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1.
Oral administration of psoralen and whole body exposure to UVA (oral PUVA) has been used for the treatment of 113 patients with severe atopic dermatitis (AD). 8-Methoxypsoralen (8-MOP) was given at a dose of 0.5-0.6 mg/kg two hours prior to UVA (3-8 J/cm2) irradiation. Patients were treated three times a week while hospitalized. Other medications which had been given before PUVA therapy were permitted. At four and eight weeks after PUVA therapy, the severity score of AD had decreased by 51% and 80%, and the cumulative doses of UVA were 51.2 J/cm2 and 115.3 J/cm2, respectively. The amounts and strength of topical cortico-steroids were decreased during PUVA therapy. No adverse effects that required discontinuation of the PUVA therapy were observed. After discharge, maintenance therapy with UVB phototherapy and/or conventional treatment of AD kept the patients in remission in the outpatient clinic. The QOL of patients was greatly improved. Photochemotherapy with oral 8-MOP can be indicated in patients with severe, widespread AD, especially if standard therapy fails. This is the first report of oral PUVA therapy in a large series of Japanese patients with AD.  相似文献   

2.
BACKGROUND: Topical psoralen plus UVA (PUVA) is an effective treatment for localized forms of eczema, psoriasis, and palmoplantar pustulosis, which avoids some of the undesirable side-effects of systemic psoralens. Aims In this study, the efficacy of topical PUVA treatment with 8-methoxypsoralen (8-MOP) gel was compared with placebo plus UVA in chronic recurrent palmoplantar dermatoses. METHODS: Twenty-two patients with palmoplantar disease (11 with psoriasis vulgaris, six with eczema, and five with pustulosis) were enrolled in the study. The study design was a left-right comparison: one hand or foot was treated with 8-MOP 0.01% gel plus UVA, whilst the contralateral hand or foot received placebo and UVA for 6 weeks. Twenty minutes after application of the gel, both sides were exposed to UVA. The treatment regimen was three times a week, and the UVA dose was increased weekly by 20%. RESULTS: A comparison of the pre- and post-treatment scores with regard to the severity of the clinical picture and the infiltration of plaques showed a significant decrease (from 7.5 +/- 2.0 to 2.5 +/- 2.1 and from 2.0 +/- 0.7 to 0.3 +/- 0.5, respectively) in the sites treated with 8-MOP gel compared with placebo after 6 weeks. CONCLUSION: The results of the study indicate that at least 18 courses of local PUVA within 6 weeks, with a cumulative dose of 87 J/cm(2), are required to induce a significant decrease in the disease severity and an improvement in the infiltration of plaques due to 8-MOP gel at a concentration of 0.01% when treating chronic recurrent palmoplantar dermatoses.  相似文献   

3.
BACKGROUND: Topical photochemotherapy with bath psoralen plus ultraviolet (UV) A irradiation (PUVA) has been developed to reduce possible side-effects of oral PUVA therapy. Although the efficacy of bath PUVA therapy appears to be similar to oral PUVA therapy, provision of bathing facilities has obvious economic, logistic and sanitary implications. Cream PUVA therapy has recently been developed as a variation of topical PUVA. OBJECTIVES: To understand the photobiological effects and to increase the safety and effectiveness of this novel topical PUVA therapy, we assessed the kinetics and dose-response of phototoxicity of 8-methoxypsoralen (8-MOP) cream in order to develop a treatment schedule for this treatment option. METHODS: Ninety-eight patients (63 men and 35 women) undergoing cream PUVA therapy were studied. The phototoxic properties of topically applied 8-MOP in three different water-in-oil creams as vehicles were assessed. In a dose-response study, four concentrations of 8-MOP cream (0.0006-0.005%) were used for determination of the minimal phototoxic dose (MPD). The kinetics of photosensitization were tested by determination of MPDs after different application times of 8-MOP cream (10, 20, 30 and 60 min). The persistence of phototoxicity was assessed by UVA exposure at defined time intervals after application of 8-MOP cream (0, 30, 60 and 120 min). RESULTS: The concentration required to produce sufficient but not undue photosensitization of the skin was 0.001% 8-MOP. The duration of application leading to the lowest MPD was 30 min. Greatest photosensitization was achieved when UVA irradiation was performed between 0 and 30 min after 8-MOP removal. These findings showed no significant difference between the three vehicles used. CONCLUSIONS: Based on our data we recommend application of 0.001% 8-MOP in a water-in-oil cream for 30 min. Irradiation with UVA should be performed within 30 min after removal of 8-MOP cream, as there is a rapid decrease in photosensitivity thereafter.  相似文献   

4.
Detection of DNA-psoralen photoadducts in mammalian skin   总被引:1,自引:0,他引:1  
An immunofluorescence (IF) method for the detection of 8-methoxypsoralen (8-MOP) photoadducts to DNA has been developed to assess nuclear damage in keratinocytes and melanocytes after psoralen plus UVA (PUVA) treatment, both under in vitro and in vivo conditions. Cryostat sections of the albino and pigmented guinea pig and human skin were used for in vitro studies to establish minimal and maximal drug concentration and UVA dosimetry for the detection of DNA-8-MOP photoadducts. Limits of detection were as low as 10 ng/cm2 8-MOP and 1 J/cm2 UVA for skin sections and sodium bromide-split epidermal sheets. Guinea pigs treated with topical PUVA revealed positive IF stain in epidermal cell nuclei at a threshold dose of 100 micrograms/cm2 8-MOP and 13 J/cm2 UVA. Pretreatments of cryostat cuts with ethanol and alkali before IF test enhanced the sensitivity of detection in vivo about 10-fold and enabled us to follow the repair of DNA damage after treating normal guinea pig skin with a dose of 50 micrograms/cm2 8-MOP plus 6 J/cm2 UVA. The most interesting findings were as follows: A sensitive method to detect PUVA-induced nuclear damage in epidermal and dermal cells was developed. PUVA treatment induced nuclear DNA damage to melanocytes as well as to adjacent keratinocytes, and melanocytes appeared to be 10 times less vulnerable to photo-damage than keratinocytes. There was a greater propensity for the proliferative cells to be damaged by PUVA. PUVA induced nuclear damage up to 700 micron depth in the dermis. The usefulness of the IF test in detecting DNA damage in microgram and ng amounts in vivo and in following the repair of damaged DNA induced by PUVA.  相似文献   

5.
BACKGROUND/PURPOSE: Ultraviolet-A radiation (UVA) of the oral mucosa after photosensitization with either systemic methoxsalen (8-MOP) or topical trioxsalen (TMP), i.e. mouth-PUVA, has been reported to be successful in the treatment of oral lichenoid lesions. In the case of PUVA treatment of skin disorders, local immune suppressive effects have been demonstrated, and the antigen presenting epithelial Langerhans cells (LCs) have been shown to be especially sensitive to ultraviolet treatments. Our aim was to compare the photobiological effects of PUVA in oral mucous membrane (OMM) using topical TMP or systemic 8-MOP photosensitization. METHODS: Rat OMM photosensitized with topical TMP or systemic 8-MOP was treated with PUVA using UVA doses of 1-8 J/cm2. The LCs were demonstrated in epithelial sheets of the treated OMM with ATPase staining. RESULTS: Both treatments caused a sim ilar, dose-dependent depletion of ATPase-positive LCs, with a maximal depletion of 80% or 73% with 8 J/cm2 at 2 days after irradiation as photosensitized with TMP or 8-MOP, respectively. This contrasts with earlier published findings in human skin, where topical TMP is an order of magnitude greater a sensitizer than 8-MOP, and PUVA-induced depletion of LCs occurs maximally 5 days after irradiation. CONCLUSION: The depletion of LCs of rat OMM after PUVA treatment is greater using topical TMP compared to systemic 8-MOP, but the difference is significantly smaller than reported earlier in human skin.  相似文献   

6.
Palmoplantar psoriasis and eczema can be chronic recalcitrant dermatoses. Oral psoralen plus ultraviolet A (PUVA) has proven effective for these, but has a number of unwanted side effects. Previous studies have shown that regional PUVA therapy using the 8-methoxypsoralen (8-MOP) soak method followed by immediate UVA irradiation is also beneficial and well tolerated. The purpose of this audit was to determine the efficacy of hand and foot PUVA soaks by reviewing the experience of the Massachusetts General Hospital's Phototherapy Unit with this treatment modality. Phototherapy records of all patients who underwent hand and foot PUVA soaks from 1994 to 1998 were reviewed. Details regarding the treatment procedure, patient compliance, patient response and incidence of side effects were noted and summarized. Of the 56 patients who underwent at least 20 treatments, 29% had excellent response, 42% had minimal to moderate response, and 29% had poor response. The average number of treatments to induce clearing was 41. The average maximum treatment dose at clearing was 5.85 J/cm2, while the average cumulative dose to achieve clearing was 267.17 J/cm2. 8-MOP PUVA soak therapy is quite useful for chronic hand and foot dermatoses. Patient compliance must be emphasized to obtain favorable results.  相似文献   

7.
We investigated possible alterations induced by psoralen and ultraviolet A radiation (PUVA) on platelet function both in vitro and in vivo. In vitro, using conventional aggregometry and adenosine diphosphate (ADP), collagen, ristocetin and arachidonic acid as aggregating agents, platelet aggregation was determined on platelet-rich plasma (PRP) from normal subjects at basal conditions and following the addition of increasing concentrations of 8-methoxypsoralen (8-MOP) with and without exposure to ultraviolet A (UVA) light (5 J/cm2) and compared with UVA light exposure alone. At basal conditions and following exposure to UVA light alone, no changes in the normal platelet aggregation patterns were observed. Exposure to UVA light of PRP containing 8-MOP also demonstrated no abnormality in the platelet aggregation patterns at 8-MOP concentrations of 200 ng/ml. However, abnormal platelet aggregation as a response to ADP and collagen was observed at higher concentrations of 8-MOP, which was augmented upon exposure to UVA light. In vivo, platelet aggregometry was performed on PRP from 4 patients submitted to PUVA treatment at basal conditions, 2.5 h after oral ingestion of 8-MOP (0.6-0.8 mg/kg) and after 4 PUVA sessions. No patient showed modification of the platelet aggregation profile after either 8-MOP ingestion or PUVA treatment. Our study shows that 8-MOP at high concentrations in vitro impairs platelet aggregation by ADP and collagen augmented by UVA light exposure, but PUVA therapy causes no detectable abnormality in platelet function in vivo.  相似文献   

8.
BACKGROUND: Alopecia areata is a burden for many patients and often resistant, even to extensive therapy. Orally administered PUVA therapy has been shown among numerous systemic and topical treatment modalities to be a therapeutic alternative. However, the clinical use of oral PUVA is often limited by systemic side effects. Bath-PUVA therapy offers an alternative solution because of the negligible systemic absorption of psoralen with this technique. Through use of a "PUVA-turban" it is now possible to administer a dilute bathwater solution containing 8-methoxypsoralen (8-MOP) to the scalp. OBJECTIVE: The purpose of this study was to determine whether PUVA turban therapy is effective in treating alopecia areata in different clinical stages. METHODS: We treated 9 patients with severe, rapidly progressing, treatment-resistant alopecia areata with PUVA-turban treatment as a modification of bath-PUVA therapy. At each treatment session a cotton towel was soaked with a 0.0001% 8-MOP solution (1 mg/L) at 37 degrees C, wrung gently to remove excess water, and wrapped around the patient's head in a turban fashion for 20 minutes. This was directly followed by UVA radiation. Treatment sessions were initially performed 3 to 4 times per week. RESULTS: The cumulative UVA doses given over treatment periods of up to 24 weeks were 60.9 to 178.2 J/cm(2), with single doses ranging from 0.3 to 8.0 J/cm(2). After up to 10 weeks of treatment, hair regrowth could be noticed in 6 of 9 patients. Two patients did not respond to the treatment, and one patient showed only vellus hair regrowth. CONCLUSION: PUVA-turban therapy can be considered a useful method of administering a dilute psoralen solution selectively to the scalp of patients. It has been shown to be a well-tolerated and, in some patients, efficient therapeutic alternative in the treatment of alopecia areata.  相似文献   

9.
BACKGROUND: Bath-PUVA treatment, originally established in Scandinavia, offers several advantages over oral PUVA and has become increasingly popular in recent years. Outside Scandinavia 8-methoxypsoralen (8-MOP) is the prevailing photosensitizer for this PUVA modality and is used arbitrarily in a wide range of concentrations. Up to the present, data are lacking on the impact of 8-MOP bath-water concentration on UVA dosimetry. OBJECTIVE: We investigated the influence of increasing 8-MOP bath-water concentrations on photosensitivity in bath-PUVA treatment. METHODS: Fifteen healthy volunteers without abnormal photosensitivity or recent exposure to ultraviolet radiation were included in an intraindividually controlled comparison study. In all volunteers the minimal phototoxic dose (MPD) was determined on the volar side of their forearms after immersion for 20 minutes in 4 different 8-MOP bath-water concentrations (0.5, 1, 2.5, and 5 mg/L). The correlation between 8-MOP concentration and photosensitivity (defined as the reciprocal value of the MPD) was analyzed by linear regression analysis. In addition, the time course of erythema formation and the UVA dose-erythema response curve was assessed for each psoralen concentration. RESULTS: The median MPD and the 25%-75% interquartile were 5.7 J/cm(2) (5.7-8), 4 J/cm(2) (4-5.7), 2.8 J/cm(2) (2.8-5.7), and 2 J/cm(2) (2-2.8) at an 8-MOP concentration of 0.5, 1, 2.5, and 5 mg/L, respectively. Linear regression analysis revealed a significant correlation between 8-MOP bath-water concentration and photosensitivity (r = 0.98; P =.019). Bath-PUVA-induced erythema peaked after a median time interval of 3 days, with a range of 2 to 4 days. The slope of the UVA dose-erythema response curve was similar for all psoralen concentrations. CONCLUSION: UVA dose requirements in bath-PUVA treatment decrease linearly with increasing 8-MOP concentrations. A single MPD assessment at 72 hours after the UVA exposure is inappropriate for accurate determination of the patients' photosensitivity. The hazard of wrong UVA dosimetry is comparable at all psoralen concentrations.  相似文献   

10.
Oral 8-MOP and TMP were compared in the PUVA therapy for vitiligo. Group A (25 cases) was initiated on 0.3 mg/kg of 8-MOP with 1/2 Joule/cm2 of UVA and weekly increments of 1/2 Joule/ cm2 and Group B was started on 0.6 mg/kg of TMP with 1 Joule/cm2 of UVA and weekly increments of 1 Joule/cm2. Therapy was given thrice a week. Repigmentation was evaluated by using a 0-6 scale. At the end of 60 sittings, on acceptable cosmetic response was seen over the face, neck and upper extremities in both groups, while trunk and lower extremities showed lesser response. 8-MOP gave earlier response, needing a lower cumulative UVA dose i.e. 75 J/cm2 as compared to TMP i.e. 106 J/cm2. Phototoxicity was seen more often with 8-MOP. In conclusion, in Indians, 8-MOP is the drug of choice in PUVA therapy of vitiligo provided precautions against phototoxicity are adequate.  相似文献   

11.
PUVA therapy is widely used for early stage mycosis fungoides. While the efficacy of PUVA with oral 8-methoxypsoralen (8-MOP) is well documented, the use of its topical variation, bath-water PUVA therapy with 8-MOP has not been studied. The purpose of this study was to assess the effect of 8-MOP bath-water PUVA therapy in adult patients with early stage mycosis fungoides. We retrospectively evaluated the outcomes of bath-water delivery of 8-MOP (1 mg l(-1)) in 16 patients with early stage mycosis fungoides. In all patients complete response was achieved after a mean duration of 63 days requiring 29 treatments and a mean cumulative UVA dose of 33 J cm(-2). The time to relapse after complete clinical clearance was 45.6 (+/-9.2) weeks. In comparison, oral PUVA therapy with 8-MOP resulted in complete response after 64.5 days (25.8 treatments) with a mean relapse-free period of 30 (+/-3.5) weeks. We conclude that bath-water PUVA therapy with 8-MOP is a valuable photo-therapeutic alternative, which should be considered for patients in whom systemic psoralen cannot be used.  相似文献   

12.
The effect of 8-methoxypsoralen plus UVA radiation (PUVA) on cell killing and induction of transformation was studied in the C3H mouse embryo 10T1/2 cell line. Dose-response data for both survival and transformation were obtained as a function of 8-methoxypsoralen (8-MOP) concentration and UVA dose. PUVA treatment caused cell death and induced transformation in a dose-dependent manner. Treatment of cells with 8-MOP alone (10 micrograms/ml) or UVA alone (90 J/m2) had no effect on either cell killing or transformation. The product of 8-MOP concentration and UVA dose calculated at 10% survival and 10(-3) transformation frequency levels were quite similar regardless of 8-MOP concentration or UVA dose. This suggests that there exists a simple reciprocal relationship between 8-MOP concentration and UVA dose. Both type II and type III foci induced by PUVA treatment were tumorigenic in vivo. These data provide further evidence for the carcinogenicity of PUVA treatment. In addition, the system described here could serve as a valuable model for studying the relationships between transformation and the specific cellular and molecular lesions induced by PUVA treatment.  相似文献   

13.
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。  相似文献   

14.
BACKGROUND: Localized skin lesions of the genito-anal region such as in lichen sclerosus et atrophicus or in lichen planus are a burden for many patients, and therapeutic efforts, including therapies with potentially hazardous side-effects, are often unsatisfactory. Recently, PUVA bath photochemotherapy has been proven highly effective in the treatment of various inflammatory skin diseases, including localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as PUVA bath therapy for palmoplantar dermatoses. OBJECTIVE: We evaluated the clinical effects of PUVA cream photochemotherapy in patients with genital lesions of inflammatory skin diseases. METHODS: Twelve patients with lichen sclerosus et atrophicus, lichen planus, vulvar eczema and pruritus vulvae were included in the study. PUVA cream therapy was performed up to 4 times a week. RESULTS: PUVA cream photochemotherapy induced a significant clinical improvement of genital lesions in most patients, as revealed by clinical examination. Clinical improvement (reduction in size of lesions of erythema, and/or of pruritus) was achieved in most patients after 10-20 treatments and was reduced in patients that had only received 5-15 treatments. Cumulative doses ranged between 4.5 and 180 J/cm(2); all patients tolerated PUVA cream phototherapy well without any side-effects. CONCLUSION: PUVA cream phototherapy represents a highly effective therapy that should be further investigated as an alternative treatment for patients with genital lesions of inflammatory skin diseases.  相似文献   

15.
Summary Topical photochemotherapy with psoralen and its derivatives 4.5′,8-trimethylpsoralen (TMP) and 8-methoxypsoralen (8-MOP), with UVA irradiation, was evaluated with regard to minimum phototoxic dose, concentration, timing of UVA irradiation and systemic and local side-effects, in healthy volunteers. Psoralen (0.005%) in aqueous gel was found to be superior to TMP and 8-MOP in aqueous gel. No hyperpigmentation was seen after topical PUVA treatment with psoralen in aqueous gel. Patients with plaque-type psoriasis (n = 7), palmoplantar psoriasis (n = 7) and hyperkeratotic eczema (n = 2) were treated. Topical PUVA therapy was effective in most psoriasis patients, without the occurrence of local or systemic side-effects. Moreover, hyperkeratotic eczema patients who did not respond to conventional therapy showed partial remission. These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.  相似文献   

16.
The effects of topical PUVA treatment on the epidermal cyclic AMP system were investigated. 8-methoxypsoralen (8-MOP), 0.3% in ethanol was applied to the backs of pigs which were then irradiated with UVA. A significant increase in the epidermal beta-adrenergic adenylate cyclase response was observed 24 h after low (1.1 J/cm2) and moderate (2.1 J/cm2) dose irradiation. There was no significant change in the adenosine- or histamine-mediated adenylate cyclase responses. 8-MOP application or UVA irradiation alone had no effect on the beta-adrenergic adenylate cyclase response. PUVA treatment with a higher irradiation dose (4.2 J/cm2) produced no increase in the beta-adrenergic response and adenosine- and histamine-mediated adenylate cyclase responses were decreased. Cyclic AMP phosphodiesterase activity was decreased by PUVA treatments using UVA doses of 1.1 and 2.1 J/cm2; however, the change was not statistically significant. The increased beta-adrenergic response was also observed in the presence of the cyclic AMP phosphodiesterase inhibitor, isobutylmethylxanthine. These results indicate that epidermal adenylate cyclase responsiveness is affected by topical PUVA treatment in vivo.  相似文献   

17.
Forty-four patients with chronic plaque psoriasis were randomly allocated to treatment with bath-water-delivered 8-methoxypsoralen (bath 8-MOP) or oral 8-methoxypsoralen (oral 8-MOP) PUVA therapy. There was a significant reduction in extent of the lesions and psoriasis area and severity index (PASI) after 20 treatments with each modality. There was a fourfold reduction in cumulative ultraviolet A (UVA) dose in the bath group. Side-effects of erythema and nausea were less with bath therapy.  相似文献   

18.
Twenty-five patients with alopecia totalis (AT) or alopecia universalis and 124 patients with alopecia areata (AA) were treated with photochemotherapy, combining topical 8-methoxypsoralen (8-MOP) with UV irradiation of the scalp at a phototoxic dose. The mean energy required was 15 J/cm2 for AA and 42 J/cm2 for AT. Ninety-four patients had multiple bald patches and 12 with AT had complete or > 50% hair regrowth. Positive treatment results did not seem to depend on the age of onset or the duration of the disease. Few side-effects of topical psoralens plus UVA (PUVA) treatment were noted, except a for few days of slight erythema caused by the high dose of UV.  相似文献   

19.
We investigated the influence of 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet radiation (PUVA) on lymphocyte migration in vitro. Nylon wool-purified, mouse splenic T lymphocytes showed locomotive responses to casein, normal mouse serum (NMS), and zymosan-activated mouse serum (ZAS). Migratory responses to casein and NMS, and to ZAS were remarkably suppressed in lymphocytes exposed to 0.5 J/cm2 UVA plus 0.1 micrograms/ml 8-MOP and to 0.8 J/cm2 UVA plus 8-MOP, respectively. The PUVA treatment used in the present study had no effect on random movement and lymphocyte viability. T lymphocytes cultured in the absence of mitogenic agent for 24 h demonstrated a greater increase in their migration activity than noncultured cells, while lymphocytes cultured after 1.0 J/cm2 PUVA pretreatment remained low. These findings suggest that the therapeutic effect of PUVA on inflammatory skin disorders may be due in part to the suppression of lymphocyte migration.  相似文献   

20.
The alterations of keratinocyte surface and basement membrane markers by treatment with 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet (UVA) light (PUVA) were examined in guinea pig skin using immunofluorescence (IF) microscopy. Following a single PUVA treatment (UVA doses: 1.8 - 7.2 J/cm2), reactivity with pemphigus and pemphigoid sera, rabbit anti-guinea pig epidermal cell serum, and fluorescein-conjugated concanavalin A was decreased in intensity in a dose-dependent fashion. Fluorescence became distinctly less pronounced by day 2 postirradiation and recovered between days 6-10. IF with rabbit antiglomerular basement membrane antibodies, which cross-reacted with the basement membrane of the skin, apparently was unaltered within this energy dose range. 8-MOP or UVA alone did not change the reactivity with any reagent. These results suggest that PUVA treatment affects keratinocyte membrane markers and pemphigoid antigens but not some of the basement membrane antigens.  相似文献   

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