What is Behcet's disease?

What is Behçet's Disease?

Behçet's disease is a chronic, relapsing systemic vasculitis of unknown etiology characterized by recurrent oral ulcers plus at least two of the following: genital ulcers, uveitis/retinal vasculitis, or specific skin lesions. 1

Pathophysiology

• The disease results from a complex interplay between genetic predisposition and environmental triggers that lead to dysregulated immune responses, ultimately causing systemic vasculitis affecting both arteries and veins 1
• HLA-B51 antigen represents the strongest genetic susceptibility factor for developing the disease 2, 3
• The pathogenesis involves epistatic interaction between HLA-B51 and endoplasmic reticulum aminopeptidase 1 (ERAP1) in antigen-presenting cells, which disrupts T-cell homeostasis leading to downregulation of regulatory T cells and expansion of Th1 and Th17 cells 2
• Neutrophil activation and intense neutrophil infiltration of affected organs develop in the early stage of inflammation 2

Epidemiology

• The disease shows striking geographic variation, with prevalence of 80-370 cases per 100,000 persons in Turkey compared to only 1-3 cases per million in the United States 1
• It is particularly common in populations along the ancient "Silk Road" extending from Eastern Asia to the Middle East and Mediterranean regions 2, 3
• The disease typically appears around the third or fourth decade of life with roughly equal gender distribution 2, 3

Clinical Manifestations

Mucocutaneous Features (Hallmark Symptoms)

• Recurrent oral aphthous ulcers are the most common and often the first manifestation 1, 2
• Genital ulcers occur frequently and are part of the diagnostic criteria 1, 2
• Cutaneous vasculitic lesions including erythema nodosum-like lesions and papulopustular lesions 2, 4
• These mucocutaneous and joint manifestations can impair quality of life but typically do not cause permanent damage and often respond well to treatment 5

Major Organ Involvement (Poor Prognosis)

• Ocular involvement with uveitis and retinal vasculitis can lead to blindness if untreated 1, 6
• Vascular involvement occurs in approximately one-third of patients, affecting both arteries and veins, and can cause life-threatening complications 1
• Neurological involvement (parenchymal or vascular) carries significant morbidity 6
• Gastrointestinal involvement can mimic inflammatory bowel disease and may be severe 6, 4
• These major organ involvements are associated with poor prognosis and can cause serious damage or death if left untreated 6

Disease Course

• The disease follows a relapsing and remitting course, with inflammatory exacerbations that generally decrease in frequency and severity over time 5
• Young men with early disease onset experience a more severe disease course and require more aggressive treatment and closer follow-up 1, 5, 6
• As disease manifestations abate over time, treatment can often be tapered and eventually discontinued 5
• Post-thrombotic syndrome is frequent with recurrent deep vein thrombosis and may result in difficult-to-treat leg ulcers 1, 6

Treatment Approach

• Treatment should be individualized based on organ involvement and disease severity 1
• Pharmacological agents include corticosteroids, colchicine, azathioprine, and TNF-α inhibitors 1
• For parenchymal neurological involvement, high-dose intravenous methylprednisolone followed by oral tapering, along with immunosuppressants such as azathioprine, cyclophosphamide, interferon-alpha, or TNF-alpha inhibitors should be used 6
• Cyclosporine A must be avoided in patients with central nervous system involvement due to potential neurotoxicity 1, 6
• Anticoagulants should generally be avoided in Behçet's disease with venous thrombosis due to bleeding risk, especially with coexisting pulmonary arterial aneurysms 1
• Young men with early disease onset may benefit from early systemic immunosuppression given their higher risk of severe disease 1, 6

Important Clinical Caveats

• Regular monitoring of disease activity through clinical symptoms and inflammatory markers is essential 6
• For patients with ocular involvement, regular ophthalmologic examinations are crucial to prevent blindness 6
• Patients with a history of major organ involvement should continue to be monitored even if symptoms have improved 5
• Pre-existing autoimmune rheumatic and/or systemic diseases should not preclude treatment for Behçet's disease 1