eMedicine Specialties > Rheumatology > Vasculitis

Behcet Disease

Author: Augusto C Posadas, MD, Fellow, Department of Medicine, Section of Rheumatology, University of Arizona School of Medicine
Coauthor(s): Jeffrey R Lisse, MD, FACP, Professor, Department of Internal Medicine, Chief, Section of Rheumatology, University of Arizona School of Medicine
Contributor Information and Disclosures

Updated: Jun 22, 2009

Introduction

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.

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.

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 up to 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.

Clinical

History

In 1990, the International Study Group (ISG) for Behçet's Disease clarified criteria for the diagnosis of Behçet disease.2 The ISG group compared the clinical findings of 914 patients with a history of aphthous ulcers with those of controls. Initial criteria for diagnosis require the occurrence of at least 3 episodes of oral herpetiform or aphthous ulcerations within a 12-month period observed directly by a physician or reported by the patient. To confirm the diagnosis, at least 2 of the following must also be demonstrated:

  • Recurrent painful genital ulcers that heal with scarring
  • Ophthalmic lesions, including anterior or posterior uveitis, hypopyon, or retinal vasculitis
  • Skin lesions, including erythema nodosum–like lesions, pseudofolliculitis, or papulopustular or acneiform lesions
  • Positive results from pathergy skin testing, defined as the formation of a sterile erythematous papule 2 mm in diameter or larger that appears 48 hours following a skin prick with a sharp sterile needle (22-24 gauge [a dull needle may be used as a control])

Considering the above diagnostic criteria, case presentation often includes the following characteristics:

  • Multiorgan system involvement, often beginning with mucocutaneous involvement and usually sparing the liver, kidneys, and heart
  • Age of 25-35 years at onset
  • Organ-specific manifestations characterized by exacerbations and a relapsing/remitting course

Pertinent site-specific manifestations include the following:

  • Skin and mucous membranes
    • Painful oral lesions (aphthous or herpetiform) are one of the criteria for diagnosis and may be the first manifestation (70% of cases).

      Oral aphthous ulcers secondary to Behçet dis...

      Oral aphthous ulcers secondary to Behçet disease.

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      Oral aphthous ulcers secondary to Behçet dis...

      Oral aphthous ulcers secondary to Behçet disease.

    • Oral lesions are usually not distinguishable from other causes but often have a high recurrence rate (often >5 times/y despite only 3 times/y specified in ISG criteria) and appear as multiple lesions or crops (often >6 simultaneous lesions at a given time).
    • Oral lesions are commonly found in keratinized areas of the oropharynx, often excluding the nonkeratinized surfaces of the dorsal tongue, gums, and hard palate.
    • Skin lesions often occur in the genital region of both sexes. In males, scrotal involvement is most characteristic; however, lesions can also develop on the penile shaft. In females, the labial area is most commonly involved, with lesions occasionally developing in the vagina and on the perineum. Genital ulcerations typically heal with scarring and are more painful in men.
    • Nodules that resemble erythema nodosum are more common in the lower extremities of females. They are tender, erythematous, and nodular and usually resolve after 2-3 weeks but often recur.
    • Acneiform papulopustular lesions are more common in men and are usually found on the trunk and extremities, although they may develop anywhere on the body.
    • Extragenital ulcerations that heal with scarring are rare and affect only 3% of patients.15 These are very specific for Behçet disease. They can be found in the axillae, neck, breast, interdigital skin of the feet, and groin.
    • Positive pathergy test findings are more common in Turkish and Japanese populations, as well as patients with ophthalmic and neurologic manifestations.
  • Ocular lesions
    • Ocular presentations (anterior or posterior uveitis, hypopyon, retinal vasculitis) represent the first manifestation of disease in 10% of patients with Behçet disease but usually occur following oral ulceration.11
    • Symptoms commonly include blurred vision, periorbital pain, photophobia, scleral injection, and excessive lacrimation.
    • Men, particularly of Iranian and Japanese descent, tend to present with more severe eye involvement.
    • Highly recurrent posterior uveitis can lead to blindness.
    • Ocular symptoms usually present in the first years of illness. Cases that cause blindness commonly develop within the first 7 years. The prognosis is better for persons who develop symptoms later in the disease course.
  • Neurologic manifestations
    • Collectively, neurologic symptoms tend to be an unusual late manifestation, 1-8 years after disease onset.
    • Memory tends to be affected in most cases, particularly affecting recall and learning.
    • Orientation, arithmetic, and language are often unaffected.
    • Symptoms are usually parenchymal in nature, predominantly with brainstem involvement.
    • Behavioral changes, primarily apathy or disinhibition, occur in 54% of patients.14
    • Seizures and bulbar signs with ophthalmoplegia are less common.
  • Vasculopathy
    • Behçet disease can cause aneurysms in the pulmonary arterial tree that often prove to be fatal. Pulmonary artery aneurysmal involvement is associated with right-sided cardiac thromboses and can manifest as hemoptysis, cough, chest pain, or dyspnea.
    • Vasculitis of the small and large vessels can cause a panoply of symptoms depending on location of the lesions.
    • Arterial disease predominantly affects males and only rarely occurs in women.16
    • Venous involvement (usually in the form of superficial thrombophlebitis) is more common than arterial involvement.15 Superficial thrombophlebitis presents in a linear fashion with overlying erythema and is often confused with erythema nodosum. In males, formation of these linear areas of vasculopathy leads to sclerosis and stringlike thickening in the affected areas.
    • Symptoms correlate with the vessel involved and may be devastating. For example, extension of an inferior vena caval clot to the hepatic vein may be the mechanism of Budd-Chiari syndrome in Behçet disease.16
  • Arthritis
    • Arthritis and arthralgias occur in as many as 60% of patients and primarily affect the lower extremities, especially the knee. Ankles, wrists, and elbows can also be primarily involved.
    • The arthritis is nondeforming and asymmetric in nature and can assume a monoarticular, oligoarticular, or polyarticular pattern of involvement.
    • Symptoms relapse and remit and rarely become chronic.
  • Gastrointestinal/genitourinary manifestations
    • GI involvement affects 3-16% of patients with Behçet disease.17
    • Areas affected often include the esophagus and ileocecal area.
    • Symptoms include abdominal pain, bloating, and GI bleeding.
    • Complications often result from deep ulceration of intestinal sections.
    • GU involvement can include epididymitis, neurogenic bladder, and sterile urethritis.
  • Renal manifestations
    • Renal manifestations may be underreported. A recent study found that 1-29% of patients with Behçet disease developed such manifestations.18
    • Associated amyloidosis may develop.
    • The first presentation is often nephritic-range proteinuria found incidentally.
    • Crescenteric and proliferative glomerulonephritis, as well as IgA nephritis, have also been reported in some cases.19,18

Physical

  • Oral ulcers
    • Oral lesions represent the most common, and often the first, manifestation of Behçet disease. Even when they are not the first manifestation, they are considered a primary criterion for diagnosis and eventually occur in most patients.
    • Ulcers are aphthous or herpetiform in nature and can occur in various keratinized areas of the oral cavity. They can be very painful, can last up to 3-5 weeks, and can vary in size. Large ulcers (>10 mm in diameter) heal with scarring as do their genital counterparts.
  • Genital ulcers
    • In females, these lesions commonly appear in the labial folds but can also be found in the vulva and vagina.
    • In males, they are usually scrotal in nature but can also develop in the perianal region and penile shaft.
    • Genital ulcers last longer than oral lesions, are deeper, and typically scar after healing.
    • Ulcerations in women may correlate with menstruation.
  • Skin
    • Pseudofolliculitis and acneiform lesions, found more commonly in males with Behçet disease, primarily affect the trunk and extremities.
    • Erythema nodosum, which is more common in females with the disease, are occasionally differentiated from alternate etiologies based on ulceration, which is a characteristic more unique to Behçet disease.
  • Ocular manifestations
    • Anterior uveitis with and without hypopyon formation
    • Posterior uveitis that may cause blindness
    • Glaucoma
    • Synechiae
    • Retinal vasculitis
    • Infarctions
    • Hemorrhage
    • Edematous appearance of the disc, with retinal detachment
    • Leaky retinal vessels revealed by fluorescein angiography, leading to atrophy and fibrosis in some cases
  • Neurologic manifestations
    • Pyramidal tract lesions with spastic paralysis and dementia have been demonstrated in some patients with Behçet disease.14
    • Neurologic signs may include mental status changes; seizures; clonus; positive Babinski sign; difficulty with speech, swallowing, and emotional lability; and acute deafness.
    • Apathy or disinhibition is common.
    • Difficulty with recall and learning has been demonstrated.
    • Peripheral nerve involvement is rare.
  • Vascular manifestations
    • Lower-extremity superficial thrombophlebitis often presents in a linear fashion with overlying erythema and tenderness.
    • Palpation of sclerosed thrombophlebitis yields subcutaneous stringlike quality.
    • Deep venous thrombosis (DVT) develops in some cases and typically manifests as local tenderness or as disparity in limb girth.
    • Saadoun et al found that cerebral venous thrombosis (CVT) was present in 7.8% of a large cohort of patients with Behçet disease. The main complication of CVT was severe visual loss due to optic atrophy. Papilledema and concurrent prothrombotic risk factors were independently associated with the occurrence of sequelae; peripheral venous thrombosis and concurrent prothrombotic risk factors were associated with relapse of thrombosis. Anticoagulant therapy proved safe and effective in up to 90% of patients.20
    • Arterial vasculitis may manifest as claudication symptoms.
  • Arthritis
    • Inflammatory peripheral arthritis is common, occurring in about half of patients with Behçet disease.
    • The arthritis has a predominance for the lower extremities but may occur in any pattern.
    • Diffuse arthralgias are also common.
    • Arthritis is usually not destructive or deforming.
    • Joint-fluid content often reflects only inflammatory properties.
    • Aseptic necrosis develops in rare cases.
  • Gastrointestinal manifestations
    • Ulcerative lesions can cause abdominal pain, bloody diarrhea, and occasional intestinal perforation.
    • GI lesions are indistinguishable from those associated with inflammatory bowel disease but commonly occur in the ileocecal region.
  • Genitourinary manifestations
    • Glomerulonephritis can cause hematuria. The glomerulonephritis can be crescenteric or proliferative. IgA nephritis has also been reported.19,18
    • Epididymitis manifests as scrotal tenderness.
    • Neurogenic bladder can present with typical symptoms of urinary retention.
  • Other lesions
    • Cardiac manifestations include coronary vasculitis and thrombosis, pericarditis, myocarditis, endocarditis with granulomatous changes or fibrosis, regurgitation, and diastolic dysfunction (5-17% of cases).
    • Lung involvement occurs in up to 18% of patients with Behçet disease. Pulmonary vasculitis, hypertension, and pleural effusions have been reported. Aneurysms represent a dreaded complication of Behçet disease and may result in massive hemoptysis.

Causes

  • The specific etiology of Behçet disease remains elusive, but, as described in Pathophysiology, the interplay between infectious-agent exposure and genetic factors may have a role. An environmentally triggered hyperactive primed state of autoimmunity ensues, resulting in two types of vascular damage. The first is vasculitic lesions that may be widespread. Sequelae depend on the various organ systems affected.
  • Some of the pathologic changes are due to thrombosis and/or clot formation caused by the development of a hypercoagulable state. The mechanism is still undetermined; however, studies have demonstrated excessive thrombin formation and the potential role of impaired fibrinolytic kinetics in the generation of the hypercoagulable/prothrombotic state. Pathologic activation of the procoagulant cascade via endothelial injury has also been demonstrated in patients with Behçet disease.21

More on Behcet Disease

Overview: Behcet Disease
Differential Diagnoses & Workup: Behcet Disease
Treatment & Medication: Behcet Disease
Follow-up: Behcet Disease
Multimedia: Behcet Disease
References
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References

  1. Adamantiades B. A case of recurrent hypopyon iritis. Medical Society of Athens. 1930;586-93.

  2. International Study Group for Behçet's Disease. Criteria for diagnosis of Behçet's disease. International Study Group for Behçet's Disease. Lancet. May 5 1990;335(8697):1078-80. [Medline].

  3. Emmi L, Brugnolo F, Salvati G, et al. Immunopathological aspects of Behçet's disease. Clin Exp Rheumatol. Nov-Dec 1995;13(6):687-91. [Medline].

  4. Kaneko S, Suzuki N, Yamashita N, Nagafuchi H, Nakajima T, Wakisaka S, et al. Characterization of T cells specific for an epitope of human 60-kD heat shock protein (hsp) in patients with Behcet's disease (BD) in Japan. Clin Exp Immunol. May 1997;108(2):204-12. [Medline].

  5. Hasan A, Fortune F, Wilson A, Warr K, Shinnick T, Mizushima Y, et al. Role of gamma delta T cells in pathogenesis and diagnosis of Behcet's disease. Lancet. Mar 23 1996;347(9004):789-94. [Medline].

  6. Direskeneli H, Eksioglu-Demiralp E, Yavuz S, Ergun T, Shinnick T, Lehner T, et al. T cell responses to 60/65 kDa heat shock protein derived peptides in Turkish patients with Behçet's disease. J Rheumatol. Mar 2000;27(3):708-13. [Medline].

  7. Frassanito MA, Dammacco R, Cafforio P, Dammacco F. Th1 polarization of the immune response in Behçet's disease: a putative pathogenetic role of interleukin-12. Arthritis Rheum. Sep 1999;42(9):1967-74. [Medline].

  8. Sugi-Ikai N, Nakazawa M, Nakamura S, Ohno S, Minami M. Increased frequencies of interleukin-2- and interferon-gamma-producing T cells in patients with active Behçet's disease. Invest Ophthalmol Vis Sci. May 1998;39(6):996-1004. [Medline].

  9. Hallett MB, Lloyds D. Neutrophil priming: the cellular signals that say 'amber' but not 'green'. Immunol Today. Jun 1995;16(6):264-8. [Medline].

  10. Sakane T, Takeno M, Suzuki N, Inaba G. Behçet's disease. N Engl J Med. Oct 21 1999;341(17):1284-91. [Medline].

  11. Sakane T, Suzuki N, Takeno M. Innate and acquired immunity in Behçet's disease. 8th International Congress on Behçet's Disease. Reggio Emilia, Italy, 7-9 October 1998. Program and Abstracts: 56.

  12. Takeno M, Shimayano Y, Suzuki N, Sakane T. Prolonged survival of autoprimed neutrophils from patients with Behçet 's disease.: 8th International Congress on Behçet's Disease. Reggio Emilia, Italy, 7-9 October 1998. Program and Abstracts: 57.

  13. Krause I, Yankevich A, Fraser A, Rosner I, Mader R, Zisman D, et al. Prevalence and clinical aspects of Behcet's disease in the north of Israel. Clin Rheumatol. Apr 2007;26(4):555-60. [Medline].

  14. Akman-Demir G, Serdaroglu P, Tasçi B. Clinical patterns of neurological involvement in Behçet's disease: evaluation of 200 patients. The Neuro-Behçet Study Group. Brain. Nov 1999;122 ( Pt 11):2171-82. [Medline].

  15. Alpsoy E, Zouboulis CC, Ehrlich GE. Mucocutaneous lesions of Behcet's disease. Yonsei Med J. Aug 31 2007;48(4):573-85. [Medline].

  16. Calamia KT, Schirmer M, Melikoglu M. Major vessel involvement in Behçet disease. Curr Opin Rheumatol. Jan 2005;17(1):1-8. [Medline].

  17. Kobayashi K, Ueno F, Bito S, et al. Development of consensus statements for the diagnosis and management of intestinal Behçet's disease using a modified Delphi approach. J Gastroenterol. Sep 2007;42(9):737-45. [Medline].

  18. Hemmen T, Perez-Canto A, Distler A, et al. IgA nephropathy in a patient with Behçet's syndrome--case report and review of literature. Br J Rheumatol. Jun 1997;36(6):696-9. [Medline].

  19. Hashimoto T, Toya Y, Kihara M, Yabana M, Inayama Y, Tanaka K, et al. Behçet's disease complicated by IgA nephropathy with nephrotic syndrome. Clin Exp Nephrol. Jun 2008;12(3):224-7. [Medline].

  20. [Best Evidence] Saadoun D, Wechsler B, Resche-Rigon M, Trad S, Le Thi Huong D, Sbai A, et al. Cerebral venous thrombosis in Behçet's disease. Arthritis Rheum. Apr 15 2009;61(4):518-26. [Medline].

  21. Kiraz S, Ertenli I, Oztürk MA, et al. Pathological haemostasis and "prothrombotic state" in Behçet's disease. Thromb Res. Jan 15 2002;105(2):125-33. [Medline].

  22. Aktulga E, Altac M, Muftüoglu A, et al. A double blind study of colchicine in Behçet's disease. Haematologica. Jun 1980;65(3):399-402. [Medline].

  23. Calis M, Ates F, Yazici C, Kose K, Kirnap M, Demir M, et al. Adenosine deaminase enzyme levels, their relation with disease activity, and the effect of colchicine on adenosine deaminase levels in patients with Behçet's disease. Rheumatol Int. Aug 2005;25(6):452-6. [Medline].

  24. Estrach C, Mpofu S, Moots RJ. Behçet's syndrome: response to infliximab after failure of etanercept. Rheumatology (Oxford). Oct 2002;41(10):1213-4. [Medline].

  25. Akman-Demir G, Baykan-Kurt B, Serdaroglu P, et al. Seven-year follow-up of neurologic involvement in Behcet syndrome. Arch Neurol. Jul 1996;53(7):691-4. [Medline].

  26. Akpolat T, Akkoyunlu M, Akpolat I, et al. Renal Behçet's disease: a cumulative analysis. Semin Arthritis Rheum. Apr 2002;31(5):317-37. [Medline].

  27. Al-Araji A, Sharquie K, Al-Rawi Z. Prevalence and patterns of neurological involvement in Behcet's disease: a prospective study from Iraq. J Neurol Neurosurg Psychiatry. May 2003;74(5):608-13. [Medline].

  28. al-Dalaan A, al-Balla S, al-Sukait M. The Prevalence of Behcet's Disease in Al Qassim Region of Saudi Arabia. Revue du Rhumatisme (English). 1996;63:539.

  29. al-Dalaan A, al-Sedairy S, al-Balaa S, et al. Enhanced interleukin 8 secretion in circulation of patients with Behçet's disease. J Rheumatol. May 1995;22(5):904-7. [Medline].

  30. Behcet H. Uber rezidiverendeaphthose durch ein virus verursachte Geschwure am Mund, am Auge, und an den Genitalien. Dermatol Wochenschr. 1937;105:1152-7.

  31. Benamour S, Zeroual B, Bettal S. Digestive manifestations of Behcet's disease based on a series of 74 cases. In: Godeau P, Wechsler B, eds. Behcet's Disease. New York, NY: Elsevier Science; 1993:255-60.

  32. Borhani Haghighi A, Pourmand R, Nikseresht AR. Neuro-Behçet disease. A review. Neurologist. Mar 2005;11(2):80-9. [Medline].

  33. Brama I, Fainaru M. Inner ear involvement in Behcet's disease. Arch Otolaryngol. Apr 1980;106(4):215-7. [Medline].

  34. Direskeneli H. Behcet's disease: infectious aetiology, new autoantigens, and HLA-B51. Ann Rheum Dis. Nov 2001;60(11):996-1002. [Medline].

  35. Goker B, Goker H. Current therapy for Behçet's disease. Am J Ther. Sep-Oct 2002;9(5):465-70. [Medline].

  36. Gul A. Standard and novel therapeutic approaches to Behçet's disease. Drugs. 2007;67(14):2013-22. [Medline].

  37. Hamuryudan V, Moral F, Yurdakul S, et al. Systemic interferon alpha 2b treatment in Behçet's syndrome. J Rheumatol. Jun 1994;21(6):1098-100. [Medline].

  38. Hamuryudan V, Ozyazgan Y, Hizli N, et al. Azathioprine in Behcet's syndrome: effects on long-term prognosis. Arthritis Rheum. Apr 1997;40(4):769-74. [Medline].

  39. Hamuryudan V, Yurdakul S, Kural AR, et al. Diffuse proliferative glomerulonephritis in Behçet's syndrome. Br J Rheumatol. Feb 1991;30(1):63-4. [Medline].

  40. Hazleman BL. Rheumatic disorders of the eye and the various structures involved. Br J Rheumatol. Mar 1996;35(3):258-68. [Medline].

  41. Houman MH, Hamzaoui K. Promising new therapies for Behcet's disease. Eur J Intern Med. May 2006;17(3):163-9. [Medline].

  42. Kaklamani VG, Vaiopoulos G, Kaklamanis PG. Behcet's Disease. Semin Arthritis Rheum. Feb 1998;27(4):197-217. [Medline].

  43. Kastner DL. Intermittent and Periodic Arthritic Syndromes: Behcet's Disease. In: Koopman WJ, ed. Arthritis and Allied Conditions. 13th ed. Baltimore, Md: Williams & Wilkins Co; 1997:1291-7.

  44. Kural-Seyahi E, Fresko I, Seyahi N, et al. The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore). Jan 2003;82(1):60-76. [Medline].

  45. Kötter I, Gunaydin I, Zierhut M, et al. The use of interferon alpha in Behçet disease: review of the literature. Semin Arthritis Rheum. Apr 2004;33(5):320-35. [Medline].

  46. Larsson H. Treatment of severe colitis in Behcet's syndrome with thalidomide (CG-217). J Intern Med. Oct 1990;228(4):405-7. [Medline].

  47. Marquardt JL, Snyderman R, Oppenheim JJ. Depression of lymphocyte transformation and exacerbation of Behcet's syndrome by ingestion of english walnuts. Cell Immunol. Nov 1973;9(2):263-72. [Medline].

  48. O'Duffy JD. Vasculitis in Behçet's disease. Rheum Dis Clin North Am. May 1990;16(2):423-31. [Medline].

  49. Ozyazgan Y, Yurdakul S, Yazici H, et al. Low dose cyclosporin A versus pulsed cyclophosphamide in Behcet's syndrome: a single masked trial. Br J Ophthalmol. Apr 1992;76(4):241-3. [Medline].

  50. Ronco P, Wechsler B, Saillant G, Godeau P. [Aseptic osteonecrosis during corticosteroid treatment of Behçet's disease (author's transl)]. Nouv Presse Med. May 9 1981;10(21):1707-10. [Medline].

  51. Rozenbaum M, Rosner I, Portnoy E. Remission of Behcet's syndrome with TNFalpha blocking treatment. Ann Rheum Dis. Mar 2002;61(3):283-4. [Medline].

  52. Schiff S, Moffatt R, Mandel WJ, et al. Acute myocardial infarction and recurrent ventricular arrhythmias in Behcet's syndrome. Am Heart J. Mar 1982;103(3):438-40. [Medline].

  53. Seaman G, Pearce RA. Disease Manifestation in a population drawn from the U.K. Behcet's Syndrome Society. Revue du Rhumatisme (English). 1996;63:539.

  54. Serdaroglu P, Yazici H, Ozdemir C, et al. Neurologic involvement in Behçet's syndrome. A prospective study. Arch Neurol. Mar 1989;46(3):265-9. [Medline].

  55. Sfikakis PP. Behcet's disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis. Nov 2002;61 Suppl 2:ii51-3. [Medline].

  56. Sfikakis PP, Markomichelakis N, Alpsoy E, et al. Anti-TNF therapy in the management of Behcet's disease--review and basis for recommendations. Rheumatology (Oxford). May 2007;46(5):736-41. [Medline].

  57. Shahram F, Davatchi F, Akbarian M. The 1996 Survey of Behcet's disease in Iran, study of 3153 cases. Revue du Rhumatisme (English). 1996;63:538.

  58. Shimizu T, Ehrlich GE, Inaba G, et al. Behçet disease (Behçet syndrome). Semin Arthritis Rheum. May 1979;8(4):223-60. [Medline].

  59. Stratigos AJ, Laskaris G, Stratigos JD. Behcet's disease. Semin Neurol. Dec 1992;12(4):346-57. [Medline].

  60. Suzuki N, Kaneko S, Ichino M, et al. In vivo mechanisms for the inhibition of T lymphocyte activation by long-term therapy with tacrolimus (FK-506): experience in patients with Behçet's disease. Arthritis Rheum. Jun 1997;40(6):1157-67. [Medline].

  61. Suzuki Y, Hoshi K, Matsuda T, et al. Increased peripheral blood gamma delta+ T cells and natural killer cells in Behçet's disease. J Rheumatol. Apr 1992;19(4):588-92. [Medline].

  62. Trent JT, Kerdel FA. Tumor necrosis factor alpha inhibitors for the treatment of dermatologic diseases. Dermatol Nurs. Apr 2005;17(2):97-107. [Medline].

  63. Turan B, Gallati H, Erdi H, et al. Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Bechcet's disease; soluble TNFR-75 as a biological marker of disease activity. J Rheumatol. Jan 1997;24(1):128-32. [Medline].

  64. van Laar JA, Missotten T, van Daele PL, et al. Adalimumab: a new modality for Behçet's disease?. Ann Rheum Dis. Apr 2007;66(4):565-6. [Medline].

  65. Yazici H, Pazarli H, Barnes CG, et al. A controlled trial of azathioprine in Behcet's syndrome. N Engl J Med. Feb 1 1990;322(5):281-5. [Medline].

  66. Yazici H, Tuzun Y, Pazarli H, et al. Influence of age of onset and patient's sex on the prevalence and severity of manifestations of Behcet's syndrome. Ann Rheum Dis. Dec 1984;43(6):783-9. [Medline].

  67. Yurdakul S, Hamuryudan V, Yazici H. Behcet syndrome. Curr Opin Rheumatol. Jan 2004;16(1):38-42. [Medline].

  68. Zouboulis CC, Diawari D, Kirch W. Adamantiades-Behcet's disease in Germany: Data of the German registry in 1996. Revue du Rhumatisme (English). 1996;63:538.

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Further Reading

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Keywords

Behçet disease, Behcet disease, Behçet syndrome, Behcet syndrome, Behçet's disease, Adamantiades-Behçet disease, BD, inflammatory arthritis, sacroiliitis, ulcerative lesions, aphthous ulcers, oral ulcers, oral lesions, skin lesions, genital ulcers, phlebitis, uveitis, iritis, hypopyon, retinal vasculitis, erythema nodosum, pseudofolliculitis, papulopustular lesions, pathergy, vasculopathy, superficial thrombophlebitis, deep venous thrombophlebitis, Budd-Chiari syndrome, mouth and genital ulcers with inflamed cartilage, MAGIC, autoimmune disease

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Contributor Information and Disclosures

Author

Augusto C Posadas, MD, Fellow, Department of Medicine, Section of Rheumatology, University of Arizona School of Medicine
Disclosure: Nothing to disclose.

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: Nothing to disclose.

Medical Editor

Kristine M Lohr, MD, MS, Program Director, Professor, Department of Internal Medicine, Division of Rheumatology and Women's Health, University of Kentucky School of Medicine
Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and American Medical Women's Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Lawrence H Brent, MD, Associate Professor of Medicine, 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 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; Wyeth Honoraria Speaking and teaching; Abbott Immunology Honoraria Speaking and teaching

CME Editor

Alex J Mechaber, MD, FACP, 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, Professor of Medicine, Temple University 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: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

 
 
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