Behçet’s disease is a multisystemic disorder with a significant prevalence among the young and middle-aged people from the Mediterranean, Middle East and Far East.
It has been named “silk road disease” for this reason. Turkey and Japan are among the top two countries where the disease mostly occurs. First described by Turkish dermatologist Hulusi Behçet (1889-1948), Behçet’s disease has a characteristic diagnostic criterion which includes recurrent oral ulceration followed by at least two of the signs that include genital ulcers, ocular involvement and skin lesions or a specific pathergy test which provokes pustular inflammation resulting from skin scratching.
Behçet’s disease is known to be both an autoimmune and autoinflammatory disorder. The main pathologic hallmark of Behçet’s disease is systemic vasculitis that can affect both large and small vessels and capillaries. As a disease in which cellular and humoral components both innate and acquired immunity are activated, an association between HLA-B51 haplotype and Behçet’s disease is also demonstrated.
The most common Behçet’s disease symptoms are uveitis and oral and genital ulcers, usually painful lesions with central necrotic bases that require several weeks to recover. Mucosal ulcerations can also appear in the lower gastrointestinal tract.
Behçet uveitis (see slide show below) is commonly considered as a panuveitis that can result in severe visual impairment unless it’s not managed properly. Systemic vascular involvement related to Behçet’s disease presents as occlusive vasculitis, aneurysm and thrombosis that can affect all types of vessels from the large arteries, such as aorta and pulmonary arteries, to cerebral veins and superficial or deep peripheral vessels. A particular involvement of brain stem parenchyma affecting the central nervous system is also known as neuro-Behçet syndrome, which has a serious prognosis.
Effects on the Eye
Behçet’s disease is important because of the severity of its ocular manifestations and their treatment.
The most typical is nongranulomatous anterior uveitis. It typically shows bilateral involvement, and begins with the onset of unilateral anterior uveitis. Episcleritis and scleritis can rarely accompany the anterior involvement. A sterile hypopyon which shifts due to gravitation is dominantly seen in Behçet’s anterior uveitis. Severe aqueous cell and flare reaction is common, but fibrinous reaction is less common than anterior uveitis related to spondylarthropathies.
The posterior ocular involvement of Behçet’s uveitis is mainly responsible for the severity of visual prognosis. Vitritis, retinal vasculitis, retinitis and papillitis are the hallmark lesions of Behçet posterior and panuveitis. You can detect the onset of uveitis by pearl-like precipitates that appear over the retinal surface and later disappear. Retinal vasculitis of Behçet’s uveitis is best demonstrated by fundus fluorescein angiography, revealing widespread perivascular leakage that can cover all peripheral retina.
Vascular involvement can occasionally present with occlusive vasculitis that causes vitreal and retinal hemorrhages. The intense posterior ocular inflammation can result in late-stage manifestations like papillary and retinal neovascularization, vascular fibrotic sheathing, epiretinal membrane and retinal detachment.
Behçet’s disease has a relapsing-remitting course, with each relapse having the potential to leave sequelae in the body as well as in the eye. Therefore, prompt follow-up and intervention with adequate treatment is crucial to control disease progression and avoid further complications, including irreversible vision loss.
Diagnosing active inflammation through proper ocular examination should be strengthened with multimodal imaging that consists of color fundus photography, fundus fluorescein angiography and optical coherence tomography to detect and document all available ocular findings, particularly in the posterior pole. The most common findings for disease activity include aqueous cell and flare reaction, vitreous haze, vascular sheathing/leakage and pearl-like lesions over the retinal surface.
The primary treatment options for Behçet’s disease and uveitis are corticosteroids which are either used systemically for posterior and panuveitic inflammation or topically for more limited anterior uveitis. However, since you want to control Behçet’s disease for the long-term and corticosteroids might have considerable adverse effects, immunosuppressive and immunomodulatory treatment options are usually applied together with or in the absence of systemic corticosteroids.
Conventional immunosuppressants like cyclosporine, azathioprine and methotrexate are frequently used for long-term treatment, whereas increasing evidence emerges in favor of the biological agents such as anti-TNF (infliximab, adalimumab) and interferon, demonstrating superior treatment efficacy and tolerability. There are newer biological agents that have mechanisms of action for inhibiting inflammatory pathways of IL-6 (tocilizumab), IL-17 (secukinumab) or IL-12-23 (ustekinumab).
Thanks to the development of research and clinical practice, we understand more about the etiology, disease mechanism and management of Behçet’s disease. Although there still remains multiple knowledge gaps about the nature of Behçet’s disease, I am encouraged by efforts to allow better recognition and management options. They show great promise to prevent life- and vision-threatening complications and provide an increased quality of life for patients.
About the authors:
||Cem Kesim MD, FEBO, is an ophthalmologist based in Istanbul.
||Murat Hasanreisoglu MD, FEBO, is a professor at the Koç University School of Medicine, Department of Ophthalmology in Istanbul.