Kumar Bhushan, Saraswat Abir, Kaur Inderjeet
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012, India.
Int J Dermatol. 2002 Jul;41(7):444-8. doi: 10.1046/j.1365-4362.2002.01530.x.
Methotrexate (MTX) is one of the most effective antipsoriatic drugs available. Although it is undeniably hepatotoxic, it can be used safely in most patients with severe psoriasis if established guidelines are followed. Current opinion on the monitoring of hepatic damage is divided, however, and the need for repeated liver biopsies during MTX therapy is being re-examined. We have used MTX in a short-term protocol in our patients with psoriasis for the past 20 years, and have recently attempted to minimize or eliminate the need for liver biopsies using this regimen. Data on 244 psoriatics who were given MTX from 1981 to 2000 have been reviewed. Our protocol entailed the use of weekly oral MTX at the full therapeutic dose during episodes of peak disease activity, with tapering off of MTX when the disease subsided in response to treatment combined with natural/seasonal remission. Intensive topical and heliotherapy were encouraged throughout to facilitate the earliest possible drug withdrawal and the longest possible drug-free interval before the next relapse. Strict inclusion criteria were applied before starting MTX. A total of 243 cycles of MTX therapy have been given to 197 evaluable patients. More than 75% improvement occurred in 88% of patients in 8.5 +/- 5.1 weeks. The mean cumulative dose was 709.3 +/- 369.2 mg and the mean duration of follow-up was 16.5 +/- 9.1 months. Fifteen (6.1%) patients had serious adverse effects requiring the cessation of therapy. Only three patients had deranged liver function tests. Thirty-four pre-MTX and 13 post-MTX liver biopsies were taken, which revealed grade I or II changes that were nonprogressive. Our experience with short-term MTX therapy has enabled us to safely administer MTX to our patients with minimal recourse to liver biopsy. In developing countries, where advanced noninvasive methods for the assessment of liver damage are unaffordable or unavailable, this interrupted, short-term regimen may present an acceptable and safe method of using MTX in carefully selected patients with severe psoriasis.
甲氨蝶呤(MTX)是目前最有效的抗银屑病药物之一。尽管它具有不可否认的肝毒性,但如果遵循既定指南,大多数重度银屑病患者仍可安全使用。然而,目前对于肝损伤监测的观点存在分歧,MTX治疗期间重复进行肝活检的必要性正在重新审视。在过去20年里,我们在银屑病患者中采用了短期治疗方案使用MTX,最近还尝试通过该方案尽量减少或避免肝活检的需求。我们回顾了1981年至2000年期间接受MTX治疗的244例银屑病患者的数据。我们的方案是在疾病活动高峰期,以全治疗剂量每周口服MTX,当疾病因治疗反应及自然/季节性缓解而消退时逐渐减少MTX剂量。在整个治疗过程中鼓励强化局部治疗和光疗,以促进尽早停药,并在下次复发前尽可能延长无药间期。开始MTX治疗前应用严格的纳入标准。共对197例可评估患者进行了243个周期的MTX治疗。88%的患者在8.5±5.1周内病情改善超过75%。平均累积剂量为709.3±369.2mg,平均随访时间为16.5±9.1个月。15例(6.1%)患者出现严重不良反应,需要停止治疗。只有3例患者肝功能检查结果异常。进行了34次MTX治疗前和13次MTX治疗后的肝活检,结果显示为I级或II级且无进展性变化。我们短期MTX治疗的经验使我们能够在尽量少进行肝活检的情况下,安全地为患者使用MTX。在发展中国家,先进的肝损伤评估无创方法难以负担或无法获得,这种间断的短期治疗方案可能为精心挑选的重度银屑病患者提供一种可接受且安全的MTX使用方法。