Description

• Behçet syndrome (BS) represents a chronic, relapsing, multisystem, autoinflammatory disorder.
  • Precise etiology remains incompletely understood; strong but diverse genetic component
  • Clinical manifestations are driven by hyperactive innate and adaptive immune responses, resulting in a highly variable presentation and potential involvement of any organ system.
• Variable clinical manifestations:
  • Classic description of “triple symptom complex”: oral and genital mucocutaneous ulceration + ocular involvement (primarily panuveitis and retinal vasculitis)
  • Other frequent symptoms include papulopustular cutaneous lesions, gastrointestinal (GI) pain, arthritis, and vascular involvement.
• Three distinct clinical subtypes with different expression profiles and disease pathways (1):
  • Mucocutaneous BS (only cutaneous)
  • Ocular BS (any involvement)
  • Vascular BS (large vein thrombosis)
  • Note: oral ulcers present in all subtypes
• Synonym(s): Behçet disease; Behçet triad; mucocutaneous ocular syndrome; Franceschetti-Valero syndrome; Adamantiades syndrome; Morbus Behçet; or Silk Road disease

Epidemiology

• Predominant age: 20 to 40 years old; rare in pediatric and geriatric populations
• Predominant gender: female > male in United States, with males affected more severely, especially in the Middle East and Central Asia

Prevalence

• Rare in the United States, Northern Europe, and sub-Saharan Africa; endemic in Japan, the Middle East, and the Mediterranean region; more prevalent in the region of the ancient Silk Road, linking China to Italy
• 5.2/100,000 population in the United States
• 20 to 421/100,000 in Turkey

Etiology and Pathophysiology

Complex and diverse genetic and epigenetic basis, with precise etiology unknown. Multiple implicated factors including HLA-B genes (especially B51), high production of tumor necrosis factor (TNF) and IL-8, low production of IL-10, and polymorphisms in chemokines and adhesion factors. Common bacteria (streptococci) and viruses (herpes simplex virus [HSV]) appear to have a role in triggering immune responses, particularly from neutrophils and γδ T lymphocytes. Increased IL-12 drives Th1 response, targeting heat shock proteins (due to homology with streptococci, producing various autoantibodies, and inducing endothelial injury [likely responsible for prothrombotic state]) (1,2,3).

Risk Factors

Familial clustering and earlier onset in successive generations have been described; as noted various genetic associations, including IL-10, IL-6, IL-1β, IL-23R, toll-like receptors, and epigenetic factors (microRNAs and DNA methylation of multiple genes); multiple infectious triggers as above

Commonly Associated Conditions

• Amyloidosis (late finding)
• Ankylosing spondylitis (10% of patients with joint involvement; not associated with HLA-B5 or HLA-B27)
• Myelodysplastic syndrome (especially in patients with GI involvement) and trisomy 8 (modifies disease expression with an increase in fever)