a measure of pain intensity. Therapy treatment included performance intervention (e.g., self-care, home management and return to school activities), integration of her right upper extremity in tasks, work simplification, joint protection techniques, stress loading activities when she was ready (e.g., scrubbing and carrying) and psychosocial interventions for pain management (e.g., relaxation techniques and cognitive behavioral therapy techniques).

Ten weeks after the blocks, Dolores is able to function well enough to return to her schoolwork but not to play tennis, a meaningful occupation that supports her lifestyle. She has mild, continuous, burning pain, and she favors the affected right upper extremity. Her prognosis is guarded, and if her pain or other symptoms flare up, she will need further evaluation and treatment. In addition to eliminating her pain, she would like to get back to tennis.

Introduction

Complex regional pain syndrome type I (CRPS-1) is a multisymptom, multisystem disorder characterized by motor, trophic, sensory or autonomic changes in an extremity, in the absence of peripheral nerve injury.¹ There are currently two classifications of complex regional pain syndrome (CRPS): Type I, formerly known as reflex sympathetic dystrophy (RSD), occurs without a distinguishable nerve lesion; and type II, formerly known as causalgia, has an identifiable nerve lesion.^2,3 CRPS has also been known as Sudeck’s atrophy, algoneurodystrophy, neurovascular dystrophy and sympathetically maintained pain.

CRPS-1 is difficult to diagnose and treat, and it often goes unrecognized. Minor or major trauma involving an extremity usually precipitates this condition, causing patients to seek out emergency care and primary care treatment of severe, burning pain. The disorder is accompanied by hyperesthesia and severe, burning pain characterized by allydonia. Vasomotor and dystrophic changes can affect any extremity and can spread if treatment is not started immediately.⁴ However, many healthcare providers are not familiar with CRPS-1 and its deleterious consequences. Patients may go undiagnosed and untreated as they are shuttled from clinician to clinician seeking pain relief. In addition, patients may be treated with great skepticism and disbelief if the provider is unfamiliar with CRPS-1. The syndrome can be misdiagnosed as “psychogenic,” adding stress to the affected patients until the condition has advanced to irreversible pain and disability.¹

Healthcare professionals in all settings are in key positions to identify these patients early on. With increased awareness in the medical community, patients may potentially receive the appropriate care in a timely manner. This review outlines the identification, investigation and management of patients with CRPS-1.

Epidemiology

CRPS-1 affects four times as many females as males, and their average age range is between 35 and 45 years, although the disease may afflict older adults and young children as well.^4,5 Children and infants can suffer manifestations as severe and difficult to treat as those found in adults.^3,5 Typically, an individual presents with a history of symptoms precipitated by trauma, lesion to the peripheral or central nervous system, immobilization or surgery, followed by intense pain at the site of injury. CRPS-1 may also develop post myocardial infarction or concurrently in patients who have cancer or other medical conditions. Additional inciting events include stroke and shingles.⁶ In 10% to 30% of individuals diagnosed with CRPS-1, there is no identifiable precipitating event.^3,7 The upper extremity is affected 1.5 times more than the lower extremities,⁷ and fractures constitute approximately 44% to 55% of traumatic onset CRPS-1.^7,8

Clinical Features

The following are common clinical features of individuals diagnosed with CRPS-1:^3,9

• Onset is in a single extremity, though bilateral involvement has been reported.
• Pain is out of proportion to the injury, if any.
• Pain is described as severe, burning and unrelenting.
• Edema.
• Bone demineralization.
• Excess perspiration in affected extremity.
• Muscle spasms, dystonia, tremor or diffuse weakness.
• Overgrown nails.
• Changes in limb hair texture.
• Limb may feel cool and moist or red and dry.
• Course is unpredictable and can migrate to other body parts.
• Characterized by remissions and exacerbations.

It was thought that patients with CRPS-1 passed through three stages of disease characterized by progressive changes in the skin and joints, pain and edema. However, this has been refuted, as research has shown that CRPS-1 evokes various symptoms in different patients.^1,10

The clinical presentation differs between adults and children with CRPS-1. CRPS-1 in children is more commonly seen in females with a mean age of 11-13.¹¹ The lower extremities are affected more than the upper extremities, with the foot being most involved. In a retrospective study, researchers reported colder skin temperature, female predominance, lower extremity injury and fewer neuro-sympathetic conditions in children with CRPS-1.¹¹ Dystonia has been associated with a younger age at onset of CRPS-1.¹²

Etiology

In the midst of many proposed hypotheses, the pathophysiology of CRPS-1 is still unknown and misunderstood by many therapists. Investigators have suggested theories involving central versus peripheral mechanisms of origin, sympathetic nervous system dysfunction, and an exaggerated inflammatory response.¹³ It is also thought that skin fibers send signals and release norepinephrine, therefore changing cell dynamics and reducing pain thresholds in the dorsal horn of the spinal cord.³ Research has also proposed that neuropeptides, such as substance P, calcitonin gene-related peptide and somatostatin, may exert an excitatory response which causes vascular changes and causes pain.³ Citations can be found that allude to a genetic component or predisposition to CRPS-1.^14,15,16

None of the proposed theories, however, explain the unusual symptoms and their sequence. Some consider CRPS-1 to be a chronic pain syndrome because persistent, severe, burning pain is a hallmark of the condition. The pain, which does not follow any nerve, dermatomal or plexus distribution, is exacerbated by psychological stress, physical stress or mobility.^3,13 Some authors conclude that the nature, extent and severity of patient manifestations are not related to the type and degree of the precipitating trauma.¹³

Diagnosis

Below is the taxonomy agreed upon by the International Association for the Study of Pain (IASP) in 1994 in order to standardize the symptomatology of CRPS type I and II.^5,10,17

• Continuing pain, which is disproportionate to any inciting event
• The patient must report at least one symptom in three of the four following categories:
  • Sensory: reports of hyperesthesia and/or allodynia
  • Vasomotor: reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
  • Sudomotor/edema: reports of edema and/or sweating changes and/or sweating asymmetry
  • Motor/trophic: reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail and skin)
• Must display at least one sign in two or more of the following categories:
  • Sensory: evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch)
  • Vasomotor: evidence of temperature asymmetry and/or skin color changes and/or asymmetry
  • Sudomotor/edema: evidence of edema and/or sweating changes and/or sweating asymmetry
  • Motor/trophic: evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
  • There is no other diagnosis that better explains the signs and symptoms

Therapists treating these patients should understand that CRPS-1 is a diagnosis adapted from the patient’s history, physical findings and IASP diagnostic criteria.^1,10,17 The IASP criteria were developed for adults and have yet to be validated for children. A therapist’s evaluation should include assessment of movement, sensation and discoloration. Documentation of swelling, allydonia and hyperalgesia associated with pain is vital to accurately diagnose and treat these patients.¹⁸

Hyperalgesia (an exquisite, hypersensitive pain experience) and allydonia (when ordinary, painless stimulus, such as light touching, is experienced as painful) are always present. Hyperesthesia is pain as a result of sensitivity to stimulation, particularly to touch. These three components are hallmark sensory signs of CRPS-1 pain. A common complaint is constant burning pain with severe discomfort that causes the patient to possessively guard the affected extremity and avoid movement. These findings relate to an earlier 2001 report that proposed that disuse alone could produce CRPS-1 manifestations in healthy subjects. Twenty-three healthy subjects volunteered to wear fiberglass arm casts for four weeks. Researchers reported CRPS-1-like manifestations in participants after four weeks of cast immobilization, indicating involvement of brain centers associated with sensory processing, pain and motor function.¹⁹ Thus, therapists who care for individuals who complain of prolonged, burning pain in an extremity with atrophic changes need to consider the possibility of CRPS-1 and suggest this to other healthcare colleagues to facilitate early diagnosis and treatment.

Differential Diagnoses

Below is a list of various conditions that may mimic upper or lower extremity CRPS type I or II:²⁰

• Vascular: deep vein thrombosis, vascular insufficiency, thrombophlebitis
• Inflammatory: cellulitis, lymphedema
• Neuropathy: diabetic neuropathy, entrapment neuropathy, thoracic outlet syndrome, peripheral neuropathy, carpal tunnel syndrome
• Tumor: pancoast tumor

Diagnostic Testing

Currently, there are no diagnostic tests specifically for CRPS-1. However, several diagnostic tests have been offered to support the diagnosis.²¹ Electromyograms and nerve conduction tests may be used to assess motor function. Autonomic dysfunction may be assessed via thermography, sympathetic block or Doppler flowmetry. Lastly, radiographs and scintigraphy may offer insight into trophic changes. Routine lab values in the early stages are normal or only reflect other underlying diseases. Plain film radiographs are not useful during early stages because characteristic deossification usually takes from four to six weeks to occur. There is radiographic evidence of osteoporosis and increased uptake on bone scintigraphy of the affected limb involved with a chronic disease state. Even neurodiagnostic studies are normal unless nerve injury or entrapment is present.¹⁵ Diagnosis may also be confirmed with nerve blocks such as guanethidine,²² which relieve early pain if it is sympathetically maintained, and thermography, especially within the first 72 hours.²³

Because sudomotor manifestations — sympathetic autonomic activity that stimulates sweat glands — have been associated with as many as 92% of these patients, tests that measure these functions, such as resting sweat output and quantitative sudomotor axon reflex tests, can facilitate diagnosis. One study used capillary microscopy to evaluate degenerative changes relative to impaired nutritive skin blood flow and transcutaneous oximetry to measure oxygenation and temperature of superficial skin. The researchers found changes in the blood flow of patients with CRPS-1 that they related to sympathetic dysfunction.²⁴ Also, recent research findings document significant changes in the innervation of various target tissues affected and evidence of secondary tissue changes as the pathology progresses. Examples include more notable vasoconstriction with hypoperfusion in affected vessels leading to hypoxia, acidosis and further pain in the areas.^1,24,25

In 1999, a quantitative research study was completed using control subjects to test vascular abnormalities in CRPS-1. The study measured cutaneous Doppler blood flowmetry, cutaneous thermometry with an infrared thermometer and venous norepinephrine levels on the affected and unaffected limbs. Results of the study demonstrated that CRPS-1 is an aberrant response within the central nervous system and the underlying sympathetic interaction might be found in tissue, bones and muscles.²⁴

There is limited evidence for the diagnostic value of the aforementioned tests in patients with CRPS-1. The lack of definitive diagnostic measures may lead to misdiagnosis, delayed treatment and further disability. Further research is needed to identify the most prognostic or therapeutic test to better manage CRPS-1. Patients are treated symptomatically as there is no diagnostic test that is considered a gold standard.¹

Once these diagnostic tests and a detailed history reveal CRPS-1, therapists assess the extent that the condition limits participation in ADLs and meaningful life occupations. Therapists may also provide psychosocial interventions regarding living with pain and decreased quality of life.

Treatment Options

Healthcare professionals play an extremely important role in early identification of CRPS-1 through comprehensive health histories, assessments and documentation. Patients may seek treatment up to five years before an appropriate diagnosis is made. Because early interruption of the transmission of pain via sympathetic neuronal pathways seems to offer the only hope for remission, prompt recognition and early treatment are vitally important to patient outcomes. Pain relief remains the cornerstone of treatment for CRPS-1, so clinicians need to make it a priority with these patients. Treatments for CRPS-1 have included pharmacology, sympathetic nerve blocks, spinal cord stimulators, physical and occupational therapy, and psychological support.

Pharmacological Considerations: Newly diagnosed patients with CRPS-1 may be prescribed nonsteroidal anti-inflammatory agents, narcotic analgesics, topical analgesics and lidocaine patches. Analgesics, individually titrated for around-the-clock pain relief, need to be used judiciously. Nevertheless, patients seldom get complete pain relief from analgesics alone.² If there is no significant improvement within four weeks, the physician will likely consider the use of steroids or sympatholytic therapy.

Sympathetic Nerve Blocks: Sympathetic nerve blocks completed early in the diagnosis of CRPS-1 seem to be helpful for some patients. It is well recorded in the literature that patients treated early can go into remission early in diagnosis with stellate ganglion blocks.³ Nerve blocks may include paravertebral, stellate ganglion blocks, epidural blocks, or the intra-arterial infusion of alpha-adrenergic blocking agents. Many of these patients will have completed numerous blocks before achieving remission. Alternatively, some patients undergo many painful blocks without any relief of their burning pain.³ For some patients, repetitive blocks become less and less effective until pain control is no longer dependent on manipulating the sympathetic nervous system. At this point, the CRPS-1 is chronic and centrally maintained by the autonomic nervous system. The value and scientific merit of nerve block therapies is now being questioned.^2,23 A recent Cochrane database systematic review found weak evidence to support the use of sympathetic blockades for the treatment of CRPS-1.²⁶

Spinal Cord Stimulator: Pain specialists will place spinal cord stimulators on patients who have demonstrated no success reducing pain and limb function with oral pain medications, nerve blocks and interventional therapies after six months of treatment. In 2000, Dutch researchers conducted a study on patients with CRPS-1 and the use of spinal cord stimulators. Their findings suggest that CRPS-1 pain is controlled by the sympathetic nervous system, the use of spinal cord stimulation has an effect on sympathetic tone, and pain relief can be achieved despite vasoconstriction.²⁷ Sympathectomies have also been used to interrupt CRPS-1 pain cycles in the past; but over the years, they have not proven to be effective.¹

Alternative treatments have also been documented in the literature and can help relieve CRPS-1 signs and symptoms. Patients turn to acupuncture, hypnosis, behavior modification, tai chi and hyperbaric oxygen treatments in desperate need of pain control. Most of these approaches offer only temporary symptomatic relief of pain.

Therapy: Rehabilitation therapy plays a major role in management of individuals with CRPS-1 and is considered the mainstay of treatment.³ The primary goals of therapy are to decrease pain and edema; improve range of motion, sensation and weight-bearing; and ultimately improve function of the affected extremity in addition to improving functioning in daily life and maintenance of meaningful activities in spite of pain.

Therapy is aimed at improving function, typically after pain relief has been established. Initially, therapy needs to be started slowly and gently while the patient learns to trust the therapist. Education about passive pain-coping strategies, notably immobility and guarding, and evidence that demonstrates immobility causing CRPS-1 manifestations need to be addressed in all patient plans of care. It is difficult to encourage individuals who are in pain to use their extremities or participate in treatment, such as exercise. Learned disuse is a significant concern with individuals with CRPS-1. A therapist can put interventions in the treatment plan that will incorporate the effected extremity as a functional assist or, at the very least, the extremity can be used as a stabilizer. As function improves and pain subsides, introduce adaptive equipment such as built up handles so an individual can begin using his or her extremity functionally. As an individual is more involved in personally relevant meaningful activities, they have improved self-efficacy. The sense of control of pain and engagement in meaningful activities is germane to pain management.^28,29

Aggressive rehabilitation may exacerbate inflammation and CRPS-1 symptoms and consequently worsen the condition. However, limiting the use of the affected extremity due to pain may lead to further decline in function. A recent case series suggests ‘pain exposure therapy’ is effective in those individuals who are unresponsive to standard treatment.³⁰ One hundred and six individuals with upper or lower extremity CRPS-1 were prescribed physiotherapy that focused on functional improvement while neglecting pain. Physical function and tolerance to weight bearing improved in 90% of patients, and full recovery was seen in 43% of patients.

Currently, there is no consensus for the best treatment for CRPS-1. In 2005, a systematic review provided numerous treatment techniques beneficial for adult CRPS-1. These included therapeutic exercise, mirror feedback, motor imaging, relaxation techniques, acupuncture and transcutaneous nerve stimulation.³¹ Additional treatments found to be effective include therapeutic exercise, patient education, massage and transcutaneous nerve stimulation.³² Rehabilitation and methodology has varied between studies and therefore it is not possible to determine the individual effectiveness of specific treatment techniques. It appears a combination of various treatments tailored to the patient enhance outcomes and functioning in meaningful and daily occupations.

Neural mobilizations and manual therapy have also been documented to treat CRPS-1. Case reports have demonstrated the integration of neural mobilization and manual therapy to the thoracic spine to improve functional use of the extremity and reduce skin temperature, pain and edema in patients with upper and lower extremity CRPS.^33,34 The incorporation of strain-counterstrain techniques into a comprehensive strength and gait training regimen was shown to improve short-term function in an adolescent patient with CRPS-1 after an ankle sprain.³⁵

Short- and long-term rehabilitation using a multimodal intensive therapy program, in addition to psychological counseling, resolved symptoms and promoted return to full function for children with CRPS-1. Cognitive-behavioral therapy combined with physical therapy has been shown to improve pain and function in the long-term in children with CRPS-1.³⁶

As the patient’s pain decreases and tolerance to weight bearing improves, stress-loading exercises should be initiated as soon as possible.³⁷ Stress loading should be considered in all ADL treatment. A gradual progression of carrying objects and stress loading (e.g., scrubbing) has been shown to be effective in improving function in upper extremity CRPS-1. Although the efficacy of short-term rehabilitation has been reported in individuals with upper extremity CRPS-1, the long-term benefit is still unknown.^38,39

One case study reviewed a combination of a nerve block and therapy intervention, including stress loading: In addition to improvement in objective measurements, the client made considerable improvements in occupational performance, including achieving independence in self-care (including writing) and meal preparation. The client was also independent in community activities, including driving with a spinner knob (a piece of adaptive equipment that allows one-handed driving).⁴⁰

Current rehabilitation practice remains largely empirical and directed by patient symptoms. Although weak evidence supports the use of current rehabilitation guidelines, most outcome studies report therapy is beneficial and a critical component of treatment for CRPS-1.

Psychosocial Considerations

Psychosocial aspects of care for CRPS-1 are extremely important. Individual and group therapy are recommended to deal with the chronic pain and disruptions in activities of daily living, sexuality, employment and relationships. Patients with chronic pain are often stigmatized, especially when the causative condition is as misunderstood as CRPS-1. Many patients suffer from periods of disbelief from practitioners, families and friends because of ignorance and misdiagnosis. As a result, these patients can become distrustful and cynical, sometimes causing withdrawal from others.

Individuals with CRPS-1 often demonstrate profound emotional and behavioral manifestations as a result of dealing with chronic pain.⁴¹ Practitioners have alleged that particular personality types are more prone to develop CRPS-1, but there is little evidence to support this view.⁴² The psychological symptoms (e.g., depression, anger, fear, anxiety) seen in CRPS-1 are now considered the result and not the cause of the disorder.

Recovery is long and difficult. The patient must learn to deal with chronic pain and disability that is disruptive to lifestyle and requires adaptations in daily activities. It has been shown that only 6% of individuals with CRPS have adequate level of knowledge regarding their condition.⁴³ These individuals may need education regarding the disease and assistance in setting realistic goals for themselves. Patients may also need help in dealing with an uncertain future and financial concerns created by the disease process.⁴⁴ Socioeconomic ramifications are considerable and incapacitating aspects of the syndrome may prohibit patients from attending school or work. Hardships may be compounded when insurers refuse to compensate for extended illnesses that are not understood or properly diagnosed.⁴⁴ Thus, therapists’ strategies of education, advocacy, and therapeutic use of self, as they are guided by the therapy practice framework, are important. In addition, a key component is to assist individuals with emotional regulation skills. When working with individuals with CRPS-1, the therapist can integrate cognitive behavioral therapy approaches (which are effective in chronic pain management), progressive relaxation, relaxation techniques (using biofeedback), and assertiveness training.⁴⁵

Additional Considerations

Little attention has been given to diet and chronic pain. Patients with CRPS-1 also tend to lead a sedentary lifestyle, which aggravates dietary issues like weight gain, muscle wasting, and deconditioning. Patients must be assessed holistically. Therapists need to teach patients healthy lifestyle changes, such as the need for exercise and smoking cessation, and maintenance of typical routines and lifestyle patterns.^25,42

Clinicians need to conduct frequent, comprehensive assessments due to the unpredictability of the syndrome. Further trauma to the affected extremity, such as blood pressure readings, needs to be avoided, and patients and or significant others must be instructed to provide information to all healthcare providers regarding this limitation. Because the sympathetic nervous system affects all areas of the body, any change in the patient’s baseline assessment needs to be investigated. Some patients have developed seemingly unrelated symptomatology, such as frequent fevers, cardiac dysrhythmias, spontaneous purpura, frequent falls and seizure activity, all with no demonstrable causes.

Prognosis

Depending on the severity of the initial injury, diagnosis time and treatment efficacy, an individual may achieve remission of CRPS-1. In a retrospective study of 168 patients with CRPS-1, the mean duration of symptoms was approximately eight months.⁷ While early diagnosis and treatment are needed to provide relief, they do not guarantee a cure. Some patients who were diagnosed and treated early continue to exhibit symptoms of CRPS-1, even up to 12 years after diagnosis.46 Others have had remissions, only to have the condition return months or years later. Approximately 22% of patients will continue to report long-lasting complaints.⁴⁷ It appears that symptoms of CRPS-1 undergo periods of remissions and exacerbations that may spread proximally, centrally or to a different body site altogether if left untreated.^2,3 Researchers found severe CRPS-1 in a large group of children and young adults, in whom previous investigators believed symptoms were less severe.²⁵ Treatment of children with CRPS-1 is more favorable than in adults. However, studies have described continued functional limitations with activities of daily living after five years in upper extremity CRPS-1.⁴⁸ Amputation of the affected limb due to intractable pain has been reported in refractory cases, with only minimal change in pain after amputation.²⁰ To date, it is still unknown why some people develop mild cases of CRPS-1 that respond to treatment, while others develop severe cases in which the condition progresses to affect the entire body.

Conclusion

CRPS-1 is a multifaceted neuropathic pain disorder characterized by motor, trophic and sensory changes in an extremity without nerve injury, usually precipitated by minor or major trauma to the affected limb. The pathophysiology of CRPS-1 is still poorly understood and consequently difficult to manage. Diagnosis is usually based on patient history, clinical examination and diagnostic criteria. Treatment should focus on improving pain control, managing psychosocial stress and physical function in daily life activities via an interdisciplinary approach. Specifically for therapists, interventions involve emotional regulation skills; education and advocacy; and maintenance of routines, patterns, and meaningful occupations. CRPS-1 symptoms may be self-limiting, undergo periods of remission and exacerbations, or persist for a lifetime. Early diagnosis, multidisciplinary treatment and vigilance will potentially contribute to improved outcomes for those afflicted with this devastating, painful and disabling syndrome.

There is statistically significant evidence of a positive correlation between performance satisfaction and performance scores (r=0.982, p<0.05) as well as a significant correlation between performance and pain intensity and satisfaction and pain intensity.⁴⁷ It is evident CRPS-1 is a complicated condition that impacts the individual physically and psychosocially; and it is essential that healthcare providers use a client-centered holistic approach to care.⁴⁹

Resources for Healthcare Professionals

• Reflex Sympathetic Dystrophy Syndrome Association
  http://www.rsds.org
• Complex Regional Pain Syndrome: Treatment Guidelines http://www.rsds.org/3/clinical_guidelines/index.html#diagnosis
• Institutes of Neurological Disorders and Stroke
  http://www.ninds.nih.gov/index.htm
• National Foundation for the Treatment of Pain
  http://www.paincare.org
• American Chronic Pain Association
  http://www.theacpa.org
• American Pain Society
  http://www.ampainsoc.org
• American RSD Hope
  http://www.rsdhope.org

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