Complex regional pain syndrome underdiagnosed
CRPS type 1 is an under-recognized problem in limbs recovering from fracture or immobilized post-stroke.
TABLE 2
Accuracy of diagnostic criteria for CRPS type 1
| CRITERIA TESTED | STUDY OF ACCURACY | STUDY QUALITY | CONTROL GROUP | SN | SP | LR+ | LR- | PV+ | PV- |
|---|---|---|---|---|---|---|---|---|---|
| IASP | Bruehl et al, 199911 | 3 (non-indep. ref. standard | Patients with diabetic neuropathy, polyneuropathy, postherpetic neuralgia, and radiculopathy | 98% | 36% | 1.5 | 0.1 | 0.21 | 0.99 |
| IASP | Galer et al, 199812 | 3 (non-indep. ref. standard) | Patients with diabetic neuropathy | 100% | 55% | 2.2 | 0 | 0.28 | 1.0 |
| Bruehl’s | Bruehl et al, 199911 | 3 (non-indep. ref. standard) | Patients with diabetic neuropathy, polyneuropathy, postherpetic neuralgia and radiculopathy | 70% | 94% | 12 | 0.3 | 0.67 | 0.94 |
| Sn, sensitivity; Sp, specificity; LR+, positive likelihood ratio; LR-, negative likelihood ratio; PV+, positive predictive value (probability of disease given a positive test); PV-, negative predictive value (probability of disease given a negative test). PV+ and PV- assume baseline likelihood of disease of 15%. | |||||||||
TABLE 3
Interobserver reliability of diagnostic criteria for CRPS type 1
| DIAGNOSTIC CRITERIA TESTED | STUDY QUALITY | STUDY SIZE | INTEROBSERVER RELIABILITY |
|---|---|---|---|
| IASP15 | 2 (small cohort study) | 6 diagnosticians | Poor |
| Bruehl’s15 | 2 (small cohort study) | 6 diagnosticians | Borderline moderate |
| Veldman’s16 | 2 (small cohort study) | 3 diagnosticians | Good |
Factors undermining objective evaluation
Despite clinically based diagnostic criteria, researchers and physicians continue to use office, laboratory, and radiographic tests to diagnose CRPS type 1,1,10 perhaps in an attempt to provide a more objective basis for the diagnosis. However, the evaluation of these methods has been plagued by difficulties.
First, because current clinical diagnostic criteria are not yet optimized or even standardized in the literature, there is no gold standard by which to measure the accuracy of these tests.
Second, patients in different studies have been diagnosed with CRPS type 1 by varying criteria.
Third, CRPS type 1 presents differently in different people, and symptoms and signs vary over time in the same person. As a result, the sets of diagnostic criteria have been designed with various clinical findings, and CRPS patients may meet only a few at any one time.
For example, if a group of CRPS type 1 patients were tested for sweating abnormalities, only 24% at best might be expected to test positive (see TABLE 4 for representative frequency of symptoms and signs),17 resulting in an apparent sensitivity of 24% for sweating abnormalities. This is why it is important for clinicians to consider patients’ report of typical signs even when these signs are not present on exam when making a diagnosis of CRPS type 1.
TABLE 4
Frequency of symptoms and clinically observed signs in CRPS type 1
| Variables | SIGNS (%) | Symptoms (%) |
|---|---|---|
| Allodynia | 74 | — |
| Decreased range of motion | 70 | 80 |
| Color changes | 66 | 87 |
| Hyperalgesia | 63 | — |
| Temperature asymmetry | 56 | 79 |
| Edema | 56 | 80 |
| Weakness | 56 | 75 |
| Sweating changes | 24 | 53 |
| Skin changes | 20 | 24 |
| Dystonia | 14 | 20 |
| Nail changes | 9 | 21 |
| Hair changes | 9 | 19 |
| Tremor | 9 | 24 |
| Hyperesthesia | — | 65 |
| “Burning” pain | — | 81 |
| By exam or report in patients meeting IASP criteria for CRPS, adapted from Harden et al, 1999.17 | ||
Diagnostic instrumentation adds little
Some investigators have tried using instruments to measure the clinically apparent signs included in diagnostic criteria— volumetry to measure edema, thermometry to measure skin temperature differences, and resting sweat output (RSO) to measure sweating.
Confounding nature of CRPS 1. The value of these tests is limited by factors such as the duration of CRPS type 1, time of day, relaxation of the subject, ambient temperature, body temperature, and exact placement of the measuring device,18,19 so it is not clear that objective measurement is practical or adds precision. In fact, in a study comparing testing to clinical diagnosis, instrumentation added little to the overall accuracy of diagnosing CRPS type 1 (LOE: 2, prospective cohort study).14
Sympathetic nerve block unhelpful. Other investigators have focused on testing to improve or replace clinical diagnostic criteria. Although at one time a response to sympathetic block was considered diagnostic for CRPS type 1,4 subsequent studies have demonstrated there is a significant placebo response to sympathetic block, that many persons with CRPS type 1 do not respond, and that some persons with other neuropathic pain conditions do respond. A negative or positive response to sympathetic block cannot rule CRPS type 1 in or out (LOE: 2, systematic reviews with only a few high-quality studies).20-22
Radiographic findings add nothing. Bone scanning (scintigraphy) and radiography have been used frequently in the diagnosis of CRPS type 1. Although 3phase scintigraphy looking for different uptake of radioisotope between affected and unaffected limbs has been touted as an objective and definitive test for CRPS type 1,23 this method also suffers from the subjective interpretation of the radiologist and poor interobserver reliability.24 Researchers disagree on whether the typical appearance on scintigraphy is periarticular cuffing 25,26 or diffuse uptake of radioisotope,27 and about whether delayed phase scintigraphy is adequate 26 or whether 3-phase scintigraphy is necessary.27
To make the interpretation of these scans more objective, quantitative analysis of bone scans has been undertaken; however, subjective interpretation was required to decide where to measure the uptake and what degree of difference between affected and unaffected limbs was considered positive for CRPS type 1.27
