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).
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)
- 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 for further discussion of pathergy testing
- Pathergy test – insertion of sterile needle intradermally
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
- Frequently expressed in individuals who live along the Silk Route (Mediterranean to Far East)
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
ARUP Laboratory Tests
Preferred first-line reflex panel for the evaluation of ANCA-associated vasculitis
Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay
Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)
Quantitative Immunoturbidimetry
References
Choosing Wisely
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Dec 2020]
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Hatemi G, Yazici Y, Yazici H. Behçet's syndrome. Rheum Dis Clin North Am. 2013;39(2):245-261.
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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):338-347.
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Krause I, Weinberger A. Behçet's disease. Curr Opin Rheumatol. 2008;20(1):82-87.
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Mat C, Yurdakul S, Sevim A, et al. Behçet's syndrome: facts and controversies. Clin Dermatol. 2013;31(4):352-361.
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Saadoun D, Wechsler B. Behçet's disease. Orphanet J Rare Dis. 2012;7:20.
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Singer O. Cogan and Behcet syndromes. Rheum Dis Clin North Am. 2015;41(1):75-91, viii.
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Yazici H, Fresko I, Yurdakul S. Behçet's syndrome: disease manifestations, management, and advances in treatment. Nat Clin Pract Rheumatol. 2007;3(3):148-155.
Medical Experts
Peterson

Components: ANCA, IgG; myeloperoxidase antibody, and serine proteinase 3 antibody