Unraveling The Mystery Of CRPS
Complex regional pain syndrome (CRPS) has emerged as one of the more controversial topics in podiatry in recent years. Not only are there no clear-cut answers in regard to the etiology of the condition, standard terminology for describing the condition has been equally elusive in the past. With this in mind, expert panelists discuss various issues in diagnosing and treating this condition. Q: We have all heard different terms used for this condition, including reflex sympathetic dystrophy (RSD), complex regional pain syndrome (CRPS), causalgia and Sudek’s Atrophy. What is the current preferred terminology and definition for this complex condition? A: Nearly 80 different terms have been used in the past to describe this condition and this reflects “the lack of understanding of the pathophysiology of the condition,” according to Jeffrey C. Christensen, DPM. Lawrence Fallat, DPM, concurs. He says the different terminology caused so much diagnostic confusion that the International Association for the Study of Pain (IASP) developed standardized definitions. All the panelists agree that the condition is currently referred to as either CRPS type I (CRPS I), which was previously referred to as RSD or sympathetically maintained pain (SMP), or CRPS type II (CRPS II), which was previously called causalgia. Nelson Hendler, MD, MS, says CRPS I involves circumferential pain and the presence of both thermal and mechanical allodynia. Dr. Christensen says CRPS I may have these criteria: 1) the presence of an initiating noxious event or a cause of immobilization; 2) continuing pain, allodynia or hyperalgesia with which the pain is disproportionate to any inciting event; 3) evidence of edema, changes in skin blood flow or abnormal sudomotor activity in the region of pain; and 4) this diagnosis is excluded by the existence of conditions that would otherwise account for the degree of pain and dysfunction. Dr. Christensen says the last three criteria must be satisfied when considering a diagnosis of CRPS I. Dr. Hendler disagrees. Steven Mandel, MD, says some researchers have suggested there may be three “subtypes” of RSD. The first subtype is a limited syndrome with vasomotor signs predominating while the second subtype would be a limited syndrome marked by neuropathic pain and sensory abnormalities. Dr. Mandel says the third subtype would be CRPS, in which one would see motor trophic changes and related diffuse changes with osteopenia on bone scan. Discussing the differences between CRPS I and CRPS II, Dr. Mandel notes that with CRPS I, there is more of an occult lesion and a lesser injury that affects unmyelinated axons. In cases of CRPS II, one is dealing with a major nerve injury that is often caused by motor involvement, according to Dr. Mandel. Dr. Hendler says CRPS II is pain in the distribution of a mixed peripheral nerve that has both thermal and mechanical allodynia, usually with EMG/NCV abnormalities. Dr. Christensen says the following criteria must be satisfied when considering a diagnosis of CRPS II: • continuing pain, allodynia or hyperalgesia after a nerve injury, but not necessarily limited to the distribution of the injured nerve; • evidence of edema, changes in skin blood flow or abnormal sudomotor activity in the region of pain; and • this diagnosis is excluded by the existence of conditions that would otherwise account for the degree of pain and dysfunction. Dr. Hendler disagrees with these criteria, emphasizing that continuing pain, allodynia or hyperalgesia that occurs after a nerve injury must be limited to distribution of the injured nerve in cases of CRPS II. He also maintains that, in these cases, it is not common to see edema, changes in skin blood flow changes or abnormal sudomotor activity in the region of pain. Q: What causes CRPS? A: Drs. Fallat and Hendler agree that the exact mechanism that causes CRPS is unclear. However, Drs. Christensen, Fallat and Hendler say trauma can be a precipitating factor. Dr. Fallat says trauma can cover the full spectrum from gunshot wounds and crush injuries to seemingly minor injuries such as repetitive motion injuries or a sprained ankle. Dr. Christensen says the ankle sprain is the most common cause of CRPS in the foot and ankle. Dr. Hendler says there may be a genetic predisposition to CRPS. Dr. Mandel concurs and notes that some authors have discussed an interaction between trauma severity and genetic factors conferring CRPS. Dr. Mandel also notes that some researchers have found a correlation between bone mineral density and the severity of RSD-like symptoms among patients who had a stroke. CRPS may also be related to neurogenic inflammation, according to Dr. Mandel. He says there may be a central effect that stimulates sympathetic activity or a central process that exacerbates pain in some patients independent of the peripheral nervous system. With neurogenic inflammation, Dr. Mandel says some authors have suggested that an increased release of neuropeptides from peripheral nociceptors may be a possible pathophysiological mechanism that triggers the combination of trophic changes, edema, vasodilatation and pain seen with CRPS. Dr. Mandel says some believe CRPS is an exaggeration of posttraumatic inflammation. Dr. Mandel points out that CRPS is considered a neuropathic pain syndrome that has a mixed time-dependent profile. He explains that regional information, sensitization of primary somatosensory afferents (peripheral sensitization and sensitization of spinal neurons) and central sensitization may play important roles in terms of etiology and subsequent treatment. Q: What precautions should a podiatric physician take in order to avoid causing CRPS? A: Drs. Christensen, Fallat and Hendler agree that even when one has the best surgical technique, surgery is still a form of trauma that may cause CRPS. Dr. Hendler says it’s a good idea to inform patients that CRPS may be one of the sequelae of surgery. According to Dr. Christensen, adhering to sound surgical principles — such as making incisions parallel to nerve tracks and using atraumatic technique when one encounters nerves — may help reduce the risk of CRPS occurrence. CRPS typically happens without physician negligence, according to Robert L. Goldstucker, Esq. In order to avoid potential liability in cases of CRPS, Goldstucker says one should ensure prompt recognition, make an appropriate referral and provide prompt treatment while the patient is waiting for the appointment with the specialist. Goldstucker notes that describing the nature and location of the pain with CRPS specific terminology allows others to discern whether the patient was suffering from CRPS while he or she was under your care. Utilizing the appropriate terminology also establishes to the jury that you knew what you were looking for, according to Goldstucker. Q: Some would argue that CRPS is a “wastebasket” diagnosis or a diagnosis of exclusion. Do you agree with this or would you argue against this conclusion? A: Unfortunately, Dr. Christensen says there are physicians who may label patients with RSD or CRPS even though there may be an underlying explanation for their pain. Drs. Christensen and Mandel agree the main problem is the lack of a definitive confirmatory diagnostic test for CRPS. As a result, Dr. Christensen says patients can be misdiagnosed and then it is difficult to prove the patient doesn’t have the condition. Dr. Mandel concurs, noting that patients are frequently “overdiagnosed” with CRPS. Dr. Hendler emphasizes that if physicians limit their diagnosis of CRPS I to patients who have pain that pervades the limb and have thermal and mechanical allodynia, then they can avoid overdiagnosing the condition.He found that 71 percent of patients diagnosed with CRPS I actually had nerve entrapments.1Q: How does the podiatric physician in a busy practice make or suspect the diagnosis of CRPS in a timely fashion? A: Drs. Christensen, Fallat and Mandel agree that one should have an index of suspicion for CRPS when a patient has unremitting pain (especially rest pain) that is out of proportion to his or her injury or condition. In cases of CRPS, Dr. Fallat notes these patients will have pain that persists with rest and it may even increase, especially at night. He says one should also suspect CRPS when patients complain of pain at a time in which they should be recovering from surgery or an injury. Dr. Fallat says the pain may be intense and can be located at the surgery/injury site, at another location on the foot or involve the entire limb. If you suspect CRPS, Dr. Hendler recommends doing the Hendler alcohol drop and swipe test. Simply take an alcohol pad and squeeze it until alcohol drops on the patient’s affected limb. If he or she has an immediate response of intense pain, the patient has cold thermal allodynia, which is an essential diagnostic sign of CRPS, according to Dr. Hendler. Practitioners should subsequently take the leftover alcohol swab and stroke the limb with the pad. If the patient has an immediate response of intense pain, Dr. Hendler says this is mechanical allodynia, which is found in CRPS, nerve entrapments and radiculopathy. In regard to clinical and radiographic signs for CRPS, Dr. Mandel cites the American Medical Association’s Guides to the Evaluation of Permanent Impairment. He says vasomotor changes include changes in skin color, a cooler skin temperature and edema. According to Dr. Mandel, pseudomotor changes include skin that is dry or overly moist, trophic changes, soft tissue atrophy (especially in the fingertips), joint stiffness, decreased passive motion, nail changes and blemished, curved or talon-like hair growth changes. Drs. Fallat and Mandel say X-rays are usually normal but may reveal changes indicative of pronounced osteoporosis. Dr. Fallat adds that the pain with CRPS is frequently of a burning nature and can be aggravated with motion. With these patients, Dr. Fallat says their skin may be warm, dry and red with mild edema. He cautions that these symptoms often appear six weeks after surgery when many patients may still have post-op swelling and pain. In these cases, Dr. Fallat says it is easy to assume that the injury or surgery hasn’t healed yet or that the patient has a narcotic dependency or simply doesn’t want to return to work, but he emphasizes physician vigilance in evaluating complaints of continued pain. Dr. Fallat adds that subsequent findings may include a sweaty cyanotic limb. According to Dr. Mandel, untreated CRPS may progress from acute changes (increased hair and nail growth on the affected limbs) to atrophy of the skin, muscles and bones. However, Dr. Mandel cautions that nutritional blood flow in the affected limb may also contribute to atrophy and ulcerations in these patients. Dr. Mandel also points out that sympathetic pain is not unique to CRPS as diabetic patients may have regional selective denervation and painful feet. Patients with CRPS may also show signs of behavorial changes. Dr. Mandel says one may notice a higher incidence of verbal expressions of anger, indicating psychological stresses. He adds that health and quality of life issues may come into play as well as a patient’s energy, self-care, social behavior and sleep may be “significantly diminished.” Q: What ancillary tests can be helpful in diagnosing or confirming CRPS? A: Tests such as plain film radiographs, thermography, bone scans, lumbar sympathetic blocks and other lesser known tests have been used to help support the clinical diagnosis, according to Dr. Christensen, but he notes that none of these tests are definitive. Dr. Fallat says there are no laboratory tests that will aid in diagnosing CRPS. While an early severe patchy osteoporosis on X-rays may indicate CRPS, Dr. Fallat says it is not diagnostic. Citing a recent article by Stanton-Hicks on testing for CRPS, Dr. Mandel says the author discussed using quantitative sensory testing and autonomic testing that included a quantitative pseudomotor axon reflex test (QSART) for sweating abnormalities, and a cold pressor test in conjunction with thermographic imaging, observing vasoconstrictor response and using laser Doppler salometry to monitor background vasomotor control.2 If podiatrists suspect CRPS, Dr. Hendler says they should order a three-phase bone scan and send the patient for sympathetic blocks as soon as possible. Dr. Fallat says a triphasic technetium bone scan may show asymmetrical blood flow of the extremities with periarticular uptake. Although he concedes the scan is not 100 percent specific for CRPS, Dr. Fallat says these findings support the suspicion of CRPS. While Dr. Mandel says the bone scan is the primary ancillary test for supporting one’s clinical diagnosis of CRPS, he says DEXA scans and MRIs with gadolinium can be beneficial with later stages of CRPS. Dr. Fallat says one can make a definitive diagnosis with a sympathetic block. He explains that resolution of pain and increased warmth of the leg are diagnostic of CRPS, even if the relief only lasts for the duration of the local anesthetic. Citing the aforementioned Stanton-Hicks article, Dr. Mandel disagrees about the diagnostic merits of sympathetic blocks.2 While sympathetic blocks and cutting sympathetic nerves, including a sympathectomy, may facilitate sympathetically maintained pain, Dr. Mandel says this procedure is helpful but not definitive in diagnosing CRPS. Q: When and where should podiatrists refer a patient with suspected CRPS? A: Dr. Hendler recommends that podiatrists refer patients whom they suspect of having CRPS to a physician who is affiliated with an academic institution and has published articles about the disorder. He says a brief Internet search of the medical literature can help one locate the closest qualified physician. Goldstucker cautions against making the referral to a mono-modal pain clinic that may have less interest in determining the etiology of the patient’s pain than it does in beginning a lifetime of treatment. All of the panelists concurred that the patient should be referred to a local pain specialist (whether it’s an anesthesiologist, psychiatrist or neurologist), who can lead a multispecialty team in addressing pain control, limb rehabilitation and psychological issues that are related to CRPS. “There is no reason that DPMs can’t be part of the treatment team,” emphasizes Dr. Christensen, “especially when there are underlying foot pathologies that coexist with CRPS.” Q: When a patient is diagnosed with CRPS in the lower extremity, what are the usual treatment protocols? A: All the physician panelists agree that early diagnosis and treatment increase the likelihood of successful outcomes. After making a clinical diagnosis of CRPS and before the patient is evaluated in the pain clinic, Dr. Fallat says he will initially prescribe a NSAID. Drs. Fallat and Mandel agree that physical therapy is the cornerstone of first-line treatment in order to keep the patient’s joints mobilized. In addition to physical therapy and patient education, Dr. Christensen says initial treatment may include pharmacotherapy with anti-seizure or anti-depression medications. In cases of severe pain, Dr. Fallat says he may prescribe a narcotic analgesic. Dr. Mandel concurs with Drs. Christensen and Fallat. In cases of escalating symptoms with moderate to severe sympathetic dysfunction, Dr. Mandel says one may use regional anesthetic blocks in addition to physical therapy. When the response to initial treatment is poor, Dr. Christensen says one may initiate a series of lumbar sympathetic blocks. Dr. Hendler says patients should be scheduled for lumbar sympathetic blocks immediately after CRPS has been diagnosed. If there is a delay in receiving the blocks, Dr. Hendler says one may temporarily prescribe high dose steroids and Lidoderm patches 5% locally until the blocks can be performed. In regard to the treatment value of sympathetic blocks, Dr. Mandel says some authors have suggested that patients who have a good response to sympathetic blocks prior to spinal cord stimulation are likely to have a positive response during the spinal cord stimulation trials and have long-term relief after the placement of spinal cord stimulators. In his experience, though, Dr. Mandel notes that while spinal cord stimulation may offer significant pain reduction for patients with CRPS, he cautions that it may have only minimal effects on mechanical hyperalgesia and no long-term effects on pain thresholds for pressure, warmth or cold. However, Dr. Mandel says studies have indicated that electrical stimulation of the spinal cord, in the form of dorsal column stimulation, can reduce pain and improve the quality of life for those with CRPS. Dr. Christensen says implantation of a dorsal column nerve stimulator or an implantable morphine pump may be necessary in more severe, recalcitrant cases of CRPS. For those patients who fail with the morphine pump, Dr. Mandel says one may consider intrathecal Baclofen, which can be especially beneficial for patients with dystonia. In regard to other possible treatments, Dr. Mandel notes employing a laterally directed cervical epidural catheter can be effective for producing continuous unilateral anesthesia and sympathetic blockade. He says topical ketamine has been used to help treat acute dystrophic changes of CRPS. Dr. Mandel also notes that subcutaneous infusion of lidocaine may provide effective pain relief but local injections of the drug have not been shown to provide significant long-term benefit. Chemical sympathectomy has a very limited effect, according to Dr. Mandel, but he says it may help with cutaneous allodynia. Q: If a patient reports a history of CRPS, when can podiatrists consider performing an elective surgical procedure on the foot or ankle safely? What precautions should DPMs take? A: Goldstucker cautions that DPMs should only perform elective surgery after consulting with and getting clearance from the physician who is charge of the patient’s pain management. Dr. Hendler emphasizes a multidisciplinary approach in these cases. Drs. Christensen and Hendler agree that an anesthesiologist should utilize an indwelling epidural catheter for these patients. Specifically, Dr. Hendler says these patients should have analgesic infusion for two days prior to surgery and for three days post-op. Dr. Christensen adds that the post-op time can help get the patient past the inflammatory phase of wound healing. He advocates taking these precautions even if the patient’s CRPS is in remission. Dr. Hendler recommends having an anesthesiologist available to perform lumbar sympathetic blocks in case there are signs of CRPS recurrence. While Dr. Mandel says there have been isolated reports and anecdotal evidence on the merits of presurgical anesthesia, peroperative anesthesia or perioperative blocks in these cases, he notes that they have not been proven by way of evidence-based studies. Dr. Downey is Chief of the Division of Podiatric Surgery at the Presbyterian Medical Center in Philadelphia. He is a Fellow of the American College of Foot and Ankle Surgeons and is on the faculty of the Podiatry Institute. He practices privately in Philadelphia, Radnor and Doylestown, Pa. Dr. Christensen is a Fellow of the American College of Foot and Ankle Surgeons, and is in private practice in Everett, Wa. Dr. Fallat is a Clinical Assistant Professor within the Department of Family Medicine at the Wayne State University School of Medicine in Detroit. He is the Director of Podiatric Surgical Residency for the Oakwood Healthcare System in Dearborn, Mich. He is board-certified by the American Board of Podiatric Surgery and is a Fellow of the American College of Foot and Ankle Surgeons. Mr. Goldstucker is an attorney with Nall and Miller, LLP in Atlanta. He is also a lead attorney with Podiatry Insurance Company of America (PICA). Dr. Hendler is a psychiatrist who is Past President of the Reflex Sympathetic Dystrophy Association of America. He is the Clinical Director of the Mensana Clinic in Stevensen, Md. Dr. Hendler is an Assistant Professor of Neurosurgery at Johns Hopkins University School of Medicine and an Associate Professor of Physiology at the University of Maryland School of Dental Surgery. Dr. Mandel is a Clinical Professor of Neurology at Jefferson Medical College in Philadelphia. He is a Fellow of the American Academy of Neurology and the American Academy of Disability Evaluating Physicians. He frequently lectures on complex regional pain syndrome.
References 1. Hendler, N. Differential Diagnosis of Complex Regional Pain Syndrome Type 1 (RSD), Pan-Arab Journal of Neurosurgery 2002; 6(2):1-9. 2. Stanton-Hicks, M. Complex regional pain syndrome. Anesthesiology Clinics of North America 2003; 21(4): 733-744. Recommended Reading 3. Hendler, N. "Complex Regional Pain Syndrome Type I and Type II," Chapter 20, Pain Management (6th edition). Edited by Richard Weiner, PhD. CRC Press, Boca Raton, Fla.