What are the treatment options for Behçet’s disease (Behçet syndrome)?

Treatment of Behçet Syndrome

Treat Behçet syndrome based on organ involvement: use colchicine and topical corticosteroids for mucocutaneous/joint disease, but immediately initiate aggressive immunosuppression with high-dose glucocorticoids plus azathioprine for sight-threatening eye disease, vascular, neurological, or gastrointestinal involvement to prevent irreversible organ damage and death. 1, 2

Treatment Algorithm by Organ System

Mucocutaneous and Joint Disease

For oral and genital ulcers:

• Start with topical corticosteroids for symptomatic relief 1, 3
• Initiate colchicine 1-2 mg/day as first-line systemic therapy, particularly effective for erythema nodosum and genital ulcers 1, 2, 3
• Colchicine is especially effective in women and has proven efficacy in randomized controlled trials for arthritis and erythema nodosum 2, 3

For acute monoarticular arthritis:

• Use intra-articular corticosteroids 1

For refractory mucocutaneous disease:

• Escalate to azathioprine, interferon-alpha, or TNF-alpha antagonists 3

Ocular Involvement (Posterior Segment Disease)

This is a medical emergency requiring immediate aggressive treatment:

Mandatory first-line therapy:

• Azathioprine 2.5 mg/kg/day PLUS systemic corticosteroids (never use corticosteroids alone) 1, 2, 3
• Start with high-dose intravenous methylprednisolone 1 g/day for 3-7 days, followed by oral prednisolone 1 mg/kg/day 3

For severe eye disease (>2 lines visual acuity drop or retinal vasculitis):

• Add either infliximab OR cyclosporine A (2-5 mg/kg/day) to the azathioprine-corticosteroid regimen 1, 2, 3
• Alternatively, use interferon-alpha with or without corticosteroids 2
• Infliximab shows rapid response (1-5 days) and is particularly effective for refractory disease 3

Critical pitfall: Never use cyclosporine A if any CNS involvement exists, even if inactive, due to significant neurotoxicity risk 1, 2, 3

Vascular Involvement

For acute deep vein thrombosis:

• Mandatory treatment with glucocorticoids PLUS immunosuppressives (azathioprine, cyclophosphamide, or cyclosporine A) 1, 2, 3
• Do NOT use anticoagulation as primary therapy—immunosuppression is the treatment of choice 2, 3

For pulmonary and peripheral arterial aneurysms:

• High-dose glucocorticoids PLUS cyclophosphamide 2, 3
• Anticoagulation of pulmonary artery aneurysms is contraindicated due to bleeding risk 1

For refractory venous thrombosis:

• Escalate to monoclonal anti-TNF antibodies (infliximab or adalimumab) 1, 2

Critical pitfall: Avoid anticoagulants, antiplatelet agents, or antifibrinolytic agents for venous thrombosis in Behçet's disease due to risk of bleeding, especially with coexisting pulmonary arterial aneurysms 2, 3

Neurological Involvement

For acute parenchymal Neurobehçet's disease:

• High-dose intravenous methylprednisolone followed by oral prednisolone 1 mg/kg/day 2, 3
• Combine with azathioprine 2.5 mg/kg/day from the outset as the preferred steroid-sparing agent 1, 2

For cerebral venous thrombosis:

• High-dose glucocorticoids followed by tapering 3

For severe or refractory neurological disease:

• Escalate to TNF-alpha inhibitors, particularly infliximab 1, 2

Critical pitfall: Never use cyclosporine A in patients with any CNS involvement due to significant neurotoxicity risk 1, 2, 3

Gastrointestinal Involvement

For acute exacerbations:

• Glucocorticoids for rapid ulcer healing 1
• Add disease-modifying agents: sulfasalazine, 5-ASA, or azathioprine 1, 3

For severe or refractory gastrointestinal disease:

• Monoclonal anti-TNF antibodies (infliximab or adalimumab) and/or thalidomide 1, 3

Before considering surgery (except emergencies):

• Trial sulfasalazine, corticosteroids, azathioprine, TNF-alpha antagonists, or thalidomide sequentially 2

Corticosteroid Dosing and Tapering Protocol

Initial dosing:

• Oral prednisolone 1 mg/kg/day for acute attacks 3
• For severe organ involvement: IV methylprednisolone 1 g/day for 3-7 days, then oral prednisolone 1 mg/kg/day 3

Tapering protocol:

• Begin tapering by 5-10 mg every 10-15 days after achieving clinical response 3
• Aim for maintenance dose of 5-10 mg/day 3
• Continue maintenance for at least 2 years and at least 12 months after normalization of inflammatory markers 3

Always combine with steroid-sparing agents to minimize long-term steroid exposure 3

High-Risk Populations Requiring Aggressive Treatment

Young males with early disease onset:

• More severe disease course with higher risk of major organ involvement 1, 2
• Require more aggressive immunosuppression from the outset 1, 2
• Need closer monitoring and increased caution during follow-up 1, 2

Management of Refractory Disease

For patients failing conventional immunosuppression across any organ system:

• TNF-alpha inhibitors (infliximab or adalimumab) represent the next therapeutic step 2, 4, 5
• Infliximab combined with azathioprine shows particular promise for severe or refractory cardiac involvement 2

Screen for tuberculosis before initiating infliximab, especially in endemic areas 3

Surgical Considerations for Vascular Disease

For aortic and arterial aneurysms:

• Anastomotic pseudoaneurysms occur in 12.9% within 18 months due to ongoing inflammation at suture lines 6
• Endovascular repair with stent grafts has been described as an alternative 6
• Ensure adequate immunosuppression before and after surgical intervention 6

Long-Term Management and Prognosis

Disease course:

• Behçet's disease follows a chronic relapsing-remitting course with unpredictable exacerbations 1
• Disease manifestations typically decrease in frequency and severity over time 1, 2
• Treatment may be tapered and potentially discontinued in stable patients 1, 2

Monitoring during remission:

• Regular assessment of inflammatory markers (ESR, CRP) 2
• Organ-specific assessments remain essential even during remission 2
• Bone DEXA scanning at 1-2 yearly intervals while on steroids 3

Prognostic factors:

• Ocular, vascular, neurological, and gastrointestinal involvement are associated with poor prognosis and can cause serious damage and death if untreated 1, 4, 5
• Male sex, younger age of onset, and increased number of organs involved at diagnosis are associated with more severe disease 7, 8