Behçet Syndrome

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).

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Clinical Overview

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

ARUP Lab Tests

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

Medical Experts

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

References

Guidelines

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
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Oct 2018]
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

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 Y�, 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

Testing Algorithms

Vasculitis in Adults Testing Algorithm

Read more about Vasculitis in Adults Testing Algorithm

Content Review:

June 2017

Last Update: June 2018