Variability in phenotype clusters of Behçet's syndrome: A systematic review

Behçet's syndrome (BS) is a multisystem vasculitis, and distinct clinical phenotypes with clustering of certain organ manifestations were proposed. However, studies from different cohorts have shown variability in the defined phenotypes. This was attributed to geographic and ethnic differences, but different studies from the same country have also shown variability in phenotype clusters. We aimed to explore the variability in clinical phenotype clustering across different countries and cohorts and possible reasons for these.

An electronic search was carried out in PubMed, EMBASE, and Cochrane Library for studies that assessed phenotype clusters in BS cohorts. Two reviewers independently performed the screening of titles, abstracts, and full texts using Covidence.

A total of 15 studies that assessed 17 different cohorts were identified. Several differences were identified in the clusters that were reported in these cohorts. Factors that were identified by this systematic review as possible causes of these differences were study design, statistical analysis method (hierarchical cluster analysis vs. factor analysis), patient population (pediatric vs. adult), setting, diagnostic/classification criteria (International Study Group vs. International Criteria for Behçet's Disease), disease duration, the definition of organ involvement (such as including cerebral sinus thrombosis in nervous system or vascular involvement), ascertainment of manifestations (such as gastrointestinal involvement confirmed by endoscopy or not), and time component for clustering of manifestations.

There is important variability in the phenotype clusters that are reported in different studies and this variability seems to stem from methodologic differences between the studies.