What is reflex sympathetic dystrophy

Reflex sympathetic dystrophy also called complex regional pain syndrome type 1, is a syndrome characterized by a continuing (spontaneous and/or evoked) regional pain that is seemingly disproportionate in time or degree to the usual course of pain after trauma or other lesion. Reflex sympathetic dystrophy usually follows minor injuries without a confirmed nerve injury, particularly a fracture of a limb or soft tissue lesion, preceding the onset of symptoms ¹. Reflex sympathetic dystrophy pain is regional (not in a specific nerve territory or dermatome) and usually has a distal predominance of abnormal sensory, motor, sudomotor, vasomotor/edema and/or trophic findings. Reflex sympathetic dystrophy syndrome symptoms vary in severity and duration, although some cases are mild and eventually go away. In more severe cases, individuals may not recover and may have long-term disability. Reflex sympathetic dystrophy syndrome shows variable progression over time.

Although it is more common in women, reflex sympathetic dystrophy syndrome can occur in anyone at any age, with a peak at age 40. Reflex sympathetic dystrophy syndrome is rare in the elderly. Very few children under age 10 and almost no children under age 5 are affected.

The key symptom of reflex sympathetic dystrophy syndrome is continuous, intense pain that is out of proportion to the severity of the injury. In some people, signs and symptoms of complex regional pain syndrome go away on their own. In others, signs and symptoms may persist for months to years. Treatment is likely to be most effective when started early in the course of the illness.

Reflex sympathetic dystrophy causes

Reflex sympathetic dystrophy syndrome occurs as a result of varying degrees or types of tissue trauma but has even been documented in the absence of injury or due to periods of prolonged immobilization ². The most common injury associated with developing reflex sympathetic dystrophy syndrome is a fracture which occurs in > 40% of reflex sympathetic dystrophy syndrome cases. Other common inciting injuries or insults include sprains, contusions, crush injuries, and surgery. Reflex sympathetic dystrophy syndrome even has been reported to arise after seemingly innocuous interventions such as intravenous line placement. Increased psychological distress experienced during the physical injury associated with the onset of reflex sympathetic dystrophy syndrome may affect its severity and prognosis.

The underlying mechanism is multifactorial and involves at least abnormal neuronal transmission, autonomic dysregulation, and central sensitization. This contributes to the variation in clinical presentation. At the site of injury, there is a proinflammatory and immunological response which includes B-cell activation and increased production of interleukins, bradykinin, substance P, and osteoprotegerin (an osteoclastogenesis inhibitory factor). Peripheral sensitization ensues which results in persistent noxious primary afferent traffic into the dorsal horn leading to “wind up” and central sensitization. This, in turn, may result in eventual remodeling in the spinal cord and somatosensory cortex. There is an alteration of the sympathetic nervous system; sympatho-afferent coupling occurs, and there is an increased expression of adrenergic receptors on nociceptive fibers, which during times of sympathetic activation may explain the presence of autonomic features. The genetic and immune-related factors are subjects of ongoing research.

Reflex sympathetic dystrophy symptoms

The key symptom of reflex sympathetic dystrophy syndrome is continuous, intense pain that is out of proportion to the severity of the injury. It has been described as “burning,” “pins and needles” sensation, or as if someone were squeezing the affected limb. The pain gets worse over time. Reflex sympathetic dystrophy syndrome most often affects one of the arms, legs, hands, or feet, and the pain often spreads throughout the entire affected arm or leg, even though the injury might have only involved a finger or toe ¹. In rare cases, pain can sometimes even travel to the opposite extremity. There is often increased sensitivity in the affected area, known as allodynia, in which normal contact with the skin is experienced as very painful.

Symptoms may change over time and vary from person to person. People with reflex sympathetic dystrophy syndrome also experience changes in skin temperature, skin color, swelling of the affected limb and hypersensitivity (particularly to cold and touch). This is due to abnormal microcirculation caused by damage to the nerves controlling blood flow and temperature. As a result, an affected arm or leg may feel warmer or cooler compared to the opposite limb. The skin on the affected limb may change color, becoming blotchy, blue, purple, pale, or red. Once these changes occur, the condition is often irreversible.

Other signs and symptoms of reflex sympathetic dystrophy syndrome may include ³:

• sensitivity to touch or cold
• swelling of the painful area
• changes in skin temperature, color
• changes in skin texture on the affected area; it may appear shiny and thin
• joint stiffness and swelling
• abnormal sweating pattern in the affected area or surrounding areas
• changes in nail and hair growth patterns
• muscle weakness and/or muscle spasms
• problems coordinating muscle movement, with decreased ability to move the affected body part
• abnormal movement in the affected limb, most often fixed abnormal posture (called dystonia) but also tremors in or jerking of the limb.

Symptoms may change over time and vary from person to person. In some people, signs and symptoms of go away on their own. In others, symptoms can persist for months to years ³.

Reflex sympathetic dystrophy diagnosis

Currently there is no specific test that can confirm reflex sympathetic dystrophy syndrome. Its diagnosis is based on a person’s medical history, and signs and symptoms that match the definition. Since other conditions can cause similar symptoms, careful examination is important. As most people improve gradually over time, the diagnosis may be more difficult later in the course of the disorder.

Testing also may be used to help rule out other conditions, such as arthritis, Lyme disease, generalized muscle diseases, a clotted vein, or small fiber polyneuropathies, because these require different treatment. The distinguishing feature of reflex sympathetic dystrophy syndrome is that of an injury to the affected area. Such individuals should be carefully assessed so that an alternative treatable disorder is not overlooked.

Various objective testing measures have been utilized to include thermography, triple phase bone scan, and the quantitative sudomotor axon reflex test. While these studies provide further data, they are not necessary to make the diagnosis of reflex sympathetic dystrophy syndrome.

Magnetic resonance imaging or triple-phase bone scans may be requested to help confirm a diagnosis. While reflex sympathetic dystrophy syndrome is often associated with excess bone resorption, a process in which certain cells break down the bone and release calcium into the blood, this finding may be observed in other illnesses as well.

The Budapest consensus panel implemented a set of decision rules for proposed clinical criteria (sensitivity 0.85, specificity 0.7) ². In addition to continuing pain which is disproportionate to the inciting event, they must demonstrate the following symptoms and signs.

Patients should report at least one symptom in three of the four following categories:

1. Sensory: Reports of hyperalgesia and/or allodynia,
2. Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry,
3. Sudomotor/edema: Reports of edema and/or sweating changes and/or sweating asymmetry,
4. Motor/trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, skin, nails).

Additionally, patients must display at least one sign at the time of evaluation in two or more of the following categories:

1. Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch or deep somatic pressure),
2. Vasomotor: Evidence of temperature asymmetry and/or skin color changes and/or asymmetry,
3. Sudomotor/edema: Edema and/or sweating changes and/or sweating asymmetry,
4. Motor/trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, skin, nails).

Finally, there is no other diagnosis that better explains the signs and symptoms.

Reflex sympathetic dystrophy treatment

Although there is a possibility that patients with reflex sympathetic dystrophy syndrome may spontaneously improve, considering the debilitating nature of this syndrome, physical and occupational therapy including mirror therapy is imperative in the treatment of reflex sympathetic dystrophy syndrome ².

The following therapies are often used:

• Rehabilitation and physical therapy. An exercise program to keep the painful limb or body part moving can improve blood flow and lessen the circulatory symptoms. Additionally, exercise can help improve the affected limb’s flexibility, strength, and function. Rehabilitating the affected limb also can help to prevent or reverse the secondary brain changes that are associated with chronic pain. Occupational therapy can help the individual learn new ways to work and perform daily tasks.
• Psychotherapy. Reflex sympathetic dystrophy syndrome and other painful and disabling conditions often are associated with profound psychological symptoms for affected individuals and their families. People with reflex sympathetic dystrophy syndrome may develop depression, anxiety, or post-traumatic stress disorder, all of which heighten the perception of pain and make rehabilitation efforts more difficult. Treating these secondary conditions is important for helping people cope and recover from reflex sympathetic dystrophy syndrome.
• Medications. Several different classes of medication have been reported to be effective for reflex sympathetic dystrophy syndrome, particularly when used early in the course of the disease. However, no drug is approved by the U.S. Food and Drug Administration specifically for reflex sympathetic dystrophy syndrome, and no single drug or combination of drugs is guaranteed to be effective in every person. Drugs to treat reflex sympathetic dystrophy syndrome include:
  • bisphosphonates, such as high dose alendronate or intravenous pamidronate
  • non-steroidal anti-inflammatory drugs (NSAIDs) to treat moderate pain, including over-the-counter aspirin, ibuprofen, and naproxen
  • corticosteroids that treat inflammation/swelling and edema, such as prednisolone and methylprednisolone (used mostly in the early stages of reflex sympathetic dystrophy syndrome)
  • drugs initially developed to treat seizures or depression but now shown to be effective for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, nortriptyline, and duloxetine
  • botulinum toxin injections
  • opioids such as oxycodone, morphine, hydrocodone, and fentanyl. These drugs must be prescribed and monitored under close supervision of a physician, as these drugs may be addictive.
  • N-methyl-D-aspartate (NMDA) receptor antagonists such as dextromethorphan and ketamine, and
  • topical local anesthetic creams and patches such as lidocaine.

All drugs or combination of drugs can have various side effects such as drowsiness, dizziness, increased heartbeat, and impaired memory. Inform a healthcare professional of any changes once drug therapy begins.

• Sympathetic nerve block. Some individuals report temporary pain relief from sympathetic nerve blocks, but there is no published evidence of long-term benefit. Sympathetic blocks involve injecting an anesthetic next to the spine to directly block the activity of sympathetic nerves and improve blood flow.
• Surgical sympathectomy. The use of this operation that destroys some of the nerves is controversial. Some experts think it is unwarranted and makes reflex sympathetic dystrophy syndrome worse, whereas others report a favorable outcome. Sympathectomy should be used only in individuals whose pain is dramatically relieved (although temporarily) by sympathetic nerve blocks.
• Spinal cord stimulation. Placing stimulating electrodes through a needle into the spine near the spinal cord provides a tingling sensation in the painful area. Electrodes may be placed temporarily for a few days in order to assess whether stimulation is likely to be helpful. Minor surgery is required to implant all the parts of the stimulator, battery, and electrodes under the skin on the torso. Once implanted, the stimulator can be turned on and off, and adjusted using an external controller. Approximately 25 percent of individuals develop equipment problems that may require additional surgeries.
• Other types of neural stimulation. Neurostimulation can be delivered at other locations along the pain pathway, not only at the spinal cord. These include near injured nerves (peripheral nerve stimulators), outside the membranes of the brain (motor cortex stimulation with dural electrodes), and within the parts of the brain that control pain (deep brain stimulation). A recent option involves the use of magnetic currents applied externally to the brain (known as repetitive Transcranial Magnetic Stimulation, or rTMS). A similar method that uses transcranial direct electrical stimulation is also being investigated. These stimulation methods have the advantage of being non-invasive, with the disadvantage that repeated treatment sessions are needed.
• Intrathecal drug pumps. These devices pump pain-relieving medications directly into the fluid that bathes the spinal cord, typically opioids, local anesthetic agents, clonidine, and baclofen. The advantage is that pain-signaling targets in the spinal cord can be reached using doses far lower than those required for oral administration, which decreases side effects and increases drug effectiveness. There are no studies that show benefit specifically for reflex sympathetic dystrophy syndrome.

Emerging treatments for reflex sympathetic dystrophy syndrome include:

• Intravenous immunoglobulin (IVIG). Researchers in Great Britain report low-dose IVIG reduced pain intensity in a small trial of 13 patients with reflex sympathetic dystrophy syndrome for 6 to 30 months who did not respond well to other treatments. Those who received IVIG had a greater decrease in pain scores than those receiving saline during the following 14 days after infusion.
• Ketamine. Investigators are using low doses of ketamine—a strong anesthetic—given intravenously for several days to either reduce substantially or eliminate the chronic pain of reflex sympathetic dystrophy syndrome. In certain clinical settings, ketamine has been shown to be useful in treating pain that does not respond well to other treatments.
• Graded Motor imagery. Several studies have demonstrated the benefits of graded motor imagery therapy for reflex sympathetic dystrophy syndrome pain. Individuals do mental exercises including identifying left and right painful body parts while looking into a mirror and visualizing moving those painful body parts without actually moving them.

Several alternative therapies have been used to treat other painful conditions. Options include behavior modification, acupuncture, relaxation techniques (such as biofeedback, progressive muscle relaxation, and guided motion therapy), and chiropractic treatment.

Reflex sympathetic dystrophy prognosis

The outcome of reflex sympathetic dystrophy syndrome is highly variable. Younger persons, children, and teenagers tend to have better outcomes. While older people can have good outcomes, there are some individuals who experience severe pain and disability despite treatment. Anecdotal evidence suggests early treatment, particularly rehabilitation, is helpful in limiting the disorder, a concept that has not yet been proven in clinical studies. More research is needed to understand the causes of reflex sympathetic dystrophy syndrome, how it progresses, and the role of early treatment.

References

1. Complex Regional Pain Syndrome Fact Sheet. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Complex-Regional-Pain-Syndrome-Fact-Sheet
2. Guthmiller KB, Varacallo M. Complex Regional Pain Syndrome (CRPS), Reflex Sympathetic Dystrophy (RSD) [Updated 2019 Jun 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430719
3. Complex regional pain syndrome. https://www.mayoclinic.org/diseases-conditions/complex-regional-pain-syndrome/symptoms-causes/syc-20371151