The effects of non-interval PUVA treatment on Langerhans cells and contact hypersensitivity.

Although application of topical psoralen followed immediately by ultraviolet-A irradiation (non-interval PUVA) was reported to be effective in the treatment of psoriasis, its precise mechanisms of action have not yet been explored. Since regular topical PUVA therapy, consisting of the topical application of psoralen followed by UVA exposure 1-2 h later, can change the number and morphology of Langerhans cells (LCs) and inhibit contact hypersensitivity (CHS), we investigated whether these same effects may be induced by non-interval PUVA. Our results showed that no differences exist between these two types of PUVA treatment. Non-interval PUVA treatments of 3 J/cm2 produced no erythematous reactions and resulted in changes in the number and morphology of LCs. The non-interval regimen also inhibited CHS to dinitrofluorobenzene applied to the treated skin by inducing the suppressor lymphocytes. These results suggest that there might be a link between the observed changes of the LCs and the effectiveness of non-interval PUVA therapy in the treatment of psoriasis, through a mechanism other than the inhibition of DNA synthesis of psoriatic keratinocytes.     

The Effects of Non-Interval PUVA Therapy on the Plaque Stage of Mycosis Fungoides

The effectiveness of non-interval topical PUVA treatment was studied in four patients with mycosis fungoides at the plaque stage. Five regions of each patient were exposed to UVA immediately, 30 minutes, 60 minutes, 90 minutes, and 120 minutes, after topical application of 8-methoxypsoralen, respectively. The effects of these treatments were evaluated by clinical appearance and histological findings after the 20th treatment. All five regions were more improved clinically and histologically than the control region, which was not given PUVA therapy. There were no clear differences clinically among these five regions. Biopsy specimens from each region revealed the disappearance of epidermotropism and a marked decrease in atypical mononuclear cell infiltrations in the dermis. From these data, we concluded that there were no clear differences between these five treatments clinically or histologically and that non-interval PUVA therapy is useful for the early stages of mycosis fungoides. To our knowledge, this is the first report of non-interval PUVA therapy for mycosis fungoides.     

即时型PUVA对郎格罕细胞和接触过敏的影响

在实验动物中研究了即时型光化学疗法对表皮郎格单细胞数量和形态的影响及对接触过敏反应的抑制，并与常规使用的光化学疗法进行了对比，结果表明二种方法间无差异，３Ｊ/ｃｍ２的即时型光化学疗法无红斑反应并能引起郎格罕细胞数量和形态的变化，并且通过诱导抑制性淋巴细胞抑制接触过敏反应。还探讨了有关致癌的可能性。     

Photochemotherapy for pustular psoriasis (von Zumbusch)

Photochemotherapy (PUVA) with oral methoxsalen and UV-A was instituted in 8 patients with generalized pustular psoriasis (von Zumbusch). Complete clearing of skin lesions and of systemic symptoms was achieved in all patients. Patients who had been on systemic treatment prior to PUVA had to be treated with considerably more UV-A energy than patients who had received topical therapy alone. Seven patients were kept in complete remission by maintenance therapy for an observation period of up to 1½ years. Side effects of systemic pre-PUVA treatment resolved during several months of maintenance therapy.     

Long-term risks of psoralen and UV-A therapy for psoriasis

It has been more than eight years since photochemotherapy with methoxsalen and UV-A (psoralen and UV-A [PUVA]) was introduced for the treatment of psoriasis. This treatment remained under investigation until May 1982 because of concerns about possible chronic toxic effects. With recent Food and Drug Administration approval of PUVA therapy for severe psoriasis, strict drug labeling for administration and patient use and continued monitoring of side effects have become essential. The full effects of PUVA in regard to carcinogenicity, prematurely induced aging of the skin, pigmentary changes, immunologic alterations, and ocular side effects are still unknown. A review of the risks of PUVA therapy is presented, with the aim of maintaining a proper perspective for its limited use in treating selected patients.     

Are topical corticosteroids useful adjunctive therapy for the treatment of psoriasis with ultraviolet radiation? A review of the literature

Adjunctive topical corticosteroids are often administered with UV-B phototherapy or oral psoralen plus UV-A (PUVA) photochemotherapy for the treatment of psoriasis. Five studies comparing PUVA alone with PUVA and topical corticosteroid preparations showed more rapid rates of clearing and a smaller total UV-A exposure with the latter regimen. However, one study demonstrated a higher relapse rate in association with corticosteroid use. Further studies to better define these risks are recommended. Six of seven reports evaluating the use of topical corticosteroid preparations with UV-B phototherapy failed to demonstrate an advantage to this regimen when compared with UV-B phototherapy alone. Therefore, the use of a topical corticosteroid preparation with UV-B phototherapy for the treatment of psoriasis is not recommended.     

Treatment of palmoplantar psoriasis with monochromatic excimer light (308-nm) versus cream PUVA

Palmoplantar psoriasis is a chronic disease, which is very resistant to treatment and often leads to severe disabilities. Photochemotherapy employing psoralens combined with UVA irradiation (PUVA) is a well-accepted therapy for palmoplantar psoriasis. Its topical application (bath PUVA; cream PUVA) avoids the typical side effects of orally applied psoralens. We compared the efficacy of cream PUVA therapy with monochromatic excimer light therapy, a treatment modality employing 308-nm UVB radiation generated by a new kind of light source. Ten patients with psoriasis of the palms and soles were randomly assigned to receive cream PUVA on one side and 308-nm UVB on the contralateral side. Based on the psoriasis area and severity index (PASI) score, clinical assessment was carried out before and 5 weeks after the beginning of the study. At the end of the treatment period both test groups showed a remarkable PASI score reduction (308-nm UVB, 63.57%; cream PUVA, 64.64%). No relevant adverse effects were observed, except for mild irritation in a few patients. After a 12-week follow-up, a relapse of the disease was only observed in one patient. Thus, mono-chromatic excimer light cleared palmoplantar psoriasis as rapidly as cream PUVA. In contrast to cream PUVA, monochromatic excimer light therapy is not associated with prior drug application. This might lead to a lower incidence of adverse reactions and better compliance. Therefore, monochromatic excimer light therapy seems to be a useful new therapeutic option for palmoplantar psoriasis.     

Differentiation of the antipsoriatic and phototoxic effectiveness of topical PUVA therapy

Using a 0.075% 8-methoxypsoralen solution, minimal phototoxic doses and improvement of psoriasis lesions were investigated in 15 patients suffering from chronic stationary psoriasis. The time interval between topical 8-methoxypsoralen application and long-wave ultraviolet light irradiation was increased stepwise. The mean minimal phototoxic dose declined with increasing time interval and reached its minimum 2 h after 8-methoxypsoralen application. In spite of that, antipsoriatic efficiency was maximal 15 min after application. In order to obtain a favorable relationship between antipsoriatic efficiency and unwanted side effects when using topical PUVA treatment, irradiation should be started 15 min after 8-methoxypsoralen application.     

Use of psoralen plus UV-A therapy in the autonomous community of Valencia, Spain

BackgroundPhotochemotherapy with 8-methoxypsoralen and long-wavelength UV-A (PUVA) has been extensively used for the treatment of various skin diseases since its approval in 1982 by the US Food and Drug Administration.MethodsA retrospective study was performed of patients treated with PUVA, including topical and systemic treatment, over a period of 14 years. All patients were treated using a standard PUVA therapy regimen.ResultsA total of 877 patients were analyzed for the period 1982 to 1996. Forty-one skin diseases were treated, including 341 cases of psoriasis and 71 cutaneous T-cell lymphomas. The aim of the study was to describe the characteristics of the patients treated with PUVA therapy during that period and compare the results with those observed in other regions.ConclusionsAlthough PUVA therapy is widely used in a large number of countries for the treatment of various skin diseases, few studies have described the characteristics of the patients and the differences in the parameters of PUVA according to the disease.     

Efficacy of localized phototherapy and photodynamic therapy for psoriasis: a systematic review and meta‐analysis

Localized phototherapy including topical psoralen plus ultraviolet A (PUVA) and targeted ultraviolet B (UVB), and photodynamic therapy (PDT) have been increasingly used in the treatment of localized psoriasis. Yet, there are no systematic reviews or meta‐analyses that scientifically evaluated the pooled efficacy of these treatments in psoriasis. We searched Medline, Embase, and Cochrane databases during the period of January 1980 to June 2012. Our systematic search resulted in 765 studies, 23 of them were included in the review. The primary outcome was 75% reduction in severity score from baseline. A meta‐analysis using random effect model found topical PUVA to be more effective than non‐laser targeted UVB [odds ratio: 3.48 (95% confidence interval 0.56–21.84), P = 0.183]. The pooled effect estimate of the efficacy (75% reduction in severity score) of topical PUVA, targeted UVB, and PDT were as follows: 77% (topical PUVA), 61% (targeted UVB), and 22% (PDT). Topical PUVA and targeted UVB phototherapy are very effective in the treatment of localized psoriasis. Topical PUVA seems more effective than non‐laser targeted UVB phototherapy. On the other hand, PDT has low efficacy and high percentage of side effects in treating localized psoriasis.     

Controlled study of PUVA and adjunctive topical therapy in the management of psoriasis

In a random study of 116 patients with psoriasis vulgaris, oral psoralen photochemotherapy (PUVA) used alone was compared to PUVA plus adjunctive topical therapy with tar, dithranol, or topical corticosteroids. PUVA plus topical corticosteroids produced more rapid clearing of psoriasis but despite maintenance therapy, the frequency of recurrences of the disease during the early phase of follow-up was significantly higher with that treatment, as compared to all other treatments. Dithranol plus PUVA also cleared psoriasis quicker than PUVA alone but patient acceptability for that regimen was low. The addition of tar to PUVA therapy appeared to have little influence on results.     

Abnormal lymphocyte function following long-term PUVA therapy for psoriasis

The surface markers and function of peripheral blood lymphocytes were examined in patients on long-term therapy with methoxsalen and UV-A radiation (PUVA). Ten patients with psoriasis were selected because they had received a high exposure to PUVA therapy, i.e., more than 200 treatments over 2–6 years with cumulative exposure doses of 1700–6000 J/cm² UV-A radiation. Results were compared to those obtained with lymphocytes from untreated patients and UV-B treated patients with psoriasis. The PUVA-treated patients had low levels of E rosette-forming cells in the peripheral blood and markedly impaired lymphocyte responses following stimulation with optimal and suboptimal doses of mitogens. The sensitivity of lymphocytes to in vitro treatment with PUVA was similar in the three groups of patients. The results of this study indicate that long-term PUVA therapy alters the function and cell-surface markers or distribution of lymphocytes.     

Creme-PUVA-Photochemotherapie bei chronisch stationärer Psoriasis vulgaris

PUVA-bath therapy has developed into first line topical PUVA therapy in the treatment of psoriasis. Because of logistical and economic problems, bath PUVA may be difficult to administer. Recently, cream-PUVA therapy has been described as an alternative mode of topical therapy. We treated two patients with moderate plaque-type psoriasis with this new topical approach. 0,0006% 8-methoxypsoralen cream was applied for 1 hour, directly followed by increasing doses of UVA. The number of treatments needed for clearance were 34 and 40. The cumulative UVA dosages were 71.6 and 84 J/cm(2) respectively. Our data document that cream-PUVA therapy is an effective and safe variation of topical PUVA therapy, which may develop into first line photochemotherapy for patients with moderate plaque-type psoriasis.     

Turbo-PUVA: dihydroxyacetone-enhanced photochemotherapy for psoriasis: a pilot study.

BACKGROUND: Dihydroxyacetone (DHA), a colorless sugar in "sunless" tanning lotions, binds to stratum corneum to form a UV-A-protective brown pigment. Bound DHA polymer is shed faster from hyperproliferative skin sites such as psoriatic plaques. We tested the hypothesis that selective shedding of DHA pigment during psoralen-UV-A (PUVA) treatment of psoriasis may allow higher UV-A doses, thus accelerating clearing while protecting uninvolved skin. Concurrent use of lactic acid was investigated as an aid in removing scale and residual DHA from psoriatic plaques. OBSERVATIONS: Thirty psoriatic patients with more than 20% body surface area involvement were recruited. The 6 PUVA study groups were (1) standard American style, (2) American style plus lactic acid, (3) DHA-PUVA or "topical ultraviolet-resisting barrier to optiimize PUVA" (Turbo-PUVA), (4) Turbo-PUVA with lactic acid, (5) European style, and (6) European style plus DHA. Combinations of lactic acid and European-style treatment were not studied. Each subject received up to 30 oral PUVA treatments twice weekly 3 days apart. The DHA-PUVA groups used 15% DHA lotion twice weekly. Lactic acid groups used 7% lotion daily except on treatment days. Psoriasis area and severity index scores were recorded weekly. Turbo-PUVA allowed higher UV-A exposures with minimal burns, showed faster clearing, and required fewer treatments for 90% clearing (P<.001). CONCLUSIONS: Protection of uninvolved skin by DHA during PUVA treatment allows higher UV-A exposures to be tolerated, demonstrates faster clearing, and requires fewer treatments to clear psoriasis. By reducing the total body dose received, Turbo-PUVA may also reduce long-term risks.     

Comparison of therapeutic efficacy of topical PUVA, oral etretinate, and combined PUVA and etretinate for the treatment of psoriasis and development of PUVA lentigines and antinuclear antibodies

Sixty-two and 38 psoriatic patients were treated with topical PUVA and combined etretinate and topical PUVA (Re-PUVA), respectively. In both groups, 50% of the patients showed initial recovery after 6 weeks and over 90% after 14 weeks. Re-PUVA was more effective than PUVA alone in obtaining complete clearance (p<0.05). To clear psoriasis in 50% of the patients, PUVA and Re-PUVA required 63 and 26 weeks, respectively. Furthermore, the integrated clearance rates after 70 weeks were 50% in PUVA and 63% in Re-PUVA. Each therapy showed a similar remission period; psoriasis recurred in 50% of the patients after 4 months. In addition, 17 patients were treated with oral etretinate, and Re-PUVA was found to be more effective than etretinate monotherapy. Another aim was to determine whether etretinate would inhibit the development of PUVA side effects. Adding etretinate failed to inhibit the production of PUVA lentigines but clearly suppressed antinuclear antibody (ANA) expression. Six of 56 patients treated with PUVA alone developed ANA during the treatment. In marked contrast (p=0.05), ANA was detected in none of 34 patients treated with Re-PUVA.     

Eficacia y seguridad en terapia con psoralen-UVA (PUVA) tópica en psoriasis palmoplantar. Experiencia en una serie de 48 pacientes

IntroductionPalmoplantar psoriasis is an uncommon clinical form of psoriasis. Although localized to the palms and soles, it has a considerable impact on the patient's function and quality of life.ObjectivesTo study the effectiveness and safety of psoralen-UV-A (PUVA) therapy in palmoplantar psoriasis and investigate predictors of clinical response.Material and methodsWe performed a retrospective chart review of all patients with palmoplantar psoriasis treated with topical PUVA therapy at our hospital between 2008 and 2011. Data were collected on effectiveness (using physician global assessment [PGA] scores), safety, and a range of clinical, epidemiological, and treatment-related variables.ResultsWe studied 48 patients (33 women and 15 men) with a mean age of 51 years. Treatment was considered to be effective (PGA score of 0 or 1) in 63% of cases. In addition to PUVA, systemic therapy was required in 47.9% of patients; the drug most often used was acitretin. Adverse effects were reported for 25% of patients during treatment. The most common effect was mild erythema, present in 18% of cases.ConclusionsIn our experience, topical PUVA is an appropriate treatment alternative for palmoplantar psoriasis; it offers similar response rates to systemic treatments, but has a better tolerance and safety profile. Associated systemic treatment, with acitretin in most cases, improved the probability of a satisfactory response to PUVA and should be considered in patients who do not respond adequately after 8 to 10 sessions.     

Phototherapy of psoriasis: review and update

Along with topical and systemic therapy, phototherapy is one of the three fundamental treatment options for managing psoriasis. The use of UVB continues to be one of the most important therapeutic interventions for mild to moderate psoriasis. An advance in UVB phototherapy has been the introduction of narrowband UVB lamps (311 nm). UVB lamps are superior to conventional broadband UVB in clearing psoriasis. PUVA is very effective therapy and is still the most effective form of phototherapy for severe, extensive form od the disease. There has been a trend towards whole-body PUVA-bath. Advantages of PUVA bath are lack of gastrointestinal side effects and no need for post-treatment eye photoprotection because there is no systemic photosensitization. UVB and PUVA can be administered in combination with a variety of topical and systemic treatments to achieve more effective results more quickly. The most recent form of phototherapy, 308-nm excimer laser, holds promise for becoming a useful tool in the treatment of stable, localized psoriasis.     

A new psoralen-containing gel for topical PUVA therapy: development,and treatment results in patients with palmoplantar and plaque-type psoriasis,and hyperkeratotic eczema

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.     

PUVA treatment of alopecia areata

Twenty-three patients with alopecia areata were treated with photochemotherapy combining oral or topical methoxsalen and UV-A irradiation of the scalp or of the whole body. Eleven of 17 patients with multiple plaques of alopecia areata, alopecia totalis, and alopecia universalis, who were treated with oral methoxsalen and total body irradiation, had complete or more than 90% hair regrowth. Three patients had a relapse. The mean energy required was 505 joules/sq cm. In six cases, topical applications of methoxsalen or oral methoxsalen combined with local irradiation of the scalp were treatment failures. In the patients responding to treatment, the result did not seem to depend on the age of onset or the extent or duration of disease. However, patients with long-lasting alopecia had a higher risk of recurrence notwithstanding a good initial regrowth of hair. Few side effects of psoralens and UV-A (PUVA) treatment were noted. The mean follow-up period was 18.6 months after the completion of treatment. We discuss the possible mechanisms of action of PUVA in the treatment of alopecia areata.     

Phototherapy of psoriasis: comparative experience of different phototherapeutic approaches

BACKGROUND: Broad-band UVB alone or in combination with different topical drugs (anthralin, calcipotriol), systemic PUVA and bath-PUVA therapy are very effective and well-established treatment modalities for psoriasis. OBJECTIVE: The aim of this retrospective study was to assess which of these routinely applied phototherapeutic modalities might be most effective and safe for the treatment of plaque-type psoriasis. METHODS: Patients (n = 203) with moderate to severe (pretreatment Psoriasis Area and Severity Index score between 12 and 35) chronic plaque-type psoriasis treated between 1992 and 1998 at our department with either UVB (with/without anthralin or calcipotriol; n = 97), systemic PUVA (n = 19) or bath-PUVA therapy (n = 87) were evaluated for efficacy, duration of treatment, number of treatments necessary for complete remission (CR), cumulative light dose, side effects of therapy and duration of remission after therapy. RESULTS: No statistically significant difference comparing the efficacy of bath-PUVA (CR in 72.4%), PUVA (CR in 89.5%) and UVB phototherapy (CR in 69.1%) was found. Although the duration of therapy was significantly longer for bath-PUVA (66 +/- 42 days) as compared to UVB treatment (50 +/- 27 days), the mean number of treatments did not differ significantly between bath-PUVA (28 +/- 12), UVB therapy (30 +/- 12) and PUVA (26 +/- 13). Significantly fewer side effects of phototherapy were observed with bath-PUVA (14.9%) therapy compared to UVB treatment (30.9%). Also, the duration of remission after successful therapy was significantly longer for bath-PUVA (8.4 +/- 3.5 months) as compared to UVB phototherapy (5.1 +/- 4.2 months). CONCLUSION: Bath-PUVA therapy has some advantages over UVB phototherapy in the treatment of psoriasis: fewer UV-related acute side effects and a longer period of remission after therapy. However, the choice of treatment with either UVB, bath-PUVA or systemic PUVA should also be based on a history of previous response to treatment and patient considerations, including compliance and responsibility for following the precautions to avoid potential side effects.