Behcet Disease 

  • Author: Augusto C Posadas, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Aug 26, 2011
 

Background

Behçet disease (BD) is characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. Hippocrates may have described Behçet disease in the fifth century BC; however, the first description of the syndrome was attributed to the Turkish dermatologist Hulusi Behçet in 1924. In 1930, the Greek physician Adamantiades reported a patient with inflammatory arthritis, oral and genital ulcers, phlebitis, and iritis.[1] Since then, the syndrome has been referred to as Behçet disease.

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Pathophysiology

Theories behind the pathogenesis of Behçet disease currently point toward an autoimmune etiology. Current research suggests that exposure to an infectious agent may trigger a cross-reactive immune response. Proposed infectious agents have included herpes simplex virus (HSV), Streptococcus species, Staphylococcus species, and Escherichia coli, all of which commonly inhabit the oral cavity.

The International Study Group for Behçet's Disease has emphasized the presence of recurrent oral ulcers as a primary consideration in the diagnosis of Behçet disease.[2] In response, the pathogens above have been targeted for study in hopes of establishing a direct link between their presence and disease activity. Unfortunately, researchers have been unable to generalize results across geographic populations so far.

The study of heat shock proteins (HSPs) has provided some insight into possible mechanisms that contribute to the development of Behçet disease. Through discovery that HSP 60 and HSP 65 share greater than 50% homology with mycobacterial HSP, enhanced T-cell response has been elicited with exposure to both bacterial and human homogenates in Behçet disease patients compared to controls in UK, Japanese, and Turkish populations. HSP 65, found in high concentrations in oral ulcers and active skin lesions in patients with Behçet disease, has also been demonstrated to stimulate production of antibodies that exhibit cross-reactivity with streptococcal species present in the mouth.[3, 4] These examples provide further support that exposure to an infectious agent may initiate cross-reactive autoimmune responses in persons with Behçet disease.[3, 5, 4]

Systemic involvement of multiple organs is observed in Behçet disease, rooted primarily in the development of vasculitic or vasculopathic lesions in the affected areas. These areas may demonstrate microscopic evidence of inflammatory tissue infiltration with both T cells and neutrophils.[6, 3, 7, 8]

Studies of T lymphocytes have suggested a T-helper type 1 (TH1)–predominant response. Both CD4+ and CD8+ lymphocytes demonstrate higher concentrations in peripheral blood with characteristic and corresponding elevations of cytokines (interleukin-2 [IL-2] and interferon-γ [IFN-γ]). Serum levels of IL-12 have also been shown to be elevated in patients with Behçet disease, possibly helping drive the response.

Attempts at determining if tissue antigens have a role in channeling the immune response have been unsuccessful. Elevated peripheral levels of γδ+ T cells in patients with Behçet disease compared with those in healthy subjects imply a nidus for their production. To support this, an antigen-driven expansion of oligoclonal Vβ+ T-cell receptor (TCR)–specific cell lines has been demonstrated. However, generalization of these results is not applicable because of the high degree of interindividual variability in TCR expression.

Considering the degree of neutrophilic infiltration demonstrated in characteristic Behçet disease lesions, including hypopyon, pustular lesions, and pathergy reactions, activity and function of these cells has been explored extensively. Unfortunately, existing studies offer inconsistent results regarding cell adhesion and chemotactic behavior, superoxide production, and phagocytic properties. Thus, the specific role of neutrophils in Behçet disease has been difficult to characterize. Some studies portend that cytokine release in Behçet disease may, by an unknown mechanism, place neutrophils in a static pre-excitatory “primed” state, eventually triggered into hyperactivity by environmental stimuli at a lower threshold than in individuals who do not have Behçet disease.[9, 10, 11, 12]

HLA-B51 has been shown to be more prevalent in Turkish, Middle Eastern, and Japanese populations, corresponding with a higher prevalence of Behçet disease in these populations. However, HLA-B51 has not been shown to affect the severity of symptoms. Presentation in males serves as the only proven predictor of severity, causing many of the complications of Behçet disease in higher proportion to their female counterparts.

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Epidemiology

Frequency

United States

The prevalence of Behçet disease in the United States is 0.12-0.33 cases per 100,000 population.[13]

International

The incidence and prevalence of Behçet disease are highest along the old Silk Road, extending from the Middle East to China.

Turkey has the highest prevalence of Behçet disease, with 420 cases per 100,000 population. The prevalence in Japan, Korea, China, Iran, and Saudi Arabia ranges from 13.5-22 cases per 100,000 population. The prevalence in North America and Europe is much less, with 1 case per 15,000-500,000 population.[13, 11]

Mortality/Morbidity

Epidemiology studies have reported that Behçet disease carries an overall mortality rate of as much as 16% at 5 years.

Coronary/pulmonary arterial aneurysm rupture in association with Behçet disease carries a high mortality rate.

Neurologic involvement has been associated with mortality rates up to 20% at 7-year follow-up in one Turkish study.[14]

Thrombosis may lead to death.

CNS involvement can lead to permanent deficits or death.

Eye involvement can result in blindness.

Race

The prevalence of Behçet disease is highest among Middle Eastern and Japanese persons.

Sex

The sexual prevalence varies by country.

In the Middle East, Behçet disease is more common among males, with male-to-female ratios of 3.8:1 (Israel), 5.3:1 (Egypt), and 3.4:1 (Turkey). In Germany, Japan, and Brazil, the disease is slightly more common in females. In the United States, Behçet disease is more common in females (5:1 female-to-male ratio).[13, 11]

Males are more likely to develop severe presentations of Behçet disease. Pulmonary aneurysms, eye involvement, thrombophlebitis, and neurologic disease are all more common in males. However, females are more likely to develop erythema nodosum –like skin lesions.

Age

Behçet disease is most common among persons aged 20-40 years. Cases that develop before age 25 years are more likely to involve eye disease and active clinical disease.

The mean age at onset is 25-30 years.

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Contributor Information and Disclosures
Author

Augusto C Posadas, MD  Rheumatologist, Saguaro Physician Group, Tucson, AZ

Disclosure: Abbott Honoraria Speaking and teaching

Coauthor(s)

Jeffrey R Lisse, MD, FACP  Professor, Department of Internal Medicine, Chief, Section of Rheumatology, University of Arizona School of Medicine

Jeffrey R Lisse, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, American Geriatrics Society, and Sigma Xi

Disclosure: Genentech Consulting fee Consulting; Centacor Consulting fee Consulting; Novartis Consulting fee Review panel membership

Specialty Editor Board

Kristine M Lohr, MD, MS  Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Lawrence H Brent, MD  Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology

Disclosure: Genentech Honoraria Speaking and teaching; Genentech Grant/research funds Other; Amgen Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Abbott Immunology Honoraria Speaking and teaching; Takeda Honoraria Speaking and teaching; UCB Speaking and teaching; Omnicare Consulting fee Consulting; Centocor Consulting fee Consulting

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

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