Steroids for Complex Regional Pain Syndrome?
Question: Is the treatment of complex regional pain syndrome with steroids effective in adults?
Answer: Complex regional pain syndrome (CRPS) broadly describes chronic pain that affects one or more limbs, most often after injury. Less broadly, CRPS describes a debilitating neurologic syndrome characterized by pain and hypersensitivity, vasomotor skin changes, and functional impairment. This pain syndrome has had many names, including causalgia, Sudeck’s atrophy, the shoulder-hand syndrome, and reflex sympathetic dystrophy.
CRPS generally follows a fracture or traumatic event, such as surgery, stroke, crush injury, myocardial infarction, neoplasms, immobilization, and sprains.1,2 CRPS is considered a neuroinflammatory disorder; however, there is speculation that autoimmune responses, abnormal cytokine production, and sympathetic-sensory disorders play a major role.
Pain often is exaggerated in comparison to the initial event, with additional swelling, limited range of motion, and/or changes in skin color and temperature in the affected area. The pain can present as paresthesia or burning, dull, tearing, achy pain. To properly diagnose CRPS, practitioners must rule out other possible diagnoses, including arthritis, stress fractures, neuropathies, vascular disorders, and somatoform disorders.1,2
Clinical Diagnosis and Treatment
The clinical diagnostic criterion for CRPS is pain that is magnified in relation to the original cause with no other diagnosis that can better explain signs and symptoms. In addition, the patient must have one symptom from 3 of the following categories—sensory, vasomotor, edema, and motor—and one sign from 2 of the categories.
Initial treatment of CRPS should be individualized based on the severity and duration of diagnosis. Many patients start with occupational or physical therapy to improve their physical abilities—however, the physician should discuss regimens with the physical therapist prior to initiating treatment to make sure the program will not aggravate CRPS. Mirror box therapy and guided imagery have also been shown to be effective.3 Although therapy may increase range of motion, proper pain control must be a priority. Analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) are recommended initially, but patients may need to add anticonvulsants or antidepressants (beware of weight gain) to manage neuropathic pain. Many pharmacologic interventions have been studied for the treatment of CRPS, but their place in therapy is unknown due to inconsistent efficacy data. There have been promising studies of the use of IV ketamine in subanesthetic doses.4
Interventions, such as stellate ganglion nerve blocks are most effective if done early, and epidural spinal injections are only effective if there is disc herniation. Spinal cord stimulators have been shown to be effective when one limb is involved.3 The key to management of CRPS involves a multidisciplinary approach that allows for appropriate treatment but prevents polypharmacy.5 Diet may also play a major role since there are more neurotransmitters in the stomach than in the brain. Studies of gluten-free diet have been shown to cause significant decrease in pain within days and weeks of an elimination diet.3
In the acute phases of CRPS, inflammation is common and can be targeted with corticosteroid therapy. Corticosteroids have level 1 evidence for anti-inflammatory use in the management of CRPS, meaning they are effective and recommended.5 Corticosteroids are most beneficial in patients that present with redness, swelling, and heat due to inflammation.6 Since most trials of corticosteroids have included patients with acute CRPS, it is difficult to relate the data to patients with chronic CRPS, where inflammation may be less prominent.3 Anti-inflammatory activity is attributed to the decrease in inflammatory mediators, such as histamine, prostaglandins, kinins, and leukotrienes.7
Some of the strongest data for the use of corticosteroids in CRPS involves patients with a history of stroke, who are at a high risk for shoulder trauma.8 In one randomized controlled trial with oral prednisolone and piroxicam, those taking prednisolone had a statistically and clinically significant improvement in primary outcomes, including edema, pain, range of motion, and activities of daily living, at 1 month.9 However, similar patients with a history of stroke were given oral methylprednisolone and had no differences in these outcomes compared to placebo after 1 month of therapy and then 6 months later.10 These results may be difficult to apply to patients whose CRPS is due to reasons other than stroke, or whose causal event is unknown.
Other controlled trials evaluating the use of corticosteroids in chronic CRPS are limited by small samples and short durations of treatment.11-14
The risk of long-term adverse drug-related effects, such as osteoporosis, adrenal insufficiency, and immunosuppression, may outweigh potential benefit.7 Multiple routes of administration of corticosteroids have been studied, including oral, intrathecal, intravenous, and intravenous regional anesthesia.11-15 It may be beneficial to evaluate these different forms of administration in future studies.
Additional research on the use of corticosteroid therapy for CRPS is necessary, with uniformity in corticosteroid formulation and patient diagnostic criteria. The need for standard measurements of pain, physical function, and quality of life also is apparent. The majority of the studies have evaluated patients who have CRPS-I, and it is difficult to determine if their results can be applied to patients with CRPS-II. The use of short-term corticosteroid therapy may be beneficial to patients who are in the early stages of CRPS and have signs of inflammation; however, the efficacy and safety of chronic corticosteroid use is unclear.