Manifestations and predictors of neurologic involvement in Behçet's disease

Behçet's disease (BD) is a multisystem inflammatory disorder primarily affecting mucocutaneous tissues. Central nervous system (CNS) involvement, Neuro-BD (NBD), is a potentially severe manifestation of BD with a variable prevalence (1-59%).

We aimed to characterize BD patients with CNS involvement and to identify predictors of this clinical subtype.

We performed a single-centre observational retrospective study using data from patients fulfilling the 2013 International Criteria for BD registered at the Rheumatic Diseases Portuguese Registry (Reuma.pt) between October 2014 and May 2023. NBD was defined according to International Consensus Recommendation Criteria for NBD diagnosis. Demographic, clinical and treatment data were collected.

We included 157 patients with BD, 116 (74%) of them were females and 127 (81%) Caucasian with a mean±SD age at diagnosis of 32.0±12.2 years and the median (IQR) follow-up was 11.0 (11.8) years. NBD was diagnosed in 24 (15%) patients, with two (1%) cases identified at disease onset. The mean age at NBD diagnosis was 31.6±8.7 years, occurring 4.7 (1.0) years after BD onset. Among NBD patients, 15 (63%) had parenchymal, eight (33%) non-parenchymal and one (4%) mixed CNS involvement. Compared to patients without NBD, those with NBD were more likely to be non-Caucasian (27% vs 17%, p=0.026), have genital ulcers at disease onset (68% vs 34%, p=0.002) and present with ocular manifestations during the disease course (58% vs 35%, p=0.028). NBD patients more frequently received systemic glucocorticoids (100% vs 78%, p=0.008) and conventional synthetic disease-modifying anti-rheumatic drugs (86% vs 62%, p=0.035), particularly cyclophosphamide (48% vs 1%, p<0.001). Mortality was also significantly higher among NBD (13% vs 2%, p=0.026). On multivariable analysis, genital ulcers at presentation (OR 4.50, 1.68-12.06) and ocular involvement during the disease course (OR 2.69, 1.01-6.76) were independent predictors of CNS involvement.

In summary, our cohort showed a 15% prevalence of CNS involvement, with parenchymal affection being the predominant form. Genital ulcers at onset and ocular manifestations emerged as independent predictors of NBD, serving as potential clinical markers for identifying high-risk patients. The high mortality rate observed among these patients underscores the severity of NBD and the critical need for prompt recognition.