Behçet's Disease: Symptoms, Causes & Treatment

Behçet's disease (BD) is a rare, chronic systemic inflammatory disorder of uncertain etiology, classified as a variable-vessel vasculitis. It affects vessels of all sizes — arteries, veins, and capillaries — causing a characteristic constellation of recurrent oral ulcers, genital ulcers, ocular inflammation (uveitis), skin lesions, arthritis, and serious vascular and neurological involvement. BD has a striking epidemiological 'Silk Road' distribution — highest prevalence in Turkey (~421/100,000), Middle Eastern countries (including Jordan), Central Asian republics, and Japan — reflecting genetic (HLA-B51) and environmental factors along the ancient trade routes.

BD is primarily a clinical diagnosis based on the International Study Group (ISG) or International Criteria for Behçet's Disease (ICBD) criteria, as no pathognomonic laboratory test exists. The hallmark is recurrent painful oral aphthous ulcers, but ocular disease (posterior uveitis, panuveitis, retinal vasculitis) represents the most vision-threatening manifestation and may lead to permanent blindness if inadequately treated. Major vascular involvement — venous thrombosis (Budd-Chiari syndrome, cerebral venous sinus thrombosis, DVT), pulmonary artery aneurysms, and aortic aneurysms — accounts for the highest mortality. Neuro-Behçet (central nervous system inflammation) occurs in 5–30% and may cause progressive encephalopathy, brainstem involvement, and cognitive decline.

The pathogenesis involves immune dysregulation with neutrophil hyperactivation, T-lymphocyte imbalance (Th1 and Th17 skewing), and endothelial injury. HLA-B51 is the strongest genetic risk factor (present in 60–70% of Turkish BD patients vs. 20% controls). No curative therapy exists; management is symptom-based with colchicine, immunosuppressants, and biologics for severe disease.

• Recurrent painful oral aphthous ulcers (≥3 episodes/year) — the cardinal symptom present in virtually all patients; multiple, round, well-circumscribed, 2–10 mm; heal without scarring in 1–2 weeks
• Genital ulcers: painful, similar morphology to oral ulcers; in women on labia majora; in men on scrotum; heal with scarring (diagnostically helpful)
• Ocular inflammation: anterior uveitis (photophobia, pain, redness) or posterior uveitis/panuveitis (floaters, visual loss); retinal vasculitis — the major cause of BD blindness
• Skin lesions: erythema nodosum (tender red nodules on shins), pseudofolliculitis, papulopustular lesions, positive pathergy test
• Arthritis: non-erosive, non-deforming oligoarthritis (knees, ankles, wrists)
• Vascular: DVT, Budd-Chiari syndrome, pulmonary artery aneurysm (hemoptysis), aortic aneurysm
• Neurological: headache, meningoencephalitis, brainstem syndrome, cerebral venous sinus thrombosis

• Unknown etiology — complex interaction of genetic predisposition (HLA-B51 the strongest risk factor) and environmental triggers
• Immune dysregulation: neutrophil hyperactivation, Th1/Th17 skewing, endothelial cell injury, vascular inflammation in all vessel sizes
• Suspected microbial triggers: streptococcal antigens (cross-reactive with self-antigens), HSV-1 — epidemiological links, not proven causation
• Positive pathergy reaction (skin hypersensitivity to minor trauma) — present in 40–70% of BD patients in Middle Eastern/Japanese cohorts; less common in Western patients

Clinical diagnosis using ICBD criteria (2014): ≥4 points from: oral ulcers (2), genital ulcers (2), ocular lesions (2), skin lesions (1), positive pathergy test (1), neurological manifestations (1), vascular manifestations (1). No pathognomonic laboratory test exists. HLA-B51 testing: positive in 60–70% of Middle Eastern patients — supportive but not diagnostic. Pathergy test: prick the forearm with a sterile needle — a ≥2 mm papule/pustule at 24–48 hours is positive (specificity ~90%). CRP and ESR: elevated during flares. Other tests exclude mimics: ANA/anti-dsDNA (lupus), ANCA (ANCA-vasculitis), Crohn's disease serology.

No curative treatment. Colchicine: first-line for mucocutaneous (oral/genital ulcers, skin) and joint manifestations. Topical corticosteroids (triamcinolone paste) for oral ulcers. Systemic immunosuppression for organ-threatening disease: azathioprine (ocular, vascular involvement), cyclosporine A (posterior uveitis — effective but nephrotoxic), methotrexate. Biologics for refractory disease: TNF inhibitors (infliximab, adalimumab) — highly effective for refractory uveitis, mucocutaneous, and neurological BD; approved in several countries. Interferon-alfa: effective for uveitis and mucocutaneous disease. Anticoagulation for thrombotic complications. Apremilast: PDE4 inhibitor, approved for oral ulcers in some countries.

• Permanent blindness from untreated posterior uveitis or retinal vasculitis — still occurs in 25% of BD uveitis patients without adequate immunosuppression
• Pulmonary artery aneurysm rupture: massive hemoptysis — high mortality
• Neuro-Behçet: progressive cognitive decline, dementia, cerebellar ataxia
• Aortic aneurysm from large vessel arteritis
• Budd-Chiari syndrome from hepatic venous thrombosis

• No known primary prevention. Early diagnosis and sustained treatment prevent organ-threatening complications (blindness, vascular events)
• Regular ophthalmological monitoring in all BD patients — ocular disease may be asymptomatic early
• Colchicine maintenance reduces mucocutaneous recurrence frequency