Behçet’s syndrome (BS) is a multisystemic disorder displaying a marked variability across different geographic areas. The
main aim of this study was to analyze demographic and clinical features of a cohort of BS patients diagnosed in three tertiary
referral centers in Italy and detect potential associations between the different manifestations. Medical records of 396 patients
(218 females, 178 males) were retrospectively analyzed. Mean age at onset was 30.00 ± 18.75 years with a female-to-male
ratio of 1.22:1. Mucocutaneous features were the most frequent starting manifestations of BS, followed by eye inflammation.
Erythema nodosum (p = 0.007), arthritis/arthralgias (p = 0.0115), and central nervous system (CNS) signs (p = 0.014)
were significantly over-represented in female patients, whereas male gender was associated with lower mean age at onset
(p = 0.031), higher frequency of pseudofollicular lesions, and uveitis (p = 0.00134 and p < 0.0001 respectively), particularly
for posterior segment involvement and panuveitis (p < 0.0001). Regarding the association between disease features, genital
ulcers were negatively associated with uveitis (p < 0.0001) and vascular involvement (p < 0.0001). Other negative associations
were detected between uveitis and gastrointestinal involvement (p = 0.008), pseudofolliculitis and CNS signs (p = 0.031),
vascular involvement (p = 0.002) and erythema nodosum (p = 0.013). Logistic regression identified male gender and genital
ulcers, respectively, with a higher (OR 2.199 [1.397–3.461], p < 0.001) and lower risk (OR 0.157 [0.090–0.273], p < 0.0001)
of developing major organ involvement. Our evaluations found that the disease had started mostly in the second and third
decade with most severe features in the male gender, and that patients presenting with mucocutaneous manifestations were
less prone to develop major organ involvement.