Coven T R, Murphy F P, Gilleaudeau P, Cardinale I, Krueger J G
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY, USA.
Arch Dermatol. 1998 Oct;134(10):1263-8. doi: 10.1001/archderm.134.10.1263.
Psoriasis vulgaris can be effectively treated with trimethylpsoralen (TMP) bath PUVA therapy (psoralen plus UVA), but no data exist on the extent to which psoriatic pathology is affected by this treatment, or on its cellular mechanism of action.
Eleven patients with recalcitrant psoriasis vulgaris were treated with TMP bath PUVA therapy and observed through clinical and histological measures. Clinical resolution of psoriasis was achieved in 10 of 11 patients. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 90% of individuals treated with TMP bath PUVA. Epidermal acanthosis was reduced by 40% at 2 weeks and 66% by the end of treatment. Epidermal improvement correlated best with reduction in intraepidermal T lymphocytes, which were reduced by 76% at 2 weeks of treatment and 93% at the end of treatment. Furthermore following TMP bath PUVA therapy, the numbers of epidermal CD1a+ Langerhans cells were markedly reduced, and CD86+ cells were eliminated. Through in vitro assays, TMP was found to be about 10,000-fold more active as a lymphotoxic agent compared with 8-methoxypsoralen (8-MOP). Additionally, at physiologic concentrations, lymphocytes were killed more readily by TMP PUVA (TMP plus UVA) than were keratinocytes.
Treatment with TMP bath PUVA was effective in treating moderate to severe psoriasis, even in darker pigmented individuals. It is likely that this treatment ameliorates psoriasis through direct effects on activated leukocytes in lesional skin.
寻常型银屑病可通过三甲补骨脂素(TMP)浴光化学疗法(补骨脂素加紫外线A,PUVA)有效治疗,但尚无关于该疗法对银屑病病理影响程度及其细胞作用机制的数据。
11例顽固性寻常型银屑病患者接受了TMP浴PUVA治疗,并通过临床和组织学方法进行观察。11例患者中有10例实现了银屑病的临床缓解。接受TMP浴PUVA治疗的个体中,90%实现了表皮增生(以角蛋白16表达为标志)的组织病理学缓解。治疗2周时表皮棘皮症减少了40%,治疗结束时减少了66%。表皮改善与表皮内T淋巴细胞减少最相关,治疗2周时减少了76%,治疗结束时减少了93%。此外,TMP浴PUVA治疗后,表皮CD1a + 朗格汉斯细胞数量明显减少,CD86 + 细胞被清除。通过体外试验发现,与8 - 甲氧基补骨脂素(8 - MOP)相比,TMP作为淋巴细胞毒性剂的活性高约10000倍。此外,在生理浓度下,TMP光化学疗法(TMP加紫外线A)比角质形成细胞更容易杀死淋巴细胞。
TMP浴PUVA治疗对中重度银屑病有效,即使在色素沉着较深的个体中也是如此。这种治疗可能通过对皮损皮肤中活化白细胞的直接作用改善银屑病。