Behçet Syndrome

Diagnosis

Indications for Testing

  • Mucocutaneous ulcers associated with systemic symptoms

Criteria for Diagnosis

Laboratory Testing

  • Nonspecific testing – helpful in excluding other diseases
    • CBC – usually normal
    • Urinalysis – usually normal
    • Erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) – may be elevated
    • ANCA – negative rules-out ANCA-associated vasculitis

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 

Clinical Background

Behçet syndrome is a multisystem, chronic inflammatory disease that is usually characterized by oral ulcers, genital ulcers, and uveitis. It is categorized as a variable vessel vasculitis when vasculitis is found to be present (Chapel Hill 2012).

Epidemiology

  • Incidence – 1-2/100,000 in U.S.
  • Age – 20-40 years
    • Rare in children or  individuals >50 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

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

  • Genetics
    • HLA-B51
  • Environmental exposures

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)
    • Must recur >3 times/year to meet International Study Group Criteria (1990)
  • 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, superficial thrombophlebitis
  • 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
  • Vascular – deep venous thrombosis

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
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

May help in ruling out infectious process

   
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Screen for hematuria, proteinuria, and RBC casts

   
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Initial evaluation for suspected vasculitis

   
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Initial evaluation for suspected vasculitis

   
Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Initial evaluation for suspected ANCA-associated vasculitis

If screen is positive, titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination