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Behçet's syndrome
is a multisystem, relapsing, chronic vasculitic disorder with prominent 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 for acute severe ocular or neurologic manifestations
or immunosuppressants for severe chronic lesions.
Behçet's syndrome involves small and large arteries and veins. Arterial thrombosis and superficial and deep venous thrombosis often occur.
The syndrome occurs nearly equally in men and women, typically beginning during their 20s. Occasionally, the syndrome develops in children. Incidence varies by location. Behçet's syndrome 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.
Symptoms and Signs
Mucocutaneous:
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 occurred in many parts of the world but is less common among North American and northern European patients than among Middle Eastern and Asian patients.
Ocular:
The eyes are affected in 25 to 75% of patients. The following may occur:
Musculoskeletal:
Relatively mild, self-limiting, and nondestructive arthralgias or frank arthritis, especially in the knees and other large joints, occur in 50% of patients. Sacroiliac inflammation can occur.
Vascular:
Superficial and deep venous thromboses are common. Large vessels are affected in about 1/3 of patients. Perivascular and endovascular inflammation may lead to hemorrhage, stenosis, aneurysms, and thrombosis in arteries and veins. Superior and inferior vena cava occlusion, Budd-Chiari syndrome, and other venous obstructive lesions can also occur.
Disease of the aorta and large blood vessels may be life threatening. Hemoptysis may occur if fistulas between the pulmonary artery and bronchus develop.
Neurologic and
psychiatric:
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, 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's syndrome.
GI:
Abdominal discomfort, abdominal pain, and diarrhea with intestinal ulcers, occurring primarily in the ileum and colon and closely resembling Crohn's disease, may occur.
Diagnosis
Behçet's syndrome should be suspected in young adults with recurrent oral aphthous ulcers, unexplained ocular findings, or genital ulcers. Diagnosis is clinical and may require months 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 α2- and γ- globulins; mild leukocytosis).
Differential diagnosis includes reactive arthritis, SLE, Crohn's disease, ulcerative colitis, ankylosing spondylitis, and herpes simplex infection. Behçet's syndrome 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.
Prognosis
Behçet's syndrome 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 syndrome results in death, usually due to neurologic, vascular (eg, aneurysms), or GI manifestations. Many patients eventually go into remission.
Treatment
Treatment depends on the clinical manifestations.
Mucosal disease can be managed symptomatically. 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. Etanercept 50 mg sc once/wk or 25 mg sc twice/wk may suppress mucocutaneous lesions. Etanercept can be given in colchicine is ineffective. Interferon-α2a 6 million units 3 times/wk can also be given if colchicine is ineffective.
Azathioprine 2.5 mg/kg 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 once/day may be reserved for patients with severe ocular manifestations and may be used with azathioprine to treat refractory uveitis. Interferon-α2a 6 million units 3 times/wk and infliximab (a tumor necrosis factor inhibitor) 3 to 10 mg/kg 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.
The efficacy of corticosteroids is unsubstantiated, despite their wide use. 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).
Whether immunosuppressants should be added to anticoagulation therapy when patients have thromboses has not been established.
Last full review/revision May 2008 by Carmen E. Gota, MD
Content last modified May 2008
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