Narrowband UVB and cream psoralen-UVA combination therapy for plaque-type psoriasis

BACKGROUND: Psoralen-UVA (PUVA) and narrowband UVB (311-nm) therapy are considered to be first-line phototherapies for patients with moderate to severe psoriasis. To reduce side effects as a result of systemic resorption of psoralens, topical PUVA therapies have been developed and proven to be effective in the treatment of psoriasis. OBJECTIVE: We sought to evaluate the combination therapy of narrowband UVB plus cream PUVA on selected psoriatic plaques compared with narrowband UVB or cream PUVA alone. METHODS: A total of 30 patients (Psoriasis Area and Severity Index score of 8-15) were included in the randomized study. The combination therapy consisting of narrowband UVB whole-body irradiation followed by cream PUVA therapy for selected psoriatic plaques was evaluated in 10 patients with chronic plaque-stage psoriasis. For comparison, the therapeutic efficacy, number of treatments, and cumulative UV doses until remission (Psoriasis Area and Severity Index score < 4) of cream PUVA therapy or narrowband UVB alone was determined in 10 patients, respectively. RESULTS: Both monotherapies induced clearance of psoriatic lesions in all patients within 5 to 7 weeks. Mean number of treatments for cream PUVA was 24 +/- 5; for narrowband UVB was 21 +/- 3. The mean cumulative UVA dose was 45.0 +/- 16.3 J/cm(2) and the mean cumulative UVB dose was 17.1 +/- 4.1 J/cm(2). Combination therapy resulted in complete clearance of lesions in all patients after 3 to 4 weeks. Mean number of treatment was 14 +/- 2, mean cumulative UVA dose was 18.7 +/- 4.7 J/cm(2), and mean cumulative UVB dose was 8.2 +/- 3.3 J/cm(2). The number of treatments (P <.001, analysis of variance), UVA dose (P <.001, t test), and UVB dose (P <.001, t test) were significantly reduced compared with both monotherapies. CONCLUSIONS: Our results indicate that a combination therapy of narrowband UVB plus cream PUVA appears to have a significantly higher efficacy compared with either monotherapy. The cumulative UV doses were significantly lower in the combination therapy. We conclude that cream PUVA can be used in addition to narrowband UVB for areas that tend to clear less quickly than the rest of the body.     

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.     

Randomized half-side comparison of narrowband UVB and trimethylpsoralen bath plus UVA treatments for psoriasis

The efficacy of trimethylpsoralen bath PUVA and UVB TL01 were compared in chronic plaque psoriasis. Patients were randomly assigned to receive UVB TL01 on one side and bath PUVA on the contra-lateral side. Altogether 17 patients received treatments and 15 completed the trial. The decrease in the PASI score was greater with UVB TL01 than PUVA. At the end of the treatment period, the difference was highly significant (p < 0.001). The difference was already significant at week 3 (p = 0.014). The relative median decrease in the PASI score was 77% (24-100%) with UVB and 45% (8-100%) with PUVA. The median cumulative UVB dose was 39.92 (range 13.95-81.56) J/cm2 and the corresponding UVA dose was 8.06 (range 3.31-12.51) J/cm2. All patients relapsed within 4 months. Narrowband UVB improved psoriasis clinically and statistically more efficiently than trimethylpsoralen bath PUVA, and UVB was better tolerated.     

Interactions between tazarotene and ultraviolet light

Tazarotene in combination with phototherapy is being used clinically for the treatment of plaque psoriasis. This study investigates the dose of UVB light required to induce minimal erythema and the dose of UVA light required to induce immediate pigment darkening, with and without pretreatment with tazarotene 0.1% gel. The photostability of tazarotene is also assessed. Pretreatment with tazarotene 0.1% gel 3 times per week for 2 weeks before phototherapy significantly reduced the mean minimal erythema dose (MED) for UVB from 56.25 to 42.50 mJ/cm(2) (P <.01), and significantly reduced the mean UVA exposure required to induce immediate pigment darkening from 20.18 to 18.50 J/cm(2) (P <.05). A thin application of tazarotene gel immediately before phototherapy had no significant effect on the mean MED for UVB, whereas a thick application of the gel increased the MED slightly, from 56.25 to 62.50 mJ/cm(2) (P =.1). Tazarotene remained chemically stable when used in conjunction with UVB or UVA phototherapy. To reduce the patient's potential to burn or tan, we recommend initiating UVB phototherapy at 50% to 75% of the MED when it is used in combination with tazarotene. We also recommend initiating PUVA therapy at slightly lower doses than usual. Lower total doses of UVA or UVB may be needed when patients with psoriasis are treated concomitantly with tazarotene.     

Chronic actinic dermatitis developed during phototherapy for psoriasis

A patient with psoriasis vulgaris had been successfully treated with PUVA and UVB therapy. During maintenance phototherapy, he suddenly became photosensitive and developed eczematous eruption. Minimal response doses to UVB and UVA were extremely low--1.09 mJ/cm2 and 0.3 J/cm2, respectively. No chemical substances were identified as the responsible photosensitizer. The condition was diagnosed as chronic actinic dermatitis (CAD). PUVA therapy was unsatisfactory because it was not possible to administer an adequate dose of UVA. Oral cyclosporine, topical corticosteroid and sunscreen were used with beneficial therapeutic effects on psoriasis and CAD. As far as we know, the development of CAD during phototherapy has not been previously reported.     

Phototherapy in pediatric patients

The treatment of children with psoriasis, atopic dermatitis (AD), pityriasis lichenoides, and scleroderma poses a therapeutic problem because all therapeutic options are associated with numerous side effects. Therefore ultraviolet A and B (UVA and UVB) phototherapy is presented as a possible alternative to some of these therapies, primarily topical and systemic corticosteroids, in children. Our results in treating children with phototherapy and psoralen plus UVA (PUVA) bath phototherapy over the past 5 years are reported. UVB therapy (TL01) was used in 20 psoriatic children (6 boys, 14 girls; ages 6-14 years) during the stage of disease exacerbation and in 9 children (3 boys, 6 girls; ages 8-16 years) with pityriasis lichenoides. Combined UVA/UVB phototherapy was applied in 21 AD children (7 boys, 14 girls; ages 4-15 years). Photochemotherapy with local application of a PUVA bath was used in six children (2 boys, 4 girls; ages 9-16 years) with circumscribed scleroderma and in one girl with systemic scleroderma. All children received short courses of phototherapy with either no maintenance or short maintenance. All three therapeutic protocols resulted in a certain degree of improvement in most of the study patients. None of the patients exhibited any early phototherapy side effects. We conclude that phototherapy and PUVA bath are valuable and safe therapeutic options for selected children who do not respond to other treatments.     

Treatment of persistent severe atopic dermatitis in 113 Japanese patients with oral psoralen photo-chemotherapy

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.     

Comparison of trioxsalen bath and oral methoxsalen PUVA in psoriasis

Fifty patients with chronic plaque psoriasis were treated with trioxsalen bath PUVA and 43 patients with oral methoxsalen PUVA. The two treatment regimens gave similar results; 75% and 77% of the patients had excellent or good clearing and a follow-up of one year revealed relapses in 61% and 58% of the patients, respectively. The cumulative UVA dose remained significantly lower in bath PUVA (mean 23.5 J/cm2) than in oral PUVA (mean 131 J/cm2). Nausea and headache occurred in 21% of the patients receiving oral PUVA but in none in the bath PUVA group. Local side-effects were found in 30% of the patients receiving bath PUVA and in 17% of the patients in the oral PUVA group.     

Time course of skin photosensitivity following trimethylpsoralen bath PUVA

One aspect of bath photochemotherapy (PUVA) that requires clarification is the duration of psoralen-induced cutaneous photosensitisation under conditions simulating clinical use. Using a half back comparison study technique, we investigated the persistence of trimethylpsoralen (TMP)-induced photosensitivity in skin irradiated to simulate a first PUVA exposure compared with un-irradiated skin. Baseline UVA minimal erythema dose and minimal phototoxic dose (MPD) were determined in 13 healthy volunteers. After readings at 72 h, subjects were bathed in TMP bath water for 15 min and one half of the back was immediately exposed to 40% of the MPD. Test sites (1.5 cm2) on both halves of the back were then irradiated with a UVA dose series at 15 min, 5, 10, 24, 34, 48 and 72 h after the bath. MPD readings were recorded visually at 72 h after each UVA exposure. The UVA MED was >25 J/cm2 in all the subjects. At each time point, a phototoxic index (PI) was calculated as UVA MED/MPD. In un-irradiated skin, photosensitivity returned to normal (PI=1) within 24 h after the TMP bath. In contrast, skin pre-irradiated to simulate the first PUVA treatment was still significantly photosensitive (PI=2.3; P=0.002) at 48 h. Contrary to previous recommendations, these data suggest that patients should be advised to avoid ambient or artificial sources of UVA throughout their course of TMP bath PUVA to reduce the risk of phototoxic erythema.     

Cream psoralen plus ultraviolet A therapy for granuloma annulare

BACKGROUND: Treatment modalities for granuloma annulare (GA) often remain unsatisfactory or can be accompanied by potentially hazardous side-effects. Psoralen plus ultraviolet (UV) A (PUVA) bath photochemotherapy has been reported to be highly effective in the treatment of GA. Another form of topical PUVA therapy, using 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as bath PUVA therapy in the treatment of palmoplantar dermatoses. OBJECTIVES: To assess the efficacy of cream PUVA photochemotherapy in patients with GA. METHODS: Five patients with GA were treated. The diagnosis was confirmed by pretreatment skin biopsies. Cream PUVA therapy was performed four times a week: the mean number of treatments was 26 (range 17-40) and mean cumulative UVA dose was 55.9 J cm-2 (range 18.2-109.2). RESULTS: Cream PUVA photochemotherapy induced significant clinical improvement (one patient) or clearance (four patients) of GA in all patients. Clearance was documented clinically and histopathologically. CONCLUSIONS: Cream PUVA phototherapy can be highly effective in patients affected by localized forms of GA.     

Malignant melanoma in association with phototherapy.

A 54-year-old Caucasian male suffering from psoriasis had been treated in 1978 and 1980 with PUVA (cumulative UVA dose 492.5 J/cm2) and from 1980 to 1989 with UVB (cumulative UVB dose 264.5 J/cm2). Other occasional treatment had comprised the topical administration of glucocorticosteroids, dithranol or tar. In 1989, on the upper part of the patient's back a newly developed pigmented skin lesion was excised under the clinical diagnosis of a pigmented, dysplastic nevus. Histological examination revealed a superficial spreading malignant melanoma (0.4 mm thick, Clark level II). In this case, exposure to high cumulative doses of therapeutic UV irradiation might have played an etiological role for the development of malignant melanoma.     

New aspects in uv and photochemotherapy

Recent data show that from a pharmacological point of view topical (cream or bath) PUVA therapy is superior to systemic PUVA. Due to a significant reduction of side effects compared to systemic PUVA, bath PUVA has now started to replace oral PUVA therapy. Narrowband UVB has proved to be superior to broadband UVB in the treatment of psoriasis and is effective for a number of dermatoses such as vitilgo, atopic dermatitis and polymorphic light eruption. UVA1 phototherapy is highly effective in the treatment of moderate to severe atopic dermatitis and sclerosing diseases of the skin. Data dealing with UVA1 phototherapy for other indications are still preliminary. High-dose UVA1 is has been widely replaced by medium-dose UVA1, as a number of studies have shown similar therapeutic efficacy of both dose regimens.     

Combination of photochemotherapy (PUVA) and ultraviolet B (UVB) in the treatment of psoriasis vulgaris

Nineteen patients with psoriasis vulgaris were treated with a combination of psoralen-ultraviolet A (PUVA) and ultraviolet B (UVB) on the right side of their bodies and with PUVA therapy alone on the left side. Herein is an analysis of the results. There were no significant differences in the mean number of treatments, the mean UVA dose at clearing, or the mean cumulative UVA dose between the PUVA-UVB side and the PUVA side. However, in 4 cases, the PUVA-UVB side cleared more rapidly than the PUVA side. Interestingly, patients who received PUVA-UVB on one side and PUVA on the other required fewer treatments, a lower ultraviolet (UV) dose at clearing, and a lower cumulative UV dose than did patients who were treated with only PUVA monotherapy or UVB monotherapy, following the same protocol. This combined method may be useful in the treatment of chronic psoriatic patients, because of rapid clearing and a marked reduction in the total cumulative UV radiation. However, further follow-up studies are indicated due to the long-term side effects of combined UV radiation.     

A comparison of systemic photochemotherapy with 8-methoxypsoralen (8-MOP) and with trimethylpsoralen (TMP) in vitiligo

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.     

Role of ultraviolet A in phototherapy for psoriasis

Multiple studies have demonstrated that the doses of ultraviolet A (UVA) (320-400 nm) achieved with ultraviolet sources presently used for phototherapy for psoriasis are inadequate to induce coal tar phototoxicity (as manifested by delayed erythema). Some centers still use a phototherapy protocol that combines UVA, ultraviolet B (UVB), and tar for the treatment of generalized psoriasis. We designed a bilateral comparison study to determine whether the addition of UVA to one side, in doses sufficient to induce an immediate burning or smarting sensation in tar-treated skin, would add to the beneficial effects of UVB. The psoriasis of ten of thirteen ambulatory patients cleared in a mean of 26.1 treatments. Despite a mean cumulative UVA dose of 130.8 joules/cm2, none of the thirteen patients showed a better response on the side that received additional UVA. A "nonaggressive" inpatient protocol was designed to maximize the chances of demonstrating a beneficial effect of UVA. The psoriasis of eight of twelve patients cleared in a mean of 21.0 treatments. Despite a mean cumulative UVA dose of 40.3 joules/cm2, the twelve patients showed no difference in clearing between sides. The threshold for smarting increased throughout the treatment and provided a convenient guide to the delivery of increasing doses of UVA. In doses sufficient to induce coal tar phototoxicity manifested by the smarting reaction, UVA does not add to the known benefits of UVB phototherapy.     

窄谱中波紫外线治疗慢性光线性皮炎的方案及影响因素分析

目的 探讨窄谱中波紫外线(NB-UVB)光疗法治疗慢性光线性皮炎(CAD)的方案及影响治疗实施的相关因素.方法 对2008年1月至2015年6月间在复旦大学附属华山医院皮肤科接受NB-UVB光疗的CAD患者的人口学资料、光生物学测试结果、治疗参数和临床反应进行回顾性分析.采用SAS9.3软件对完成与未完成NB-UVB光疗者的临床资料通过t检验或x2检验进行比较.结果 共79例CAD患者接受NB-UVB光疗,均为Fitzpatrick Ⅳ型皮肤,其中61例(77％)完成治疗,18例(23％)因无法耐受而退出.完成治疗者中,NB-UVB起始照射剂量为(0.08±0.01) J/cm2,终点照射剂量为(0.32±0.08) J/cm2,累积照射量为(5.9±2.5)J,治疗次数为(28±8)次.52例(85％)在照射剂量达到0.30 J/cm2时皮损基本清除.19例患者在光疗结束后再次进行光试验,其中16例对UVA敏感的患者中6例UVA-MED恢复正常,6例明显改善;16例对UVB敏感的患者中11例UVB-MED恢复正常,3例明显改善.单因素分析显示,患者性别、年龄、病程、长波紫外线(UVA)敏感度、UVB敏感度以及光斑贴试验和斑贴试验结果在完成治疗和未完成治疗患者之间比较,差异均无统计学意义(P＞0.05).结论 于春季开始、起始剂量为0.08 J/cm2、终点剂量为0.30 J/cm2、疗程28次左右是适合CAD患者的NB-UVB光脱敏方案,可有效降低患者对UVA和UVB的敏感性.不同性别、年龄、病程以及光敏感程度的CAD患者均可尝试用NB-UVB光疗法治疗.     

Effectiveness of medium-dose ultraviolet A1 phototherapy in localized scleroderma

Background Recently, ultraviolet (UV) A1 phototherapy has been suggested as an effective treatment for localized scleroderma (LS); however, the optimal dose of UVA1 still has not been determined. Objective We aimed to evaluate the therapeutic effectiveness of medium‐dose (30 J/cm²) UVA1 phototherapy and to show that 13 MHz ultrasound is a valuable tool for assessing the results of UVA1 phototherapy in LS. Methods Thirty‐five patients with LS were treated with medium‐dose (30 J/cm²) UVA1. In total, 30–45 treatments and 900–1350 J/cm² cumulative UVA1 doses were evaluated by clinical scoring in all patients. In 14 patients, skin thickness was also determined by 13 MHz ultrasound examination. Results In all patients, medium‐dose UVA1 therapy softened sclerotic plaques, and marked clinical improvement was observed in 29 of 35 (82. 85%) patients. Ultrasound measurements showed that skin thickness was significantly reduced. No side effects were observed during or after treatment. Conclusion Medium‐dose UVA1 phototherapy is a highly effective, safe, and well‐tolerated therapeutic modality for treatment of all types of LS. A 13 MHz ultrasound probe may be used for evaluating UVA1 phototherapy results.     

Papular dermatitis (subacute prurigo, “itchy red bump” disease): Pilot study of phototherapy

Background: Some patients with a subacute or chronic pruritic erythematous papular eruption are refractory to treatment. We previously described a number of these patients with papular dermatitis or subacute prurigo. Objective: The purpose of this study was to examine the effectiveness of different types of phototherapy for treatment of papular dermatitis. Methods: We reviewed the medical records of 11 patients who were diagnosed with papular dermatitis and who underwent phototherapy within the last 5 years. Results: Eleven patients had a total of 17 phototherapy courses: psoralen–UVA (PUVA; 9), UVA/UVB light (3), and UVB alone (5). Within the PUVA treatment group, three of nine patients experienced total clearing, and six of nine patients experienced partial improvement. Although patients in all groups relapsed with time, overall the PUVA-treated patients had the best response rate and the best chance of the condition remaining clear after treatment was stopped. Conclusion: PUVA may be an effective treatment for papular dermatitis. The frequency of relapse indicates that maintenance treatments may be necessary for long-term control of the disease. (J Am Acad Dermatol 1998;38:929-33.)     

Phototherapy in the management of atopic dermatitis: a systematic review

BACKGROUND/PURPOSE: Atopic dermatitis (AD) is a common and extremely burdensome skin disorder with limited therapeutic options. Ultraviolet (UV) phototherapy is a well tolerated, efficacious treatment for AD, but its use is limited by a lack of guidelines in the optimal choice of modality and dosing. Given this deficit, we aim to develop suggestions for the treatment of AD with phototherapy by systematically reviewing the current medical literature. METHODS: Data sources: All data sources were identified through searches of MEDLINE via the Ovid interface, the Cochrane Central Register of Controlled Trials, and a complementary manual literature search. STUDY SELECTION: Studies selected for review met these inclusion criteria, as applied by multiple reviewers: controlled clinical trials of UV phototherapy in the management of AD in human subjects as reported in the English-language literature. Studies limited to hand dermatitis and studies in which subjects were allowed unmonitored use of topical corticosteroids or immunomodulators were excluded. DATA EXTRACTION: Included studies were assessed by multiple independent observers who extracted and compiled the following data: number of patients, duration of treatment, cumulative doses of UV radiation, adverse effects, and study results. Data quality was assessed by comparing data sets and rechecking source materials if a discrepancy occurred. RESULTS: Nine trials that met the inclusion criteria were identified. Three studies demonstrated that UVA1 is both faster and more efficacious than combined UVAB for treating acute AD. Two trials disclosed the advantages of medium dose (50 J/cm(2)) UVA1 for treating acute AD. Two trials revealed the superiority of combined UVAB in the management of chronic AD. Two additional studies demonstrated that narrow-band UVB is more effective than either broad-band UVA or UVA1 for managing chronic AD. CONCLUSION: On the basis of available evidence, the following suggestions can be made: phototherapy with medium-dose (50 J/cm(2)) UVA1, if available, should be used to control acute flares of AD while UVB modalities, specifically narrow-band UVB, should be used for the management of chronic AD.     

Rate of acute adverse events for narrow-band UVB and Psoralen-UVA phototherapy

BACKGROUND: Ultraviolet (UV) radiation therapies are commonly used to treat a wide range of dermatological conditions. However, no published data exist regarding the rate of acute adverse events occurring within the different UV therapy modalities. AIM: The aim of this study was to determine the rate of acute adverse events experienced by patients receiving narrow-band UVB or photochemotherapy in 3 neighboring dermatology units. METHOD: Standardized adverse event forms from all 3 units were retrospectively analysed over a 12-month period between October 2003 and September 2004. The treatments included were narrow-band UVB and systemic, bath and hand/foot PUVA. RESULTS: A total of 8784 treatments were given over the study period. The total number of acute adverse events recorded for all phototherapy treatments was 70 (0.8%). The rates of acute adverse events for each treatment modality were 0.6% for narrow-band UVB, 1.3% for systemic PUVA, 1.3% for bath PUVA and 0.8% for hand/foot PUVA. Adverse events were due to patient non-compliance with standard operating procedures in 15 cases (21%) and operator error in 2 (3%). Only 4 of the acute adverse events were considered to be severe, accounting for 0.05% of all treatments. CONCLUSIONS: The rates of acute adverse events with phototherapy in this analysis were low, in particular the rate of severe adverse events. The highest rate was seen with both systemic and bath PUVA. The number of adverse events resulting from operator error was low. These published rates for adverse events associated with narrow-band UVB and PUVA may help other units when analyzing their own rate of adverse events.