What is Behçet's disease?

Behçet's Disease: An Overview

Behçet's disease is a chronic, relapsing, multisystem inflammatory vasculitis characterized primarily by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions, with potential involvement of vascular, neurological, and gastrointestinal systems that can lead to significant morbidity and mortality if left untreated. 1

Definition and Epidemiology

Behçet's disease (BD) is a systemic vasculitis that can affect blood vessels of any size, both arteries and veins. It was first described in 1937 by Hulusi Behçet based on a triad of symptoms: uveitis, aphthous stomatitis, and genital ulcers 1.

Key epidemiological features include:

• Highest prevalence in countries along the ancient Silk Road, particularly in Turkey (80-370 cases per 100,000)
• Much lower prevalence in the United States (1-3 cases per million) 1
• More common and typically more severe in males
• Usually begins in the third or fourth decade of life
• Strong genetic association with HLA-B51 allele 1

Clinical Manifestations

Cardinal Features:

• Mucocutaneous manifestations:

  • Recurrent oral aphthous ulcers (painful, round lesions with defined borders)
  • Genital ulcers (similar to oral ulcers but may cause scarring)
  • Skin lesions (erythema nodosum, pseudofolliculitis, pathergy)

• Ocular involvement (occurs in ~50% of patients):

  • Uveitis (anterior, posterior, or panuveitis)
  • Retinal vasculitis
  • Can lead to blindness if untreated 2

Other System Involvement:

• Vascular involvement (affects ~1/3 of patients):

  • Venous thrombosis (superficial or deep)
  • Arterial aneurysms and occlusions
  • One of few vasculitides that commonly affects veins 1

• Neurological involvement:

  • Parenchymal lesions
  • Cerebral venous thrombosis

• Gastrointestinal involvement:

  • Ulcerations
  • Bleeding
  • Perforation 1

• Articular involvement:

  • Non-erosive arthritis

Diagnostic Criteria

The International Study Group for Behçet's disease criteria require:

• Recurrent oral ulceration (at least 3 times in 12 months)

Plus at least 2 of the following:

• Recurrent genital ulceration
• Eye lesions (uveitis or retinal vasculitis)
• Skin lesions (erythema nodosum, pseudofolliculitis, papulopustular lesions)
• Positive pathergy test (development of a sterile pustule at the site of needle prick) 1

Pathogenesis

The exact etiology remains unknown, but current understanding suggests:

• Genetic predisposition (HLA-B51)
• Dysregulated immune response (predominantly Th1/Th17)
• Possible environmental triggers or infectious agents
• Endothelial dysfunction and vasculitis 3

Treatment Approach

Treatment is guided by the type and severity of organ involvement:

1. Mucocutaneous Involvement

• First-line: Topical steroids for oral and genital ulcers
• For prevention of recurrence: Colchicine (especially effective for erythema nodosum and genital ulcers)
• For refractory cases: Consider azathioprine, thalidomide, interferon-alpha, or TNF-alpha inhibitors 1

2. Ocular Involvement

• Posterior segment disease: Requires immunosuppressive therapy with:
  • Azathioprine
  • Cyclosporine-A
  • Interferon-alpha
  • Anti-TNF antibodies
• Acute sight-threatening uveitis: High-dose glucocorticoids, infliximab, or interferon-alpha
• Important: Systemic glucocorticoids should only be used in combination with immunosuppressives 1

3. Vascular Involvement

• Deep vein thrombosis: Glucocorticoids and immunosuppressives (azathioprine, cyclophosphamide, or cyclosporine-A)
• Arterial aneurysms: High-dose glucocorticoids and cyclophosphamide; consider anti-TNF antibodies for refractory cases
• Caution: Anticoagulants should be used carefully and only after ruling out pulmonary artery aneurysms 1

4. Neurological and Gastrointestinal Involvement

• Requires aggressive immunosuppression
• Corticosteroids, azathioprine, cyclophosphamide
• Anti-TNF agents for refractory cases 4

Prognosis and Monitoring

• BD typically follows a relapsing-remitting course
• Disease activity often decreases over time
• Prognosis depends on organ involvement:
  • Ocular, vascular, neurological, and gastrointestinal involvement associated with worse outcomes
  • Men with early age of onset typically have more severe disease 1
• Regular monitoring for disease activity and treatment-related complications is essential

Key Considerations in Management

• Early diagnosis and prompt treatment are crucial to prevent irreversible organ damage
• A multidisciplinary approach involving rheumatology, ophthalmology, dermatology, and other specialties as needed
• Treatment intensity should match disease severity
• Disease manifestations may improve over time, allowing for potential tapering of medications 1