Psoralen Plus Ultraviolet A Treatment Research Articles

Interventions for mycosis fungoides.

Interventions for mycosis fungoides.

SOAP PUVA.

Psoralen plus ultraviolet A (PUVA) photochemotherapy combines the use of psoralen and long-wave ultraviolet A (UVA) radiation. The phototherapeutic effects of PUVA result from photochemical reactions. PUVA therapy can be administered in various methods such as conventional UV chambers, psoralen with sunlight as source of UV light PUVASOL, bath PUVA, bath suit PUVA, soak PUVA, and turban PUVA. The advantage of using topical psoralen is that it avoids the adverse effects associated with the oral PUVA therapy and is being increasingly used in the treatment of psoriasis. However, it is known to cause increased phototoxicity, and in conditions like vitiligo, the spotty repigmentation is not cosmetically acceptable. Psoralen bath plus UVA therapy is known as bath PUVA therapy. Bath PUVA treatment for psoriasis was first reported by Fischer and Alsins in 1976. Bath PUVA is administered by mixing 37.5 mL of 1% 8-methoxypsoralen in 100 Lof water to obtain a concentration of 3.75 mg/L.[1] In bath suit PUVA, bathing suit of flannel material (stitched to suit the patient) is dipped in this solution for 5 min and worn for 15 min with a raincoat over it to prevent evaporation of the solution, and the patient is then immediately exposed to UVA in a whole-body phototherapy chamber. Bath PUVA needs plenty of water. Bath tub is not easily available and bath suit needs special suit, and treatment is cumbersome. We planned to modify the therapy by mixing psoralen with cleansing lotion and coined it as SOAP PUVA. The choice is due to the solubility factor as 8-MOP being insoluble in water. We reported a novel method of delivering 8-MOP uniformly all over the skin within a short time and on subsequent exposure to UV light. Because8-MOP was not soluble in water, we tried to dissolve it in commercially available moisturizing lotion (cetaphil) and synthetic detergent (cetaphil cleansing lotion). As it dissolved well in cleansing lotion, we decided to use it for our study [Figure 1]. As the method was new, we initially tried to standardize the procedure and determine the minimal pigmentation dose (MPD). The project was done in a single healthy subject with no existing dermatological disease requiring phototherapy. We started by using 1:100 dilution of methoxsalen that was prepared by mixing 0.1 mL of methoxsalen with 9.9 mL of cleansing lotion. The mixture was applied over the back [Figure 2]. The paste was left over for 5 min after which it was wiped with water-soaked gauze. The template cloth was worn along with goggles to protect the eyes. The area was exposed to UVA light (0–3J) with 0.5-J increments. The plan was to observe for MPD after 48 h and delayed pigmentation upto 7 days. No erythema and pigmentation was observed upto 7 days. We increased the concentration to 1:80, and the same procedure was repeated with no erythema or pigmentation. The concentration was increased to 1:60 and the same procedure was repeated. Erythema was observed at 2.5 J after 48 h [Figure 3] and pigmentation was observed after 5 days.Figure 1: Psoralen completely soluble in cleansing lotionFigure 2: Psoralen and cleansing lotion mixture applied over the backFigure 3: Erythema observed after 48 h at 2.5 JOral PUVASOL is effective but is time-consuming because the exposure to UV light occurs after 2 h and the intensity of sunlight varies. It also becomes difficult for children and working women. To overcome these issues bath PUVA was introduced, but it requires consumption of a large quantity of water. Pai and Srinivas introduced bathsuit tPUVA [2] to overcome this but the suit had to be worn for 15 min and was practically difficult. The main purpose of this study was to identify the method and use it with exposure to sunlight. The plan was to increase the concentration of psoralen rather increase the exposure time because we wanted to deliver it in a shorter period and the irradiance of sunlight was much lower than the irradiance of UV light in artificial chambers. The limitation was that it was done on a single subject, and the results might have varied. We plan to conduct further studies on a larger scale to determine the ideal dilution and use it as a viable alternative for delivering PUVA therapy. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Combined therapy of psoralen plus ultraviolet A followed by narrow band ultraviolet B photochemotherapy for early stage mycosis fungoides

Only a few clinical reports in the treatment of early mycosis fungoides (MF)(IA, IB, IIA stage) are available in the literature. The purpose of this study was to compare the efficacy and safety of narrow-band UVB and psoralen plus ultraviolet A (PUVA) photochemoterapy in 24 patients with early-stage MF, and explore a new approach for the treatment of early mycosis fungoides. A total of 24 identified early mycosis fungoides patients received PUVA, NB-UVB and a combined therapy of PUVA followed by NB-UVB (n = 9/6/9) irradiation. A retrospective study was carried out to analyze the sex, age of onset, TNM stage, treatment, and duration of treatment, and times of treatment, duration of maintenance treatment, effective and recurrence in these patients. The data were analyzed using SPSS 17.0 and a two-sided test at the α = 0.05 level of significance was conducted. Of the 24 patients studied, the average treatment was 104.5 (95% CI, 75.71-133.29) times. The average duration of treatment was 12.88 (95% CI, 9.90-15.85) months. The average maintenance treatment time was 11.08 (95% CI, 2.13-20.04) months. The effective rate (CR+PR) of PUVA treatment was 88.9%, recurrence rate was 11.1% (n = 9). In the NB-UVB treatment group, the effective rate was 100.0%, and the recurrence rate was 33.3% (n = 6). In the PUVA followed by NB-UVB (combination therapy) treatment group, the effective rate was 77.8% and the recurrence rate was 55.6% (n = 9). There were no significant differences among the three groups in terms of number of treatments, treatment duration, maintenance treatment duration, effective rate and recurrence rate (P > 0.05). PUVA and NB-UVB are effective and safe in the targeted therapy of early stage mycosis fungoides. The combined therapy of PUVA followed by NB-UVB can reduce the total PUVA dose and risk of developing skin cancer.

Primary cutaneous T cell lymphomas: photochemotherapy immunomodulation with analysis of the inflammatory-expansive cellular dynamic

Primary cutaneous T cell lymphomas (CTCLs) are characterized by hyperproliferation of malignant CD4+ T cells with primary localization on the skin. The common characteristics are the migration of the malignant mature T-lymphocytes into the epidermis, with hyperproliferation of malignant CD4+ T cells and epidermotropism. Sézary syndrome (SS) is the leukemic variant. It was established that CTCLs arise from a clonal expansion of CD4+ T cells with an identical rearrangement of the T cell receptor. The purpose of this study was to evaluate the immunomodulation effect of photochemotherapy-A (psoralen plus ultraviolet A (PUVA)). Pre- and post-PUVA punch skin biopsies of nine patients were stained immunohistochemically for CD34+, CD8+, CD7+, CD16+, CD56+, CD1a+, Bcl2+, p53+, CD45RA+, and CD45RO+ cells. The results showed a pre-PUVA cells/mm(2) without significant difference among expansive or reactive cells. Post-PUVA analysis showed a significant decrease in the mean of expansive-reactive cells. PUVA immunomodulated decreasing cellular infiltrate. These findings could contribute to the comprehension of how PUVA acts. We achieved ectoscopic clearance of the lesions, although post-PUVA, there still was a mononuclear pathological infiltrate. This result demonstrates that the PUVA treatment should only be withheld when the histological analysis is normal.

Implications of Bax, Fas, and p53 in the pathogenesis of early-stage mycosis fungoides and alterations in expression following photochemotherapy

Background:The underlying molecular basis of mycosis fungoides (MF) has not yet been clarified. However, defects in apoptosis may contribute to its pathogenesis.Aim:We investigated the expression of Bax, Fas, and p53 in early-stage MF patients and any alterations in expression following photochemotherapy.Materials and Methods:Bax, Fas, and p53 expressions were studied by immunohistochemistry in both keratinocytes and lymphocytes on paraffin-embedded skin specimens from 27 early-stage MF patients.Results:Bax, Fas, and p53 staining was shown in the lymphocytes in 0/27, 26/27, and 11/27 patients at the time of diagnosis, whereas these ratios were 0/27, 9/27, and 0/27, respectively, after psoralen plus ultraviolet A (PUVA) treatment. The decrease in p53 and Fas expression in the lymphocytes was found statistically significant. Bax, Fas, and p53 staining in the keratinocytes was shown in 5/27, 27/27, and 25/27 patients at the time of diagnosis, whereas these ratios were 0/27, 22/27, and 4/27, respectively, after PUVA treatment. The decrease in p53, Fas, and Bax expression in the keratinocytes was found statistically significant.Conclusion:Although Bax seems unrelated with early-stage MF, Fas and p53 expression in the lymphocytes may contribute to the understanding of the pathogenesis of this disease.

Optimization of the comet assay for the sensitive detection of PUVA-induced DNA interstrand cross-links

Psoralen plus ultraviolet A (PUVA), commonly used for the treatment of hyperproliferative skin disorders, has been found to be associated with an increased risk of squamous cell cancer. Interstrand cross-link (ICL) formation by PUVA treatment is considered the major factor contributing to the carcinogenesis. However, it remains unclear how PUVA causes, or promotes cancers, in humans. As an initial step in understanding the mechanisms of mutagenesis and carcinogenesis of PUVA photochemotherapy, we have optimized and subsequently utilized a modified alkaline comet assay involving a post-lysis gamma-irradiation at 9 Gy to sensitively measure the formation and repair of PUVA-induced ICLs in the immortalized human keratinocyte cell line HaCaT. A clear dose-dependent response of HaCaT cells to PUVA exposure was observed with a combination of a fixed UVA dose at 0.05 J/cm(2) and a dose of 8-methoxypsoralen ranging from 10 to 100 microM. Results also indicated that the ICL repair was concentration dependent. We have also demonstrated that PUVA-induced monoadduct formation, at an estimated ratio of 3:1 to ICLs in the present experimental conditions, does not interfere with the detection of the ICLs in the modified alkaline comet assay. Furthermore, comparison of the amount of ICL formation between the single-dose UVA treatment and a split-dose protocol was performed. The split-dose protocol was believed to generate more ICLs than the single-dose treatment, thus more effective in PUVA photochemotherapy. Our results demonstrate that comparable amounts of ICLs were formed in HaCaT cells for each dose of UVA, using either the split-dose or single-dose protocols.

Formation of 8‐hydroxy‐2′‐deoxyguanosine in the DNA of cultured human keratinocytes by clinically used doses of narrowband and broadband ultraviolet B and psoralen plus ultraviolet A

Psoralen plus ultraviolet A (PUVA) and narrowband ultraviolet B (UVB) are widely used in skin disease phototherapy. Recently, the efficacy of UVB therapy has been greatly improved by narrowband UVB, compared to conventional broadband UVB. The objectives of the current study were to evaluate the influence of UVB-induced and PUVA-induced oxidative stress on cultured keratinocytes. We analyzed 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in human keratinocytes (HaCaT cell line) using a high-performance liquid chromatography system equipped with an electrochemical detector. Non-irradiated human keratinocytes contained a baseline of 1.48 +/- 0.22 (mean +/- SD) 8-OH-dG per 10(6) deoxyguanosine (dG) residues in cellular DNA, which increased linearly with higher doses of UVB. When their abilities to induce 8-OH-dG were compared to each other, based on the minimal erythemal and therapeutically used doses, by irradiating them with broadband UVB at 100 mJ/cm(2), the amount of 8-OH-dG increased to 3.42 +/- 0.46 residues per 10(6) dG, while a narrowband UVB treatment at 1000 mJ/cm(2), with biological effects comparable to those elicited by 100 mJ/cm(2) broadband UVB, increased it to 2.06 +/- 0.31 residues per 10(6) dG. PUVA treatment, with 100 ng/mL 8-methoxypsoralen and 5000 mJ/cm(2) UVA, increased the 8-OH-dG level to 4.52 +/- 0.42 residues per 10(6) dG. When HaCaT cells treated with 2000 mJ/cm(2) narrowband UVB were cultured and the amount of 8-OH-dG was monitored in the living cells, 65.6% of the residues were repaired 24 h after treatment. Our study provides a warning that widely used narrowband UVB and PUVA induce cellular oxidative DNA damage at the therapeutically used doses, although to a lesser degree than broadband UVB with the same clinically effective dose.

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

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. 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. 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. 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.

A comparison of psoralen plus ultraviolet A (PUVA) monotherapy, tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis

Numerous studies have shown that the additional administration of topical or systemic antipsoriatic agents might serve as an effective means to increase the efficacy of photochemotherapy [psoralen plus ultraviolet (UV) A (PUVA)] for psoriasis. To compare the therapeutic response to tacalcitol plus PUVA, tazarotene plus PUVA and PUVA monotherapy in patients with chronic plaque-type psoriasis. In addition, we also assessed the duration of remission induced by each regimen and the tolerability of the two combination treatments. Thirty-one patients with chronic plaque-type psoriasis were included in this observer-blinded, intrapatient comparison trial. PUVA treatment was given four times weekly. Additionally, tacalcitol ointment and 0.1% tazarotene gel were applied separately on two target areas once daily in the evening. At the onset of therapy and every 2 weeks thereafter the response to treatment was determined by the Psoriasis Severity Index score, which assesses the degree of erythema, infiltration and scaling of the psoriatic lesions. After complete or near complete clearing patients were followed-up until relapse. Twenty-four patients completed the study. The treatment requirements to induce complete or near complete clearing were significantly lower for both combination treatments than for PUVA monotherapy (P < 0.01). The median cumulative UVA dose and number of exposures were 30.6 J cm-2 (95% confidence interval, CI 22.5-71.2) and 14 (95% CI 11-16) for tacalcitol plus PUVA, 32.3 J cm-2 (95% CI 22.5-73.8) and 14 (95% CI 11-19) for tazarotene plus PUVA, and 37.0 J cm-2 (95% CI 29.5-83.9) and 16 (95% CI 14-22) for PUVA monotherapy. No difference between the three regimens was observed with regard to duration of remission. Adverse reactions occurred more often with 0.1% tazarotene than with tacalcitol but were in general mild and completely reversible upon using a lower concentration of 0.05% tazarotene. Tacalcitol ointment and tazarotene gel are both comparably effective in improving the therapeutic result of PUVA therapy in patients with chronic plaque-type psoriasis. Besides accelerating the treatment response, both agents, by virtue of their UVA dose-sparing effect, might also help to reduce possible long-term hazards of PUVA treatment.

Isolation and Identification of Psoralen plus Ultraviolet A (PUVA)-Induced Genes in Human Dermal Fibroblasts by Polymerase Chain Reaction-Based Subtractive Hybridization

Premature aging of the skin is a prominent side-effect of psoralen photoactivation, a therapy used for a variety of skin disorders. Recently, we demonstrated that treatment of human dermal fibroblasts with 8-methoxypsoralen and ultraviolet A irradiation resulted in a permanent growth arrest with a switch of mitotic to postmitotic fibroblasts. Furthermore, an upregulation of matrix-degrading metalloproteinases and a high level of de novo expression of the senescence-associated beta-galactosidase was detected in the PUVA-treated postmitotic fibroblasts. The molecular basis for this PUVA-induced change in the functional and morphologic phenotype of fibroblasts resembling or mimicking replicative senescence is, however, unknown. Herein after, we have used a polymerase chain reaction-based subtractive hybridization protocol to identify human genes that are induced by PUVA treatment. Application of polymerase chain reaction-Select resulted in the cloning of four PUVA genes. Sequence analysis and homology searches identified three cDNA clones of known genes related to cell cycle regulation (p21waf1/cip1), stress response (ferritin H) and connective tissue metabolism (tissue inhibitor of metalloproteinases-3), whereas one cDNA clone represented a novel gene (no. 478). Northern blot analyses were performed to confirm a PUVA-dependent increase in specific mRNA levels in human dermal fibroblasts in vitro. This report on the identification of growth arrest related genes in PUVA-treated fibroblasts may stimulate further research addressing the causal role of these known and novel genes in extrinsic and intrinsic aging processes on a molecular and cellular level.

Correlation between bathing time and photosensitivity in 8-methoxypsoralen (8-MOP) bath PUVA.

Bath PUVA (psoralen plus ultraviolet A) using 8-methoxypsoralen has become increasingly popular in recent years as an effective treatment option for a continuously expanding range of skin disorders. Among the various variables of bath PUVA treatment, the impact of bathing time on photosensitivity has never been investigated in detail. We therefore determined the threshold UVA dose for erythema induction after different bathing periods. A marked influence of bathing time on photosensitivity was found. Increasing the soaking period from 5 min to 30 min resulted in a greater than 60% reduction of the minimal phototoxic and minimal perceptible phototoxic dose. Our results demonstrate that the duration of the psoralen bath is a critical parameter in bath PUVA treatment and has a major influence on UVA dose requirements.

PUVA treatment of vitiligo: a retrospective study of Turkish patients.

Psoralen plus ultraviolet A (PUVA) is considered to be the treatment of choice for subtotal vitiligo; however, it is time consuming and carries certain health risks for both patients and physicians. This study attempts to evaluate the efficacy of the treatment in Turkish vitiligo patients. We have performed a retrospective study of 33 patients with vitiligo who received systemic PUVA therapy during the period 1985 to 1997, and have evaluated their response to treatment. Overall, 28 patients (84%) showed some improvement; 12 patients experienced a repigmentation of 51-75% and six patients achieved greater than 75% repigmentation. Face and trunk lesions showed better repigmentation than other areas, whereas hands, feet, perioral, and periorbital areas were generally refractory to treatment. The age of the patient, age at onset of the disease, sex, disease duration, and degree of depigmentation prior to initiation of therapy had no influence on PUVA-induced repigmentation. The distribution of vitiliginous skin must be taken into consideration before the initiation of PUVA therapy, as the response to treatment varies greatly with different body sites; hands, feet, perioral, and periorbital regions are particularly treatment resistant.