Behçet’s syndrome, described by the Turkish dermatologist Hulûsi Behçet, was classically described as a triad of symptoms including recurring oral ulcers, recurring genital ulcers, and eye lesions. The concept of the disease has changed from a triad of signs and symptoms to a multisystem disorder.
The highest incidence of Behçet’s syndrome has been reported in eastern Asia, where 1 in 10,000 is affected, and the eastern Mediterranean, where it is a leading cause of blindness in young men; however, cases have been reported worldwide, including in North America, where it is estimated that 1 in 500,000 persons is affected. The highest incidence of Behçet’s syndrome is in young adults, but cases of Behçet’s syndrome in children are being reported with increasing frequency.
ETIOLOGY
Behçet’s syndrome is caused by immunocomplexes that lead to vasculitis of small and medium-sized blood vessels and inflammation of epithelium caused by immunocompetent T lymphocytes and plasma cells.Increased neutrophil activity has also been noted.There is a genetic component to the disease, with a strong association with HLA-B51. Studies of the immune abnormalities associated with Behçet’s syndrome have included findings described above for patients with RAS. This has led some investigators to believe that Behçet’s syndrome and RAS are both manifestations of a similar disorder of the immune response.
CLINICAL MANIFESTATIONS
The most common single site of involvement of Behçet’s syndrome is the oral mucosa. Recurring oral ulcers appear in over 90% of patients; these lesions cannot be distinguished from RAS (Figure 4-24). Some patients experience mild recurring oral lesions; others have the deep large scarring lesions characteristic of major RAS. These lesions may appear anywhere on the oral or pharyngeal mucosa. The genital area is the second most common site of involvement and involves ulcers of the scrotum and penis in males and ulcers of the labia in females. The eye lesions consist of uveitis, retinal infiltrates, edema and vascular occlusion, optic atrophy, conjunctivitis, and keratitis.
Generalized involvement occurs in over half of patients with Behçet’s syndrome. Skin lesions are common and usually manifest as large pustular lesions. These lesions may be precipitated by trauma, and it is common for patients with Behçet’s syndrome to have a cutaneous hyper-reactivity to intracuta
neous injection or a needlestick (pathergy). Positive pathergy is defined as an inflammatory reaction forming within 24 hours of a needle puncture, scratch, or saline injection.
Arthritis occurs in greater than 50% of patients and most frequently affects the knees and ankles.The affected joint may be red and swollen as in rheumatoid arthritis, but involvement of small joints of the hand does not occur, and permanent disability does not result.
In some patients, central nervous system involvement is the most distressing component of the disease. This may include brainstem syndrome, involvement of the cranial nerves, or neurologic degeneration resembling multiple sclerosis that can be visualized by magnetic resonance imaging of the brain. Other reported signs of Behçet’s syndrome include thrombophlebitis, intestinal ulceration, venous thrombosis, and renal and pulmonary disease. Involvement of large vessels is life threatening because of the risk of arterial occlusion or aneurysms.
Behçet’s syndrome in children, which most frequently presents between the ages of 9 and 10 years, has similar manifestations as does the adult form of the disease, but oral ulcers are a more common presenting sign in children, and uveitis is less common.
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Oral lesions are the presenting symptom in over 95% of children with Behçet’s syndrome. A variant of Behçet’s syndrome, MAGIC syndrome, has been described. It is characterized by Mouth And Genital ulcers with Inflammed Cartilage.
DIAGNOSISBecause the signs and symptoms of Behçet’s syndrome overlap with those of several other diseases, particularly the connective-tissue diseases, it has been difficult to develop criteria that meet with universal agreement. Five different sets of diagnostic criteria have been in use during the past 20 years. In 1990, an international study group reviewed data from 914 patients from seven countries.A new set of diagnostic criteria was developed that includes recurrent oral ulceration occurring at least three times in one 12-month period plus two of the following four manifestations:
1. Recurrent genital ulceration 2. Eye lesions including uveitis or retinal vasculitis 3. Skin lesions including erythema nodosum, pseudofol-
liculitis, papulopustular lesions, or acneiform nodules in postadolescent patients not receiving corticosteroids
4. A positive pathergy test
TREATMENT
The management of Behçet’s syndrome depends on the severity and the sites of involvement. Patients with sight-threatening eye involvement or central nervous system lesions require more aggressive therapy with drugs with a higher potential for serious side effects.Azathioprine combined with prednisone has been shown to reduce ocular disease as well as oral and genital involvement.Pentoxifylline, which has fewer side effects than do immunosuppressive drugs or systemic steroids, has also been reported to be effective in decreasing disease activity, particularly eye involvement.Cyclosporine or colchicine in combination with corticosteroids has also been shown to be useful in severe disease.Colchicine and thalidomidehave been shown to be useful in mucocutaneous and gastrointestinal manifestations. Systemic corticosteroids remain a mainstay of treatment and are particularly useful in rapidly controlling the disease until immunosuppressive agents begin to work. Plasmapheresis has also been used successfully in emergencies.
Oral mucosal lesions not adequately controlled by systemic therapy may be treated with topical or intralesional steroids in regimens described in the section on RAS.
Arthritis occurs in greater than 50% of patients and most frequently affects the knees and ankles.The affected joint may be red and swollen as in rheumatoid arthritis, but involvement of small joints of the hand does not occur, and permanent disability does not result.
In some patients, central nervous system involvement is the most distressing component of the disease. This may include brainstem syndrome, involvement of the cranial nerves, or neurologic degeneration resembling multiple sclerosis that can be visualized by magnetic resonance imaging of the brain. Other reported signs of Behçet’s syndrome include thrombophlebitis, intestinal ulceration, venous thrombosis, and renal and pulmonary disease. Involvement of large vessels is life threatening because of the risk of arterial occlusion or aneurysms.
Behçet’s syndrome in children, which most frequently presents between the ages of 9 and 10 years, has similar manifestations as does the adult form of the disease, but oral ulcers are a more common presenting sign in children, and uveitis is less common.
116
Oral lesions are the presenting symptom in over 95% of children with Behçet’s syndrome. A variant of Behçet’s syndrome, MAGIC syndrome, has been described. It is characterized by Mouth And Genital ulcers with Inflammed Cartilage.
DIAGNOSISBecause the signs and symptoms of Behçet’s syndrome overlap with those of several other diseases, particularly the connective-tissue diseases, it has been difficult to develop criteria that meet with universal agreement. Five different sets of diagnostic criteria have been in use during the past 20 years. In 1990, an international study group reviewed data from 914 patients from seven countries.A new set of diagnostic criteria was developed that includes recurrent oral ulceration occurring at least three times in one 12-month period plus two of the following four manifestations:
1. Recurrent genital ulceration 2. Eye lesions including uveitis or retinal vasculitis 3. Skin lesions including erythema nodosum, pseudofol-
liculitis, papulopustular lesions, or acneiform nodules in postadolescent patients not receiving corticosteroids
4. A positive pathergy test
TREATMENT
The management of Behçet’s syndrome depends on the severity and the sites of involvement. Patients with sight-threatening eye involvement or central nervous system lesions require more aggressive therapy with drugs with a higher potential for serious side effects.Azathioprine combined with prednisone has been shown to reduce ocular disease as well as oral and genital involvement.Pentoxifylline, which has fewer side effects than do immunosuppressive drugs or systemic steroids, has also been reported to be effective in decreasing disease activity, particularly eye involvement.Cyclosporine or colchicine in combination with corticosteroids has also been shown to be useful in severe disease.Colchicine and thalidomidehave been shown to be useful in mucocutaneous and gastrointestinal manifestations. Systemic corticosteroids remain a mainstay of treatment and are particularly useful in rapidly controlling the disease until immunosuppressive agents begin to work. Plasmapheresis has also been used successfully in emergencies.
Oral mucosal lesions not adequately controlled by systemic therapy may be treated with topical or intralesional steroids in regimens described in the section on RAS.