Paired comparison of bathwater versus oral delivery of 8-methoxypsoralen in psoralen plus ultraviolet: A therapy for chronic palmoplantar psoriasis

BACKGROUND: Both bath psoralen plus ultraviolet A (PUVA) and oral PUVA with 8-methoxypsoralen (8-MOP) have been successfully used for the treatment of recalcitrant palmoplantar psoriasis. This trial was designed to assess the efficacy and side effects of the different treatment modalities in a randomized half-side comparison. Methods: Eight patients with moderate-to-severe psoriasis on soles (n = 6) and/or palms (n = 8) were randomly assigned to receive bath PUVA treatment on one side and oral PUVA on the other. Initial treatment dose was 50% of the minimal phototoxic dose evaluated for bath PUVA and oral PUVA. Treatment was given three times a week for 4 weeks. Before treatment and every week a severity index (SI) was assessed by summing the scores of erythema, infiltration, scaling and vesicles evaluated on a scale from 0 to 4. After 4 weeks of treatment the half-side trial was finished and the treatment was continued on both sides with the more effective treatment regimen. RESULTS: Both bath PUVA and oral PUVA achieved a reduction of the mean initial SI from 5.9 (95% confidence intervals (CI) 4.5-8.0) to 3.3 (1.8-6.0) (44% SI reduction, P < 0.005, Student's paired t-test) and 6.0 (5.0-7.8) to 2.9 (1.8-4.0) (52% SI reduction; P < 0.005), respectively. The statistical comparison of the entire 4-week study period revealed a significant better effect in lesions treated with oral PUVA compared with bath PUVA (P = 0.033). However, at 4 weeks, there was no significant difference between the achieved SI reduction of oral PUVA and bath PUVA. Systemic side effects (nausea and/or dizziness) were only observed after oral PUVA. CONCLUSION: This study gives evidence that in the first 4 treatment weeks oral PUVA is slightly more effective than bath PUVA but the former has more systemic side effects.     

口服阿维A结合光化学疗法治疗寻常型银屑病临床疗效观察

目的：评价口服阿维A结合光化学疗法治疗寻常型银屑病的疗效及不良反应。方法：60例寻常型银屑病患者随机分为两组，分别给予单一光化学治疗、口服阿维A及光化学治疗。结果：口服阿维A结合光化学治疗的疗效显著优于单一光化学治疗，长波紫外线的总暴露量可明显减少，可缩短近一半疗程。结论：口服阿维A结合光化学疗法是一种值得推广职至重度寻常型银屑病的方法。     

补骨脂素长波紫外线和窄谱中波紫外线治疗寻常性银屑病临床疗效观察

目的:观察补骨脂素长波紫外线(PUVA)和窄谱中波紫外线(NB-UVB)治疗寻常性银屑病的临床疗效及其影响因素。方法:分别采用PUVA和311nmNB-UVB照射治疗146例寻常性银屑病患者,并以银屑病面积和严重度指数(PASI)评价疗效,分析照射剂量等对疗效和复发的影响。结果:NB-UVB治疗寻常性银屑病的疗效与PUVA相当,NB-UVB组患者的治疗时间明显短于PUVA组,NB-UVB组患者1年内复发率高于PUVA组。结论:NB-UVB治疗寻常性银屑病与PUVA相比,不良反应较少,起效较快。     

Comparison of the relative therapeutic efficacy of 7-methyl pyridopsoralen and 8-methoxypsoralen in photochemotherapy in psoriasis treatment

A newly-synthesized, monofunctional psoralen derivative, 7-methyl pyrido (3,4-C) psoralen (MPP) was compared with 8-methoxypsoralen (8MOP) with respect to their therapeutic efficacy in photochemotherapy of psoriasis. Psoriatic lesions of six patients were treated with topical application of MPP plus UVA (MPP PUVA) or with 8MOP plus UVA (8MOP PUVA). The UVA doses used in each treatment were 7.5 or 10 J/cm² with MPP and from 1.2 to 3.6 J/cm² with 8MOP. In every patient, marked improvement was observed after 2 to 6 treatments with MPP PUVA or 8MOP PUVA. Three patients showed clearance of each psoriatic lesion treated 9 to 17 times with MPP or 8MOP PUVA. Althought MPP required much higher UVA doses than 8MOP, MPP PUVA was as effective as 8MOP PUVA in treating psoriasis. When irradiating with identical doses of UVA, MPP PUVA appeared to be less active than 8MOP PUVA. None of the patients developed any severe dermatitis reactions during 20 exposures to MPP PUVA, indicating that the probability of inducing allergic contact and photocontact dermatitis may be extremely low. Erythemogenic and pigmentogenic activities of MPP and 8MOP were also compared. The data demonstrated that 8MOP is more than 8 times as effective as MPP for both activities. With the UV doses used in this study, however, every patient produced marked pigmentation after MPP PUVA therapy. Finally, the UVA dose-dependency of MPP PUVA was studied with an additional patient. Both therapeutic and pigmentogenic effects increased as a function of the UVA dose; it appeared impossible to clear psoriasis without producing pigmentation.     

A reappraisal of the use of 5-methoxypsoralen in the therapy of psoriasis

5-methoxypsoralen (5-MOP) is considered an alternative to 8-methoxypsoralen (8-MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy and tolerability of 5-MOP (1.2 mg/kg)-UVA versus 8-MOP (0.6 mg/kg)-UVA therapy in 25 patients of skin type III and IV, affected by relapsing plaque-type psoriasis of similar body involvement; indeed, the same patients were given 8-MOP during 1 year and 5-MOP during the subsequent year after relapsing. Both treatments cleared psoriatic lesions with a comparable number of exposures, but 5-MOP required significantly higher cumulative UVA doses. The difference was due to the lower phototoxicity of 5-MOP, as assessed by the determination of the minimal phototoxic dose, and to its higher tanning activity, as assessed by the weekly grading of pigmentation. Nevertheless, therapy by 5-MOP-UVA seemed particularly interesting in that it showed a higher tolerability since only 1 patient experienced nausea, whereas during therapy with 8-MOP-UVA nausea and/or vomiting occurred in 7 patients, sunburn in 6 and itching in 3. Since we have treated the same patients with the two drugs, our results were not influenced by interindividual variations of phototoxic responses, tanning ability and susceptibility to develop psoralen-induced short-term side-effects. It was concluded that, although long-term side-effects of the 5-MOP-UVA treatment have still to be determined, such treatment of psoriasis should be reappraised due to its higher tolerability in comparison to 8-MOP-UVA treatment.     

改良PUVA疗法治疗慢性斑块性银屑病疗效分析

目的：探索用改良PUVA疗法治疗慢性斑块性银屑病的疗效和安全性。方法：67例寻常型银屑病患者口服8-MOP0．6mg/kg后照射UVA和UVB，每周3次，共治疗8周，用PASI积分评价疗效，并记录不良反应。结果：治疗开始2-4周后出现疗效，随着治疗时间的延长，PASI总积分逐渐下降，有效率逐渐提高，在治疗结束时痊愈率达到96．5％，有效率达100％。27例患者(40．3％)出现不良反应，绝大多数为轻度，没有因不良反应停止治疗的病例。结论：改良PUVA疗法治疗慢性斑块性银屑病具有良好疗效和安全性。     

Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy

PUVA-bath therapy developed into a first line topical PUVA therapy, and gel and cream preparations have been described as alternative modes of topical 8-MOP application. Because bath-PUVA can be difficult to manage, topical PUVA therapy using 8-MOP gel or cream preparations may become an important alternative when treating localised skin diseases. However, controlled comparisons of efficacy with this alternative topical PUVA therapy are lacking. We therefore compared the efficacy of PUVA-cream therapy with PUVA-bath therapy in 12 patients with recalcitrant dermatoses of the palms and soles using a left/right trial design. These patients responded well to both treatment modalities, meaning that both could be used successfully to treat recalcitrant dermatoses of the palms and soles.     

Hepatitis from 5-methoxypsoralen occurring in a patient with previous flucloxacillin hepatitis

A 55-year-old woman with psoriasis vulgaris was treated with oral 5-methoxypsoralen and UVA photochemotherapy. After 40 treatments over 3 months she became unwell with hepatitis attributable to the psoralen. Six years earlier she developed cholestatic hepatitis to flucloxacillin. A previous history of drug-induced reactions should be sought before prescribing further drugs with similar adverse effects.     

Topical 8-methoxypsoralen enhances the therapeutic results of targeted narrowband ultraviolet B phototherapy for plaque-type psoriasis

Targeted broadband ultraviolet B (UVB) phototherapy as well as 308‐nm excimer laser have been reported to significantly improve or clear localized psoriatic plaques within 5 to 10 treatments when medium fluences [i.e. 4–6 multiples of minimal erythema doses (MED)] were used. Our study was conducted to determine the effects of different concentrations of topical 8‐methoxypsoralen (8‐MOP) cream when used in combination with targeted UV phototherapy with regard to number of treatments and cumulative UV doses to clear localized psoriasis. Ten evaluable patients with stable plaque‐type psoriasis completed the study. Three different concentrations of 8‐MOP creams (0.001%, 0.01% and 0.1%) were applied prior to irradiation with 4 MEDs of targeted narrowband UVB (NB‐UVB), whereas 0.001% 8‐MOP cream was used in conjunction with 5 J/cm² UVA. All irradiations took place once weekly for 12 weeks. Psoriasis severity index (PSI) score was used to evaluate the efficacy of the treatment. With area‐under‐the‐curve analysis, 0.1% 8‐MOP/NB‐UVB was superior to other modalities in reducing the PSI scores. The number of treatments and cumulative NB‐UVB doses necessary to achieve PSI‐95, a 95% reduction in the scores, was also lower in the 0.1% 8‐MOP/NB‐UVB group, although the differences were not statistically significant. We conclude that topical 8‐MOP cream enhances the therapeutic effects of targeted NB‐UVB phototherapy without significantly increasing the short‐term adverse effects.     

HLA-G在寻常性银屑病中的表达

以往的研究显示,人类白细胞抗原G(HLA-G)是一种免疫耐受分子,它与许多临床疾病有密切联系[1].我们应用免疫组化标记亲合素生物素-链霉亲合素法(LAB-SA)对寻常性银屑病皮损中HLA-G进行检测,以探讨HLA-G在寻常性银屑病中的表达.     

基质金属蛋白酶-8在寻常型银屑病患者血清及皮损中的表达研究

 目的:探究基质金属蛋白酶-8（MMP-8）在寻常型银屑病（PV）炎症反应中的作用。方法:将20例PV患者根据银屑病面积和严重程度指数（PASI）分为轻度组6例、中度组6例及重度组8例。用ELISA法检测并比较PV患者组及正常对照组(12例)血清中MMP-8浓度;用荧光定量PCR扩增并比较不同病情严重程度组间皮损处以及外观正常的周边皮肤MMP-8相对表达量;用免疫组化法观察MMP-8在皮损部位的分布状况。结果:血清MMP-8浓度比较：轻度组明显低于对照组(t=2.54,P=0.022）、重度组（t=2.69,P=0.020）。PV患者皮损部位MMP-8表达明显高于皮损相邻部位外观正常的皮肤（t=2.91,P=0.009）;重度组PV皮损部位MMP-8表达明显高于轻度组（t=3.45,P=0.005）及中度组（t=2.74,P=0.018）。在PV皮损部位,MMP-8主要表达于表皮基底细胞及棘细胞,而在皮损周边部位,MMP-8在基底细胞中表达较明显。真皮中MMP-8主要表达于小血管处。结论:MMP-8在炎症反应较强的皮损中表达上升,推测其通过调控炎症反应及促进血管新生等参与PV的免疫病理进程。     

Topical anthralin for psoriasis vulgaris: evaluation of 70 Japanese patients

In order to determine the usefulness of anthralin in the treatment of psoriasis, we evaluated the effectiveness of topical anthralin therapy in patients with psoriasis vulgaris in our hospital. Seventy patients with plaque-type psoriasis (58 men and 12 women), aged 17-79 years-old (mean; 47.6 years-old), who were treated at the Department of Dermatology, Tokyo Medical and Dental University, between 1992 and 1999, were retrospectively evaluated. Mean psoriasis activity and severity index (PASI) score before therapy was 24.6. Patients were treated with 0.1-2.0% topical anthralin. Responses were determined by clinical examination. The mean PASI score decreased to 8.7 after three months. The most effective anthralin concentration was 0.4-0.5%. The overall response rate was 85.7%, complete remission was obtained in 21.4%, and partial remission in 64.3%. Ten patients (14.3%) were anthralin-resistant. In all patients who entered complete remission, recurrence was noted within six months after stopping anthralin. Minor skin irritation and pigmentation occurred in most of the patients; however, no severe side effects were noted during the treatment. Our study indicated that anthralin is effective for chronic plaque-type psoriasis.     

Pharmacokinetics of 8-methoxypsoralen in serum and suction blister fluid

Summary Micronized 8-methoxypsoralen (8-MOP), with a smaller crystal size, produced significantly higher serum level profiles than nonmicronized 8-MOP. Furthermore, the absorption of the micronized drug was more rapid, resulting in peak serum levels within 1 h in 75% of the patients. Our blister fluid studies suggest, however, that reduction of the photosensitizer concentration is slower in skin than in serum. This implies that despite markedly reduced 8-MOP serum level after 2 h the skin remains sufficiently sensitized up to that point of time.     

Photoallergic dermatitis from 8-methoxypsoralen

Summary A 36 year old woman with psoriasis vulgaris developed generalized photoallergic dermatitis to 8-methoxypsoralen after 16 uneventful treatments with 8-methoxypsoralen und UVA (PUVA). The diagnosis of photoallergy was confirmed by re-exposure to oral 8-methoxypsoralen and total body UVA irradiation; phototests using topical and oral 8-methoxypsoralen with a high intensity monochromator or with a new high intensity light apparatus for the delivery of UVA; and histological studies. Photoallergy occurred only with UVA, but not with UVB or UVC. There was no photoallergy following trimethylpsoralen.     

Twice- vs. thrice-weekly MPD PUVA in psoriasis: a randomized-controlled efficacy study

BACKGROUND: Oral psoralen-ultraviolet A (PUVA) has been the treatment of choice of moderate to severe forms of psoriasis, however there is no standardized worldwide protocol. Twice- and thrice-weekly regimens had been used. In this study we compare the efficacy of these regimens. METHODS: Two PUVA regimens in 28 patients with clinical diagnosis of psoriasis, with symmetric and no less than 20% of body surface area involvement, using a half-body study, were compared. Each patient body half was randomized to receive either twice- or thrice-weekly PUVA. A blinded trained dermatologist assessed the PASI score in each body half at the beginning of the study and at clearance or after 25 sessions. RESULTS: Twenty-three patients completed the study. There were no significant differences in the efficacy of both treatments considering the median percentage of PASI decrease (92.9% for the body half with the twice-weekly regimen and 94.8% for the thrice-weekly treatment, P=0.179). There were significant differences comparing the median number of sessions needed for clearance and the median cumulative doses, favouring the twice-weekly regimen (15 vs. 22, P=0.000, and 142.5 vs. 241.4 J/cm(2), P=0.001, respectively). CONCLUSION: The treatment of psoriasis patients with twice- or thrice-weekly PUVA in this study was equally effective, the number of sessions required and the cumulative doses of UVA were lower with the twice-weekly regimen.     

Demonstration of giant and anular nexus in the psoriatic epidermis

Summary To determine whether a tan produced by 8-MOP and UVA protects from subsequent solar light irradiation, volunteers were irradiated with unfiltered Xenon arc light before and 10 days after a 1 week's course of four 8-MOP-UVA treatments. Evaluation of the minimal erythema doses and of histological changes before and after 8-MOP-UVA treatment revealed that the 8-MOP-UVA induced tan protected against the erythemogenic and cell damaging effects of Xenon arc light. Unscheduled repair DNA synthesis, used as a measure for UVB-induced DNA damage and repair, was also investigated in skin irradiated with the Xenon arc before and after 8-MOP-UVA induced tanning. Both the number of grains per sparse labeled cell and the number of sparse labeled cells per 1000 cells, were found to be significantly lower in tanned skin; taking decreased unscheduled repair DNA synthesis as a measure for decreased DNA-damage, these findings also demonstrate a photoprotective effect of the 8-MOP-UVA induced tan.     

Treatments of generalized pustular psoriasis: a multicenter study in Japan

This study analyzed data from treatments of 385 cases of generalized pustular psoriasis (GPP) from 325 hospitals in Japan. Retinoid treatment was effective in 84.1% of patients, methotrexate in 76.2%, cyclosporine in 71.2%, oral PUVA therapy in 45.7%, and tonsillectomy in 16.7%. Short-term therapy with systemic corticosteroid for GPP during only the phase with severe systemic clinical findings may be also effective (75.4%). However, these treatments for GPP each differed in clinical effects, prognosis, and side effects. These findings may be useful in creating guidelines for treatment of generalized pustular psoriasis. Further studies based on these specific clinical effects are necessary.