• Reflex Sympathetic Dystrophy Syndrome Association (RSDSA). Complex regional pain syndrome: treatment guidelines. Milford (CT): Reflex Sympathetic Dystrophy Syndrome Association (RSDSA); 2006 Jun. 67 p. [51 references]

This is the current release of the guideline

This guideline updates a previous version: Reflex Sympathetic Dystrophy Syndrome Association (RSDSA). Clinical practice guidelines (second edition) for the diagnosis, treatment, and management of reflex sympathetic dystrophy/complex regional pain syndrome (RSD/CRPS). Milford (CT): Reflex Sympathetic Dystrophy Syndrome Association (RSDSA); 2002 Feb. 46 p. [47 references]

Diagnostic Considerations

Revised Complex Regional Pain Syndrome (CRPS) Criteria Proposed by the Budapest Consensus Group

General Features of the Syndrome:

CRPS describes an array of painful conditions that are characterized by a continuing (spontaneous and/or evoked) regional pain that is seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion. The pain is regional (not in a specific nerve territory or dermatome) and usually has a distal predominance of abnormal sensory, motor, sudomotor, vasomotor and/or trophic findings. The syndrome shows variable progression over time.

There are two versions of the proposed diagnostic criteria: a clinical version meant to maximize diagnostic sensitivity with adequate specificity, and a research version meant to more equally balance optimal sensitivity and specificity.

Clinical Diagnostic Criteria for CRPS

1. Continuing pain, which is disproportionate to any inciting event
2. 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, skin)
3. Must display at least one sign* at time of evaluation in two or more of the following categories:
   • Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)
   • 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)
4. There is no other diagnosis that better explains the signs and symptoms

*A sign is counted only if it is observed at time of diagnosis.

Research Diagnostic Criteria for CRPS

1. Continuing pain, which is disproportionate to any inciting event
2. Must report at least one symptom in each 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, skin).
3. Must display at least one sign* at time of evaluation in two or more of the following categories:
   • Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement).
   • 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).
4. There is no other diagnosis that better explains the signs and symptoms.

*A sign is counted only if observed at time of diagnosis.

Interdisciplinary Management

Because the symptoms of CRPS patients encompass all the bio-psycho-social complexities of chronic pain, the best hope of helping our patients is the adoption of a systematic, stable, empathetic and, above all, interdisciplinary approach that addresses those symptoms. Drugs, psychotherapy, and interventions should be efficiently deployed for patients who either cannot begin or fail to progress using the interdisciplinary approach (outlined in sections three through five in the original guideline document). Many patients will require medication and psychotherapy from the beginning to be successful in the pivotal functional restoration algorithm (see "A Sample Stepwise, Functional Restoration Algorithm" below). Treatment guidelines that center on progressive functional restoration delivered by an interdisciplinary team are traditional, have substantial empiric and anecdotal support, and have been assessed and ultimately codified by three large, expert, consensus-building conferences. Although high level evidence supporting the rationale for interdisciplinary treatment of CRPS is fairly sparse (as it is for any treatment of CRPS), much stronger evidence exists for the efficacy of the interdisciplinary approach in other pain conditions, such as chronic low back pain. That functional restoration can and should be the central intervention and outcome standard in CRPS is a theory that must be tested. Until then, the interdisciplinary approach for treating patients with CRPS remains the most pragmatic, helpful, and cost-effective therapeutic approach available today.

A Sample, Stepwise, Functional Restoration Algorithm

From the outset, in appropriate cases, the patient should have access to medications and/or psychotherapy and/or injections. If the patient cannot begin, or fails to progress, at any step or in any regard, the clinical team should consider starting (or adding) more or stronger medications (see Pharmacotherapy below) and/or more intensive psychotherapies (see Psychological Interventions below) and/or different interventions (see Interventional Therapies below).

Pharmacotherapy

Pharmacotherapy Guide. The Following Strategies Are Suggested for Patients Who Have Been Diagnosed with CRPS but Who Cannot Begin or Progress in the Functional Restoration Algorithm *:

*It is important to remember that these suggestions are overruled by individual patient presentation.

**It is also important to not that certain drugs, such as biphosphonates, may be associated with analgesia as well as the more primary action.

A methodical, patient approach to pharmacotherapy in CRPS is essential. To attempt to identify prominent mechanisms involved in the pain generation, and to try to match drug mechanisms of action to these is the sine qua non of the drug therapy of CRPS. It is often necessary to use more than one drug, or "rational polypharmacy," and the goal is often as much to relieve the pain as to allow progress in interdisciplinary rehabilitation. This is theoretically the best hope for comprehensive management of the syndrome, as drug therapy alone is never enough.

In most cases, no single drug will provide sufficient analgesia long term, nor will it completely prevent the need for abortive/rescue agents. This clinical reality usually requires two or even multiple medications to adequately manage the pain. Thus, the problem of drug-drug interaction is critical to consider, but unfortunately the literature is very weak in this regard. The traditional sources of information, such as the Physician's Desk Reference®, are somewhat helpful, but it is important to consider competitive metabolic or catabolic pathways, such as the liver cytochrome P450 catabolic systems. For instance, the 2D6 enzyme pathway catabolizes codeine, heterocyclic drugs, tramadol, mexiletine, and methadone (among others), and the prudent clinician would keep this in mind when combining these drugs. It is also important that if a drug-drug interaction is observed, this information should be reported and published.

Refer to the original guideline document for more information on individual drugs.

Psychological Interventions

There is no solid evidence that psychological factors are necessarily involved in the onset of chronic CRPS. However, there are theoretically plausible pathways through which psychological factors in some cases could affect the development of CRPS. Evidence is mixed that CRPS patients are in any way psychologically unique compared to other chronic pain patients, although the hypothesis that they are as a group more emotionally distressed has received some support. Once CRPS has developed, emotional factors may have a greater impact on CRPS pain intensity than in non-CRPS pain conditions, possibly through the impact of dysphoric psychological states on catecholamines. Meta-analytic reviews document the efficacy of various psychological interventions for many types of non-CRPS chronic pain, and suggest that such interventions are likely to be beneficial for CRPS patients as well. Adequate randomized controlled studies of psychological interventions in CRPS patients are not available to guide this aspect of CRPS management, although numerous uncontrolled studies suggest the likely utility of several approaches. These approaches include various forms of relaxation training, biofeedback, and cognitive and behaviorally focused interventions. Successful implementation of these interventions requires recognition of the unique issues in CRPS patients, particularly the pervasive learned (or centrally mediated) disuse often seen in such patients. Clinical experience using techniques like those described above in an integrated multidisciplinary context indicates that many CRPS patients can achieve significant improvements in functioning and ability to control pain.

Psychological Intervention Treatment Algorithm

Interventional Therapies

With a new understanding of CRPS as encompassing both sympathetically independent pain (SIP) and sympathetically maintained pain (SMP) in varying degrees among different patients, sympatholysis remains an important diagnostic (SMP vs. SIP) and therapeutic modality (in the SMP subgroup). Because of the considerable difficulty in "clinically assessing" the successful sympathetic block, and because "clinically successful" blocks provide varying degrees of sympatholysis, the role of local anesthetic injection sympathetic blockade versus intravenous regional anesthesia (IVRA), intravenous (IV), or epidural sympatholysis is unknown and largely based on local practice patterns. Additionally, with the notable paucity of good quality supportive outcomes studies, the clinician is left to utilize these blocks or sympathectomy-inducing infusions within the context of a broad algorithm of interdisciplinary treatment, while awaiting further pathophysiological data and outcomes research to guide our practice to the most beneficial treatments.

The decision to proceed with radiofrequency (RF) ablative techniques versus other nondestructive alternatives is a complex one, with less evidence for the ablative versus augmentative treatments. Due to the adverse long-term post sympathectomy syndromes, this author currently recommends against surgical ablative sympathectomy. Future studies may expand on the role of pulsed RF (cold RF) techniques or such unstudied techniques as cryosurgery as alternative therapies to treat SMP.

Our recommended strategy (and tactic) is to use interventional treatments for CRPS patients who are having difficulty either starting or progressing in the functional restoration/interdisciplinary algorithm. If patients are not progressing because of high pain levels (especially associated with autonomic dysfunction), then a stepwise progression — from the less invasive blocks, to infusions or catheter infusion therapies, and ultimately perhaps to neurostimulation — is recommended in order to facilitate the patient's functional improvement and pain control. One suggested algorithm developed by an expert panel for the integrated use of these procedures is shown below and has been previously published.

Interventional Pain Treatment Algorithm for CRPS*

Inadequate or partial response to any given therapy should lead to a stepwise progression down through these modalities (moving from less to more invasive) in conjunction with other noninterventional treatments.

*Adapted from Stanton-Hicks M, Burton A, Bruehl S, et al. An updated interdisciplinary clinical pathway for CRPS: report of an expert panel. Pain Practice. 2002;2:1-16.

An additional clinical algorithm titled "Overall Treatment Algorithm (see other algorithms presented in the "Major Recommendations" field) is provided in the original guideline document.

The type of supporting evidence is not specifically stated for each recommendation.

• Reflex Sympathetic Dystrophy Syndrome Association (RSDSA). Complex regional pain syndrome: treatment guidelines. Milford (CT): Reflex Sympathetic Dystrophy Syndrome Association (RSDSA); 2006 Jun. 67 p. [51 references]

Not applicable: The guideline was not adapted from another source.

2002 Feb (revised 2006 Jun)

Reflex Sympathetic Dystrophy Syndrome Association - Private Nonprofit Organization

Funding has been provided by grants from the National Organization of Rare Disorders, Purdue Pharma L.P., and Celegene Corporation; donations from Reflex Sympathetic Dystrophy Syndrome Association (RSDSA) members; and from memorial gifts.

Scientific Advisory Committee

Editor: R. Norman Harden, MD

Contributing Authors: R. Norman Harden, MD; Stephen Bruehl, PhD; Allen Burton, MD; Melanie Swan, OTR/L; Brienne R. Costa, CTRS; Jennifer Barthel, MS; CRC; Amie L. King, PT

Not stated

This is the current release of the guideline

This guideline updates a previous version: Reflex Sympathetic Dystrophy Syndrome Association (RSDSA). Clinical practice guidelines (second edition) for the diagnosis, treatment, and management of reflex sympathetic dystrophy/complex regional pain syndrome (RSD/CRPS). Milford (CT): Reflex Sympathetic Dystrophy Syndrome Association (RSDSA); 2002 Feb. 46 p. [47 references]

This NGC summary was completed by ECRI on December 11, 2002. The information was verified by the guideline developer on January 27, 2003. This summary was updated by ECRI on January 12, 2005 following the release of a public health advisory from the U.S. Food and Drug Administration regarding the use of some non-steroidal anti-inflammatory drug products. This summary was updated on April 15, 2005 following the release of heightened warnings for nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). This summary was updated by ECRI on June 16, 2005, following the U.S. Food and Drug Administration advisory on COX-2 selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). This summary was updated by ECRI on November 28, 2006. The updated information was verified by the guideline developer on November 30, 2006. This summary was updated by ECRI Institute on November 9, 2007, following the U.S. Food and Drug Administration advisory on Antidepressant drugs. This summary was updated by ECRI Institute on January 10, 2008, following the U.S. Food and Drug Administration advisory on Carbamazepine.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.