Behçet Syndrome

Diagnosis

Indications for Testing

Mucocutaneous ulcers associated with systemic symptoms

Criteria for Diagnosis

• International Criteria for Behçet disease – scored by sign/symptom and points; four or more points is diagnostic (International Team for the Revision of the International Criteria for Behçet's Disease [ITR-ICBD], 2014)
  • Ocular lesions – two points
  • Genital aphthosis – two points
  • Oral aphthosis – two points
  • Skin lesions – one point
  • Neurological manifestations – one point
  • Vascular manifestations – one point
  • Positive pathergy test – one point
    • Optional test; the primary scoring system does not include pathergy testing, but if conducted, one extra point may be assigned for positive result

Laboratory Testing

• Nonspecific testing
  • Some laboratory tests may be helpful in excluding other diseases
    • Antineutrophil cytoplasmic antibody (ANCA) – negative result rules out ANCA-associated vasculitis
    • ​CBC – usually normal
    • Urinalysis – usually normal
    • C-reactive protein (CRP)
      • Preferred test to detect acute phase inflammation (Choosing Wisely: 20 Things Physicians and Patients Should Question, 2017; American Society for Clinical Pathology)
      • May be elevated
      • If CRP not available, order erythrocyte sedimentation rate (ESR)
• Other testing
  • Pathergy test – insertion of sterile needle intradermally
    • Positive test – demonstrates erythematous sterile papule within 48 hours
    • Refer to Criteria for Diagnosis for further discussion of pathergy testing

Differential Diagnosis 

• Vasculitis
  • Microscopic polyangiitis
  • Polyarteritis nodosa
• Mucocutaneous ulcers
  • Inflammatory bowel disease (IBD)
  • Celiac disease
  • Systemic lupus erythematosus (SLE)
  • Viral (eg, herpes simplex virus [HSV])
  • Inflammatory diseases (eg, familial Mediterranean fever)
• Gastrointestinal symptoms
  • Reactive arthritis (formerly referred to as Reiter syndrome)
  • Celiac disease
  • IBD
• Dermatologic symptoms
  • Stevens-Johnson syndrome
  • Immunobullous skin disease
  • HSV
• Autoimmune
  • SLE
  • Sjögren syndrome
  • Multiple sclerosis (MS)
• Sarcoidosis

Background

Epidemiology

• Incidence – 1-2/100,000 in U.S.
• Age – 20-40 years
  • Rare in children and individuals >50 years
• Sex – M>F in Mediterranean populations; M<F in Asian and U.S. 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

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 (CNS) disease

Risk Factors

• Genetics
  • HLA-B51
• Environmental exposures
  • Infections – streptococcal antigens
  • Tobacco use

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
  • Arterial aneurysms
• Abnormal cellular immune responses and lymphocyte functions

Clinical Presentation

• Disease severity varies
  • Middle Eastern countries – disease most severe in young men; severe uveitis common
  • U.S. – disease most severe in women; uveitis less common
• Constitutional – fever, fatigue, malaise
• Mucocutaneous – recurrent oral (aphthous ulcers) and genital ulcers (most common sign)
• Musculoskeletal – peripheral arthritis, myositis, enthesitis
• 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 (rare in U.S.), superficial thrombophlebitis, leukocytoclastic vasculitis, pyoderma granulosum
• Gastrointestinal – ulcers predominate in ileum and colon, emesis, diarrhea
• Ophthalmologic – anterior/posterior uveitis (bilateral disease common), hypopyon, retinal scars
• Otorhinologic – paranasal sinus disease
• Bronchopulmonary – aneurysms of arteries in the lungs
• Cardiac – pericarditis, myocarditis, valvular disease
• Vascular – deep venous thrombosis, Budd-Chiari syndrome, arterial aneurysm