Treatment of Behçet's Disease

Introduction to Treatment

The European League Against Rheumatism recommends that the initial treatment for Behçet's disease should be tailored to the specific organ involvement, with colchicine as first-line therapy for mild mucocutaneous and joint manifestations, while systemic corticosteroids combined with immunosuppressants such as azathioprine are recommended for more severe organ involvement 1, 2

Treatment Based on Organ Involvement

For patients with mucocutaneous involvement, the European League Against Rheumatism suggests that topical corticosteroids should be first-line treatment for isolated oral and genital ulcers 3, 4
Colchicine (1-2 mg/day) is effective for erythema nodosum and mild mucocutaneous lesions, particularly in women, according to the European League Against Rheumatism 3, 5
The American College of Rheumatology recommends that for resistant cases, consider azathioprine, interferon-alpha, or TNF-alpha antagonists 4, 5
For joint involvement, the European League Against Rheumatism recommends that colchicine (1-2 mg/day) is the initial treatment of choice for arthritis in Behçet's disease 2, 5
Arthritis in Behçet's disease typically follows a mild, transient course without deformities or erosions, mainly affecting large joints such as knees and ankles, as stated by the European League Against Rheumatism 5, 6
For eye involvement, the American Academy of Ophthalmology recommends that any patient with inflammatory eye disease affecting the posterior segment should receive azathioprine and systemic corticosteroids 3, 5
For severe eye disease (>2 lines drop in visual acuity or retinal disease), the American Academy of Ophthalmology suggests adding either cyclosporine A or infliximab to the azathioprine and corticosteroids regimen 3, 7
The American Heart Association recommends that for acute deep vein thrombosis, use immunosuppressive agents such as corticosteroids, azathioprine, cyclophosphamide, or cyclosporine A 1, 8
For pulmonary and peripheral arterial aneurysms, the American Heart Association recommends high-dose glucocorticoids and cyclophosphamide 2, 5
The American Neurological Association recommends that acute attacks of parenchymal involvement should be treated with high-dose glucocorticoids followed by slow tapering, together with immunosuppressives such as azathioprine 2, 4
For cerebral venous thrombosis, the American Neurological Association recommends high-dose glucocorticoids followed by tapering 2
The American Gastroenterological Association recommends that medical treatment with sulfasalazine, corticosteroids, azathioprine should be tried before surgery, except in emergencies 3, 6
For severe/refractory cases, the American Gastroenterological Association suggests considering TNF-alpha antagonists and/or thalidomide 2

Common Pitfalls and Caveats

The European League Against Rheumatism recommends avoiding cyclosporine A in patients with central nervous system involvement due to potential neurotoxicity 7
The American Heart Association recommends that anticoagulants should generally be avoided in Behçet's disease with venous thrombosis due to risk of bleeding, especially with potential coexisting pulmonary arterial aneurysms 9
The European League Against Rheumatism suggests that young men with early disease onset have higher risk of severe disease and may benefit from early systemic immunosuppression with azathioprine 1
The American Heart Association recommends that post-thrombotic syndrome is frequent with recurrent deep vein thrombosis and may result in difficult-to-treat leg ulcers 1

Initial Steroid Dosing Regimen for Behçet's Disease

Steroid Dosing Based on Organ Involvement

For patients with Behçet's disease requiring systemic corticosteroid therapy, the European League Against Rheumatism recommends initial treatment with high-dose glucocorticoids, typically starting with oral prednisolone at 1 mg/kg/day for acute attacks, followed by a gradual taper over 2-3 months based on clinical response 10, 11
For isolated oral and genital ulcers, the American College of Rheumatology suggests topical corticosteroids as the first-line treatment, but for more extensive mucocutaneous lesions requiring systemic therapy, start with oral prednisolone 1 mg/kg/day 12, 11
For posterior segment inflammation, the European League Against Rheumatism recommends starting with high-dose intravenous methylprednisolone pulses (1 g/day for 3-7 days), followed by oral prednisolone at 1 mg/kg/day, and combining with azathioprine 2.5 mg/kg/day as a steroid-sparing agent 12
For severe eye disease, consider adding either cyclosporine A or infliximab to the regimen, as recommended by the American Academy of Ophthalmology 10

Steroid Tapering Protocol

After achieving clinical response, the European League Against Rheumatism suggests beginning tapering prednisolone by 5-10 mg every 10-15 days, aiming to reach a maintenance dose of 5-10 mg/day, and continuing maintenance therapy for at least 2 years and for at least 12 months after normalization of inflammatory markers 12, 13

Important Considerations and Precautions

The American College of Rheumatology recommends always combining systemic corticosteroids with appropriate steroid-sparing agents to minimize long-term steroid exposure, and providing calcium and vitamin D supplementation to all patients on corticosteroids 12, 13
The European League Against Rheumatism suggests performing bone DEXA scanning at 1-2 yearly intervals while on steroids, and monitoring for steroid-related side effects including hyperglycemia, hypertension, and mood changes 13

Monitoring Response

The American College of Rheumatology recommends assessing clinical symptoms and inflammatory markers (ESR, CRP) regularly, and considering repeat imaging for neurological or vascular involvement 12, 10
For ocular involvement, regular ophthalmologic examinations are essential, as recommended by the American Academy of Ophthalmology 12
If inadequate response after 3 days of high-dose steroids, consider early introduction of biologics such as infliximab, as suggested by the European League Against Rheumatism 10

Treatment of Behçet's Disease with Retinal Vasculitis

Initial Treatment Approach

The European League Against Rheumatism recommends that any patient with Behçet's disease and inflammatory eye disease affecting the posterior segment should be on a treatment regimen that includes azathioprine (2.5 mg/kg/day) and systemic corticosteroids 14, 15
Azathioprine has been shown to decrease hypopyon uveitis attacks, stabilize visual acuity, and decrease the development of new eye disease with long-term benefits 14
Systemic corticosteroids are typically started at high doses (1 mg/kg/day of prednisolone) for rapid suppression of inflammation during acute attacks 16
Local and systemic corticosteroids are generally used during acute attacks, but should never be used alone in patients with posterior uveitis 14

Treatment for Severe or Refractory Disease

For severe eye disease (defined as >2 lines of drop in visual acuity on a 10/10 scale and/or retinal vasculitis or macular involvement), treatment should be escalated to either cyclosporine A or infliximab in combination with azathioprine and corticosteroids 14, 16, 15
Cyclosporine A (2-5 mg/kg/day) has demonstrated rapid and significant improvement in visual acuity and reduced frequency and severity of ocular attacks in three RCTs, though renal dysfunction, hypertension, and nephrotoxicity are concerns 14, 15
Infliximab has shown promising results for refractory eye disease, particularly in combination with other immunosuppressives, with rapid response times (1-5 days) 14
Interferon-alpha, alone or in combination with corticosteroids, appears to be a second-choice option for eye disease with sustained responses and high remission rates 14, 16

Common Pitfalls and Considerations

Due caution for tuberculosis is important when using infliximab, especially as endemic areas for Behçet's disease are also endemic for tuberculosis 14
Consider drug-free, long-term remission after withdrawal of successful anti-TNF treatment combined with azathioprine given for 2 years in a proportion of patients with sight-threatening ocular disease 16

Management of Behçet's Disease with Posterior Segment Involvement

Immediate Treatment Strategy

The European League Against Rheumatism recommends that any patient with Behçet's disease and inflammatory eye disease affecting the posterior segment must be on a treatment regimen that includes azathioprine and systemic corticosteroids, as corticosteroids should never be used alone in this setting 17, 18

Escalation for Severe Disease

The American College of Rheumatology suggests that given the presence of disc hemorrhages, RNFL hemorrhages, and periphlebitis, patients meet criteria for severe eye disease requiring treatment escalation with either infliximab or cyclosporine A added to the azathioprine and corticosteroid regimen 17, 18
The European League Against Rheumatism recommends avoiding cyclosporine A if any CNS involvement is present or suspected, due to potential neurotoxicity 17, 18

Managing Steroid-Induced Diabetes

Metabolic Management

The American Diabetes Association suggests coordinating closely with endocrinology or primary care to optimize glycemic control with antidiabetic medications, as uncontrolled hyperglycemia can worsen retinal disease independent of Behçet's activity 19

Surgical Management of Vascular Complications in Behçet Syndrome

Post‑operative Vascular Complications

Anastomotic pseudo‑aneurysms develop in approximately 13 % of patients within 18 months after vascular surgery, reflecting persistent inflammation at the suture line. 20

Therapeutic Options for Vascular Lesions

Endovascular repair using stent‑grafts has been reported as an alternative to open surgery for arterial aneurysms in Behçet syndrome. 20

Peri‑operative Immunosuppression

Adequate immunosuppressive therapy should be administered both before and after surgical intervention to reduce the risk of postoperative inflammatory complications. 20