Medication Summary
The drugs used to treat Behçet disease are generally immunosuppressive. Because the cause of Behçet disease is unknown, therapy is directed at diminishing symptoms by suppressing the immune system. These medications may increase the risk of infection due to the nonspecific nature of immunosuppression. Symptomatic therapy is directed at specific symptoms (eg, oral ulcers, arthritis).
Corticosteroids
Class Summary
These agents may be used orally or parenterally for systemic symptoms, topically for ulcers or ocular involvement, or intra-articularly for arthritis.
Methylprednisolone (Solu-Medrol)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Administered intravenously in severe cases.
Prednisone (Deltasone, Sterapred, Orasone)
Decreases release of inflammatory mediators, neutrophil migration, monocyte and T-cell function.
Dexamethasone (Decadron)
Has many pharmacologic benefits but significant adverse effects. Stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines (eg, TNF-alpha, IL-6, IL-2, and IFN-gamma). The inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. Suppresses lymphocyte proliferation through direct cytolysis and inhibits mitosis. Breaks down granulocyte aggregates, and improves pulmonary microcirculation.
Adverse effects of all glucocorticoids include hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose-dependent or duration-dependent.
Readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Lacks salt-retaining property of hydrocortisone.
Patients can be switched from an IV to PO regimen in a 1:1 ratio.
Immunosuppressive agents
Class Summary
These agents decrease the immune response that causes signs and symptoms of Behçet disease.
Azathioprine (Imuran)
Purine analog that inhibits DNA synthesis. The 50-mg tablets are metabolized to 6-mercaptopurine in the liver and RBCs.
Cyclophosphamide (Cytoxan, Neosar)
Potent alkylating agent that inhibits various cellular functions. Alkylation of DNA results in cross-linking, impaired DNA synthesis, and cell death.
Chlorambucil (Leukeran)
Potent alkylating agent that inhibits various cellular functions. Alkylation of DNA results in cross-linking, impaired DNA synthesis, and cell death. Onset of action is slower than cyclophosphamide.
Immunomodulators
Class Summary
These agents affect the immune system in various ways, thus decreasing the autoimmune symptoms characteristic of Behçet disease. Immunomodulators do not, however, cause the generalized immunosuppression characteristic of immunosuppressive drugs.
Colchicine
Inhibits cellular microtubule formation and may cause a transient leukopenia, followed by leukocytosis. Use in autoimmune disease primarily is empiric, and mechanism of action in decreasing inflammation is not clear, nor is it truly an immunomodulating agent.
Sulfasalazine (Azulfidine)
A conjugate of 2 drugs—sulfapyridine and 5-aminosalicylic acid—originally developed for the treatment of rheumatoid arthritis. Useful for the treatment of inflammatory bowel disease, spondyloarthropathies, rheumatoid arthritis, and Behçet disease. Enteric coated pills may decrease GI adverse effects.
Dapsone (Avlosulfon)
May be useful for erythema nodosum and genital ulcers. Not approved for this use but approved for the treatment of dermatitis herpetiformis and leprosy.
Levamisole (Ergamisol)
Used for patients with Behçet disease to treat genital and aphthous ulcers. An immunomodulator approved for the treatment of colon cancer. Restores immune function and stimulates T-cell activation and proliferation and monocyte function. Stimulates neutrophil chemotaxis, adhesion, and mobility.
Cyclosporine (Sandimmune, Neoral)
Used for uveitis. Originally used in transplant patients, and its use has been expanded to various autoimmune diseases. Inhibits cellular activation, most prominently T lymphocytes, at an early phase via calcineurin inhibition without being cytotoxic.
Tacrolimus (Prograf)
Immunomodulator produced by the bacteria Streptomyces tsukubaensis. Mechanisms of action similar to cyclosporine. Primarily used in transplants but used in Behçet disease to treat uveitis.
Thalidomide (Thalomid)
Used for aphthous ulcerations and may be effective in erythema nodosum lesions. An immunomodulatory agent whose mode of action is not fully known. May suppress TNF-alpha. Down-regulates some adhesion molecules.
Infliximab (Remicade)
A monoclonal antibody directed at TNF. Neutralizes cytokine TNF-alpha and inhibits it from binding to TNF-alpha receptor. Infliximab has been used successfully in treating CNS vasculitis, colonic ulcerations, esophageal ulcerations, panuveitis, mucocutaneous ulcers, and polyarthritis. Doses of 3, 5, or 10 mg/kg were dispensed. Infusions were given 1-4 times in a 2-mo period, with or without regular maintenance doses thereafter. Remission was achieved in all patients, with follow-up ranging from 2 mo to 2 y. No significant side effects were noted during or after the infusions. Results were usually seen within the first 24 h of the infusion. These infusions were given as adjuvants to systemic immunosuppressant therapy.
In addition, an anecdotal report from Estrach et al documents the treatment of a 38-year-old woman with severe iritis, arthritis, and ulcers that failed to respond to other immunomodulators. She was treated with etanercept, without improvement. She was then switched to infliximab. Infusions of 3 mg/kg were given at 0 and 2 weeks and then at intervals of 8 weeks for treatment of rheumatoid arthritis, together with methotrexate 7.5 mg PO once a week. According to the author, a remarkable response occurred soon after the first infusion, with marked improvement in arthralgia, resolution of urogenital ulceration and erythema nodosum, and reduction of fatigue. She remained healthy 1 yr later and continued with this therapy during remission.
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.
A 4-week double-blind placebo-controlled study of the use of etanercept in patients with Behçet disease was completed after a 4-week washout of systemic immunosuppressants. Patients with mucocutaneous lesions and arthritis were treated with etanercept 25 mg SC twice a week.
Good results were seen after the first week and were maintained throughout the study. Patients treated with etanercept had a 40% chance of remaining ulcer-free vs 5% with placebo. Another study used etanercept at the same dose for 6 months in patients with ocular involvement receiving systemic immunosuppressants. The benefits gleaned from use of etanercept were not sustained after 6-mo posttreatment follow-up.
DMARDs, PDE4 Inhibitors
Apremilast (Otezla)
Oral small molecule inhibitor of phosphodiesterase-4 specific for cyclic adenosine monophosphate (cAMP), resulting in increased intracellular cAMP levels. Indicated for oral ulcers associated with Behςet disease
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Oral aphthous ulcers secondary to Behçet disease.
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Behçet disease. T2-weighted magnetic resonance images show brainstem involvement with meningoencephalitis in an 11-year-old girl with neurologic Behçet disease.
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Histology of Behçet disease ulcers revealing neutrophilic infiltrate and vasculitis.
Tables
Sign/Symptom |
Points |
Genital aphthosis |
2 |
Oral aphthosis |
2 |
Skin lesions |
2 |
Neurologic manifestations |
1 |
Vascular manifestations |
1 |
Positive pathergy test (optional) |
1 |
