Behçet Syndrome

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Mucocutaneous ulcers associated with systemic symptoms

Criteria for Diagnosis

  • International Criteria for Behçet disease – scored by sign/symptom and points; ≥4 points is diagnostic (International Team for the Revision of the International Criteria for Behçet's Disease [ITR-ICBD], 2014)
    • Ocular lesions – 2 points
    • Genital aphthosis – 2 points
    • Oral aphthosis – 2 points
    • Skin lesions – 1 point
    • Neurological manifestations – 1 point
    • Vascular manifestations – 1 point
    • Positive pathergy test – 1 point
      • Optional test; the primary scoring system does not include pathergy testing, but if conducted, 1 extra point may be assigned for positive result

Laboratory Testing

  • Nonspecific testing
    • Some laboratory tests may be helpful in excluding other diseases
  • Other testing
    • Pathergy test – insertion of sterile needle intradermally
      • Positive test – demonstrates erythematous sterile papule within 48 hours
      • Refer to Criteria for Diagnosis section for further discussion of pathergy testing

Differential Diagnosis 

Behçet syndrome is a multisystem, chronic inflammatory disease that is usually characterized by oral ulcers, genital ulcers, uveitis with gastrointestinal, skin, and joint symptoms. It is categorized as a variable vessel vasculitis due to the high frequency of vasculitis in the disease (Jennette, Chapel Hill, 2013).

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

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
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.

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

Recommended Use 

Preferred reflex panel for managing patients with a known diagnosis of vasculitis; may be assistive in evaluating suspected vasculitis

For the workup of suspected vasculitis, the preferred panel is ANCA-associated vasculitis profile (ANCA/MPO/PR-3) with reflex to ANCA titer 

Panel includes ANCA, IgG; myeloperoxidase antibody, and serine protease 3 antibody

Reflex pattern – if screen is positive, then titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination

Guidelines

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Sep 2017]

International Team for the Revision of the International Criteria for Behçet's Disease (ITR-ICBD). The International Criteria for Behçet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol. 2014; 28(3): 338-47. PubMed

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed

General References

Hatemi G, Yazici Y, Yazici H. Behçet's syndrome. Rheum Dis Clin North Am. 2013; 39(2): 245-61. PubMed

Krause I, Weinberger A. Behçet's disease. Curr Opin Rheumatol. 2008; 20(1): 82-7. PubMed

Mat C, Yurdakul S, Sevim A, zyazgan YÃ, Tüzün Y. Behçet's syndrome: facts and controversies. Clin Dermatol. 2013; 31(4): 352-61. PubMed

Saadoun D, Wechsler B. Behçet's disease. Orphanet J Rare Dis. 2012; 7: 20. PubMed

Singer O. Cogan and Behcet syndromes Rheum Dis Clin North Am. 2015; 41(1): 75-91, viii. PubMed

Yazici H, Fresko I, Yurdakul S. Behçet's syndrome: disease manifestations, management, and advances in treatment. Nat Clin Pract Rheumatol. 2007; 3(3): 148-55. PubMed

Medical Reviewers

Tebo, Anne E., PhD, D(ABMLI), Medical Director, Immunology at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Content Reviewed: 
June 2017

Last Update: June 2017