What are the recommended treatment options for Behçet disease, including management of mucocutaneous lesions, ocular involvement, vascular complications, and neurological disease?

Behçet Disease: Treatment Recommendations

Treatment Principles

Behçet disease requires immediate aggressive immunosuppression for sight-threatening eye disease, vascular, neurological, or gastrointestinal involvement to prevent irreversible organ damage and death, while mucocutaneous and joint manifestations can be managed with symptom-based treatment. 1

The treatment intensity must be stratified by whether organ involvement threatens permanent damage—mucocutaneous lesions affect quality of life but don't cause permanent damage, whereas major organ involvement demands rapid inflammation suppression to prevent loss of function. 1 Young males with early disease onset require more aggressive treatment and closer monitoring due to their more severe disease course. 1

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Mucocutaneous Lesions

Oral and Genital Ulcers

• Apply topical corticosteroids as first-line treatment for symptomatic relief of isolated oral and genital ulcers. 2, 1
• Start colchicine as first-line systemic therapy, particularly when erythema nodosum or genital ulcers are the dominant lesions. 2, 1
• Colchicine has proven efficacy specifically for erythema nodosum and genital ulcers in women. 2

Papulopustular and Acne-Like Lesions

• Treat with topical or systemic measures identical to those used for acne vulgaris, as these lesions are primarily of cosmetic concern. 2

Refractory Mucocutaneous Disease

For patients who fail topical corticosteroids and colchicine:

• Consider azathioprine, which has demonstrated effectiveness in preventing mucocutaneous lesions. 2
• Escalate to thalidomide, interferon-alpha, TNF-alpha inhibitors, or apremilast in selected resistant cases. 2
• Thalidomide shows efficacy for oral and genital ulcers but carries serious risks of teratogenicity and potentially permanent peripheral neuropathy. 2

Leg Ulcers

• Determine whether the cause is venous stasis or obliterative vasculitis before planning treatment, ideally with input from dermatology and vascular surgery. 2

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Ocular Involvement

Posterior Uveitis or Panuveitis

Any patient with inflammatory eye disease affecting the posterior segment must receive azathioprine, cyclosporine-A, interferon-alpha, or monoclonal anti-TNF antibodies—systemic glucocorticoids should never be used alone and must always be combined with these immunosuppressives. 2, 1, 3

This combination approach is critical because:

• Azathioprine (2.5 mg/kg/day) combined with corticosteroids reduces hypopyon uveitis attacks (NNT=4) and prevents new eye disease development (NNT=2). 3
• Approximately 51.6% of patients achieve complete remission with azathioprine plus corticosteroids, with an additional 41.4% achieving partial response. 3
• Corticosteroids alone lead to new vascular involvement in up to 50% of patients. 3

Acute Sight-Threatening Uveitis

For initial or recurrent acute sight-threatening episodes, immediately administer high-dose glucocorticoids with infliximab or interferon-alpha. 2, 1

• Intravitreal glucocorticoid injection can be used as an adjunct to systemic treatment for unilateral exacerbations. 2
• Close collaboration with expert ophthalmologists is mandatory for optimal outcomes. 2, 3

Isolated Anterior Uveitis

• Consider systemic immunosuppressives for patients with poor prognostic factors: young age, male sex, and early disease onset. 2

Critical Pitfall

Never use cyclosporine-A in patients with any history of neurological involvement, even if inactive, due to its neurotoxic potential. 2, 1 While cyclosporine-A is effective for eye disease, three case-control studies indicate it may potentiate central nervous system involvement. 2

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Vascular Complications

Acute Deep Vein Thrombosis

Mandatory treatment includes glucocorticoids combined with immunosuppressives—never use anticoagulation alone. 2, 1

• For refractory venous thrombosis, escalate to monoclonal anti-TNF antibodies. 1
• New vascular involvement may occur in up to half of patients treated with steroids alone, emphasizing the necessity of combined immunosuppression. 3

Pulmonary Artery Aneurysms

Do not anticoagulate pulmonary artery aneurysms due to high bleeding risk. 1

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Neurological Disease

Parenchymal Involvement

The standard regimen is high-dose glucocorticoids combined with azathioprine 2.5 mg/kg/day. 1

• High-dose pulsed corticosteroids (typically 3-7 pulses of intravenous methylprednisolone 1 g/day) are given during acute attacks, followed by maintenance oral corticosteroids tapered over 2-3 months. 2
• For severe or refractory disease, escalate to monoclonal anti-TNF antibodies. 1
• In more severe cases, monthly pulses of cyclophosphamide are preferred over azathioprine. 2
• Interferon-alpha and TNF-alpha antagonists have shown success in resistant cases. 2

Dural Sinus Thrombosis

• Treat with brief courses of corticosteroids for increased intracranial pressure and headaches. 2

Absolute Contraindication

Never use cyclosporine-A in patients with central nervous system involvement unless absolutely necessary for intraocular inflammation that cannot be controlled otherwise. 2, 1

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Gastrointestinal Involvement

Acute Exacerbations

Use glucocorticoids for rapid ulcer healing combined with disease-modifying agents such as 5-ASA or azathioprine. 1

Severe or Refractory Disease

Escalate to monoclonal anti-TNF antibodies and/or thalidomide. 1

Diagnostic Considerations

• Confirm gastrointestinal involvement through endoscopy and/or imaging. 4
• Rule out NSAID-induced ulcers, inflammatory bowel disease, and infections like tuberculosis before attributing symptoms to Behçet disease. 4
• The ileocecal region is most commonly affected, with ulcerations that may penetrate or perforate. 5

Surgical Management

• Surgery may be required for perforation. 5

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Arthritis

For acute monoarticular arthritis, use intra-articular corticosteroids. 1

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Key Clinical Pitfalls

• Delaying immunosuppression in major organ involvement results in permanent damage—the window for preventing irreversible organ damage is during the early, active disease phase. 1, 6
• Undertreating chronic scarring ulcers causes irreversible anatomical damage, including oropharyngeal narrowing and obliterative/deforming genital scarring. 1
• Using systemic corticosteroids alone for posterior uveitis is inadequate and dangerous—always combine with immunosuppressives. 2, 3
• Ocular, vascular, neurological, and gastrointestinal involvement are associated with poor prognosis and can cause death if untreated. 1, 3

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Disease Course and Treatment Tapering

Disease manifestations typically ameliorate over time in many patients, allowing treatment to be tapered and potentially stopped during the disease course. 2, 1 Drug-free long-term remission after 2 years of successful anti-TNF treatment combined with azathioprine is feasible in a good proportion of patients with sight-threatening disease. 3