Insulin‐like growth factor‐1 in psoriatic plaques treated with PUVA and methotrexate

Background The pathogenesis of psoriasis is thought to depend on the activation of immune cells and their secreted cytokines, chemokines and growth factors like IGF‐1 which may contribute to the epidermal hyperplasia of psoriasis. Treatment of psoriasis with PUVA and methotrexate are associated with clinical improvement and decrease in epidermal hyperplasia. Objective To examine the effects of PUVA and methotrexate therapy on IGF‐1 expression in psoriatic plaques and whether this change correlates with clinical response. Methods For 24 psoriatic patients, the PASI score and levels of lesional IGF‐1 and its mRNA were determined by RT‐PCR before and after treatment with either methotrexate or PUVA. Skin biopsies from 12 healthy volunteers served as control for IGF‐1 levels in normal skin. Results Lesional skin of psoriatic patients showed a statistically significant elevation in IGF‐1 and its mRNA levels in comparison to control (P = 0.0001). Both methotrexate and PUVA treatment were associated with a significant decrease in both PASI scores and lesional IGF‐1 after 10 month treatment. Conclusion Both methotrexate and PUVA therapy for psoriasis are associated with a decrease in PASI score and IGF‐1. The IGF‐1 down‐regulation may possibly be a consequence of the decrease in cytokines and inflammatory cellular infiltrate that occur following treatment with either modalities or due to their effect on local fibroblast activity and proliferation.     

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.     

Retrospective long‐term follow‐up in patients with chronic palmoplantar dermatoses after good response to bath PUVA therapy

Background: Numerous studies have confirmed the short‐term effectiveness of 8‐methoxypsoralen bath PUVA therapy in patients with chronic palmoplantar dermatoses; however, little is known about long‐term results. Patients and methods: In this retrospective study we examined the long‐term results in 79 patients (mean age: 48 years) with chronic palmoplantar dermatoses who were treated with bath PUVA three times a week over an 8‐year period. A good clinical response (a reduction of more than 50% of the skin lesions) occurred after a mean of 23 treatments and a mean cumulative UVA dose of 39 J/cm² in 51 patients (65%). In 2007 a questionnaire was sent to these 51 patients to assess the long‐term outcome. Results: With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%). Thirty‐four patients (67%) answered the questionnaire after a mean follow‐up interval of 4.3 years (10–87 months). Among these patients, 36% reported an improved course of disease after PUVA therapy with reduced frequency and/or intensity of the skin rash, and 29% of patients reported continued complete clearance. 79% of our patients reported a long‐term reduction in the use of topical corticosteroids during the follow‐up period (mean: 4.3 years). In addition, 67% of patients reported a lasting improvement in quality of life. Conclusions: These data show that bath PUVA may have a long‐term, beneficial influence on the course of disease in a majority of patients with recalcitrant chronic palmoplantar dermatoses.     

A comparative study of different treatment frequencies of psoralen and ultraviolet A in psoriatic patients with darker skin types (randomized-controlled study)

BACKGROUND: Photochemotherapy psoralen and ultraviolet A (PUVA) is a viable option for treatment of psoriasis. However, concerns about its side effects have raised the need to change current PUVA protocols. The aim of this study is to determine whether reducing the treatment frequency of PUVA to twice/week instead of three times/week would affect the efficacy of PUVA therapy. PATIENTS AND METHODS: The study included 20 psoriatic patients, randomized into two groups, 10 patients in each group. The first group received two weekly sessions, the second group received three. The study lasted until complete clearance or for 12 weeks (endpoint). Psoriasis area and severity index (PASI) score was done prior to therapy, at mid therapy and at end of therapy (PASI final). RESULTS: No significant different in PASI final and in the percentage of reduction of PASI score between both groups (P value >0.05) was found. However, a significant difference in the total number of sessions and the total cumulative UVA doses between both groups was found (P value <0.001). CONCLUSION: Our study suggests reducing PUVA frequency and the cumulative UVA dose does not compromise the efficacy of PUVA, but it may improve its benefit/risk ratio. RESTRICTIONS: Few number of cases.     

Surveillance of psoriatic patients on biologic treatment during the COVID‐19 pandemic: A single‐center experience

There are few studies on how patients with psoriasis who are on biologic therapy are affected by the COVID‐19 pandemic. We analyzed the impact of the COVID‐19 pandemic on patients with psoriasis receiving biologic therapy, patients' current status at a single center in Turkey. A total of 133 patients (mean age; 44.6 ± 13.5 years) were on maintenance biological treatment for moderate‐to‐severe psoriasis during the pandemic. A standardized questionnaire was administered by phone interviews to determine patients' perceptions, attitudes, and adherence to therapy and identify the frequency of COVID‐19 infection, psoriasis status, and new comorbidities during the pandemic. All patients had been receiving a biological agent including ustekinumab, etanercept, adalimumab, secukinumab, infliximab, ixekizumab, or certolizumab pegol. Ninety‐one patients (68.4%) had at least one comorbid condition, including psoriatic arthritis (35.3%), hypertension (19.5%), diabetes mellitus (16.5%), obesity, coronary artery disease, and dyslipidemia. During the first 3 months of the pandemic, 52 patients (39%) suspended their biological therapies for short (n = 33) or long (n = 19) periods without medical advice for reasons of fear, worry, and anxiety. All but one patient restarted their medications as a result of therapeutic counseling. Five patients reported suspicious symptoms, but only one had PCR‐confirmed COVID‐19. Our findings suggest that biologic treatment for moderate‐to‐severe psoriasis would not pose an additional risk for COVID‐19 infection and its life‐threatening complications, even in the presence of a high frequency of cardiometabolic comorbidities, provided that all patients are informed and necessary pandemic‐directed precautions are well adopted by the patients.     

NB-UVB联合8-MOP PUVA治疗小腿斑块状银屑病疗效评价

目的: 评价NB-UVB联合8-甲氧补骨脂素（8-MOP） PUVA治疗斑块状银屑病的疗效。方法: 分别对16例银屑病患者双侧小腿进行PASI评分,一侧给予NB-UVB照射,另一侧给予NB-UVB联合8-MOP PUVA,每周3次,共治疗20次。结果: NB-UVB治疗侧治疗前后PASI评分分别为8.21±2.97和2.31±1.01,差异有统计学意义(P＜0.05);NBUVB联合8-MOP PUVA治疗侧分别为8.33±2.54和1.20±0.93,差异有统计学意义(P＜0.05)。治疗后NBUVB联合8-MOP 治疗侧较NB-UVB治疗侧PASI更低,差异有统计学意义(P＜0.05)。结论：NB-UVB联合8-MOP PUVA可明显促进小腿顽固部位皮损的消退。     

PUVA therapy damages psoriatic and normal lymphoid cells within milliseconds

Summary Results of previous investigations have indicated that photochemotherapy (PUVA) attacks membranes of target cells. Using the combination of a stopped-flow technique and laser irradiation we were able to prove that the fast PUVA effect is explainable solely by the membrane damage. Lymphoid cells of healthy persons or psoriatics were taken, within 1 ms mixed with 8-methoxy-psoralen (8-MOP) at concentrations of 1.0, 0.1, and 0.05 g/ml, and then irradiated by a 337-nm laser pulse (0.5 mJ/cm²) lasting some picoseconds. Approximately 1 ms after administration of 8-MOP to the cell surface at least 10% of the cells were damaged, as could be judged using the standard trypan blue exclusion test. This happened at 8-MOP concentrations of 1.0 or 0.1 g/ml plus laser irradiation, but a concentration of 0.05 g/ml 8-MOP plus laser exposure did not cause any effect within 8 ms after mixing. There was no difference between using lymphoid cells from healthy persons or from psoriatics. The fact that only a very short time is necessary before cell damage occurs means that, as far as the fast PUVA effect is concerned, a photochemical reaction involving nuclear DNA can be discounted.     

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。     

Cutaneous carcinoma and PUVA lentigines in Thai patients treated with oral PUVA

A total of 113 Thai patients who were treated with oral PUVA from 1979 to 1992 were examined for long-term cutaneous side effects of PUVA. Two psoriatic patients developed PUVA keratosis on non-sun-exposed areas. Both were skin type IV and had had phototherapy with UVB and sunlight previously. The total doses of UVA were 909 J/cm² and 242 J/cm² respectively. One psoriatic patient developed Bowen's disease. He had had a cumulative dose of UVA 2207 J/cm². He also had a past history of arsenic intake and phototherapy with UVB and sunlight. PUVA lentigines were seen in 58 patients (51.4%). It was associated with older age at starting PUVA, higher cumulative UVA dose and greater number of PUVA treatment. This study suggests that previous exposure to other risk factors is important for inducing skin cancer in populations with skin phototype III, IV and V treated with oral PUVA.     

Combination therapy of oral methoxypsoralen: photochemotherapy (PUVA) and an aromatic retinoid (etretinate, tigason) in the treatment of psoriasis

RePUVA is the combination of an oral aromatic retinoid, etretinate, with oral photochemotherapy, PUVA. This combination therapy has the advantage of faster clearance with fewer side effects. In Middle Road Hospital, we treated 29 patients with extensive psoriasis (more than 30% involvement) with a total 32 RePUVA treatments. There was complete clearance in 69% of patients with an average of 19 irradiations and an average total ultraviolet A (UVA) dose of 183 J/cm². This compared well with standard PUVA which needed 25 radiations and a total UVA dose of 346 J/cm². The main side effects were cheilitis, exfoliation of skin and pruritus. Biochemically, 41% of the patients showed elevations of serum triglyceride.     

Failure of short-term psoralen and ultraviolet A light maintenance treatment to prevent early relapse in patients with chronic recurring plaque-type psoriasis

Background: Photochemotherapy using psoralen and ultraviolet A light (PUVA) is a highly effective treatment option for patients with severe psoriasis. Maintenance treatment has been advocated to provide for sustained remission. However, only a few studies have been conducted to assess the efficacy of maintenance treatment and these have provided inconsistent results.
Methods: We performed a prospective intrapatient left–right comparison study in 34 patients with chronic relapsing plaque psoriasis. PUVA treatment for clearing was given four times weekly. After complete or near-complete clearing, all patients were placed on a halfside maintenance schedule with irradiation twice weekly and then once weekly for 4 weeks each. The psoriasis area and severity index score was determined at baseline, end of the clearing phase and at 2-monthly intervals after discontinuation of treatment.
Results: Using a short-term maintenance protocol, a moderate delay in relapse of psoriasis was observed in only three patients (8.8%; 95% CI: 1.8–23.6%). In the remaining patients (91.2%), maintenance treatment had no effect on the length of remission. The mean time interval until relapse without and with maintenance irradiation was 4.5 ± 3.4 and 4.6 ± 3.4 months, respectively.
Conclusion: Our data indicate that short-term maintenance treatment is not effective in preventing early relapse of psoriasis and should be avoided.     

Discrepant levels of vascular endothelial growth factor in psoriasis patients treated with PUVA, Re-PUVA and narrow-band UVB

Background: Previous reports showed that serum levels of vascular endothelial growth factor (VEGF) are increased in patients with psoriasis. However, to our knowledge, no studies have evaluated the effects of PUVA, Re-PUVA and narrow-band UVB (NB-UVB) treatments on serum levels of VEGF in patients with psoriasis.
Objective: The aim of the study was to evaluate the influence of PUVA, Re-PUVA and NB-UVB treatments on angiogenic activities in patients with psoriasis by comparing serum levels of VEGF.
Methods: Forty-six patients with psoriasis and 20 healthy subjects were included in the study. Peripheral blood samples were collected before, during and after the therapies. The efficacy of PUVA, Re-PUVA and NB-UVB was delineated by the psoriasis area and severity index. A repeated measure of ANOVA, Mann–Whitney U -test, χ² and Pearson's correlation coefficient were used for statistical analysis.
Results: The VEGF levels were significantly decreased in the PUVA group at the end of the follow-up period ( P <0.001). However, the levels were significantly increased in the groups of NB-UVB and Re-PUVA ( P <0.001).
Conclusions: We found that there was a discrepancy during the PUVA, Re-PUVA and NB-UVB treatments. We believe that VEGF plasma levels could not be a useful monitor of psoriasis activity and/or treatment response.     

Bcl‐2 expression in mycosis fungoides before and after PUVA therapy

PUVA is the first therapeutic choice in early stages of mycosis fungoides (MF). In this study the effect of PUVA on bcl‐2 expression in MF was assessed in 15 patients (three stage Ia and 12 stage Ib) and 10 controls. Two biopsies were taken from each patient before and after 24 sessions of PUVA therapy. Histopathological assessment and immunohistochemical staining for bcl‐2 was performed and showed positive bcl‐2 staining of lymphocytes in 53% of MF cases (8/15) before PUVA, with no statistically significant difference in the bcl‐2 level before and after PUVA therapy (P value 0.3). A statistically significant difference was found in the bcl‐2 level between control samples and MF patients' biopsies before (P value 0.02) and after PUVA therapy (P value 0.011). In conclusion, a lack of decline in the bcl‐2 level and the absence of clinical or histopathological correlation with the bcl‐2 level before and after PUVA therapy in MF patients suggest that PUVA‐induced apoptosis in MF cases may occur through pathways other than bcl‐2 inhibition.     

Cost‐efficacy and pharmacoeconomics of psoriatic patients in Japan: Analysis from a single outpatient clinic

Compared with topical corticosteroids, topical combined active vitamin D₃/corticosteroids and especially biologics are more expensive despite their marked efficacy in the treatment of psoriasis. The aim of the present study is to evaluate total costs as well as costs versus efficacy of various psoriasis treatments under the current Japanese health‐care insurance system. A prospective study was performed from the database of a single clinic located in Hokkaido Prefecture. Cost and quality of life of psoriatic patients were evaluated in a prospective manner during a total of 12 months from March 2017 until June 2018. Quality‐adjusted life year (QALY) of biologics was the highest among all treatments. Among the topical treatments, the cost versus efficacy of combined active vitamin D₃/corticosteroid was lowest (¥10 557/1 Psoriasis Area and Severity Index). Furthermore, incremental cost‐effectiveness ratio (ICER) of combined active vitamin D₃/corticosteroid was ¥1 024 031/QALY when compared with topical corticosteroid treatment alone. The topical combined active vitamin D₃/corticosteroid treatment showed the best cost‐efficacy in terms of medical economic burden.     

PUVA suppresses the expression of cell adhesion molecules of lymphocytes

Abstract To determine the therapeutic mechanism of PUVA in psoriasis vulgaris, the effects of PUVA on activated T lymphocytes were investigated in vitro. Peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers were activated with Con A stimulation (Con A blasts). Both untreated PBMC and Con A blasts were irradiated with UVA light in the presence of 8-methoxypsoralen (8-MOP). The expressions of CD4, CDS, VLA-4 and LFA-1 of PBMC and Con A blasts were stained with each monoclonal antibody and the intensity of fluorescence was analyzed by FACScan. PUVA-treated PBMC showed decreased response to both Con A and PHA stimulation. PUVA treatment also suppressed the IL-2 production of Con A blasts and IL-2 response of PBMC with increasing UVA fluence. The expressions of LFA-I, VLA-4, CD4, CDS and CD25 (IL-2R) molecules were decreased in PUVA-treated Con A blasts. Con A blasts were more sensitive than untreated PBMC to PUVA treatment. These results suggest that the therapeutic effects of PUVA on psoriasis vulgaris can be induced by suppression of the expression of cell surface molecules of activated T lymphocytes.