AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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}

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

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 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.
  • 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.²⁰

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Malignancy
HLA-B27–associated syndromes (ankylosing spondylitis, reactive arthritis, psoriatic arthritis)
HIV/AIDS
Hypercoagulable states (eg, protein C and S deficiency, factor V Leiden, hyperhomocysteinemia, prothrombin deficiency)
Alternate causes of uveitis
Viral and bacterial infections (eg, HSV infection, chancroid)

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory findings
• • Laboratory findings are nonspecific and reflect the inflammatory state.
  • C-reactive protein levels, erythrocyte sedimentation rate (ESR), leukocyte count, complement components, and acute-phase reactants may all be elevated during an acute attack.
  • Levels of IgA, IgG, alpha-2 globulin, IgM, and immune complexes are occasionally elevated.
  • None of these findings is specific for the diagnosis of Behçet disease, but such findings can corroborate active disease.
• Antiphospholipid antibodies: These include lupus anticoagulant, dilute Russell viper venom test (DRVVT), and anticardiolipin antibodies. Although uncommon in Behçet disease, they are worth pursuing to rule out alternate causes of thrombosis.
• Up to one third of patients with Behçet disease who have thrombosis are found to have factor V Leiden–deficiency mutations. Therefore, this, APL antibody, and other causes of hypercoagulability should be ruled out as contributing factors to thrombosis formation.
• Antineutrophil cytoplasmic antibody: Occasionally, patients are found with positive test results for perinuclear antineutrophil cytoplasmic (p-ANCA) antibody, although positive or negative results on this test do not change prognosis or therapy.
• Synovial fluid: Synovial fluid usually is cloudy with variable viscosity, and the WBC counts are 300-36,000/µL (either noninflammatory or inflammatory). Polymorphonuclear leukocytes and protein elevations are the predominant findings, and glucose levels are near normal. Thus, because synovial fluid merely demonstrates general inflammation, examination serves only to rule out the presence of aseptic joint, crystal-induced arthropathy, or other alternate identifiable cause in patients with Behçet disease.
• Cerebrospinal fluid: These findings may show local inflammation with increased WBC counts, lymphocyte predominance, and elevated protein levels, as well as Ig levels and Ig index that reflect local production of Ig. Opening pressures are very high in some patients.

Imaging Studies

• Radiography, MRI, and CT scanning: Sacroiliitis may be observed on a radiograph, MRI, or CT scan.
• Brain CT scanning: Acute areas of ischemia can be identified.
• Brain MRI/magnetic resonance angiography (MRI/MRA): Cerebral vasculopathy and acute/subacute areas of ischemia can be identified.
• Single-photon emission computed tomography (SPECT): This has been used to identify areas of cerebral hypoperfusion in Italian, Spanish, and Turkish studies among pediatric, adolescent, and adult populations.
• Angiography: This test may be used to evaluate for aneurysms.

Other Tests

• Pathergy test: Minor skin trauma induces an inflammatory papule or pustule within 24-48 hours.

Procedures

• As with laboratory studies, samples obtained via arthrocentesis and lumbar puncture are used primarily to rule out alternate causes of disease presentation, as they normally demonstrate nonspecific inflammatory findings.
• Similarly, skin biopsy results often reflect nondiagnostic findings but can be used to differentiate alternate disease entities.

Histologic Findings

Although no specific histologic findings characterize Behçet disease, biopsy samples of affected tissue often reveal leukocytoclastic vasculitis and perivascular infiltration. CNS lesions may demonstrate meningeal and cerebral inflammation, cerebral atrophy, and encephalomalacia. Thrombosis commonly develops in affected areas and must be distinguished from vasculitis as a precipitating cause for organ-specific symptoms. Other organ-system findings include the following:

• Skin - Erythema nodosum lesions with characteristic findings and occasional granulomas; folliculitis; leukocytoclastic vasculitis; dermal inflammation and perivascular infiltrates; fibrosis; and mucosal lesions, including aggregated intravascular conglomerates of neutrophils, endothelial cell swelling, fibrinoid necrosis, and a mixed perivascular infiltrate (Pathergy test reveals mononuclear cell infiltrates and keratinocytes.)
• Eye - Cataracts, posterior and anterior uveitis, retinal vasculitis and thrombosis, cytoid macular degeneration, retinal detachment, and lymphocytic infiltrates in the iris (even during clinical remissions)
• Brain - Infarctions due to vasculitis or thrombosis, meningoencephalitis, lymphocytic meningeal infiltration, or demyelinization
• Joint - Superficial inflammatory synovial infiltrates, mainly polymorphonuclear lymphocytes, and deposition of IgG in the synovium
• GI tract - Ulcerations from the buccal mucosa to the anus, intestinal perforation, peritonitis, infiltration with polymorphonuclear leukocytes and lymphocytes, hepatitis, cholecystitis, and pancreatitis
• Heart - Pericarditis, myocarditis, endocarditis, coronary arteritis, and myocardial fibrosis
• Lung - Serositis and vasculitis
• Kidneys - Glomerulonephritis

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Oral ulcerations can be successfully treated with topical steroids or sucralfate solution. Colchicine has also been used to prevent mucocutaneous relapse.^{21, 22}
• For severe mucocutaneous lesions, systemic corticosteroids, azathioprine, pentoxifylline, dapsone, interferon-alpha, colchicine, and thalidomide have demonstrated benefit.
• For genital ulceration, topical and intralesional steroids can be used. Topical sucralfate also has demonstrated benefit.
• GI lesions are primarily treated with 5-ASA derivatives, including sulfasalazine or mesalamine. However, upon lack of response, systemic corticosteroids can be used with eventual taper as dictated by decreasing C-reactive protein values on surveillance. Upon development of steroid dependence, azathioprine can be used adjunctively in an attempt to decrease the need for glucocorticoids.
• Pulmonary arterial aneurysms are treated with cyclophosphamide.
• Joint involvement may respond to prednisone, local corticosteroid injections, and nonsteroidal anti-inflammatory drugs (NSAIDs). Colchicine, sulfasalazine, and interferon-alpha are also used. Levamisole and azathioprine serve as alternative modes of therapy.
• Multiple modes of therapy have been studied for ocular symptoms, and a good response has been demonstrated with interferon therapy. TNF-inhibitor therapy with infliximab (Remicade) and etanercept (Enbrel) has also demonstrated favorable response in treating rapidly progressive anterior and posterior uveitis. Cyclosporine has been well supported in the literature as an effective therapeutic measure.
• Erythema nodosum is a special circumstance and may be treated with colchicine or dapsone.
• CNS disease is usually treated with systemic corticosteroids, chlorambucil, or cyclophosphamide.
• Thrombotic events are treated with systemic anticoagulation.
• TNF-inhibitor therapy with infliximab and etanercept has also demonstrated varying degrees of success in treating cases of severe GI and CNS manifestations of Behçet disease and has been shown to have the added benefit of improving mucocutaneous manifestations and polyarthritis.²³

Surgical Care

• GI presentations that require surgical intervention include intestinal stenosis, lesions unresponsive to medical therapy, fistula formation, perforation, and severe bleeding.
• Pulmonary aneurysms and areas that incur ischemic damage due to vasculitis or thrombosis may require resection.
• Ventricular aneurysms, coronary thrombosis, and endocardial fibrosis are occasionally amenable to surgery.
• Glaucoma, cataracts, and retinal detachment occasionally warrant surgical intervention.
• Neurosurgery may be required to correct some CNS aneurysms and clots.

Consultations

• Rheumatologist
• Specialist consultations as needed (for specific organ involvement)
• • Urologist for genital and urologic lesions
  • Neurologist for CNS involvement
  • Ophthalmologist for ocular disease
  • Gastroenterologist for intestinal disease
  • Dermatologist for possible help with recurrent skin lesions
  • Surgeon, when indicated
  • Nephrologist for proteinuria or hematuria
  • Pulmonologist or cardiologist in rare cases of intracardiac or pulmonary thrombosis and aneurysms

Diet

• No general dietary recommendations exist.
• Patients with severe bowel involvement are advised to follow GI recommendations given to patients with inflammatory bowel disease, often requiring total parenteral nutrition.

Activity

Activity is suggested as tolerated and may be limited owing to systemic symptoms or arthritis.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

The drugs used to treat Behçet disease are generally immunosuppressive. Because the cause of Behçet disease is unknown, therapy is directed at diminishing symptoms by suppressing the immune system. These medications may increase the risk of infection due to the nonspecific nature of immunosuppression. Symptomatic therapy is directed at specific symptoms (eg, oral ulcers, arthritis).

Drug Category: Corticosteroids

These agents may be used orally or parenterally for systemic symptoms, topically for ulcers or ocular involvement, or intra-articularly for arthritis.

Drug Category: Immunosuppressive agents

These agents decrease the immune response that causes signs and symptoms of Behçet disease.

Drug Category: Immunomodulators

These agents affect the immune system in various ways, thus decreasing the autoimmune symptoms characteristic of Behçet disease. Immunomodulators do not, however, cause the generalized immunosuppression characteristic of immunosuppressive drugs.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Inpatient care is based on individual organ-system involvement.
• In general, no further care is needed.

Further Outpatient Care

• As disease activity subsides, taper medications to the lowest dose that effectively controls the symptoms and disease activity.

In/Out Patient Meds

• Inpatient and outpatient medication are the same (see Medication). All agents discussed above have been found to be effective in controlling the manifestations of Behçet disease.

Transfer

• Individualize the transfer situation for each patient based on the specifics of organ-system involvement.

Deterrence/Prevention

• Continual use of immunosuppressive medications may be required to suppress disease. Use the lowest dose required to control the manifestations of illness.

Complications

• Aneurysms are especially feared.
• Thrombotic events and vasculitis may lead to ischemia distal to vascular lesions.
• Uncontrolled ophthalmologic involvement in the form of anterior and posterior uveitis can lead to vision loss.
• Neurologic involvement suggests progressive disease and can lead to permanent deficits or even death.

Prognosis

• Prognosis is related to the site and severity of involvement.

Patient Education

• For excellent patient education resources, visit eMedicine Arthritis Center, Eye and Vision Center, and Teeth and Mouth Center. Also, see eMedicine patient education articles Canker Sores, Inflammatory Bowel Disease, and Iritis.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Adverse effects of medication
• Risk of misdiagnosis or failure to ascertain the extent of organ involvement

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Oral aphthous ulcers secondary to Behçet disease.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• 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. Ca