Behçet Syndrome

Diagnosis

Indications for Testing

• Mucocutaneous ulcers associated with systemic symptoms

Criteria for Diagnosis

• International Study Group for Behçet disease criteria
  • Recurrent oral ulceration plus at least two other findings (eg, recurrent genital ulceration, eye or skin lesions, positive pathergy test)  in the absence of other clinical explanations

Laboratory Testing

• Nonspecific testing
  • CBC – differentiate between infectious and noninfectious process
  • Urinalysis – screen for hematuria
  • ESR – assess for inflammation; may be elevated
  • ANCA – rule out other vasculitis processes

Other Tests

• Pathergy test – intradermal injection of skin with 20 gauge needle using normal saline
  • Positive test – demonstrates erythematous sterile papule within 48 hours

Differential Diagnosis 

• Vasculitis
  • Microscopic polyangiitis
  • Polyarteritis nodosa
• Gastrointestinal
  • Reiter syndrome
  • Celiac disease
  • Inflammatory bowel disease
• Dermatologic
  • Stevens-Johnson syndrome
  • Immunobullous skin disease
  • Herpes simplex virus
• Autoimmune
  • Systemic lupus erythematosus
  • Sjögren syndrome
  • Multiple sclerosis
• Sarcoidosis
• Familial Mediterranean fever

Clinical Background

Behçet syndrome is a multisystem, chronic inflammatory disease that is usually characterized by oral ulcers, genital ulcers, and uveitis.

Epidemiology

• Incidence – 1-2/100,000 in U.S.
• Age – 20-40 years
• Sex – M>F in Mediterranean populations; M<F in Asian populations
  • Young males tend to have the most severe disease
• Ethnicity – rare in the U. S.
  • Much higher incidence in Mediterranean and Middle Eastern populations (along the “Old Silk Route”)

Genetics

• HLA-B51 strongly associated with disease
  • Frequently expressed in individuals who live along the Silk Route (Mediterranean to Far East)
    • Association between HLA-B51 and Behçet syndrome not established outside of the Silk Route
  • Associated with severe disease manifestations, including posterior uveitis or progressive central nervous system disease

Risk Factors

• HLA-B51
• Environmental exposures
  • Infections (streptococcal antigens)
  • Smoking

Pathophysiology

• Vascular injury to arteries and veins of all sizes – exact cause unknown
  • Small vessel disease most common
  • Venous involvement may present as thromboembolic disease
• Abnormal cellular immune responses and lymphocyte functions

Clinical Presentation

• Constitutional – fever, fatigue, malaise
• Mucocutaneous – recurrent oral (aphthous ulcers) and genital ulcers (most common sign)
• Musculoskeletal – peripheral arthritis, myositis
• Neurologic – headache, confusion, strokes, personality changes, dementia (rare), aseptic meningitis, papilledema, dural sinus thrombosis, parenchymal brain disease
• Dermatologic – erythema nodosum, papulopustular lesions, acneiform nodules, pathergy
• Gastrointestinal – ulcers predominate in ileum and colon
• Ophthalmologic – anterior/posterior uveitis (bilateral disease common), hypopyon, retinal scars
• Otorhinologic – paranasal sinus disease
• Bronchopulmonary – aneurysms of arteries in the lungs

Treatment

• Ulcers
  • Topical treatment with corticosteroids initially
  • If topical treatment unsuccessful, colchicine and dapsone may be helpful
• Systemic disease – may require oral steroids
• Uveitis – steroid eye drops
• Interferon-alpha – limited long-term use in mild-moderate disease due to influenza-like symptoms
• Thalidomide – under investigation in U.S. for treating symptoms of Behçet syndrome

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory