Approach

Treatment is guided by type and severity of involvement with a goal of preventing long-term damage.[23] Most new manifestations present within the first 5 years after the onset of symptoms, and for most patients the natural course is one of diminishing symptoms culminating in remission.

The most severe manifestation present in the patient should determine the treatment choices pursued, regardless of whether less severe manifestations are also present.

Mucocutaneous ulcers

For mild symptoms, topical treatment with a corticosteroid (i.e., triamcinolone oral paste) as needed is usually sufficient.[19]

Lesions resistant to local measures may require systemic treatment with colchicine, an oral corticosteroid, or another immunosuppressant agent (e.g., azathioprine, hydroxychloroquine, thalidomide). Follow-up of participants in a placebo-controlled clinical trial confirmed that colchicine did not reduce the need for subsequent immunosuppressive drugs.[24]

Apremilast can be used before or after colchicine has been tried. In a 12-week phase 3 trial of patients with Behcet's syndrome, apremilast significantly improved measures of disease-related quality of life and reduced the number of oral ulcers compared with placebo.[25] Adverse events associated with apremilast included diarrhoea, nausea, and headache.[25]

A tumour necrosis factor (TNF)-alpha inhibitor (e.g., infliximab, adalimumab, etanercept) may also be used in mild Behcet's syndrome resistant to corticosteroids and oral immunosuppressants.

Eye involvement

Eye involvement requires early and aggressive treatment with brief courses of corticosteroids plus longer-term treatment with an immunosuppressant.[19] The corticosteroid can be tapered in many patients after active disease has been controlled, whereas the immunosuppressants are generally continued for at least 1-2 years.

Patients with uveitis should be diagnosed and treated by an ophthalmologist. These patients require aggressive and early treatment with immunosuppressants. Azathioprine plus a corticosteroid is a commonly used drug regimen.[19]

A TNF-alpha inhibitor (e.g., infliximab or adalimumab) or ciclosporin can also be used, in combination with systemic corticosteroids and azathioprine, for control of disease activity.[26] Corticosteroids should never be used alone but should always be given with a systemic immunosuppressant.[19]

Gastrointestinal involvement

Gastrointestinal involvement must be diagnosed correctly to avoid the unnecessary use of immunosuppressive agents.[19] Treatment is with a corticosteroid plus an immunosuppressant (e.g., azathioprine), alone or in combination with infliximab.

Central nervous system involvement

Central nervous system (CNS) involvement, in particular parenchymal disease, requires the most intensive therapy. There are differences in the management approach for each type of CNS involvement; however, the recommendations are based on uncontrolled observational studies.

Parenchymal disease

Treatment of acute parenchymal disease is with high-dose corticosteroids, which are gradually tapered and given in combination with an immunosuppressive agent (e.g., azathioprine or cyclophosphamide).

A TNF-alpha inhibitor (e.g., infliximab) is an alternative or additional first-line agent in patients with severe involvement, disease that is refractory despite standard treatment, or chronic progressive parenchymal disease.[19] This recommendation is based on the results of uncontrolled studies that suggest a benefit from treatment with a TNF-alpha inhibitor; either in combination with other immunosuppressants, or as monotherapy, following unsuccessful treatment with standard agents.[27][28][29]

Acute cerebral venous thrombosis

Treatment of acute cerebral venous thrombosis in Behcet's syndrome is with a high-dose corticosteroid for rapid remission.[19] Another immunosuppressant, such as azathioprine, may be added if necessary. A short course of anticoagulation may be considered, provided the risk of bleeding is low and vascular disease at other sites is excluded. However, anticoagulation is not part of the standard treatment approach.[19][30]

Ciclosporin should be avoided in patients with nervous system involvement, even if the involvement is no longer active.[19]

Major vascular involvement

Systemic venous thrombosis

Venous thrombotic events are managed in Behcet's syndrome by controlling systemic inflammation with corticosteroids in combination with other immunosuppressants such as azathioprine, cyclophosphamide, or ciclosporin.[19] Cyclophosphamide may be reserved for patients with extensive thrombosis of larger veins such as the vena cava because of potential adverse events.[19] Anticoagulants can also be used in some patients, provided that the overall risk of bleeding is low and that co-existent pulmonary artery aneurysms are ruled out. However, anticoagulation is not part of the standard treatment approach.[19]

TNF-alpha inhibitors in combination with corticosteroids can be considered for patients with refractory venous thrombosis.[19] One retrospective study of 70 patients with Behcet's syndrome-associated venous thrombosis reported that adalimumab-based treatments were more effective than azathioprine, ciclosporin, cyclophosphamide, and methotrexate for inducing rapid resolution of venous thrombosis.[31]

Arterial involvement

Pulmonary arterial aneurysms and thromboses are treated with high-dose corticosteroids and cyclophosphamide. Embolisation of pulmonary arterial aneurysms may be necessary if there is a high risk of major bleeding. Open surgery should only be considered in life-threatening situations.[19]

Peripheral arterial aneurysms are treated with corticosteroids and cyclophosphamide. In most cases, surgery or stenting is also required. However, small arterial aneurysms may be successfully managed with medical therapy alone.[19]

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