Cluster analysis of phenotypes of patients with Behçet’s syndrome: a large cohort study from a referral center in China

Abstract

Introduction Behcet’s syndrome (BS) is a complex, heterogeneous disorder. However, classification of its subgroups is still debated. The purpose of this study was to investigate the clinical features and aggregation of patients with BS in China, based on manifestations and organ involvements. Methods This was a cross-sectional study of BS patients in Huadong Hospital of Fudan University between September 2012 and January 2020. We calculated relative risks (RRs) of clinical variables according to sex. Moreover, we conducted a hierarchical cluster analysis applied according to eighteen variables to determine subgroups of patients. Results A total of 860 BS patients were included. Male sex was associated with ocular involvement (RR 2.32, 95% CI 1.67, 3.22, P < 0.0001), vascular involvement (RR 2.00, 95% CI 1.23, 3.23, P = 0.004), cardiac lesion (RR 5.46, 95% CI 2.33, 12.77, P < 0.0001), and central nervous system involvement (RR 2.95, 95% CI 1.07, 6.78, P = 0.007) and was negatively associated with genital ulcers (RR 0.84, 95% CI 0.79, 0.91, P < 0.0001). Five clusters (C1–C5) were observed. C1 (n = 307) showed the skin and mucosa type. In C2 (n = 124), all had articular involvement, barely having major organ involvement except for 18 cases with intestinal lesions. In C3 (n = 156), the gastrointestinal type, 144 patients presented with intestinal involvement, and 36 patients with esophageal ulcers. In C4 (n = 142), all subjects presented with uveitis. C5 (n = 131) consisted of 44 patients with cardiac lesions, 58 with vascular involvement, and 26 cases having central nervous system involvement. Conclusion Our analysis confirmed sex differences in phenotypes of BS. Cluster analysis identified gastrointestinal, uveitis, and cardiovascular involvement cluster separately in different subsets, which represents the most commonly involved organs. Further research is required to replicate and clarify the patterns of phenotype in BS.

Ocular Manifestations of Behçet’s Disease: An Update on Diagnostic Challenges and Disease Management

“…Several clusters of BD manifestations have been identified, such as: “the mucocutaneous and articular phenotype”, “the extra-parenchymal neurological and peripheral vascular phenotype” and “the parenchymal neurological and ocular phenotype” [ 42 , 51 ]. Uveitis was not significantly correlated with neurological manifestations in a BD phenotype analysis in China; however, it was suggested that parenchymal involvement was rare across the race and ethnicity of the cohort [ 52 ]. Bettiol et al suggest that BD treatment should be targeted at clusters of symptoms instead of focusing on each presentation separately [ 42 ].…”

“…Bettiol et al have correlated parenchymal neurological and ocular symptoms based on literature research and have proposed to consider those patients as one phenotype and therefore adjust the treatment algorithm [ 42 ]. Nevertheless, another study on a Chinese cohort divided BD differently without connecting ocular and neurological BD into one cluster [ 52 ]. Further investigation of the various phenotypes of BD is recommended to revise the previous concept of BD management.…”

“…Further investigation of the various phenotypes of BD is recommended to revise the previous concept of BD management. Researchers suggest that the treatment of BD requires a multidisciplinary approach and should be planned according to the correlated groups of symptoms which will improve the general outcome, instead of focusing on each manifestation separately [ 24 , 42 , 52 ].…”

The Roles of Monocytes and Macrophages in Behçet’s Disease With Focus on M1 and M2 Polarization

“…The classification of disease type is necessary to inform therapeutic strategies. We and others have analyzed the phenotypic subtypes of BD and have described five subtypes ( 115 , 116 ). A disadvantage of categorizing the disease into clinical subtypes is the reduction in patient number for each subtype, especially as BD is a rare disease with a regional bias.…”

Behçet‘s Syndrome Apart From the Triple Symptom Complex: Vascular, Neurologic, Gastrointestinal, and Musculoskeletal Manifestations. A Mini Review

“…These were distributed differentially among male and female patients, with cluster 1 occurring predominantly in female patients, whereas there was a strong male predominance in the uveitis and cardiovascular cluster (number 4 and 5). All other clusters were distributed almost equally among both genders (3). A considerable number of reviews and good prospective clinical trials exist for the typical mucocutaneous and ocular manifestations of BS.…”