Behçet’s is a complex multisystem disease of unknown cause. It was first described in 1937 by a dermatology professor named Hulusi Behçet in Istanbul.
The disease, which starts between the ages of 20 and 40, is seen with equal frequency in both sexes. However, it is more severe in young people and men. While it is common in Mediterranean countries, Japan and southern Asia, it is less common in northern Europe and America. Its frequency in our country varies between 8-37/10.000 on average.
Etiopathogenesis:
Many factors have been suggested for its cause. One of them is genetic factors. Although the association of HLA -B5, HLA-B51 is common especially in patients in Mediterranean countries and Japan, no fixed inheritance pattern has been found.
It has been suggested in some studies that Behçet’s disease is triggered especially by herpes simplex virus and streptococcal infections. It is thought here that the infection may initiate the disease in genetically predisposed individuals by triggering a defect in immunoregulation.
There is a lot of evidence that immune mechanisms play a role in the pathogenesis of the disease. These include the detection of autoantibodies against the oral mucosa, the presence of immune complexes and lymphocytotoxins circulating in the blood, a decrease in the CD4/CD8 ratio and the number of Natural killer cells during attacks. In addition, an increase in the level of soluble IL-2 receptors was detected in the blood.
Light, immunofluorescent and electron microscopic examinations of the early stages of mucocutaneous lesions reveal a neutrophilic vascular reaction or leukocytoclastic vasculitis findings.
The fact that the disease progresses more severely in men and young people, is less common in children and the elderly, and acne vulgaris-like acneiform lesions are observed, suggesting the role of major sex hormones. Although no change was detected in hormone levels, it has been suggested that there may be a change in end organ responses.
Clinical Findings:
Oral aphthae———————————–97-100%
Genital aphthae————————-80-90%
Skin lesions———————–80%
Eye lesions———————–50%
Arthritis————————————-40-50%
Thrombophlebitis————————-25%
Neurological involvement———————1%-15%
Gastrointestinal involvement———–0-25%
1) Oral aphthae: Oral aphthae that recurs at least 3 times a year are often the first sign of the disease. In general, although not different from recurrent aphthous stomatitis, they can be distinguished by their more frequent recurrences and greater numbers. They can be major, minor and herpetiform. The major ones are ulcerations larger than 0.5 cm in diameter, which heal after 15 days and leave scars. Minor ulcerations less than 0.5 cm in diameter are the most common form and heal in less than 15 days. Rarely seen herpetiform aphthae are lesions of a few mm in diameter, sometimes merging with each other and causing exulcerations.
2) Genital ulcerations: They are less in number and heal later than oral aphthae. In men, it most commonly occurs in the scrotum, then the corpus penis and glans penis. After the formation of the papule, pustules and then sharply circumscribed ulcerations with a typical appearance as if perforated with a punch are formed. They leave scars. In women, it is mostly observed in the labia, then in other genital areas and rarely in the cervix.
3) Skin lesions:It can be studied in three classes:
a ) Nodular lesions: Erythema nodosum is a common finding, especially in female patients. Superficial migratory thrombophlebitis is common in men.
b) Papulopustular lesions: They are folliculitis-like papulopustular lesions mostly observed on the neck, face, trunk and extremities. A neutrophilic vascular reaction is observed in the early stages of the lesions.
c) Vasculitic lesions:Palpable purpura, pyoderma gangrenosum or Sweets syndrome-like lesions may be observed in the course of the disease.
4) Eye findings: It is the most morbid findings in patients with Behçet’s disease. The most common findings are posterior uveitis, anterior uveitis and retinal vasculitis. Uveitis with hypopyon, which was common in the past, is now rare. Eye signs are severe in men and young people and show a severe course that can go up to 20% blindness.
5) Joint findings: The characteristic finding is nonerosive, asymmetrical oligoarthritis. Pain, swelling and limitation of movement are observed in the joints. The most commonly involved joints are the knee, ankle, wrist, and elbow. Involvement of the sacroiliac joint, spine, hip and shoulder is very rare.
6) Neurological findings; headache, cerebellar, pyramidal findings can be observed. Intracranial pressure findings, meningeal irritation findings may occur. Magnetic resonance examination should be done. Although it is rare, its mortality and morbidity is high.
7) Gastrointestinal findings: It is more common in Japan. It may present with abdominal pain, nausea, vomiting, loss of appetite, and bloody diarrhea. There may be aphthous ulcerations in the gastrointestinal tract.
8) Vascular involvement: Especially vein involvement is common. Venous occlusions, superficial migratory thrombophlebitis lesions may be seen. Pulmonary and popliteal artery aneurysms are arterial findings. Hemoptysis can be observed as a result of pulmonary lesions and can be fatal.
Apart from these, cardiac involvement; includes myocarditis, coronary arteritis, endocarditis and valvular diseases. Renal disease may be mild or asymptomatic, but immunoreactive deposits have been found in the glomeruli in most patients with active Behçet’s disease.
Lab findings: It is not specific. It may be related to system involvements.
Pathergy test (nonspecific hyperreactivity of the skin): It is applied by intradermal insertion of a sterile needle into the skin of the forearm. In positive cases, a reaction that starts after 24 hours and reaches a maximum after 48 hours is expected. First, a 1-2 mm papule forms with an erythematous halo around it, which can later turn into a pustule. Although the test is more severe in men, there is no relationship between its positivity and the severity of the disease. In his histopathological examination, mononuclear cell infiltration is followed by infiltration of mast cells and polymorphonuclear cells.
Diagnosis: Since there is no definitive and distinctive laboratory finding used for the diagnosis of Behçet’s disease, clinical evaluation gains importance in the diagnosis. Therefore, many criteria have been proposed and used for diagnosis. Among these, the O’Duffy criteria are the most widely accepted. Accordingly, in order for a person to be called Behçet’s, he or she must have at least two of the following findings, apart from oral aphthae: genital aphthae, synovitis, posterior uveitis, cutaneous pustular vasculitis and meningoencephalitis. In the meantime, inflammatory bowel disease and collagen vascular diseases must be eliminated.
New international criteria are also used today to make a diagnosis. According to the International Behçet criteria, it is expected that there will be two criteria other than oral aphtha. (Table 1).
TABLE 1: International Diagnostic Criteria for Behçet
1.Oral aphthae:Aphthae observed by the doctor or expressed by the patient, recurring at least three times a year.
2.Genital ulcerations:Genital aphthae or scarring observed by the doctor or described by the patient.
3. Eye findings:Anterior uveitis, posterior uveitis, retinal vasculitis, or vitreous cell observation detected by an experienced physician.
4.Skin lesions:Erythema nodosum-like lesions or papulopustular lesions observed by the doctor.
5. Pathergy test positivity
Treatment:
The treatment of Behçet’s disease varies according to the mucocutaneous or systemic involvement. Local treatment is applied for oral and genital aphthous ulcerations in mucocutaneous Behçet’s. For this, local steroid and antibiotic pomades and antiseptic solutions are applied. If it is not enough, colchicine 0.5 mg tablets can be used 2-3 times a day. The inhibitory property of neutrophil chemotaxis of colchicine is utilized. Azothioprine is one of the immunosuppressive drugs that can be applied in this situation. Interferon-alpha is also an immunomodulator that has been successfully used in Behçet’s patients with mucocutaneous involvement in recent years. In addition, other immunosuppressive drugs such as cyclosporine-A, chlorambucil, and cyclophosphamide are used in patients with ocular and systemic involvement. Antiaggregants are added to the treatment in cases of thrombophlebitis. Although the place of systemic steroid in the treatment of Behçet’s has not been determined exactly, it has been reported to be beneficial in acute systemic cases and neurological involvement.
Course and Prognosis:
The clinical course of Behçet’s is variable. Usually, mucocutaneous and arthritic findings occur first. It progresses with relapses and remissions. The most common cause of morbidity is ocular involvement and blindness can often be prevented by applying aggressive treatment at the beginning. Death may result from neurological involvement, vascular disease, intestinal perforation, cardiopulmonary disease, or complications from immunosuppressive therapy.
exp. Dr. Nezih KARACA
RESOURCES
Jorizzo JL. Behcet’s Disease. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, Fitzpatrick TB, eds. Dermatology in General Medicine, 5th edition. New York, McGraw-Hill 1999; 2161-2165.
Scully C. The Oral Cavity. In: Champion RH, Burton JL, Burns DA, Breatnach SM, eds. Textbook of Dermatology. 6th edition. Oxford, Blackwell Science Ltd 1998; 3072-3074.
Yurdakul S, Tüzün Y, Mat MC, Özyazgan Y, Yazıcı H. Behçet Syndrome. in dermatology. Ed: Tuzun Y, Kotoğyan A, Aydemir EH, Baransu O. 2nd edition. Istanbul, Nobel Medicine Bookstores 1994; 393-398.
