Behcet Syndrome Medication

Choice of medications depends on a patient's clinical manifestations of Behçet syndrome.

• Ocular, CNS, and large vessel involvement requires corticosteroids and a second-line agent such as a cytotoxic or biologic medication. Corticosteroids have a suppressive effect on most manifestations of Behçet syndrome but do not prevent dementia or blindness and are associated with side effects that increase with duration of therapy.
• Azathioprine is widely accepted as initial therapy for significant ocular involvement, especially posterior segment disease. Cyclophosphamide, cyclosporine, and azathioprine may be used for large vessel involvement, with cyclophosphamide preferred for arterial aneurysms. Corticosteroids, azathioprine, interferon-alfa, cyclophosphamide, methotrexate, and tumor necrosis factor-alpha (TNF-alpha) blockers have been reported to be efficacious in CNS disease; cyclosporin should be avoided in CNS involvement. Increasing reports and case series suggest the efficacy of biologics in major organ system involvement, especially TNF-alpha blockade.
• Colchicine is used for treatment and prevention of ulcerations and treatment of arthritis. Corticosteroids, sulfasalazine, and azathioprine have also been shown to be useful in ulcer disease, and TNF-alpha antagonists and thalidomide have been reported to be efficacious in resistant disease.
• Close communication between subspecialists, such as ophthalmologists and neurologists, is important for patient care.

Class Summary

These agents are useful in decreasing frequency of mucosal ulcerations, the skin findings of pseudofolliculitis and erythema nodosum, and can be useful in the management of uveitis and retinal vasculitis.

Colchicine

Mechanism of action is unknown, but may have to do with decreased motility and lactic acid production of leukocytes. First-line therapy for PO ulcerations, ocular manifestations, and skin lesions.

Class Summary

This agent decreases acute inflammatory manifestations of Behçet syndrome. Depending on patient needs, this agent may be administered topically, orally, parenterally, or by intraocular injection.

Triamcinolone topical (Aristocort, Kenalog)

Topical treatment is useful to decrease the pain and inflammation of aphthous ulcers.

Betamethasone ointment (Alphatrex, Diprolene, Maxivate)

Useful to decrease the pain and inflammation of genital ulcers.

Dexamethasone injectable (Decadron)

Administered subtenon intraocular injection for retinal vasculitis.

Prednisone (Deltasone, Orasone)

Low-dose: Second-line therapy for erythema nodosum, anterior uveitis, and arthritis. High-dose: First-line therapy for GI lesions, acute meningoencephalitis, chronic progressive CNS lesions, and arthritis. Second-line treatment for retinal vasculitis and venous thrombosis.

Methylprednisolone (Medrol, Solu-Medrol)

Used as first-line therapy for acute meningoencephalitis, chronic progressive CNS lesions, and arteritis. Alternate therapy for GI lesions and venous thrombosis.

Class Summary

These agents are used for the more serious long-term effects of Behçet syndrome (ie, ocular and CNS involvement, severe vasculitis).

Azathioprine (Imuran)

Used as alternate therapy for retinal vasculitis, arthritis, chronic progressive CNS lesions, arteritis, and venous thrombosis.

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Chlorambucil (Leukeran)

Used as alternate therapy for retinal vasculitis, chronic progressive CNS lesions, arteritis, and venous thrombosis.

Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription. Many are discarding this therapy because of significant cumulative toxicity and increased risk of malignancy.

Cyclophosphamide (Cytoxan, Neosar)

Used as alternate therapy for retinal vasculitis, arthritis, chronic progressive CNS lesions, arteritis, and venous thrombosis.

A cell cycle phase–nonspecific antineoplastic agent and immunosuppressant. A prodrug that requires activation by the cytochrome P-450 system in order to be cytotoxic.

Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Because of toxicities, cyclophosphamide is being replaced by calcineurin inhibitors and antitumor necrosis factor agents where available.

Methotrexate (Folex PFS, Trexall)

An antimetabolite that interferes with the enzyme dihydrofolate reductase, leading to depletion of DNA precursors and inhibition of DNA and purine synthesis, particularly adenosine.

Unknown mechanism of action in treatment of inflammatory reactions (although may involve adenosine receptors and cell-cell adhesion); may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response.

Cyclosporine (Sandimmune, Neoral)

First-line therapy for retinal vasculitis.

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for a variety of organs. For children and adults, base dosing on ideal body weight.

Class Summary

Thalidomide has a broad range of immunomodulatory properties. Use of this drug is limited by well-documented teratogenicity and potentially irreversible peripheral neuropathy.

Thalidomide (Thalomid)

Used for aphthous ulcerations and may also be effective in erythema nodosum lesions. An immunomodulatory agent whose mode of action is not fully known. May suppress TNF-alpha. Downregulates some adhesion molecules.

Class Summary

Blockade of TNF-alpha by biologics have been shown in uncontrolled reports to be beneficial in uveitis, severe GI disease, severe ulcerations, and CNS vasculitis. Long-term efficacy is unknown.

Etanercept (Enbrel)

Soluble p75 TNF receptor fusion protein (sTNFR-Ig). Inhibits TNF binding to cell surface receptors, which, in turn, decreases inflammatory and immune responses.

Infliximab (Remicade)

Neutralizes cytokine TNF-alpha and inhibits it from binding to TNF-alpha receptor.

Class Summary

These agents are used to improve peripheral blood flow and to improve delivery of oxygen to tissue suffering from vascular disease.

Pentoxyfylline (Trental)

Inhibits production of various proinflammatory cytokines, particularly TNF. FDA-approved for use in peripheral vascular disease. May alter rheology of red blood cells, which in turn reduces blood viscosity. Has been reported to be helpful in orogenital ulcerations.