乾癬與乾癬關節炎治療的證據醫學

Evidence-Based Medicine in the Treatments of Psoriasis and Psoriatic arthritis

乾癬的盛行率約為全人口的1-3%，其中7～42%的人會合併關節炎、腎炎及虹彩炎等合併症，也會造成肌腱附著點發炎。免疫學的研究發現，乾癬病人有過多不能自然凋亡的記憶性T淋巴球，包括CD4+ 和CD8+ T型淋巴球，大多數乾癬病灶T型淋巴球帶有CD45RO表面標記。治療乾癬，需同時兼顧皮膚與關節，也必須局部治療與免疫調節相管齊下，才能真正改善自體免疫的失調。乾癬的治療，輕度患者以局部外用藥膏為主，中度患者，應考慮照光療法，重度患者，應考慮免疫調節藥物及混合療法。外用藥膏的使用原則是先用類固醇藥膏，加上水楊酸藥膏，較嚴重者加上維他命A或維他命D衍生物藥膏，全身性乾癬或頭皮可加上煤焦油藥水（polytar）。全身性類固醇及hydroxychloroquine常加重乾癬皮膚病灶，使用需小心。乾癬關節炎的治療，物理及非類固醇消炎藥是最基本的治療，中重度患者需加上免疫調節劑。免疫調節劑以高劑量Methotrexate、Cyclosporine及Sulfasalazine最有證據顯示有益。一篇隨機雙盲試驗證實Leflunomide對乾癬及乾癬關節炎有效。近年來，生物製劑有突破性的進展， Etanercept （TNF - α fusion protein; Amgen Inc/W yeth） 、Infliximab （Monoclonal antibody against TNF- α Centocor Inc） 及Alefacept （LFA-3 fusion protein against CD2; Biogen） 對乾癬的皮膚病灶及關節炎都療效甚佳，但藥價昂貴，應列為最後一線藥物。Efalizumab （anti-CDlla; Genentech Inc/XOMA Ltd/Serono SA）及interleukin-10皆有初步研究顯示有效。單用局部外用藥膏，並不能改善關節炎。只用消炎止痛藥及金製劑、hydroxychloroquine等，也不能改善皮膚病灶。對同時有皮膚病灶與關節炎的患者，Methotrexate與Cyclosporine目前最有實証的免疫調節劑。

Psoriasis affects approximately 1-3% of the general population and 7% of them can develop psoriatic arthritis (PsA). There are four types of psoriasis including gutta, plaque, erythroderma, pustular and five types of PsA including polyarthritis, oligoarthritis, spondylitis, distal inter-phalangeal and arthrtis mutilans. For patients with psoriasis, topical therapies including high-potent corticosteroid, vitamin D analogues, tar, aloe vera, salicyclic acid were all proven to be effective and relatively safe. Phototherapy by oral psoralen followed by UV A (PUV A) had strong efficacy but long-term use had the concern of skin carcinoma. Narrow band UVB, although weaker efficacy, seemed to be safer than PUV A. Methotrexate, cyclosporine were the two most evident immunosuppressive drugs for refractory patients. For patients with PsA, physiotherapy, nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, sulsasalazine and cyclosporine were proved to be effective but adverse effects need to be monitored carefully. Other therapies used to treat RA, including gold salt, anti-malarials and azathioprine, need further investigations. The newer biologic agents appear to have greater efficacy by targeting specific mediators involved in the pathogenesis of psoriasis and PsA. Among these biologics, Alefacept CLFA -3 fusion protein against CD2; Biogen). Infliximab Monoclonal antibocly against TNF-α Centocor Inc), etanercept (TNF-α fusion protein ; Amgen Inc/Wyeth), and efalizumab (anti-CD11a; Genentech Inc/XOMA Ltd/Serono SA) have achieved successful therapy without major organ toxicity. The Food and Drug Administration has recently approved alefacept for treatment of psoriasis and etanercept for PsA.