Behçet disease

**Definition/Epidemiology:** Chronic, multisystem, relapsing-remitting variable-vessel vasculitis (affects both arteries and veins, small to large). Highest prevalence along the ancient "Silk Road" (Turkey > Iran, Middle East, Japan, China). Typically presents in the 20s–30s. Men tend to have more severe disease (ocular, vascular, neurologic), while women have more mucocutaneous disease.

**Pathophysiology:** Unknown trigger, probably an immune-mediated response in a genetically predisposed person (strong association with **HLA-B51**; also ERAP1 and IL-10/IL-23R variants). Neutrophil hyperactivity, Th1/Th17 activation, and elevated TNF-α, IL-1, IL-6, and IL-17 lead to perivascular inflammation. Pathology is a neutrophilic/lymphocytic vasculitis, with no specific autoantibody (ANCA and ANA are negative).

**Clinical features:** - **Recurrent oral aphthous ulcers** (the most common and often the first sign; at least 3 episodes per year). They are painful and heal without scarring. - **Genital ulcers**, which are painful and may scar (scrotum, vulva). - **Ocular:** anterior and/or posterior uveitis, **hypopyon**, and retinal vasculitis. Can cause blindness, so it is the most feared complication. - **Skin:** erythema nodosum, papulopustular lesions (acneiform), and **pathergy** (a sterile pustule or papule 24–48 hours after a needle prick). - **Vascular:** venous thrombosis (superficial or deep, including **Budd-Chiari syndrome** and dural sinus thrombosis), and arterial aneurysms (notably **pulmonary artery aneurysms**, which can rupture and cause fatal hemoptysis). Anticoagulation is contraindicated or risky when pulmonary artery aneurysms are present. - **Neurologic:** meningoencephalitis, brainstem lesions, and cerebral venous sinus thrombosis. - **Joints:** non-erosive asymmetric oligoarthritis. - **GI:** ileocecal ulcers (mimics Crohn disease).

**Diagnosis:** Clinical. The International Study Group criteria require **recurrent oral ulcers plus any 2 of:** recurrent genital ulcers, eye lesions (uveitis/retinal vasculitis), skin lesions, or positive pathergy test. The ICBD criteria are a points-based alternative. There is no confirmatory lab test, and ESR/CRP may be elevated but are nonspecific.

**Treatment:** - Oral/genital ulcers: topical corticosteroids, colchicine, and **apremilast** (a PDE4 inhibitor, FDA-approved for oral ulcers in Behçet disease). - Skin and joint disease: colchicine. - Severe ocular, neurologic, or vascular/GI disease: systemic corticosteroids plus immunosuppressants (azathioprine, cyclosporine, cyclophosphamide for major vascular disease) and **anti-TNF agents** (infliximab, adalimumab). - Venous thrombosis: immunosuppression is the mainstay, with anticoagulation individualized (excluding pulmonary artery aneurysm).

**High-yield differentials/associations:** - Oral + genital ulcers: Behçet vs. HSV vs. Crohn vs. reactive arthritis vs. SLE vs. MAGIC syndrome (mouth and genital ulcers with inflamed cartilage, which is relapsing polychondritis plus Behçet). - Behçet is HLA-B51 (an MHC class I allele), unlike HLA-B27 seronegative spondyloarthropathies. - Young man from Turkey/Middle East/Japan with oral and genital ulcers, uveitis, and a positive pathergy test is the classic vignette. - Pulmonary artery aneurysm → hemoptysis (Hughes-Stovin syndrome is a related entity).