What is the management approach for a patient with Behcet syndrome?

Management of Behçet Syndrome

Behçet syndrome management must be stratified by organ involvement: mucocutaneous/joint disease requires symptom-based treatment starting with colchicine and topical steroids, while sight-threatening eye disease, vascular, neurological, or gastrointestinal involvement demands immediate aggressive immunosuppression to prevent irreversible organ damage and death. 1

Overarching Treatment Principles

The goal is to rapidly suppress inflammatory exacerbations and prevent relapses that cause irreversible organ damage. 1 Treatment intensity depends on whether organ involvement threatens permanent damage:

• Low-risk manifestations (oral/genital ulcers, skin lesions, arthritis): Impair quality of life but cause no permanent damage—treatment can be tailored to symptom burden versus medication risks 1
• High-risk manifestations (eye, vascular, neurological, gastrointestinal): Can cause serious damage or death—require immediate aggressive immunosuppression 1

Young males with early disease onset have more severe courses and require more aggressive treatment with closer monitoring. 1, 2 Disease manifestations typically ameliorate over time, allowing treatment tapering or discontinuation. 1

Mucocutaneous and Joint Involvement

First-Line Treatment

• Topical corticosteroids for symptomatic relief of oral and genital ulcers 1
• Colchicine as first-line systemic therapy, especially effective for erythema nodosum and genital ulcers 1
• Intra-articular corticosteroids for acute monoarticular arthritis 1

Refractory Disease

For patients failing colchicine, consider: 1

• Azathioprine
• Thalidomide
• Interferon-alpha
• TNF-alpha inhibitors
• Apremilast (FDA-approved for oral ulcers) 3

Critical caveat: Chronic ulceration causing scarring requires vigorous treatment to prevent oropharyngeal narrowing and obliterative genital scarring. 1

Ocular Involvement

Posterior Uveitis or Panuveitis (Sight-Threatening)

Start immediately with: 1

• Azathioprine (2-2.5 mg/kg/day) combined with systemic corticosteroids as first-line maintenance therapy
• For acute sight-threatening exacerbations, use one of:
  • High-dose glucocorticoids (IV methylprednisolone 1g/day)
  • Infliximab (monoclonal anti-TNF antibody)
  • Interferon-alpha
• Intravitreal glucocorticoid injection as adjunct for unilateral exacerbations 1

Isolated Anterior Uveitis

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

Vascular Involvement

Acute Deep Vein Thrombosis

Mandatory treatment: 1

• Glucocorticoids PLUS
• Immunosuppressives (azathioprine, cyclophosphamide, or cyclosporine-A)

Refractory Venous Thrombosis

• Monoclonal anti-TNF antibodies for refractory cases 1
• Anticoagulants may be added only if bleeding risk is low AND pulmonary artery aneurysms are ruled out 1

Pulmonary Artery Aneurysms

Immediate treatment: 1

• High-dose glucocorticoids PLUS cyclophosphamide
• Monoclonal anti-TNF antibodies for refractory cases
• Embolization preferred over open surgery for patients with high bleeding risk 1

Peripheral and Aortic Artery Aneurysms

• Medical treatment with cyclophosphamide and corticosteroids is necessary before any intervention 1
• Surgery or stenting should not be delayed if patient is symptomatic 1

Neurological Involvement

Parenchymal Involvement

Standard regimen: 1

• High-dose glucocorticoids (IV methylprednisolone 1g/day for up to 7 days, then oral prednisolone 1 mg/kg/day for 1 month, tapered by 5-10 mg every 10-15 days)
• Azathioprine started simultaneously
• Avoid cyclosporine-A even if neurological involvement is no longer active 1

Escalate to monoclonal anti-TNF antibodies for: 1

• Severe parenchymal involvement at onset
• Persistent or relapsing disease despite corticosteroids and azathioprine
• Chronic progressive nervous system involvement

Cerebral Venous Thrombosis

• High-dose glucocorticoids followed by tapering 1
• Anticoagulants may be added for short duration 1
• Screen for extracranial vascular disease 1

Gastrointestinal Involvement

Initial Assessment

Confirm involvement by endoscopy and/or imaging; rule out NSAID ulcers, inflammatory bowel disease, and tuberculosis. 1, 4

Acute Exacerbations

• Glucocorticoids for rapid ulcer healing 1
• Disease-modifying agents: 5-ASA for milder cases, azathioprine for more severe cases 1

Severe/Refractory Disease

• Monoclonal anti-TNF antibodies and/or thalidomide 1
• Urgent surgical consultation for perforation, major bleeding, or obstruction 1

Important caveat: While there is concern about high-dose glucocorticoids facilitating perforation, no data confirms this risk. 1

Key Pitfalls to Avoid

• Never use cyclosporine-A in patients with any history of neurological involvement, even if inactive 1
• Never anticoagulate pulmonary artery aneurysms due to bleeding risk 1
• Do not delay immunosuppression in major organ involvement—permanent damage occurs rapidly 1
• Do not undertreated chronic scarring ulcers—they cause irreversible anatomical damage 1
• Young males require more aggressive initial treatment regardless of apparent disease severity 1, 2