Angela Mailis-Gagnon, MD

ABSTRACT: Complex regional pain syndrome (CRPS) can be tricky to diagnose. The International Association for the Study of Pain established criteria that differentiated CRPS as type 1 (formerly called "reflex sympathetic dystrophy") or type 2, associated with nerve injury (formerly called "causalgia"); patients also had to have pain disproportionate to the inciting event. Newer, stricter criteria have been proposed that cluster signs and symptoms and require documentation of objective findings as well as symptoms reported by the patient. The key to identifying CRPS is to obtain a proper history, document objective findings, and rule out other disorders that can imitate the condition. Treatment tends to be multifaceted; it includes physical mobilization of the affected limb and medications to help alleviate discomfort. (

Silas Weir Mitchell (1829-1914) described "causalgia" after nerve injury during the American Civil War. Over time, the syndrome was given multiple and colorful names, such as algodystrophy, sympathalgia, and posttraumatic spreading neuralgia. The term "reflex sympathetic dystrophy" (RSD) attributed to Evans in 1946 referred to a clinical syndrome similar to that observed in causalgia but in the absence of overt nerve injury. Both entities were renamed "complex regional pain syndrome" (CRPS) at the Orlando consensus workshop in 1993, and new criteria were adopted in 1994 by International Association for the Study of Pain (IASP) taxonomy.

 Swelling is seen in the right leg 
 of a patient with complex regional pain 
 syndrome type 1.

The criteria described CRPS type 1 (formerly known as RSD) and type 2 (formerly known as causalgia) as syndromes (a) arising after an initiating noxious event in the absence (CRPS 1) or the presence of overt nerve injury (CRPS 2); (b) with spontaneous pain or allodynia/hyperalgesia not limited to the territory of a single peripheral nerve (for CRPS 1) and disproportionate to the inciting event; (c) with past or present evidence of edema, skin blood flow abnormality, or abnormal sudomotor activity; and (d) excluding other conditions that would otherwise account for the degree of dysfunction.

This taxonomy was meant to be descriptive and general rather than implying etiology or pathophysiology.

   It acknowledged that in some cases the sympathetic nervous system  (SNS)  may be involved, but the mandatory and all-inclusive role of SNS  was  minimized. In this article, we discuss the diagnosis and management  of  CRPS, with emphasis on CRPS 1.

 In a patient with recalcitrant complex 
 regional pain syndrome type 1 (photograph taken 
 while the patient was under general anesthesia), 
 fixed dystonic posturing was established within 
 3 months even though sympathetic blocks, 
 opioid analgesics, neuropathic medications, 
 and aggressive therapy were used.



  A patient with complex regional pain syndrome type 1 had fixed  posturing associated with coldness and profound allodynia 1 year after  injury (A). The patient had been immobilized inappropriately in the  "position of comfort" early after injury without much therapy to  mobilize the extremity (B).

  A patient with complex regional pain syndrome type 2 has a lateral  plantar nerve laceration (A). Widespread severe allodynia has resulted  in dry scaly skin because the patient has been unable to wash the foot  for 1 year (B).

The syndrome continues to perplex, fascinate, and frustrate clinicians and researchers alike. Although very sensitive, the 1994 criteria lacked specificity and led to over diagnosis of CRPS type 1.1 Given the high false-positive rate of IASP criteria, a combination of symptoms and signs were proposed by Harden and Bruehl2 to increase discrimination between CRPS and non-CRPS patients.

These criteria were published in an IASP-sanctioned book but are not  formally adopted yet. The new criteria proposed that the patient must  not only have pain disproportionate to the inciting event but also  report 1 symptom in 3 of 4 categories (sensory, vasomotor,  sudomotor/edema, and motor/trophic) and display at least 1 sign in 2 or  more of the above 4 categories. These criteria cluster categories of  signs and symptoms that have been proved meaningful by research  introduce a separate category of motor problems (paired with trophic  changes). The accompanying Table (see below) has been created on the basis of these  criteria and is currently in use by our own pain program, the  Comprehensive Pain Program of Toronto Western Hospital.

However, we caution that the current proposed criteria as well as the   1994 IASP classification have great difficulty accounting for patients   who present with large areas of hypoesthesia instead of hyperesthesia   (personal communication with Norman Harden, coauthor of the Harden and   Bruehl criteria). Such hypoesthesia is not rare and seems to be a   central phenomenon but is poorly understood.

At present, CRPS type 1 is considered to be a multifactorial regional syndrome.

   It affects both the peripheral nervous system and CNS and additionally   has musculoskeletal, endocrinological, and vascular ramifications.

The incidence of CRPS type 1 in the general population is reported by Sandroni and associates

   to be 5.46 persons/100,000 with period prevalence (1989-1999) of   20.57/100,000. Women are affected 4 times more often than men.   Approximately three-fourths of CRPS type 1 cases in the community   resolve spontaneously, while pain clinics address refractory CRPS. In   another study, however, the incidence was recorded to be 4 times higher   than the one reported by Sandroni and colleagues.

There is no gold standard for diagnosing CRPS type 1. However, it is the examining physician's responsibility to obtain as much objective evidence as possible and  make sure other conditions are excluded (Figures 5 through 7). 

The cornerstone of diagnosis lies with a detailed history and a  thorough physical examination. Given the overdiagnosis of CRPS type 1 by  the generous 1994 IASP criteria (which are often applied without  excluding other disorders that can imitate CRPS),

 we strongly recommend the stricter criteria proposed by Harden and Bruehl,

  even if they have not been formally adopted yet by the IASP. The  accompanying Table can serve to tabulate self reported symptoms (by the  patient) and document signs observed by the clinician at the time of  consultation. Harden and Bruehl outlined for the interested reader the  clinical application of the newly proposed criteria and the most recent  concepts about CRPS subtypes. 


Patients often are referred for having complex regional pain syndrome (CRPS) type 1 but prove to have another condition. A CRPS 1–like presentation resulting from complete immobility and limb dependency secondary to "fear of movement" in the presence of widespread hypoesthesia is shown (note that hyperesthesia is expected in CRPS). Intense mobilization and range of movement resulted in a dramatic reduction of swelling and discoloration.

 A CRPS 1–like presentation is shown (A). Note the ligature sign at the elbow in a patient with a factitious disorder (B).

In regards to common diagnostic tests available to the practicing clinician, the following should be noted:

•  Although the 3-phase bone scan historically has been regarded as important in support of the diagnosis of CRPS types 1 and 2, several studies have cast doubts as to its veracity. It is recommended that a bone scan consistent with CRPS (typical periarticular uptake in the delayed phase) not be considered equivalent to having the syndrome, because such scans have been  observed after sympathectomy, in abnormal weight-bearing use of  an extremity, in completely asymptomatic persons, or even in factitious disorders.

Clinical judgment is  necessary to make the connection between the scan and the diagnosis. The absence of such a bone scan in our view does not exclude the entity, particularly months after the onset.      Similarly, in our view, a positive bone scan result does not confirm  the disorder unless it corroborates appropriate symptoms and signs     as discussed above.

•  Sympathetic blocks have shifted from a "diagnostic" test to a therapeutic     procedure that can enhance and facilitate uncomfortable physical therapy. The concept of "sympathetically maintained pain" has lost its previous significance as CRPS-related mechanisms may shift and change over time. The response to sympathetic blocks should not be used to make the diagnosis.

•  Osteopenia seen in a plain x-ray film could be the result of intense immobilization alone. However, rapid onset of significant osteopenia after a trivial injury in the presence of serious pain and other signs and symptoms, such as those listed in the Table, should at least alert the physician to the syndrome as a part of the differential diagnosis.

•  Electromyographic and nerve conduction studies can rarely be tolerated in the presence of allodynia and hyperalgesia, and results are negative in CRPS 1. Their value lies only in confirmation of CRPS 2.

•  MRI of the involved limb may show bone marrow signal changes; thermography does demonstrate temperature differentials between the involved and uninvolved limbs.

All the tests reported here serve as adjuncts to the diagnosis of CRPS 1. In our opinion, however,  they cannot replace the important triad of (1) history, (2) objective  documentation of abnormalities, and (3) exclusion of other disorders  (disease imitators).

A patient was referred for having bilateral complex regional pain syndrome type 1 of spontaneous origin after an acute onset of bilateral leg lesions, severe allodynia, and swelling. Skin biopsy results revealed Degos disease, a rare autoimmune disease associated with peripheral skin lesions and small-fiber neuropathy. 

A series of recent articles on the nature and management of CRPS unanimously concluded that "functional restoration is the necessary and often sufficient condition "to restore health; other treatments serve primarily to facilitate this.

 We consider that CRPS type 2 is easier to diagnose, given the presence of overt nerve injury that can be documented electrophysiologically or during surgical exploration. CRPS type 1 seems, however, to be surrounded by controversy.

On the basis of the most recent concept that CRPS in general is a multifaceted disorder, its care must indeed be multidimensional.

 Mobilization of the involved limb as early as possible is the cornerstone of treatment to avoid permanent changes in the peripheral nervous system and CNS. This should include range of movement and stress-loading techniques. At the same time, pain control (oral and via sympathetic blocks, if the patient responds to them) is of paramount importance to allow for mobilization.

Although combined approaches seem more effective than single modality treatments for all forms of chronic noncancer pain, including CRPS, interdisciplinary pain rehabilitation programs may be required for patients with intractable pain. These treatments typically provide education; reconditioning physical/occupational therapy; a pharmacological approach; biofeedback/relaxation training; operant conditioning; psychotherapy (personal and family); treatment of psychiatric comorbidity; and interventional approaches, such as nerve blocks, spinal cord stimulation, and intraspinal analgesia.

In pharmacological approaches, the only evidence-based preventive strategy for CRPS is the use of vitamin C (200 mg/d) in patients who have sustained wrist fractures.

 For therapy in established CRPS, the literature suggests the following therapeutic approaches:

• A short course of oral corticosteroids can be of value, such as 30 mg/d of oral prednisone(Drug information on prednisone), until a clinical remission occurs or for a maximum of 12 weeks.

 In our program, we prefer a "crash course" that starts with 50 to 60 mg/d and decreases thereafter by 5 mg every 2 days to completion.

Articles

Complex regional pain syndrome (CRPS) can be tricky todiagnose. This review describes criteria for identifying CRPS, and gives guidance for treatment, with case studies and photographs.

Author | Angela Mailis-Gagnon, MD

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Diagnosis and Management of Complex Regional Pain Syndrome