The purpose of this review was to comprehensively summarize recent phenotype research findings in Behçet's syndrome.

Cluster analysis has recently been employed as a phenotype research tool in Behçet's syndrome. Studies reported different clustering patterns caused by biological variation and some degree of artificial heterogeneity. However, some clusters were more consistent than others: 1) oral ulcers, genital ulcers, and skin lesions 2) oral ulcers, genital ulcers, skin lesions, and arthritis 3) oral ulcers, genital ulcers, skin lesions, and uveitis 4) oral ulcers, genital ulcers, skin lesions, and gastrointestinal involvement. A number of loci suggestive of differential risk for individual disease manifestations were proposed. Peripheral blood gene expression profile and plasma proteome exhibited significant differences in patients with different organ involvements and were able to differentiate between disease phenotypes. However, these observations require further validation and functional studies.

Clustering patterns in Behçet's syndrome is highly heterogeneous. Artificial heterogeneity might obscure the true biological variation of disease expression. Preliminary genetic, transcriptomic and proteomic data suggest that different pathogenetic mechanisms may operate in different phenotypes of Behçet's syndrome.