Behçet Disease

Named after the Turkish dermatologist who first described it, Behçet disease is of unknown cause and most commonly occurs in persons of Asian, Turkish, or Middle Eastern background. The protean manifestations are believed to result from vasculitis that may involve all types of blood vessels: small, medium, and large, on both the arterial and venous side of the circulation.

Diagnostic Essentials

• Recurrent, painful oral and genital aphthous ulcers.
• Erythema nodosum–like lesions; follicular rash; pathergy phenomenon.
• Anterior or posterior uveitis. Posterior uveitis may be asymptomatic until significant damage to the retina has occurred.
• Neurologic lesions can mimic multiple sclerosis.

Clinical Findings

Symptoms and Signs

The hallmark of Behçet disease is painful aphthous ulcerations in the mouth. These lesions, which usually are multiple, may be found on the tongue, gums, and inner surfaces of the oral cavity. Genital lesions, similar in appearance, are also common but do not occur in all patients. Other cutaneous lesions of Behçet disease include tender, erythematous, papular lesions that resemble erythema nodosum. On biopsy, however, many of these lesions are shown to be secondary to vasculitis rather than septal panniculitis. These erythema nodosum–like lesions tend to ulcerate, which is a major difference between the lesions of Behçet disease and the erythema nodosum seen in sarcoidosis and IBD. An erythematous follicular rash that occurs frequently on the upper extremities may be a subtle feature of the disease. The pathergy phenomenon is frequently underappreciated (unless the patient is asked); in this phenomenon, sterile pustules develop at sites where needles have been inserted into the skin (eg, for phlebotomy).

A nonerosive arthritis occurs in about two-thirds of patients, most commonly affecting the knees and ankles. Eye involvement may be one of the most devastating complications of Behçet disease. Posterior uveitis, in essence a retinal venulitis, may lead to the insidious destruction of large areas of the retina before the patient becomes aware of visual problems. Anterior uveitis, associated with the triad of photophobia, blurred vision, and a red eye, is intensely symptomatic. This complication may lead to a hypopyon, the accumulation of pus in the anterior chamber. If not treated properly, anterior uveitis may lead to synechial formation between the iris and lens, resulting in permanent pupillary distortion.

CNS involvement can cause major morbidity in Bechet disease. Findings include sterile meningitis (recurrent meningeal headaches associated with a lymphocytic pleocytosis), cranial nerve palsies, seizures, encephalitis, mental disturbances, and spinal cord lesions. The CNS lesions may mimic multiple sclerosis radiologically. Aphthous ulcerations of the ileum and cecum and other forms of GI involvement develop in approximately a quarter of patients. Large vessel vasculitis can lead to pulmonary artery aneurysms and life-threatening pulmonary hemorrhage. Finally, patients have a hypercoagulable tendency that may lead to complicated venous thrombotic events, particularly deep venous thromboses, pulmonary emboli, cerebral sinus thrombosis, and other problems associated with clotting.

The clinical course may be chronic but is often characterized by remissions and exacerbations.

Laboratory Findings

There are no pathognomonic laboratory features of Behçet disease. Although acute-phase reactants are often elevated, there is no autoantibody or other assay that is distinctive. No markers of hypercoagulability specific to Behçet have been identified. Behçet disease has a genetic risk factor (HLA B51), but this gene is neither necessary nor sufficient to cause the disease.

Treatment

Both colchicine (0.6 mg once to three times daily orally) and topical corticosteroids (oral dexamethasone suspension 1 mg twice daily swish and spit of 0.5 mg/5 mL) may ameliorate the mucocutaneous ulcerative symptoms. Apremilast, a selective phosphodiesterase-4 inhibitor, is FDA-approved for the treatment of oral ulcers in Behçet disease. Corticosteroids (1 mg/kg/day of oral prednisone) are a mainstay of initial therapy for severe disease manifestations. Azathioprine (2 mg/kg/day orally) may be an effective steroid-sparing agent. Infliximab, cyclosporine, or cyclophosphamide is indicated for severe ocular and CNS complications of Behçet disease.