Behçet’s disease

Behçet’s disease typically presents in young adulthood, most commonly between 20 and 40 years of age. Disease manifestations vary considerably among individuals and may fluctuate over time.

Common symptoms include:

• Recurrent oral aphthous ulcers
• Genital ulcers
• Skin lesions (erythema nodosum-like lesions, papulopustular eruptions)
• Eye inflammation (uveitis)
• Joint pain and arthritis
• Fatigue

In some patients, more severe organ involvement may occur, including:

• Vascular inflammation and thrombosis
• Neurological manifestations (neuro-Behçet syndrome)
• Gastrointestinal inflammation
• Pulmonary involvement

Ocular disease is of particular clinical importance, as recurrent inflammation can lead to visual impairment or blindness if left untreated.

The prevalence of Behçet’s disease varies substantially worldwide and follows the historic “Silk Road” distribution pattern, extending from East Asia through the Middle East to the Mediterranean region.

The frequency of HLA-B51 also differs among populations. In regions with high Behçet’s disease prevalence, HLA-B51 occurs more frequently in the general population than in Northern and Western Europe.

Meta-analyses have shown that HLA-B51-positive individuals have an approximately five- to six-fold increased risk of developing Behçet’s disease compared with non-carriers. However, the majority of HLA-B51-positive individuals remain healthy throughout life.

Although HLA-B51 is present in approximately 50–80% of Behçet’s disease patients depending on ethnicity and geographic region, the disease may also occur in HLA-B51-negative individuals.

The precise cause of Behçet’s disease remains incompletely understood. Current evidence suggests that disease development results from a complex interaction between:

• Genetic susceptibility
• Immune dysregulation
• Environmental triggers
• Infectious and microbial factors

Among all known genetic associations, HLA-B51 exerts the strongest influence on disease susceptibility. HLA-B51 belongs to the major histocompatibility complex (MHC) class I family and plays a central role in antigen presentation and immune regulation.

Several mechanisms have been proposed to explain the relationship between HLA-B51 and Behçet’s disease, including:

• Altered antigen presentation
• Dysregulated innate and adaptive immune responses
• Enhanced neutrophil activation
• Interactions with ERAP1 and other susceptibility genes

Current evidence suggests that HLA-B51 contributes to disease risk in combination with additional genetic and environmental factors rather than acting as a sole causative factor.

HLA-B51 is an inherited genetic variant located within the HLA region on chromosome 6.

A positive HLA-B51 result does not establish a diagnosis of Behçet’s disease and should not be interpreted as a prediction that disease will develop. Likewise, a negative result does not exclude the
diagnosis.

Family aggregation has been reported, and first-degree relatives of affected individuals demonstrate an increased risk compared with the general population. However, Behçet’s disease is not inherited in a simple Mendelian pattern, and multiple genes contribute to disease susceptibility.

HLA-B51 testing may be considered during the diagnostic evaluation of patients with suspected Behçet’s disease, particularly when characteristic clinical manifestations are present.

Testing may be helpful in individuals with:

• Recurrent oral ulcers
• Genital ulceration
• Unexplained uveitis
• Compatible skin lesions
• Suspected systemic Behçet’s disease
• A family history of Behçet’s disease

When interpreted together with clinical findings, a positive HLA-B51 result may increase diagnostic confidence and support further specialist evaluation.

However, HLA-B51 testing should not be used as a screening tool in asymptomatic individuals. Since many healthy people carry HLA-B51, the predictive value of testing alone is insufficient for diagnosis or risk prediction. A positive result is not diagnostic, and a negative result does not exclude
disease.

Consequently, HLA-B51 testing is most valuable when performed in the context of compatible clinical symptoms and comprehensive diagnostic assessment.

• MedlinePlus Genetics. Behçet disease [Internet]. Bethesda (MD): National Library of Medicine. Available from:
• de Menthon M, Lavalley MP, Maldini C, Guillevin L, Mahr A. HLA-B51/B5 and the risk of Behçet’s disease: a systematic review and meta-analysis of case-control genetic association studies. Arthritis Rheum. 2009;61(10):1287-96. doi:10.1002/art.24642. PMID:; PMCID: PMC3867978.
• Takeuchi M, Kastner DL, Remmers EF. The immunogenetics of Behçet’s disease: a comprehensive review. J Autoimmun. 2015;64:137-48. doi:10.1016/j.jaut.2015.08.013. PMID:; PMCID: PMC4628864.
• Orphanet. Behçet disease [Internet]. Paris: Orphanet. Available from:
• Medscape. Behçet disease [Internet]. New York: WebMD LLC. Available from: