What is the management of Behcet's disease?

Management of Behçet's Disease

Treatment of Behçet's disease must be tailored to the specific organ system involved, with the primary goal of rapidly suppressing inflammation to prevent irreversible organ damage, particularly in high-risk manifestations affecting the eyes, blood vessels, nervous system, and gastrointestinal tract. 1, 2

Overarching Treatment Principles

• Aggressive early intervention is critical for posterior segment eye disease, vascular involvement, neurological manifestations, and gastrointestinal disease, as these carry poor prognosis and risk of permanent damage 1, 2
• Men with early disease onset require more aggressive treatment due to typically more severe disease course 2
• A multidisciplinary team including rheumatology, ophthalmology, dermatology, and vascular surgery is essential for optimal outcomes 1, 2
• Disease activity often ameliorates over time, allowing for treatment tapering and potential discontinuation in many patients 1, 2

Treatment by Organ System

Mucocutaneous Disease

First-line approach:

• Topical corticosteroids for oral and genital ulcers 1, 2
• Colchicine is the first systemic agent to try, particularly effective for erythema nodosum and genital ulcers 1, 2

Refractory mucocutaneous disease:

• Azathioprine for resistant cases 1, 2
• Thalidomide (with strict contraception protocols due to teratogenicity risk and monitoring for peripheral neuropathy) 1, 2
• TNF-alpha inhibitors or apremilast for severe refractory cases 1
• Interferon-alpha as an alternative option 1

Special considerations:

• Papulopustular/acne-like lesions are managed with standard acne treatments (topical or systemic) 1, 3
• Leg ulcers require vascular surgery consultation to differentiate venous stasis from obliterative vasculitis 1

Posterior Segment Eye Disease

This is a medical emergency requiring immediate aggressive treatment:

Maintenance therapy (mandatory for all patients with posterior segment involvement):

• Azathioprine is the first-line systemic immunosuppressive 1, 2
• Systemic glucocorticoids must ONLY be used in combination with azathioprine or other immunosuppressives, never as monotherapy 1, 2
• Alternative options: cyclosporine-A, interferon-alpha, or monoclonal anti-TNF antibodies (infliximab) 1, 2

Acute sight-threatening uveitis:

• High-dose glucocorticoids, infliximab, or interferon-alpha immediately 1, 2
• Intravitreal glucocorticoid injection as adjunct for unilateral exacerbations 1
• Close ophthalmology collaboration is mandatory 1, 2

Isolated anterior uveitis:

• Systemic immunosuppressives should be considered for poor prognostic factors (young age, male sex, early disease onset) 1

Vascular Disease

Acute deep vein thrombosis:

• Glucocorticoids plus immunosuppressives (azathioprine, cyclophosphamide, or cyclosporine-A) 1, 2
• Anticoagulation may be added ONLY if bleeding risk is low AND pulmonary artery aneurysms are ruled out 1

Refractory venous thrombosis:

• Monoclonal anti-TNF antibodies 1

Pulmonary and peripheral arterial aneurysms:

• High-dose glucocorticoids plus cyclophosphamide 1, 2
• This is a life-threatening emergency requiring immediate aggressive treatment 2

Neurological Involvement

Parenchymal disease:

• High-dose pulsed IV methylprednisolone (1 g/day for 3-7 days) 2
• CRITICAL: Cyclosporine-A is contraindicated in CNS involvement due to neurotoxicity risk 2

Dural sinus thrombosis:

• Corticosteroids 2

Gastrointestinal Disease

Medical therapy should be attempted before surgery (except emergencies):

• Sulfasalazine 2
• Corticosteroids 2
• Azathioprine 2
• TNF-alpha antagonists 2
• Thalidomide (with appropriate precautions) 2

Joint Involvement

Most patients respond to conservative management:

• Colchicine is first-line for arthritis 2
• Alternative options: indomethacin or benzathine penicillin 2

Common Pitfalls to Avoid

• Never use systemic glucocorticoids as monotherapy for posterior segment eye disease—this leads to treatment failure and vision loss 1, 2
• Never use cyclosporine-A in patients with CNS involvement—it causes neurotoxicity 2
• Never anticoagulate patients with pulmonary artery aneurysms—this increases bleeding risk from aneurysm rupture 1
• Do not delay aggressive treatment in young males with major organ involvement—they have worse prognosis 2
• Do not treat leg ulcers without vascular surgery input—the etiology determines management 1

Emerging and Refractory Disease Options

For patients failing conventional therapy:

• TNF-alpha inhibitors (infliximab, adalimumab) show increasing efficacy across multiple organ systems 4, 5
• IL-1 inhibitors, ustekinumab, secukinumab, and tocilizumab show promise for refractory cases 5
• Apremilast is FDA-approved specifically for oral ulcers 5