Behçet

**Definition:** Behçet disease (Behçet syndrome) is a multisystem, relapsing-remitting inflammatory disorder classified as a variable-vessel vasculitis (affects arteries and veins of all sizes). It is a classic cause of recurrent oral and genital ulcers.

**Epidemiology:** Highest prevalence along the "Silk Road" (Turkey > Iran, Middle East, Japan, China). Typically presents in the 20s-30s. In the Middle East/Mediterranean, men tend to have more severe disease; in Western countries, women are more affected overall. Strongly associated with HLA-B51 (HLA-B*51).

**Pathophysiology:** Unclear. Likely a genetically predisposed individual with an environmental or infectious trigger leading to neutrophil hyperactivity and dysregulated innate and adaptive (Th1/Th17) immunity. This causes perivascular inflammation (neutrophilic and lymphocytic) and a prothrombotic state. It is considered to sit between autoimmune and autoinflammatory disease.

**Clinical features:** - **Recurrent painful oral aphthous ulcers:** The most common and usually the first manifestation. Required for diagnosis in the International Study Group criteria. - **Genital ulcers:** Painful, often scarring (scrotum, vulva). - **Ocular:** Anterior and/or posterior uveitis, hypopyon, retinal vasculitis. A major cause of morbidity and potential blindness. - **Skin:** Erythema nodosum, papulopustular lesions (acneiform), and **pathergy** (a pustule or papule 24-48 hours after a sterile needle prick). - **Vascular:** Venous thrombosis (superficial and deep, including Budd-Chiari and dural sinus thrombosis), arterial aneurysms (notably pulmonary artery aneurysms, which can cause fatal hemoptysis). - **Neurologic:** Meningoencephalitis, brainstem lesions, aseptic meningitis (neuro-Behçet). - **Joints:** Non-erosive oligoarthritis. - **GI:** Ileocecal ulcers (mimic Crohn disease).

**Diagnosis:** Clinical, with no specific confirmatory test. - International Study Group (ISG) criteria: recurrent oral ulcers (at least 3 times in 12 months) PLUS any 2 of: recurrent genital ulcers, eye lesions (uveitis/retinal vasculitis), skin lesions (erythema nodosum, pseudofolliculitis, papulopustular lesions), or a positive pathergy test. - Newer International Criteria for Behçet Disease (ICBD) use a point system. - Labs: Nonspecific inflammatory markers (ESR/CRP) may be elevated. HLA-B51 supports but does not confirm the diagnosis.

**Treatment:** - Mucocutaneous: Topical corticosteroids, colchicine, apremilast (PDE4 inhibitor, FDA-approved for oral ulcers). - Ocular/severe or neurologic/vascular: Systemic glucocorticoids plus immunosuppressants (azathioprine, cyclosporine, TNF-α inhibitors such as infliximab/adalimumab, interferon-α). - Venous thrombosis: Immunosuppression is the mainstay (anticoagulation is controversial). Avoid anticoagulation if pulmonary artery aneurysm is present because of the risk of hemorrhage.

**High-yield board associations and differentials:** - Triad: oral ulcers, genital ulcers, uveitis. - Pathergy test positive; HLA-B51. - Differential for oral and genital ulcers: HSV, Crohn disease, reactive arthritis (HLA-B27; urethritis, conjunctivitis, arthritis), SLE, syphilis, MAGIC syndrome (mouth and genital ulcers with inflamed cartilage, i.e., Behçet plus relapsing polychondritis). - Pulmonary artery aneurysm with hemoptysis: think Behçet (also Hughes-Stovin syndrome). - Named after Turkish dermatologist Hulusi Behçet (1937).