Background: Gulf War Illness (GWI) is a chronic multisymptom illness comprised of a wide range of systemic symptoms and functional impairments. We conducted a systematic review to catalogue studies (both published and unpublished/ongoing) of validated biological tests for diagnosing GWI and studies of associations between biological measures and GWI for their promise as biomarkers.
Materials and Methods: We searched multiple electronic databases, clinical trial registries, and reference lists through February 2020 for all observational studies of diagnostic tests of GWI and completed or ongoing studies of associations between biological measures and GWI. We abstracted data on study design, demographics, and outcomes. Two reviewers independently assessed the risk of bias of included studies using established methods.
Results: We did not identify any studies validating tests of biomarkers that distinguish cases of GWI from non-cases. We included 32 completed and 24 ongoing or unpublished studies of associations between GWI and biological measures that included comparator groups that provided the most useful information. Studies (n=77) with other comparator groups, no comparator group, or with N<25 were included in a table. Considering all studies, most fell within the central nervous and immune systems and indicated a significant association of the biological measure with GWI case status. Biological measures were heterogeneous across studies.
Conclusion: Our review indicates that there are no existing validated biological tests to determine GWI case status. Many studies have assessed the potential association between a variety of biological measures and GWI, the majority of which pertain to the immune and central nervous systems. More importantly, while most studies indicated a significant association between biological measures and GWI case status, the biological measures across studies were extremely heterogeneous. Due to the great heterogeneity, the focus of the review is to map out what has been examined, rather than synthesize information.