Azathioprine for Retinal Vasculitis in Behçet's Disease
Azathioprine at 2.5 mg/kg/day combined with systemic corticosteroids is the first-line treatment for retinal vasculitis in Behçet's disease, with proven efficacy in decreasing inflammatory attacks and stabilizing visual acuity. 1
Initial Treatment Approach
- Any patient with Behçet's disease and inflammatory eye disease affecting the posterior segment (including retinal vasculitis) should receive azathioprine 2.5 mg/kg/day and systemic corticosteroids 1
- Start with oral prednisolone at 1 mg/kg/day for acute attacks, followed by a gradual taper over 2-3 months based on clinical response 2
- Consider gradual azathioprine dose escalation (starting at 50-100 mg daily and increasing to target dose over 2-4 weeks) to minimize gastrointestinal side effects 3
- Administer azathioprine with food to reduce nausea 3
Pre-Treatment Assessment
- Check thiopurine methyltransferase (TPMT) activity prior to initiating azathioprine therapy 3
- Normal TPMT activity: standard dosing (2.5 mg/kg/day)
- Intermediate (heterozygous) TPMT activity: reduced dose (1-1.5 mg/kg/day)
- Absent TPMT activity: avoid azathioprine due to high risk of severe myelosuppression
- Obtain baseline laboratory tests including complete blood count, liver function tests, and renal function tests 3
Monitoring Protocol
- Monitor liver function tests monthly for the first 3 months, then every 3 months 3
- Regular ophthalmologic examinations are essential to assess response to treatment 2, 3
- Monitor for clinical efficacy, including improvement in ocular inflammation and stabilization of visual acuity 3, 4
Treatment for Refractory Disease
- For severe eye disease (defined as >2 lines drop in visual acuity on a 10/10 scale and/or retinal vasculitis), add either cyclosporine A (2-5 mg/kg/day) or infliximab to the azathioprine and corticosteroid regimen 1
- Infliximab has shown superior efficacy compared to conventional therapy in reducing the number of relapses and improving visual outcomes in patients with retinal vasculitis who fail to respond to first-line treatment 5
- Alternatively, interferon-alpha with or without corticosteroids could be used for refractory cases 1, 2
Duration of Therapy
- Continue azathioprine treatment for at least 2 years for ocular Behçet's disease 3
- Consider indefinite maintenance therapy for severe disease, particularly with ocular involvement 3
- Long-term studies (up to 10 years) have shown sustained efficacy of azathioprine in combination with cyclophosphamide and prednisolone for ocular manifestations of Behçet's disease 6
Potential Side Effects and Management
- Hematologic toxicity (leukopenia, thrombocytopenia) can occur with azathioprine therapy 3, 4
- For mild cytopenia, reduce azathioprine dose; for severe cytopenia, discontinue medication and consult hematology 3
- Gastrointestinal symptoms (nausea, vomiting) can be managed by taking medication with food, splitting the daily dose, or temporarily reducing the dose 3
- Hepatotoxicity may occur; discontinue if significant liver function abnormalities develop 3, 7
Evidence of Efficacy
- A placebo-controlled randomized trial showed that azathioprine 2.5 mg/kg/day decreased hypopyon uveitis attacks (NNT = 4), stabilized visual acuity, and decreased the development of new eye disease (NNT = 2) 1
- Long-term follow-up showed that the beneficial effect of azathioprine continued over time 1
- In a study of 157 patients with severe uveitis related to Behçet's disease, 51.6% were complete responders and 41.4% were partial responders to azathioprine therapy 7
- Patients with retinal vasculitis and severe visual loss at diagnosis may have a less favorable response to azathioprine alone 7
Clinical Pearls and Pitfalls
- Azathioprine is a relative contraindication in pregnancy; its use should be carefully considered, weighing benefits and risks 3
- Avoid live vaccines during azathioprine treatment 3
- Young men with early disease onset have higher risk of severe disease and may benefit from early systemic immunosuppression with azathioprine 2
- Azathioprine when used in combination with systemic steroids is most effective at reducing the relapse rate of retinal vasculitis, but may be only partially effective in allowing a reduction in steroid dosage 4