What is the initial treatment for Behcet disease?

Initial Treatment for Behçet Disease

The initial treatment for Behçet disease depends critically on organ involvement: colchicine (1-2 mg/day) is first-line for mucocutaneous lesions and arthritis, while sight-threatening posterior uveitis requires immediate combination therapy with azathioprine (2.5 mg/kg/day) plus systemic corticosteroids, and major vascular or neurological involvement demands high-dose glucocorticoids with immunosuppressives such as azathioprine or cyclophosphamide. 1, 2

Treatment Algorithm by Organ System

Mucocutaneous Disease (Most Common Presentation)

For isolated oral and genital ulcers:

• Start with topical corticosteroids as first-line therapy 1, 2
• If inadequate response or recurrent lesions, escalate to colchicine 1-2 mg/day (adjusted to body weight) 1, 3
• Colchicine is particularly effective when the dominant lesion is erythema nodosum or genital ulcers, especially in women 1, 3

Evidence strength: Two randomized controlled trials demonstrated colchicine significantly reduces genital ulcers (p=0.001), erythema nodosum (p=0.002), and arthritis (p=0.014) in women over 24 months 3. The effect in men was limited primarily to arthritis 3.

For refractory mucocutaneous disease:

• Consider azathioprine, interferon-alpha, TNF-alpha antagonists, or apremilast 1, 2

Joint Involvement

Colchicine 1-2 mg/day is the initial treatment of choice for arthritis in Behçet disease 1, 2

• Arthritis typically affects large joints (knees, ankles) and follows a mild, transient course without erosions or deformities 1, 2
• Two RCTs confirmed beneficial effects of colchicine for arthritis 1

Eye Involvement (Highest Priority - Prevents Blindness)

For posterior segment inflammation (uveitis, retinal vasculitis):

• Immediately initiate azathioprine 2.5 mg/kg/day PLUS systemic corticosteroids 1, 2
• Never use corticosteroids alone - they must be combined with azathioprine or other immunosuppressives 1
• Alternative first-line options include cyclosporine-A, interferon-alpha, or monoclonal anti-TNF antibodies 1

For acute sight-threatening uveitis:

• High-dose intravenous methylprednisolone (1 g/day for 3-7 days) followed by oral prednisolone 1 mg/kg/day 2
• Add infliximab or interferon-alpha for rapid response (1-5 days) 2
• Consider intravitreal glucocorticoid injection for unilateral exacerbation as adjunct 1

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

• Escalate to cyclosporine-A (2-5 mg/kg/day) OR infliximab in combination with azathioprine and corticosteroids 1, 2
• Interferon-alpha with or without corticosteroids is an alternative 1

Critical evidence: Interferon alfa-2b significantly reduced eye involvement (RR 0.21, p<0.001) and visual acuity loss (RR 0.13, p=0.003) in newly diagnosed patients 4. Azathioprine decreases hypopyon uveitis attacks and stabilizes visual acuity with long-term benefits 2.

Vascular Involvement

For acute deep vein thrombosis:

• Glucocorticoids PLUS immunosuppressives (azathioprine, cyclophosphamide, or cyclosporine-A) 1, 2
• Avoid anticoagulants unless bleeding risk is low and pulmonary artery aneurysms are ruled out 1, 2

Critical pitfall: Venous thrombi in Behçet disease adhere to vessel walls and rarely embolize - pulmonary embolism is uncommon despite high venous thrombosis frequency 1. Anticoagulation risks fatal bleeding if coexisting pulmonary arterial aneurysms are present 1, 2.

For pulmonary or peripheral arterial aneurysms:

• High-dose glucocorticoids PLUS cyclophosphamide 1, 2
• Consider monoclonal anti-TNF antibodies for refractory cases 1
• Medical treatment is necessary before any surgical intervention 1

Neurological Involvement

For parenchymal CNS disease:

• High-dose corticosteroids (typically IV methylprednisolone 1 g/day for 3-7 days) followed by oral taper over 2-3 months 5, 2
• Add immunosuppressives: azathioprine, interferon-alpha, cyclophosphamide, methotrexate, or TNF-alpha antagonists 1, 5, 2

For dural sinus thrombosis:

• Corticosteroids alone are recommended 1, 2

Critical warning: Never use cyclosporine-A in patients with CNS involvement due to potential neurotoxicity, unless absolutely necessary for intraocular inflammation 1, 5, 2. Three case-control studies demonstrated this risk 1.

Gastrointestinal Involvement

Medical therapy before surgery (except emergencies):

• Try sulfasalazine, corticosteroids, azathioprine, TNF-alpha antagonists, or thalidomide 1, 2
• No evidence-based first-line treatment exists 1
• GI ulcers are deep and penetrating, with high perforation risk requiring emergency surgery 1

Corticosteroid Dosing Protocol

Initial dosing:

• Oral prednisolone 1 mg/kg/day for acute attacks 2
• IV methylprednisolone 1 g/day for 3-7 days for severe organ involvement (eye, CNS, vascular) 2

Tapering:

• Reduce by 5-10 mg every 10-15 days after clinical response 2
• Target maintenance dose of 5-10 mg/day 2
• Continue for at least 2 years and 12 months after inflammatory marker normalization 2

Always combine with steroid-sparing agents (azathioprine, cyclophosphamide) to minimize long-term exposure 2

Common Pitfalls to Avoid

1. Never use corticosteroids alone for posterior uveitis - always combine with azathioprine or other immunosuppressives 1, 2
2. Avoid cyclosporine-A in CNS involvement due to neurotoxicity 1, 5, 2
3. Do not routinely anticoagulate venous thrombosis - use immunosuppression instead; anticoagulation risks fatal bleeding with arterial aneurysms 1, 2
4. Screen for tuberculosis before infliximab - endemic areas for Behçet overlap with TB-endemic regions 2
5. Young men with early disease onset have higher risk of severe disease and may benefit from early aggressive immunosuppression 2

Monitoring Requirements

• Regular clinical assessment with inflammatory markers (ESR, CRP) 2
• Ophthalmologic examinations for eye involvement 2
• Bone DEXA scanning at 1-2 year intervals while on corticosteroids 2
• Monitor for steroid side effects: hyperglycemia, hypertension, mood changes 2
• Calcium and vitamin D supplementation for all patients on corticosteroids 2