Behçet Syndrome

Indications for Testing

Mucocutaneous ulcers with systemic symptoms

Criteria for Diagnosis

International Study Group for Behcet disease criteria – recurrent oral ulceration plus at least two other findings (eg, recurrent genital ulceration, eye or skin lesions, positive pathergy test) in the absence of other clinical explanations

Laboratory Testing

Nonspecific testing
- CBC – normal
- Urinalysis – no hematuria
- ESR – may be elevated
- ANCA – negative

Other tests

Pathergy test – intradermal injection of skin with 20 gauge needle with injection of normal saline
- Positive test – erythematous sterile papule within 48 hours

Differential Diagnosis

Vasculitis
- Microscopic polyangiitis
- Polyarteritis nodosa
Gastrointestinal
Dermatologic
- Stevens Johnson syndrome
- Immunobullous skin disease
- Herpes simplex virus
Autoimmune
Sarcoidosis
Familial Mediterranean fever

Behçet syndrome is a multisystem, chronic inflammatory disease that is usually characterized by oral ulcers, genital ulcers, and uveitis.

Epidemiology

Incidence – 1-2/100,000 in U.S.
Age – 20-40 years
Sex – M>F in Mediterranean populations; F>M 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 (along the “Old Silk Route”)

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

HLA-B51
Environmental exposures
- Infections (streptococcal antigens)
- Smoking

Pathophysiology

Vascular injury to arteries and veins of all sizes; exact cause is unknown
- Small vessel disease is 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)
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
Gastrointestinal – ulcers predominate in ileum and colon
Ophthalmologic – anterior/posterior uveitis (bilateral disease is common), hypopyon, retinal scars
Otorhinologic – paranasal sinus disease
Bronchopulmonary – aneurysms of arteries in the lungs

Treatment

Ulcers
- Topical treatment with corticosteroids initially
- If topical treatment is unsuccessful, colchicine and dapsone may be helpful
Systemic disease – may require oral steroids
Uveitis – steroid eye drops
Interferon-alpha – limited long-term use in mild-moderate disease due to influenza-like symptoms
Thalidomide – under investigation in the U.S. for treating symptoms of Behçet syndrome

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Differentiate between infectious and non-infectious process

Test name: Urinalysis, Complete

ARUP #: 0020350

Methodology: Reflective Photometry/Microscopic by Yellow IRIS

Use:

Screen for hematuria

Test name: Sedimentation Rate, Westergren (ESR)

ARUP #: 0040325

Methodology: Westergren

Use:

Assess for inflammation; typically elevated

Test name: Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies

ARUP #: 2002068

Methodology: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multi-Analyte Fluorescent Detection

Use:

Rule out other vasculitic processes

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

General

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

Comprehensive Review: June 2011
Last Update: February 2012

Herpes Simplex Virus

Vasculitis