Behcet’s disease is characterized by oral and genital aphthous ulcerations, arthritis, cutaneous lesions, ocular lesions, hypercoagulability, and may also manifest with neurologic, cardiac or gastrointestinal symptoms. This disease is characterized by recurrent, self-limited attacks of the above mentioned symptoms. This disorder is seen more frequently in persons of Middle Eastern or Asian dissent. The highest prevalence is in Turkey. The presence of the HLA-B51 allele is associated with Behcet's’disease. Young adults (mid 20s to 40 years) are most often affected, with disease in children and the elderly being a rare occurrence.
The diagnosis is established clinically. The O’Duffy criteria include: aphthous stomatitis, aphthous genital ulceration, uveitis, cutaneous “pustular” vasculitis, synovitis, and meningoencephalitis. In order to establish the diagnosis by the O’Duffy criteria, aphthous ulceration plus two other criteria must be present. An incomplete form of disease is present when recurrent aphthous ulcers plus one other criteria are present. The International Study Group criteria for the diagnosis of Behcet’s disease include: (1) recurrent aphthous ulcers, (2) recurrent genital ulcerations, (3) ocular lesions (anterior or posterior uveitis, cells in the vitreous on slit lamp exam, or retinal vasculitis), (4) cutaneous lesions (erythema nodosum, pseudofolliculitis, papulopustular lesions, or in postadolescent patients not on steroids, acneiform nodules), and (5) a positive pathergy test. Using the International Study Group criteria, the diagnosis is established when aphthous ulcers plus any two of the other criteria are present. Pathergy refers to the development of a pustular lesion 24 hours after trauma by needlestick. An elevated serum IgD level is often noted during active disease.
Other symptoms include:
Oral ulceration: Painful lesions located on the gingiva, tongue, and buccal mucosa which usually resolve without residual lesions in approximately 10 days. The characteristic description of the oral lesions is one of a small (usually < 1cm), round, red-rimmed, superficial lesion with a white or yellow base. Biopsy of these lesions will show neutrophilic infiltration.
Genital ulceration: In male patients, lesions appear on the scrotum or penis; whereas, in female patients, the vulva is most commonly involved.
Ocular: The most common sites of ocular lesions are the uvea and retina. Lesions often manifest as blurred vision, eye pain, photophobia, increased lacrimation, scotomas, and periglobal hyperemia. Hypopyon refers to the visible collection of pus in the anterior chamber and is characteristic of Behcet’s disease.
Cutaneous: Female patients often manifest painful erythema nodosum located in the pretibial region, face, neck, and/or buttocks. Male patients develop either pseudofolliculitis or acneiform nodules on the back, face, neck and especially around the hairline. Skin pathergy is a diagnostic criteria and refers to the development of an area of erythematous induration of greater than 2 mm diameter in response to a needle stick. The lesion reaches maximum size by two days and resolves within 5 days. Induration is necessary for diagnosis, and erythema without induration constitutes a negative test. The test is performed by using a 20- to 22-gauge needle to execute an oblique needle stick 5 mm deep into the skin of the forearm.
Articular: Mono or polyarthritis of the knees, wrists, ankles or elbows.
Neurologic: Headaches, meningoencephalitis, seizures, cerebral venous thrombosis, cranial nerve palsies, cerebellar ataxia, hemiplegia, benign intracranial hypertension, intracranial hemorrhage, aseptic meningitis, and cerebral aneurysms. Focal ischemia of the brain stem may result from vasculitic lesions.
Gastrointestinal: Ulcerations of the entire GI tract most commonly in the terminal ileum and cecum, abdominal pain, dysphagia, diarrhea, hematochezia, bloating, peptic ulcer disease, peritonitis, and Budd-Chiari syndrome. GI tract aphthous ulcers may lead to perforation. Since many of the same manifestations are seen with inflammatory bowel disease, the distinction is often difficult to make.
Cardiac: Myocardial infarction, pericarditis, endocarditis, arrhythmias, ventricular endomyocardial fibrosis, and valvular disease.
Vascular: Venous thrombosis, arterial thrombosis and aneurysm formation may manifest. Venous thrombi are more common than arterial and often involve the superior or inferior vena cava but may also affect the portal vein. Aneurysm formation tends to occur in the aorta most commonly, but the pulmonary, femoral, subclavian, popliteal and common carotid arteries may also be affected. Blood clots are often refractory to conventional therapy with heparin and warfarin and often requires treatment with chlorambucil, cyclosporine, cyclophosphamide, and/or azathioprine.
Pulmonary: Tracheobronchial ulcerations, periadventitial arterial fibrosis, intrapulmonary fibrosis, pulmonary hypertension, pleurisy, embolism, aneurysms, pneumonitis and fibrosis. Hemoptysis may occur secondary to an arterial-bronchial fistula.
Therapy may be complex and should be guided by a specialist with experience in treating Behcet’s disease. Topical and intralesional corticosteroids may be beneficial in the treatment of oral and genital ulcerations. Viscous lidocaine or oral rinses containing chlorhexidine gluconate may help decrease the discomfort of oral ulcers and allow adequate oral intake to maintain nutrition. Other therapies for aphthous ulcers or mucocutaneous involvement include: systemic corticosteroids, tetracycline, colchicine (0.6 mg TID), dapsone (100 mg/day), thalidomide (200 mg/day), methotrexate (7.5 to 20 mg/week), interferon alfa-2a (3-12 million units 3 times/week) and amlexanox paste 5%. Ocular symptoms may require therapy with systemic steroids (prednisone 1 mg/kg/day), azathiprine (1-2 mg/kg/day), cyclosporine (10 mg/day) alone or in combination. The manifestation of vasculitis or aneurysms may require cyclophosphamide, alone or in combination with corticosteroids.