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 was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis guidelines (PRISMA).[4] Review methods and criteria were outlined in advance and are registered with PROSPERO systematic review protocol (#CRD42020129103).

Eligibility Criteria

To address our primary objective, eligibility criteria were (1) studies that included a screening or diagnostic tool for CRPS, (2) tool based on self-report and/or physical examination, (3) studies that evaluated the measurement properties or feasibility of the tool, and (4) the tool's measurement properties were evaluated in a minimum of 2 peer-reviewed articles by different investigators. Studies were excluded if (1) the tool included quantitative sensory testing, radiological, genetic, laboratory, or electrical testing or (2) the tool was designed to further characterize previously diagnosed CRPS.

To address our second objective and identify and summarize tools that are used to diagnose and screen for CRPS in children and adolescents, eligibility criteria mirrored the criteria above for the primary objective, with the exception of removing criteria (3) and (4) related to studies that evaluated measurement properties, and restricted the search to studies that included patients of age 0 to 21 years. This age range was chosen because pediatric hospitals vary in their age cutoffs, ranging from 18 to 21 years as the upper limit. This secondary objective used the same exclusion criteria as described above. This secondary search, with criteria (3) and (4) removed, was completed in anticipation that the primary search may not reveal any diagnostic tools validated for use in pediatric setting. Understanding which tools are currently used in pediatric CRPS will shed light on what experts believe to be the best diagnostic tool for use in this age range.

Search Strategy

The search strategy was developed in collaboration with a medical librarian.

Potential studies were identified through electronic database searches in PsycINFO, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Database search was conducted on November 21, 2018, and updated on July 31, 2020. Records were limited to English language studies. Two separate searches were conducted, one to identify CRPS tools evaluated in all ages (primary search) and another to identify tools currently used in pediatric CRPS (secondary search). The first search included key words relevant to CRPS, measurement properties, and the names of tools that were known to these authors. The second search included words relevant to CRPS, pediatric, child, adolescent, youth, and names of tools that were known to these authors. Refer to Supplementary File 1 (available at, MEDLINE Search Strategy, for an example of the search strategy used.

Study Selection

Studies identified through the database search were uploaded into the web application Rayyan[31] to facilitate reviewing study titles and abstracts. Duplicate studies were removed. Study titles and abstracts were screened for eligibility by a research assistant. A random selection of study titles and abstracts (15%) were screened by a second member of the research team (G.M.). Discrepancies were discussed with a third member of the research team (A.H.) and resolved by consensus.

Data Collection

To meet both objectives, 2 data collection forms were created and piloted with 5 randomly selected articles and refined accordingly. Data collection was performed by authors G.M. and A.H. and research assistants M.M. and F.N.

For the primary search (examining the measurement properties of diagnostic and screening tools for CRPS), information was extracted from each included study on: (1) tool characteristics (screening or diagnostic, language, time to complete, scoring, and cost); (2) tool constructs (number of items, signs, symptoms, equipment, and pain quality); (3) study sample (size, age range, sex, country of study, and comparison group); and (4) measurement properties.

Risk of bias of individual studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) by 2 raters (A.H. and K.B.).[45] QUADAS-2 is a recommended tool for use in systematic reviews of diagnostic accuracy studies. The tool evaluates risk of bias and applicability in 4 domains: patient selection, index test, reference standard, and flow and timing. Each of the 4 domains receives a rating of high, low, or unclear for risk of bias, with the first 3 also rated for applicability. Risk of bias in each domain is assessed using signaling questions to identify potential risk of bias concerns. For example, study patient selection should be done without inappropriate exclusion criteria, and the interpretation of the index and reference standard test must be done without knowledge of the result of the other. Applicability is rated based on whether the study matched the review questions. The index test is the novel test that is being evaluated for diagnostic accuracy, and the reference standard is a test that is used as a comparator. Ideally, a reference standard is 100% sensitive and specific and reveals the absolute truth about a diagnosis, positive or negative (sometimes referred to as a gold standard test). For this review, selection of the reference standard test was based on study design where an existing tool or physician diagnosis was typically used as the reference test. Given that no widely accepted and evaluated reference standard exists, no tool used as the reference standard received higher than an "unclear" score for risk of bias within the QUADAS-2 tool.[45] Discrepancies were resolved by consensus.

With respect to the secondary search specific to the pediatric population, data extracted from each study included tool name, study setting, type of study, and study sample characteristics (including number of participants and age range).