Screening and Diagnostic Tools for Complex Regional Pain Syndrome

A Systematic Review

Giulia Mesarolia; Amos Hundert; Kathryn A. Birnie; Fiona Campbell; Jennifer Stinson


Pain. 2021;162(5):1295-1304. 

In This Article


This systematic review identified 4 diagnostic tools validated for use in adults, none validated in pediatric populations, and no screening tools for any age group. The 4 diagnostic tools identified include the Veldman criteria, IASP criteria, Budapest Criteria, and Budapest Research Criteria. Several studies suggest that early diagnosis intervention may lead to a more favorable outcome and potentially prevent disability and poor quality of life.[2,22] The importance of early diagnosis is recognized by the IASP that recommends rapid assessment of acute CRPS.[6] Furthermore, an accurate diagnosis is critical, given that CRPS has specific treatments that differ from other types of chronic pain; for example, common interventions for CRPS include specific physiotherapies (graded motor imagery), pharmacotherapy (intravenous ketamine), and interventions (spinal cord stimulation).[7]

The results of this review represent how our understanding of this rare disease has evolved. In 1993, expert consensus agreed upon the term CRPS, and defined 2 subtypes (1 and 2).[21] In the same year, 2 sets of diagnostic criteria (the IASP criteria and Veldman criteria) were published. Another critical time point was the expert consensus meeting held by the IASP in Budapest in 2003 whereby the former IASP criteria were replaced with the Budapest Criteria. These new criteria were more robust, including more diverse symptoms, particularly with the addition of motor and trophic features.

Recommendations for Clinicians in the Adult Setting

There is no gold standard laboratory, radiological, or genetic test to diagnose CRPS. This is true for many primary pain disorders, where the etiology is ill defined and can be highly variable with many contributing biological, psychological, and social factors.[27,38] In addition, CRPS is highly complex with the large number of symptoms that coexist with pain. As is the case with many pain disorders, in the absence of a gold standard test, patients are often diagnosed based on a clinical diagnosis. To aid in making a clinical diagnosis for CRPS, clinicians can use one of the 4 diagnostic tools. There are no existing screening tools for CRPS, and as such, people with suspected CRPS should undergo rapid diagnostic assessment. Reducing wait-times for patients with suspected CRPS is recommended in community-based settings and specialist pain clinics.

Of the 4 diagnostic tools reviewed in this article, there are no significant differences in the feasibility of applying the criteria. All tools require a combination of physical examination and self-report, and none require costly equipment. The Budapest Criteria are explicitly endorsed by the IASP, the international society that makes recommendations on assessment, prevention, and treatment of pain diseases. Clinicians should follow the recommendations of the IASP and use the Budapest Criteria for diagnosing CRPS in adults. This review cannot make recommendations based on the sufficiency of measurement properties of the diagnostic tools because this review did not comprehensively examine them (eg, with a tool such as the COSMIN guideline for systematic reviews of outcome measures).[37] However, based on the data that were gathered, no tool was comprehensively evaluated across all measurement property domains, which would be required to approach a strong recommendation according to COSMIN guidelines.[37] Furthermore, there is a notably high degree of variability across studies in the sensitivity of the Budapest Criteria (45%-99%) and the Budapest Research Criteria (20%-78%). This highlights the importance of using clinical expertise, and not using any diagnostic tool as a standalone assessment.

Recommendations for Clinicians in the Pediatric Setting. No studies have evaluated the measurement properties of diagnostic tools in pediatric CRPS. Recent efforts are underway by Friedrich et al.,[10] who evaluated 174 youth with CRPS using the Budapest Criteria (unpublished data). Their study found that only 63% of youth who were diagnosed clinically with CRPS met the Budapest Criteria. Several studies suggest that the clinical features of CRPS in children differ from those in adults. In particular, pediatric CRPS may be milder with a more favorable prognosis.[3,10,16] One study suggests that children present most often with sensory and motor symptoms, with trophic changes being more rare.[22]

At present, clinicians should take caution when applying any diagnostic tool to children and adolescents with suspected CRPS. For clinicians in pediatric pain clinics, a clinical diagnosis based on expertise is most appropriate. For clinicians who do not have expertise in pediatric CRPS, at this time, the Budapest Criteria may be helpful to guide diagnosis. Furthermore, it is recommended that community-based providers rapidly refer patients with suspected CRPS to pediatric pain clinics. A list of international pediatric pain clinics can be found on the IASP website,[32] These specialized centers can assist in diagnosis and treatment. As described above, pediatric pain clinics should make efforts to reduce wait-times for patients with CRPS, with a target time of one week.[6]

Recommendations for Future Research

Future research is needed to comprehensively evaluate the spectrum of measurement properties of existing diagnostic tools. This is especially true for the 9 diagnostic tools that were excluded from this review (Table 2) because there was only one study evaluating the tool's measurement properties. Two tools in particular (4 Novel Bedside Tests and CRPS Prediction Score) were only recently published, and future evaluation may reveal whether there is merit in their respective use. Studies should indicate clearly the diagnostic criteria that are used and how they are applied, including who applied them and tools that were used (eg, how temperature is measured). Future studies should use a consistent reference standard, ideally the Budapest Research Criteria. A consistent reference standard would facilitate comparing results across studies, with the potential for pooling results in meta-analyses. In future study designs, clinicians must evaluate the patient using the diagnostic criteria without knowledge of the reference standard, and therefore blinded. As symptoms of CRPS are known to fluctuate over time, study participants should be evaluated with the diagnostic criteria and the reference standard in close proximity (less than one week). Because CRPS is a rare disease, multisite research studies are crucial to minimize the limitations of drawing conclusions from small sample sizes while ensuring standardization in procedures across sites. Studies should avoid unnecessary exclusions or case-control groups that may inflate identified differences between groups.

For research studies examining adults with CRPS, for example, for interventional studies, the IASP recommends the Budapest Research Criteria for diagnosing patients with the intent of defining study populations because there is some evidence to suggest higher specificity with this tool.[13]

Future research is needed to develop and/or validate a diagnostic tool for pediatric CRPS, and a screening tool for CRPS for both children and adults. A self-report screening tool for CRPS would help clinicians who may not have the requisite knowledge, skill, or judgement to use diagnostic criteria. Furthermore, a screening tool would aid in identifying patients on waitlists who need rapid assessment to confirm diagnosis. Ideally, a screening tool would have excellent sensitivity as opposed to a diagnostic tool where a more balanced profile of sensitivity and specificity is best suited.


This review identified and summarized screening and diagnostic tools for CRPS. This review only included studies that evaluated the measurement properties of the tools when looking across the lifespan, and as such, we may have missed newly developed tools that have not yet been validated. Furthermore, we did not evaluate the sufficiency of the measurement properties and therefore cannot provide strong recommendations on this aspect. Another study limitation is with respect to our quality assessment using QUADAS-2, which is a tool for evaluating the risk of bias and applicability of diagnostic accuracy studies. QUADAS-2 was intended to evaluate studies that use a reference standard test that is 100% sensitive and specific. Because there is no such test for CRPS, most studies included in this review used another set of diagnostic criteria in place of a true reference standard. For example, Perez[35] evaluated the diagnostic accuracy of the Budapest Criteria and Veldman criteria compared with the IASP criteria as a reference standard. As a result of these limitations, no study evaluated could receive the highest possible score on the QUADAS-2 diagnostic accuracy assessment.