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In addition, the effects of the drug are temporary, and discontinuation of the treatment results in recurrence of the OUs and GUs. The effectiveness of the thalidomide is lost about 20 days after discontinuation of the drug. Neurological side effects and teratogenic risc of thalidomide limit the clinical application. In a randomised, double-blind, placebo-controlled study of 73 patients, azathioprine has been found to be an effective choice in OUs and GUs besides ocular inflammation and arthritis.

Azathioprine was significantly better than placebo in preventing the development of new eye disease. Myelotoxicity, gastrointestinal complaints, immunosuppression, opportunistic infections, and hepatotoxicity are the main side effects. Cyclophosphamide is the fast-acting alkylating agent. It has been found as a beneficial therapeutic agent for eye disease and systemic vasculitis neurologic involvement and arterial aneurysms.

Myelosuppression, pulmonary fibrosis, renal toxicity, hemorrhagic cystitis, infertility, malignancy, and alopecia are the major adverse effects of cyclophosphamide. Cyclosporin A CyA is an immunosuppressant agent which selectively inhibits T lymphocytes. CyA is still one of the most effective agents for the treatment of uveitis which reduces the frequency of ocular exacerbations and improves visual acuity. In the study of BenEzra et al. CyA treatment was found to be more effective in reducing OUs, GUs, cutaneous lesions, thrombophlebitis as well as articular symptoms and neurologic symptoms.

Therefore, CyA is also an effective alternative for mucocutaneous lesions; however, it should be reserved for the most severe cases because of its significant long-term adverse effects such as renal failure, hypertension, neurologic toxicity, and hirsutism. It is wise to remember that neurological manifestations occur more frequently in BD patients under CyA treatment.

However, their antiviral and immunomodulatory effects appear to be the possible mechanisms. In a newer study, Onal et al. Nausea, vomiting, anorexia, diarrhea, loss of weight, hematologic changes, transient raising of hepatic transaminases are seen less frequently. It also reduces the dosage of immunosuppressors. The drug had a clear effect on OUs and nodular lesions, and the response was as early as the first week. A recent position paper concluded that infliximab is recommended as an add-on therapy for severe BD, refractory or intolerant to traditional immunosuppressive regimens.

It still needs further controlled studies in large series. Rituximab is a chimeric monoclonal antibody against CD20, a B-cell differentiation marker. The authors concluded that rituximab was efficient in severe ocular manifestations of BD, and total adjusted disease activity index improved significantly after 6 months with rituximab, but not with cytotoxic combination therapy group.

Several open studies of methotrexate 7. Methotrexate is not recommended in pregnancy and lactation, and severe bone marrow depression, liver dysfunction, acute infections, renal insufficiency, and mucositis are important side effects of the drug. Mycophenolate mofetil MMF was found to be safe and effective in controlling cystoid macular oedema and in reducing the uveitis relapse rate in patients not responding to traditional immunosuppressants.

MMF is generally well tolerated; the most common side effects involve gastrointestinal and genitourinary symptoms. However, recurrences occurred in all patients after discontinuation of treatment. Pentoxifylline has also been described as alternative treatments for ocular lesions in few patients with BD. Although various treatment modalities appear, surgical intervention often is indicated for arterial aneurysms.

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