What is the best course of treatment for a patient with Behcet's disease and steroid-induced diabetes who presents with right eye disc hemorrhages, collaterals, retinal nerve fiber layer (RNFL) hemorrhages, and periphlebitis?

Management of Behçet's Disease with Posterior Segment Involvement and Steroid-Induced Diabetes

This patient requires immediate initiation of azathioprine (2.5 mg/kg/day) combined with high-dose systemic corticosteroids, with urgent consideration for escalation to infliximab or cyclosporine A given the severity of retinal vasculitis with disc hemorrhages and periphlebitis, while simultaneously addressing the steroid-induced diabetes through dose optimization and metabolic management. 1

Immediate Treatment Strategy

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. 2, 1 This is non-negotiable for posterior uveitis, as corticosteroids should never be used alone in this setting. 1, 3

Initial Immunosuppressive Regimen

• Start azathioprine at 2.5 mg/kg/day immediately as the cornerstone steroid-sparing agent, which has been shown to decrease hypopyon uveitis attacks, stabilize visual acuity, and prevent development of new eye disease with long-term benefits. 1, 3

• Initiate high-dose corticosteroids with intravenous methylprednisolone pulses (1 g/day for 3-7 days) for acute posterior segment inflammation, followed by oral prednisolone at 1 mg/kg/day. 1

• Begin tapering prednisolone by 5-10 mg every 10-15 days after achieving clinical response, aiming for a maintenance dose of 5-10 mg/day to minimize further worsening of steroid-induced diabetes. 1

Escalation for Severe Disease

Given the presence of disc hemorrhages, RNFL hemorrhages, and periphlebitis, this patient meets criteria for severe eye disease requiring treatment escalation. 2, 1

Biologic or Advanced Immunosuppression

• Add either infliximab or cyclosporine A to the azathioprine and corticosteroid regimen for severe retinal disease with vasculitis. 2, 1

• Infliximab is preferred in this case given the steroid-induced diabetes, as it allows for more aggressive steroid tapering and has demonstrated rapid response times (1-5 days) with sustained remission rates. 1, 3

• If infliximab is chosen, screen for tuberculosis first, as endemic areas for Behçet's disease overlap with tuberculosis prevalence. 1

• Cyclosporine A (2-5 mg/kg/day) is an alternative that has shown rapid improvement in visual acuity and reduced frequency of ocular attacks in RCTs, though renal dysfunction, hypertension, and nephrotoxicity are concerns that must be monitored. 1

• Interferon-alpha represents a second-choice option if both infliximab and cyclosporine A are contraindicated or ineffective, with sustained responses and high remission rates. 1

Managing Steroid-Induced Diabetes

Corticosteroid Optimization

• Aggressive steroid tapering is essential once azathioprine and biologic therapy are established, as the steroid-sparing effect of azathioprine is well-documented. 4

• Target the lowest effective corticosteroid dose (ideally ≤5-10 mg/day prednisolone) within 2-3 months to minimize hyperglycemic effects while maintaining disease control. 1

Metabolic Management

• Coordinate 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. 2

• Provide calcium and vitamin D supplementation to all patients on corticosteroids, and perform bone DEXA scanning at 1-2 yearly intervals. 1

• Monitor for additional steroid-related complications including hypertension and mood changes during the treatment course. 1

Monitoring and Follow-Up

Ophthalmologic Surveillance

• Regular ophthalmologic examinations are mandatory to detect early signs of disease progression or treatment response, with close collaboration between rheumatology and ophthalmology. 3, 4

• Assess for subclinical inflammation using modern imaging methods such as optical coherence tomography and fluorescein angiography to guide therapeutic decisions. 5

Laboratory Monitoring

• Monitor inflammatory markers (ESR, CRP) regularly to assess disease activity and guide treatment adjustments. 1

• Check complete blood count and liver function tests given azathioprine therapy, as approximately 2% of patients discontinue therapy due to side effects. 4

• Monitor renal function if using cyclosporine A due to nephrotoxicity risk. 1

Critical Pitfalls to Avoid

• Never use systemic corticosteroids alone in patients with posterior uveitis—they must always be combined with immunosuppressives like azathioprine. 1, 3

• Avoid cyclosporine A if any CNS involvement is present or suspected, due to potential neurotoxicity. 2

• Do not delay escalation to biologics if inadequate response occurs after 3 days of high-dose steroids, as young male patients with early disease onset have the most severe disease course and worst prognosis. 1, 3

Prognostic Considerations

• This patient is at high risk for poor visual outcomes given the severity of retinal vasculitis with disc hemorrhages and periphlebitis, which are associated with sight-threatening disease. 3, 6

• Aggressive early treatment with biologics has transformed outcomes and can achieve drug-free long-term remission after 2 years of successful anti-TNF treatment combined with azathioprine in a good proportion of patients. 3

• New vascular involvement may occur in up to half of patients treated with steroids alone, emphasizing the critical importance of combination immunosuppressive therapy. 3, 4