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Successful treatment of scleroderma with PUVA therapy.

PUVA therapy was carried out on four patients with scleroderma; three of them had cutaneous manifestations of progressive systemic sclerosis and one other exhibited generalized morphea. PUVA therapy was given with daily doses of 0.25J/cm2 or 0.4J/cm2 for 3-8 weeks, resulting in total doses between 3.5J/cm2 and 9.6J/cm2. All four patients responded well to this treatment; improvements of hand closure, skin sclerosis index, and flexion of fingers or knee joints were obtained. Thus, PUVA appeared to be beneficial for treating scleroderma.

Adult↗

Ocular complications of PUVA therapy.

PUVA, the combination of psoralen and long wave ultraviolet radiation is widely used in the management of psoriasis, vitiligo and several other dermatological disorders. The potential for long term treatment to cause ocular damage remains to be determined and despite the large numbers of patients who have received PUVA treatment, development of cataract is exceedingly rare. This paper discusses cataract formation, reviews the literature concerning the ocular complications of PUVA therapy and proposes guidelines for ocular protection during photochemotherapy.

Cataract↗

PUVA therapy.

PUVA is an acronym for psoralen plus ultraviolet-A radiation. This form of photochemical therapy is commonly used in the treatment of psoriasis and vitiligo, but it is also beneficial in other dermatologic diseases. An understanding of psoralen's mechanism of action and the unique properties of the various psoralen preparations is important in ensuring optimal results with this therapy.

Humans↗

Long-term stability of 8-methoxypsoralen in ointments for topical PUVA therapy ('Cream-PUVA').

8-Methoxypsoralen (8-MOP) is an established photochemotherapeutic agent for PUVA therapy. Recently, a so-called 'cream-PUVA' modality was introduced into therapy of psoriasis and other dermatoses. Little is known, however, about the stability of 8-MOP in ointments used for the topical application of this compound. Therefore, we investigated the long-term stability of 8-MOP in three different ointments, Unguentum Cordes(TM), Cold Cream Naturel(TM) and a water-containing gel on the basis of Carbopol 940. All three ointments were prepared with 8-MOP concentrations of 0.05 and 0.005%, and stored over 12 weeks at room temperature (19-20 degrees C) and at 5 degrees C. 8-MOP concentrations were measured at days 1, 8, 15, 29, 57 and 88 after preparation by thin-layer chromatography (TLC). The ointments were dissolved in an organic solvent, 10 microl were transferred onto the TLC plate and the chromatograms were developed first in toluene and then in toluene/ethyl acetate 2:1 v/v to resolve 8-MOP from the ointment constituents. The peak heights of 8-MOP were used for quantitation. The intraday variabilities are <3% for Unguentum Cordes and Cold Cream Naturel and <6% for the Carbopol 940 gel. The interday variabilities were <6.3% in all cases. In Unguentum Cordes and Cold Cream Naturel the concentrations of 8-MOP remain stable, but in Unguentum Cordes the emulsion began to break up after 8 weeks. In the Carbopol gel, only about 40% of the nominal concentrations of 8-MOP were found and they decrease significantly at storage at 5 degrees C. We conclude that the Carbopol gel seems to be unsuitable for PUVA therapy, whereas Cold Cream Naturel shows the best results.

Acrylic Resins↗

[PUVA therapy: long-term degenerative effects. I. Histological changes observed after PUVA therapy].

The authors studied PUVA induced histological alterations in a group of 7 patients compared with 6 control subjects of same age. The epidermal alterations were unprominent: a few necrotic keratinocytes and hyperpigmentation of basal layer melanocytes with a lentiginous pattern. Basement PAS positive membrane was in some cases desestructured, but this was reversible. In the papillary dermis there was homogenization and partial or total destruction of orceinophilic vertical fibers, these phenomena were also reversible. PUVA therapy induced aging of the skin which is dose related and depends also of the patients age. No phenomena of precancerous dysplasia were observed.

Adult↗

[Topical psoralen photochemotherapy (PUVA therapy) for severe atopic dermatitis (I): An analysis of correlation between effectiveness of PUVA therapy and clinical parameters].

Twenty-five patients with severe atopic dermatitis (AD) were subjected to PUVA therapy (topical 8-MOP application plus UVA irradiation). Excellent resolution was achieved in 18 cases (72%). Complete remission lasting 6.3 months in average was gained. In addition, the correlation between effectiveness of PUVA therapy and clinical parameters was statistically analyzed. As a result, an effectiveness of PUVA on AD was well correlated with sex (female), lower minimal phototoxic dose, higher severity and higher blood eosinophil counts. On the other hand, such correlation with the effectiveness was little in serum IgE levels, IgE.RAST scores to the house dust antigens and total irradiation doses.

Adolescent↗

[PUVA therapy: long-term degenerative effects. II. Study of ultrastructural changes in the skin induced by PUVA therapy].

The authors studied PUVA induced ultrastructural alterations in a group of 7 patients compared with 6 control subjects of same age. Hyperactivity of melanocytes was observed in all patients. Elastic fibers showed vacuolisation age and dose related. There was a reduplication of the basal layer of dermal capillaries and increased pinocytosis of endothelial cells, age and dose related also. The authors conclude that PUVA therapy induced alterations are degenerative; the target is located in deep dermis (capillaries and elastic fibers). No alterations of keratinocytes nor precancerous epithelial dysplasia was found. This confirms that UVA radiation is less aggressive for keratinocytes than UVB.

Adult↗

Treatment of chronic palmoplantar eczema with local bath-PUVA therapy.

BACKGROUND: Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema. Topical PUVA-paint avoids some of the unwanted side effects of systemic psoralens and has been used successfully in the treatment of palmoplantar eczema and psoriasis. However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema. OBJECTIVE: Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment. METHODS: After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen. Immediately after, the skin was irradiated with increasing doses of UVA, starting with 0.5 J/cm2. PUVA-bath therapy was performed 4 times a week up to a total of 25 treatments. No additional therapy was allowed except emollients. RESULTS: Excellent or good effects were achieved in 93% of the patients with dyshidrotic and in 86% of the patients with hyperkeratotic eczema. In the patients with dyshidrotic eczema, the cumulative doses and the highest single doses of UVA were lower than those in the patients with hyperkeratotic eczema (21.4 vs 27.9 J/cm2 and 2.4 vs 3.0 J/cm2 of UVA), but this was not statistically significant. No phototoxic reactions were observed. CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment. Compared with topical PUVA-paint, local bath-PUVA therapy has several advantages, particularly the absence of phototoxic reactions, severe hyperpigmentation, and protracted photosensitivity.

Adolescent↗

Antinuclear antibodies during Puva therapy.

During PUVA therapy 7 patients out of 34 with severe psoriasis developed circulating antinuclear antibodies (ANA) (21%). Before treatment only 3 patients of 50 (6%) considered for PUVA had detectable ANA. The ANA titres were usually low. Antibodies against native DNA as studied with the Crithidia luciliae test, were not found, and blood and urinary screening for collagenosis was negative. All 7 patients responded well to the PUVA treatment. The significance of these findings remains to be determined.

Adult↗

Pharmacokinetic behaviour of sublingually administered 8-methoxypsoralen for PUVA therapy.

BACKGROUND: Conventional oral PUVA therapy is hampered by large inter- and intraindividual variations in the bioavailability of 8-methoxypsoralen (8-MOP), caused by its low solubility in the gastrointestinal juices and large interindividual differences in hepatic metabolism rate (hepatic first pass). AIMS: New galenic formulations of 8-MOP based on solid dispersions, suspensions, and saturated solutions containing penetration enhancers were developed for sublingual administration, a drug delivery route which avoids the hepatic first pass metabolism. METHODS: Solubility properties of 8-MOP were tested in 22 potential penetration enhancers and solubilizers. Following preliminary in vivo tests of 13 sublingual 8-MOP formulations, five were administered to groups of volunteers at a nominal dose of 0.6 mg/kg body weight: two solid dispersions based on PEG 1540 (with and without Xylitol); a solution in Labrasol (glyceryl and PEG-8 caprylate/caprate), PEG 400, Transcutol (ethoxydiglycol) (1:1:1); a micronized suspension in sorbitol, water, ethanol, propylene glycol (ca. 3:1:1:5 w/v); and Oxsoralen capsules. Pharmacokinetic behaviour of 8-MOP was examined in serum; samples were analysed by HPLC. Photosensitivity was measured in seven subjects. RESULTS: The peak of maximum 8-MOP concentration in blood was sharp, rapid and reproducible: tmax of 8-MOP in blood averaged 23+/-3 min, independent of the particular formulation. Cmax was higher when 8-MOP was presented in dissolved form (solution and capsule formulations, 85+/-29 and 85+/-35 ng/ml, respectively) and lowest with the suspension (42+/-15 ng/ml). Photosensitivity peaked reproducibly at 45 min. post dosing. CONCLUSIONS: Sublingual PUVA therapy is suitable for patients with skin types I and II, in particular patients who are less suitable candidates for standard PUVA therapy (due to hepatic, renal, or cardiac insufficiency) or who have experienced side effects with standard PUVA.

Administration, Sublingual↗

[Significance of PUVA therapy for adult T-cell leukemia/lymphoma--PUVA therapy can induce apoptosis in leukemic cells].

PUVA therapy is known to be effective for treating cutaneous T-cell lymphoma (CTCL). Considering that adult T-cell leukemia/lymphoma (ATL) represents a T-lymphocytic proliferative disorder similar to CTCL, it is likely that PUVA therapy is effective for treating ATL. We applied PUVA therapy to a 53 year old man with acute (i.e. crisis)-type ATL associated with generalized erythematous papules, and succeeded in achieving a complete remission (CR). To elucidate the mechanism of PUVA therapy in this case, we compared ultrastructures of leukemic cells obtained before and after PUVA therapy by electron microscopy, and found that PUVA therapy caused apoptosis in leukemic cells in the peripheral blood. In this paper, the antitumor mechanism of PUVA is discussed, and its efficacy is emphasized.

Apoptosis↗

Does smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?

Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema. However, our own observations showed that patients with palmoplantar eczema of the dyshidrotic or hyperkeratotic type responded only partially to bath-PUVA therapy. In order to evaluate environmental influences possibly having an impact on the efficacy of this therapy, smokers and non-smokers suffering from palmoplantar eczema treated with bath-PUVA therapy were compared. A retrospective study was conducted involving 62 patients, 39 non-smokers and 23 smokers, with palmar and/or plantar eczema resistant to local corticosteroids. Bath-PUVA therapy was performed according to the European standard regimen for oral PUVA therapy. The total number of treatments and the cumulative UVA-dose were similar in smokers and non-smokers (smokers 24+/-17.7 (mean+/-SD) and 67.6+/-51.3 J/cm2 vs. non-smokers 25.7+/-16.3 and 68.5+/-49.3 J/cm2). In the group of non-smokers, 31% showed complete remission (CR; 100% clearance), 33% partial remission (PR; more than 50% clearance) and 36% no change after treatment (NC; less than 50% clearance). In contrast, the group of smokers showed only 13% CR and 22% PR, whereas 65% exhibited NC. The differences regarding complete or partial remission between the groups were statistically significant (Student t-test for paired samples; P<0.05). Regarding the different type of eczema, bath-PUVA proved to be more successful in the dyshidrotic type of eczema as compared to the hyperkeratotic type in non-smokers (P<0.05). In the group of smokers no CR was achieved in patients suffering from the dyshidrotic form of eczema. Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.

Adult↗

Bath-water PUVA therapy with 8-methoxypsoralen in mycosis fungoides.

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.

Administration, Cutaneous↗

Carcinogenic risk of bath PUVA in comparison to oral PUVA therapy.

The potential carcinogenic risk of bath PUVA therapy was compared to that of systemic (oral) PUVA. An analysis of the epidemiological data on cancer risk following bath PUVA with trimethylpsoralen does not support the conclusion that bath PUVA per se is less carcinogenic than systemic PUVA with 8-methoxypsoralen (8-MOP). Pharmacokinetic studies indicate that both the concentration of 8-MOP in the target organ for PUVA carcinogenicity (skin) at the relevant time point (time point of UVA irradiation) and the extents of biological effects in the skin are comparable following bathwater or systemic 8-MOP administration. Furthermore, the therapeutic effects of PUVA arise from the same photochemical reaction mechanisms as do the carcinogenic effects. Theoretically, the ratio of (desired) cytotoxic versus (undesired) mutagenic effects could increase with increasing efficiency of the PUVA therapy itself. On the basis of the available evidence, it is concluded that all forms of PUVA therapy, independently of the route of 8-MOP administration, contribute to a small but dose-dependent increase in nonmelanoma skin cancer risk.

5-Methoxypsoralen↗

[The Koebner phenomenon, a prognostic sign of PUVA therapy effectiveness in patients with psoriasis vulgaris--yes or no?].

INTRODUCTION: Former investigations of Koebner phenomenon had demonstrated its higher incidence in patients with severe generalized and/or unstable forms of psoriasis which expressed increased resistance to various treatment modalities. The aim of this study was to establish the correlation between the presence of Koebner phenomenon and the PUVA therapy effects, total number of PUVA treatments, total dose of UVA radiation and the duration of remission after PUVA therapy discontinuation. MATERIAL AND METHODS: Sixty patients with severe clinical picture of psoriasis vulgaris, treated with PUVA therapy, were included in this research. According to the presence of Koebner phenomenon they were divided into two groups, 20 patients with positive and 40 patients with negative Koebner reaction, who were the control group at the same time. RESULTS AND DISCUSSION: 95% of patients treated with PUVA, were cleared of psoriatic changes in the Koebner positive, as well as in the Koebner negative group. There were also no differences between the Koebner positive and Koebner negative group in the mean number of PUVA treatments, mean total dose and the last dose of UVA radiation, which led up to the clinical remission of psoriasis. Our results of investigation have demonstrated increased relapse of psoriasis, during the first 6 months after cessation of PUVA therapy, in the Koebner positive group, with a high statistical significance (p < 0.001), comparing with Koebner negative group in the same period. Furthermore, the tendency of relapse of Koebner positive and Koebner negative psoriatic patients was higher in Koebner positive group even in the first 3 months after PUVA therapy. CONCLUSIONS: PUVA therapy effects, total number of PUVA treatments, total dose of UVA radiation didn't depend on presence of Koebner phenomenon. However, Koebner phenomenon was a mark of high relapsing tendency of psoriasis in the first 6 months after PUVA therapy cessation.

Humans↗

Effects of PUVA therapy on skin surface lipids: skin surface lipid peroxidation in psoriasis vulgaris and its biological significance.

PUVA therapy (Psoralen + UVA irradiation) is an effective mode of photochemotherapy for psoriasis vulgaris. The biological significance of PUVA therapy for psoriasis vulgaris has mainly been considered to be based on DNA, especially the formation of DNA crosslinks between complementary DNA stands. On the other hand, we have already reported that skin surface lipids were oxidized by UVA irradiation in vitro and this reaction was enhanced in the presence of 8-methoxy-psoralen by a singlet oxygen mechanism. Keeping this in mind, we conducted an experiment to determine whether lipid peroxide can be formed in skin surface lipids following systemic PUVA therapy in psoriasis patients and the following results were obtained: 1) a marked increase of lipid peroxide values in skin surface lipids occurred following PUVA therapy; and 2) the amount of squalene in skin surface lipids was decreased by this treatment. These results indicate that skin surface lipids can be oxidized by PUVA therapy in vivo and this lipid peroxidation on the skin surface may be related to the effects of PUVA therapy on psoriasis vulgaris.

Adult↗

Short- and long-term effectiveness of oral and bath PUVA therapy in urticaria pigmentosa and systemic mastocytosis.

BACKGROUND: Previous studies have shown that oral PUVA is effective in urticaria pigmentosa. Long-term results, however, are unknown. OBJECTIVE: We studied the long-term effectiveness of oral PUVA treatment in urticaria pigmentosa as well as in systemic mastocytosis. In addition, the success of bath PUVA was examined in these diseases. METHODS: Twenty patients with urticaria pigmentosa and systemic mastocytosis treated by oral PUVA were examined retrospectively for a time period of up to 18 years. We studied the duration of improvement and correlated these results with the total PUVA dose, the skin type and the age of onset. Four patients were treated by bath PUVA therapy. RESULTS: In oral PUVA therapy an improvement was seen in 14 out of 20 patients (70%). There was no difference in the response rate between urticaria pigmentosa and systemic mastocytosis and there was no correlation with the total PUVA dosage. The duration of the treatment's success ranged from a few weeks to more than 10 years. 25% of the patients showed an improvement for more than 5 years. Patients with onset during childhood and early adolescence and patients with skin types I and II responded favourably to the treatment. Bath PUVA therapy was without effect in our 4 patients. CONCLUSION: Oral PUVA is very effective for the long-term treatment of urticaria pigmentosa as well as systemic mastocytosis.

Administration, Cutaneous↗

Essentials for PUVA therapy. Guidelines for photochemotherapy.

PUVA therapy is a promising new entity for treatment of a number of dermatologic diseases including psoriasis, mycosis fungoides, and vitiligo. A safe and rational approach to the management of a phototherapy center has been presented, and is intended to serve as a personal guideline for those treating patients with this modality.

Evaluation Studies as Topic↗