Behçet's spectrum disorders: genetic and immunological insights into an emerging disease concept

Behçet's spectrum disorders (BSD) describe a conceptual framework encompassing inflammatory conditions with overlapping clinical and genetic features with Behçet's disease. First introduced in 2020, the BSD concept was proposed to contextualize BD-like inflammation in pediatric and early-onset cases by linking clinical phenotypes to shared immune pathways and supporting earlier prioritization of genetic evaluation.

A literature search was conducted in the PubMed and CNKI database using the following keywords: "Behçet's spectrum disorders", "Behçet's disease", "BD-like disease".

We found several pediatric inflammatory disorders with Behçet-like mucocutaneous, gastrointestinal, or vasculitis symptoms that overlap with Behçet disease in key immunopathogenic pathways. Based on these findings, Behçet's spectrum disorders (BSD) are conceptualized as a mechanism-oriented framework encompassing a group of immune-mediated inflammatory conditions characterized by partial overlap with Behçet disease in clinical manifestations and immunopathogenic mechanisms. Within this spectrum, disorders cluster into two tiers: core BSD comprising monogenic diseases with recurrent mucosal ulceration and direct convergence on BD-defining pathways (including haploinsufficiency of A20, RELA, or NFKB1 haploinsufficiency, and ELF4 deficiency); peripheral BSD encompassing conditions with partial clinical overlap or indirect mechanistic proximity, such as polygenic disorders (recurrent aphthous stomatitis and PFAPA), BD-like vasculitic conditions such as DADA2 (deficiency of adenosine deaminase 2), and chromosomal abnormalities exemplified by trisomy 8. Although they are often misdiagnosed as Behçet disease, these conditions are biologically separate disorders that nonetheless share similar mucosal immune dysregulation.

The BSD framework may help to facilitate earlier recognition and precise diagnosis of BD-related disorders in children, particularly those with atypical or syndromic presentations. The BSD framework integrates these insights to support earlier genetic screening and mechanism-guided management. However, this framework is not intended to replace current diagnostic criteria, but rather to support earlier recognition of BD-like phenotypes in children.