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Behçet disease is a multisystem, relapsing, chronic vasculitic disorder with mucosal inflammation. Common manifestations include recurrent oral ulcers, ocular inflammation, genital ulcers, and skin lesions. The most serious manifestations are blindness, neurologic or GI manifestations, venous thromboses, and arterial aneurysms. Diagnosis is clinical, using international criteria. Treatment is mainly symptomatic but may involve corticosteroids with or without other immunosuppressants for more severe manifestations.
Behçet disease can include a vasculitis of small and large arteries and/or veins. Arterial and venous thrombosis may occur as well.
The disease occurs nearly equally in men and women but tends to be more severe in men, typically beginning during their 20s. Occasionally, the disease develops in children. Incidence varies by location. Behçet disease is most common along the silk route from the Mediterranean to China; it is uncommon in the US.
The cause is unknown. Immunologic (including autoimmune) and viral or bacterial triggers have been suggested, and HLA-B51 is associated with cases from Turkey, Iran, China, Korea, and Japan.
Neutrophil infiltration is detected in biopsy specimens from oral aphthous ulcers and erythema nodosum and pathergy lesions, but no histologic changes are pathognomonic.
Almost all patients have recurrent, painful oral ulcers resembling those of aphthous stomatitis; in most, these ulcers are the first manifestations. The ulcers are round or oval, 2 to 10 mm in diameter, and shallow or deep with a central yellowish necrotic center; they can occur anywhere in the oral cavity, often in clusters. Ulcers last 1 to 2 wk. Similar ulcers occur on the penis and scrotum, on the vulva where they are painful, or in the vagina where they may cause little or no pain.
Cutaneous lesions are common and may include acneiform lesions, nodules, erythema nodosum, superficial thrombophlebitis, pyoderma gangrenosum–type lesions, and palpable purpura.
Pathergy (an erythematous papular or pustular response to local skin injury) is defined as a papule > 2 mm that appears 24 to 48 h after oblique insertion of a 20- to 25-gauge needle into the skin. Pathergy has been noted less often in North American and northern European patients than in Middle Eastern and Asian patients.
The eyes are affected in 25 to 75% of patients. Eye manifestations may be associated with neurologic manifestations. The following may occur:
Relapsing uveitis or iridocyclitis (most common) often manifests as pain, photophobia, and red eye.
Hypopyon (a layer of pus visible in the anterior chamber) may occur.
Uveitis is typically bilateral and episodic, often involves the entire uveal tract (panuveitis), and may not resolve completely between episodes.
Choroiditis, retinal vasculitis, vascular occlusion, and optic neuritis may irreversibly impair vision and even progress to blindness.
Perivascular and endovascular inflammation may develop in arteries and veins. In arteries, thrombosis, aneurysm, pseudoaneurysm, hemorrhage, and stenosis can develop. Large-vessel arterial involvement is recognized during life in 3 to 5% of patients; however, at autopsy, one third of patients have evidence of large-vessel involvement that was asymptomatic during life. Aortic and pulmonary artery aneurysms can rupture. In situ thrombosis can cause pulmonary artery occlusion. Hemoptysis may occur if fistulas develop between the pulmonary artery and bronchus.
Venous involvement can cause superficial and deep venous thromboses. More than one vein may be affected, including the inferior and superior vena cava, the hepatic veins (causing Budd-Chiari syndrome), and the dural venous sinuses.
In situ arterial or venous thromboses, aneurysms, and pseudoaneurysms are more common than stenoses and occlusions.
CNS involvement is less common but is serious. Onset may be sudden or gradual. The first manifestations may be parenchymal involvement with pyramidal signs, small-vessel disease with a multiple sclerosis–like pattern, or nonparenchymal with aseptic meningitis or meningoencephalitis, or dural sinus thrombosis.
Psychiatric disorders including personality changes and dementia may develop years later. Peripheral neuropathy, common in other vasculitic disorders, is uncommon in Behçet disease.
Behçet disease should be suspected in young adults with recurrent oral aphthous ulcers, unexplained ocular findings, or genital ulcers. Diagnosis is clinical and often delayed because many of the manifestations are nonspecific and can be insidious.
International criteria for diagnosis include recurrent oral ulcers (3 times in 1 yr) and 2 of the following:
Laboratory tests (eg, CBC, ESR or C-reactive protein, serum albumin and total protein levels) are done. Results are nonspecific but characteristic of inflammatory disease (elevated ESR, C-reactive protein, and α 2 - and γ-globulins; mild leukocytosis).
Differential diagnosis includes reactive arthritis, SLE, Crohn disease, ulcerative colitis, ankylosing spondylitis, periodic fever syndromes, and herpes simplex infection. Behçet disease has no single pathognomonic finding but may be distinguished by its combinations of relapsing symptoms with spontaneous remissions and multiple organ involvement, particularly in patients with recurrent, deep mucosal ulcers.
Behçet disease typically has a waxing and waning course characterized by exacerbations and remissions. Mucocutaneous and ocular lesions and arthralgias are often worse early in the disease. CNS and large-vessel manifestations, if they develop, typically occur later. Occasionally, the disease results in death, usually due to neurologic, vascular (eg, aneurysms), or GI manifestations. Risk of death is highest for men and patients with arterial disease or a high number of flare-ups. Many patients eventually go into remission.
Treatment depends on the clinical manifestations. Treatment recommendations are limited by incomplete data from clinical studies (eg, cross-sectional studies, usually not prospective, limited statistical power).
Mucosal disease can be managed symptomatically. Topical corticosteroids, local anesthetics, and sucralfate are helpful. Colchicine 0.6 mg po bid may decrease the frequency and severity of oral or genital ulcers and may be effective for erythema nodosum and arthralgias. Thalidomide 100 to 300 mg po once/day may be used to treat oral, genital, and skin lesions, but lesions may recur when treatment is stopped. The anti-TNF drug etanercept, 50 mg sc once/wk or 25 mg sc twice/wk, may suppress mucocutaneous lesions. Etanercept can be given if colchicine is ineffective. Sometimes another anti-TNF drug (infliximab or possibly adalimumab) is used instead of etanercept. Interferon alfa-2a 6 million units 3 times/wk can also be given if colchicine is ineffective.
Azathioprine 2.5 mg/kg po once/day helps preserve visual acuity and prevent new eye lesions. Azathioprine is also useful for mucocutaneous lesions and arthralgia. Cyclosporine 5 to 10 mg/kg po once/day may be reserved for patients with severe ocular manifestations and may be used with azathioprine to treat refractory uveitis. Interferon alfa-2a 6 million units sc 3 times/wk and infliximab (a tumor necrosis factor inhibitor) 3 to 10 mg/kg IV at 0, 2, 4, and then every 8 wk show promise for patients with ocular manifestations.
Cyclophosphamide and chlorambucil are used in patients with refractory disease, life-threatening conditions (eg, pulmonary aneurysms), or CNS manifestations.
Topical corticosteroids may temporarily relieve ocular manifestations and most oral lesions. However, topical or systemic corticosteroids do not alter the frequency of relapses. A few patients with severe uveitis or CNS manifestations respond to high-dose systemic corticosteroids (eg, prednisone 60 to 80 mg po once/day).
Anti-TNF drugs appear to be effective for a wide range of manifestations, including severe ocular disease, in combination with another drug such as azathioprine.
Immunosuppressants help prevent recurrence of venous thrombosis, but it is unclear whether anticoagulation does. Anticoagulation is contraindicated in patients with pulmonary arterial aneurysms.
Behçet disease is a relapsing vasculitis characterized by prominent mucosal inflammation.
Among the many organ systems involved, oral and genital ulcers, skin lesions, and ocular findings, particularly in combination, are very characteristic.
Diagnose based on specific clinical criteria.
Risk factors for early death are male sex, frequent disease flare-ups, and arterial complications (eg, thrombosis, aneurysms, pseudoaneurysms).
Treat with cyclophosphamide and chlorambucil (for life-threatening disease), azathioprine or cyclosporine (for eye disease), and colchicine, thalidomide, or an anti-TNF drug (for mucosal disease).
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