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There is a group of patients with chronic course in sarcoidosis, and it is this group that many of the new steroid sparing agents have been developed. In this manuscript, I will concentrate on three new agents that have been developed for sarcoidosis; antibiotic minocycline, the cytotoxic agent leflunomide, and the anti-tumor necrosis factor agent infliximab. Minocycline and doxycycline was reported as useful for sarcoidosis, and our preliminary results on 57 sarcoidosis patients indicate that at least 40% have had some sort of response, usually for skin lesions. The drug has activity against Propiniobacterium acnes, but it also has immunomodulatory effct, therefore the mechanism of action for the drug in sarcoidosis should be considered from both aspects of an antibiotic and anti-inflammatory effect.The use of cytotoxic drugs has become a standard approach to patients with chronic sarcoidosis. Leflunomide is similar to methotrexate which have been found useful in some patients with sarcoidosis and is associated with less toxicity. We have recently reported that the response rate of the drug was slightly better for ocular disease, but the drug was effective in more than 70% of patients with pulmonary disease. We found the leflunomide was well tolerated and could be used in most patients who developed toxicity with methotrexate. Tumor necrosis factor (TNF) has been shown to be released at increased levels by alveolar macrophages by patients with active sarcoidosis. Infliximab is a chimeric monoclonal antibody which binds TNF and has been found to be effective for treatment of rheumatoid arthritis and Crohns disease. Several case reports and case series have reported the utility of infliximab for sarcoidosis. Our regimen is to give infliximab at 5mg/kg initially, week two, and then every four to six weeks. Infliximab causes lysis of cells releasing TNF, thus the effect of the drug may not be just inactivation of TNF, but also cytotoxicty of cells actively releasing TNF. Considering the increased risk for reactivation of tuberculosis, we have elected not to treat with infliximab in those tuberculosis infection was suggested on chest x-ray films.
- 日本サルコイドーシス/肉芽腫性疾患学会の論文
日本サルコイドーシス/肉芽腫性疾患学会 | 論文
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