What is Behçet disease?

What is Behçet Disease?

Behçet disease is a chronic, relapsing systemic vasculitis of unknown etiology that affects blood vessels of all sizes and types, characterized by recurrent oral aphthous ulcers, genital ulcers, ocular inflammation, and skin lesions, with potential life-threatening involvement of major organs including the vascular, neurological, and gastrointestinal systems. 1, 2

Core Pathophysiology

Behçet disease represents a unique condition at the crossroad between autoimmune and autoinflammatory syndromes 3:

• Genetic predisposition is dominated by HLA-B51, the strongest genetic susceptibility factor, particularly prevalent along the ancient "Silk Road" from Eastern Asia to the Mediterranean 4, 5
• Immune dysregulation involves T cell homeostasis perturbation with expansion of Th1 and Th17 cells, suppression of regulatory T cells (Tregs), and IL-21-driven inflammatory responses 3, 6
• Neutrophil activation with intense neutrophil infiltration characterizes the early inflammatory stage 5, 6
• Vasculitis affects both arteries and veins of any size, with endothelial dysfunction, fibrinoid necrosis, and non-granulomatous occlusive changes 7, 6

Clinical Manifestations by System

Mucocutaneous Features (Universal)

• Recurrent oral aphthous ulcers occur in virtually all patients and typically constitute the first symptom 4
• Genital ulcers affect the majority of patients and can cause obliterative scarring and deformity if inadequately treated 4
• Skin lesions include erythema nodosum (high diagnostic value), papulopustular/acne-like eruptions, and pseudofolliculitis 4
• Positive pathergy test demonstrates exaggerated skin response to minor trauma 4

Ocular Involvement (Poor Prognosis Marker)

• Posterior uveitis and retinal vasculitis can lead to severe visual impairment 2
• Anterior uveitis may present with iridocyclitis and hypopyon formation 4
• Blindness develops in up to 20% of untreated patients 4
• Ocular disease predicts poor prognosis and requires aggressive treatment 4

Vascular Disease (Approximately One-Third of Patients)

• Venous manifestations include superficial thrombophlebitis, deep vein thrombosis, varices, and cerebral sinus thrombosis 4
• Arterial disease produces aneurysms, stenotic lesions, and pseudo-aneurysms with rupture risk 4
• Pulmonary embolism is uncommon despite frequent venous thrombosis because thrombi adhere tightly to vessel walls 4
• Critical warning: Pulmonary artery aneurysm contraindicates anticoagulation due to fatal hemorrhage risk 4

Neurological Involvement (Poor Prognosis Marker)

• Parenchymal disease can affect any CNS area 4
• Dural sinus thrombosis requires targeted corticosteroid therapy 4
• MRI with contrast is the imaging modality of choice 8, 4
• CSF analysis may reveal pleocytosis and elevated protein 8, 4

Gastrointestinal Manifestations

• Deep penetrating ulcers most often located in terminal ileum, ileocecal region, and colon 4
• Perforation frequently occurs, necessitating emergency surgical resection 4
• High recurrence and re-operation rates characterize long-term outcomes 4

Articular Features

• Non-erosive arthritis is typically mild, transient, and non-deforming 4
• Large joints (knees, ankles) are most frequently involved 4

Diagnostic Approach

Clinical Criteria

The diagnosis requires recurrent oral aphthous ulcers plus at least two of the following: 2, 8

• Recurrent genital ulceration
• Uveitis or retinal vasculitis
• Specific skin lesions (erythema nodosum-like lesions carry more diagnostic weight than acneiform lesions) 8
• Positive pathergy test

Essential Clinical Evaluations

• Thorough genital examination to search for ulcers or scars 8
• Complete ophthalmologic examination is mandatory to assess for uveitis or retinal vasculitis 2, 8
• Inflammatory markers (ESR, CRP) can monitor disease activity but are not specific 2, 8

Supportive Testing

• HLA-B51 testing has moderate positive predictive value (~55%) and high negative predictive value (84-90%), but should not be used as standalone diagnostic test 8

Disease Course and Prognosis

Natural History

• Chronic relapsing-remitting course with unpredictable exacerbations 2
• Disease manifestations typically ameliorate over time in many patients, allowing treatment tapering or discontinuation 1, 2
• Young men with early disease onset have the most severe course and worst prognosis, warranting aggressive treatment 4

Prognostic Stratification

Poor prognosis indicators requiring aggressive treatment: 1, 2, 4

• Ocular involvement
• Vascular involvement
• Neurological involvement
• Gastrointestinal involvement

These can cause serious damage or death if untreated 2

Quality of Life Impact

• Mucocutaneous and joint involvement impair quality of life but do not cause permanent organ damage 1, 2
• Major organ involvement causes irreversible damage and requires immediate aggressive immunosuppression 4

Treatment Principles

Stratified Approach Based on Severity

For mucocutaneous and joint involvement only: 1

• Treatment can be tailored according to quality of life impact versus medication risks
• Topical steroids for oral and genital ulcers
• Colchicine as first-line prevention, especially for erythema nodosum or genital ulcers

For major organ involvement: 1, 2

• Immediate aggressive immunosuppression is required to prevent irreversible damage or death
• Rapid suppression of inflammation with immunosuppressives is critical to prevent loss of function
• Multidisciplinary approach with organ-specific specialists is necessary

Critical Clinical Warnings

• Chronic genital ulcers require vigorous treatment to prevent oropharyngeal narrowing and obliterative genital scarring 1, 4
• Pulmonary artery aneurysm absolutely contraindicates anticoagulation 4
• Male gender and early onset mandate more aggressive treatment and increased caution during follow-up 1