5-Methoxypsoralen plus ultraviolet (UV) A is superior to medium-dose UVA1 in the treatment of severe atopic dermatitis: a randomized crossover trial.

BACKGROUND: Ultraviolet (UV) A1 and psoralen plus UVA (PUVA) are effective treatment options for severe atopic dermatitis (AD); however, their relative efficacy has not yet been determined in a head-to-head study. OBJECTIVES: To compare UVA1 and oral 5-methoxypsoralen (5-MOP) plus UVA with respect to efficacy, tolerability and duration of response in patients with severe generalized AD. METHODS: Forty patients were included in this randomized observer-blinded crossover trial. The patients received either 15 exposures to medium-dose UVA1 as the first treatment and, in cases of relapse, another 15 exposures to 5-MOP plus UVA as the second treatment, or vice versa. All patients were followed until 12 months after discontinuation of the last treatment. The SCORAD score was determined by a blinded investigator at baseline, after 10 and 15 treatments each and during the follow-up period. In addition, all adverse events were recorded during the whole study period. RESULTS: Twenty-three patients completed the crossover treatment. Both phototherapies resulted in clinical improvement; however, PUVA reduced the baseline SCORAD score to a significantly greater extent than UVA1 (mean +/- SD 54.3 +/- 25.7% vs. 37.7 +/- 22.8%; P = 0.041). The median length of remission was 4 weeks (interquartile range 4-12) after UVA1 and 12 weeks (interquartile range 4-26) after PUVA therapy (P = 0.012). CONCLUSIONS: PUVA provides a better short- and long-term response than medium-dose UVA1 in patients with severe AD.

European S3-guidelines on the systemic treatment of psoriasis vulgaris.

Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.

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

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Objective assessment of photoageing effects using high-frequency ultrasound in PUVA-treated psoriasis patients.

BACKGROUND: Skin ageing can be differentiated into intrinsic (chronological) ageing, and photoageing due to chronic sun exposure. Photoageing is the superimposition of photodamage on the ageing process. OBJECTIVES: The aim of the study was to investigate possible differences between the skin of photochemotherapy (PUVA)-treated psoriasis patients and of untreated normal subjects using a high-frequency ultrasound system. METHODS: A total of 124 volunteers (aged 21-88 years, median 52 years, 62 female, 62 male), 62 psoriasis patients who had received PUVA therapy and 62 healthy controls, were investigated. Skin thickness and a subepidermal low-echogenic band (SLEB), a parameter for photodamage, were measured in 12 different areas. RESULTS: Female skin is thinner than male skin. The skin thickness values of PUVA patients were more markedly decreased than those of the controls for the older patients. There was a clear dependence of the occurrence of SLEB on PUVA therapy in psoriasis patients. CONCLUSIONS: Long-term PUVA treatment in psoriasis patients accelerates thinning of the skin in comparison to age-matched controls. The results show that ultrasonography is a sensitive method to investigate the effects of PUVA-induced skin ageing.

High-dose versus medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis.

BACKGROUND: Several studies have demonstrated the efficacy of UVA1 (340-400 nm) phototherapy for patients with severe atopic dermatitis. However, the optimum treatment dose has yet to be determined. Although in seminal investigations high UVA1 doses were used, comparable results were reported in recent studies with a medium-dose regimen. OBJECTIVE: Our purpose was to compare the efficacy of high-dose with medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis. METHODS: Ten adult patients with a median baseline SCORAD score of 67 were enrolled in an investigator-blinded, bilateral comparison study. Treatment was given 5 times weekly over a period of 3 weeks on an outpatient basis. Irradiation was performed by exposing one half of the patient's body to high-dose UVA1 (< or =130 J/cm(2)), and the contralateral body side received only half that dose. The clinical response was assessed after 5, 10, and 15 treatments. After completion of the study, patients were followed up for 6 months to evaluate the duration of clinical improvement. RESULTS: All but one patient responded favorably to treatment. High-dose UVA1 led to a decrease of the median SCORAD score by 33.4% after 1 week, 38.4% after 2 weeks, and 34.7% after 3 weeks. The respective values for the medium-dose regimen were 29.7%, 36.4%, and 28.2%. The difference in efficacy between the two dosages remained below the level of significance at all time points. Relapses occurred after a median of 4 weeks. Time of onset and severity of relapse were the same for both doses. CONCLUSION: Our data support previous uncontrolled observations that medium-dose UVA1 is comparably as effective as high-dose treatment for patients with severe generalized atopic dermatitis. Irrespective of the dose regimen, follow-up examinations revealed early relapse in the majority of patients.

Phototherapy for psoriasis.

This review covers the current practice of phototherapy with ultraviolet (UV) radiation without sensitizers and of psoralen photochemotherapy (PUVA) in the treatment of psoriasis. Both treatment modalities are well established in today's therapeutic armamentarium. Phototherapeutic regimens use repeated controlled UV exposures to alter cutaneous biology, aiming to induce remission of skin disease. Although UVB has been used for a longer time than PUVA, the latter has been evaluated and validated in a more detailed and coordinated fashion.

Correlation between 8-methoxypsoralen bath-water concentration and photosensitivity in bath-PUVA treatment.

BACKGROUND: Bath-PUVA treatment, originally established in Scandinavia, offers several advantages over oral PUVA and has become increasingly popular in recent years. Outside Scandinavia 8-methoxypsoralen (8-MOP) is the prevailing photosensitizer for this PUVA modality and is used arbitrarily in a wide range of concentrations. Up to the present, data are lacking on the impact of 8-MOP bath-water concentration on UVA dosimetry. OBJECTIVE: We investigated the influence of increasing 8-MOP bath-water concentrations on photosensitivity in bath-PUVA treatment. METHODS: Fifteen healthy volunteers without abnormal photosensitivity or recent exposure to ultraviolet radiation were included in an intraindividually controlled comparison study. In all volunteers the minimal phototoxic dose (MPD) was determined on the volar side of their forearms after immersion for 20 minutes in 4 different 8-MOP bath-water concentrations (0.5, 1, 2.5, and 5 mg/L). The correlation between 8-MOP concentration and photosensitivity (defined as the reciprocal value of the MPD) was analyzed by linear regression analysis. In addition, the time course of erythema formation and the UVA dose-erythema response curve was assessed for each psoralen concentration. RESULTS: The median MPD and the 25%-75% interquartile were 5.7 J/cm(2) (5.7-8), 4 J/cm(2) (4-5.7), 2.8 J/cm(2) (2.8-5.7), and 2 J/cm(2) (2-2.8) at an 8-MOP concentration of 0.5, 1, 2.5, and 5 mg/L, respectively. Linear regression analysis revealed a significant correlation between 8-MOP bath-water concentration and photosensitivity (r = 0.98; P =.019). Bath-PUVA-induced erythema peaked after a median time interval of 3 days, with a range of 2 to 4 days. The slope of the UVA dose-erythema response curve was similar for all psoralen concentrations. CONCLUSION: UVA dose requirements in bath-PUVA treatment decrease linearly with increasing 8-MOP concentrations. A single MPD assessment at 72 hours after the UVA exposure is inappropriate for accurate determination of the patients' photosensitivity. The hazard of wrong UVA dosimetry is comparable at all psoralen concentrations.

Narrow-band ultraviolet B (ATL-01) phototherapy is an effective and safe treatment option for patients with severe seborrhoeic dermatitis.

BACKGROUND: Seborrhoeic dermatitis is a common papulosquamous dermatosis affecting 2-10% of the adult population. Current treatment options are limited and not always satisfactory. Objectives We aimed to investigate the efficacy of narrow-band ultraviolet (UV) B (TL-01) phototherapy as an alternative treatment for seborrhoeic dermatitis. METHODS: Eighteen patients with severe disease were enrolled in an open prospective study. Treatment was given three times weekly until complete clearing or to a maximum of 8 weeks. A clinical score assessing erythema, scaling, infiltration and pruritus was performed at baseline and every 2 weeks thereafter. Additionally, the patients were asked to rate the intensity of pruritus on a visual analogue scale. After completion of the study the patients were followed up to determine the median time interval until recurrence. RESULTS: All patients responded favourably to treatment, with six showing complete clearance and 12 marked improvement. The median clinical score decreased from 7.5 (range 4-8) at baseline to 0.5 (range 0-3) after 8 weeks of treatment (P = 0.005). The median pruritus score decreased from 4.5 (range 0-8) at baseline to 0 (range 0-3) at week 8 (P = 0.008). Relapses occurred in all patients after a median of 21 days (range 12-40). No side-effects of treatment were observed except occasional episodes of a moderate erythemal response. CONCLUSIONS: Narrow-band UVB phototherapy appears to be a very effective and safe treatment option for patients with severe seborrhoeic dermatitis.

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.

Half-side comparison study on the efficacy of 8-methoxypsoralen bath-PUVA versus narrow-band ultraviolet B phototherapy in patients with severe chronic atopic dermatitis.

In patients with severe chronic atopic dermatitis (AD), both photochemotherapy [psoralen ultraviolet A (PUVA)] and narrow-band (TL-01) UV B phototherapy have been reported to be very effective. As no data exist on the relative therapeutic efficacy of these two regimens, we performed a randomized investigator-blinded half-side comparison study on 12 patients with severe chronic AD. Half-side irradiation with threshold erythemogenic doses of 8-methoxypsoralen bath-PUVA and narrow-band UVB was performed three times weekly over a period of 6 weeks. The severity of the disease was assessed separately for the paired halves of the patients' bodies by a modified SCORAD score at baseline and after 2, 4 and 6 weeks of treatment. Ten of the 12 patients completed the trial. All but one showed marked improvement or complete remission with both treatments. The mean baseline SCORAD score decreased by 65.7% by the bath-PUVA treatment and by 64.1% by the narrow-band UVB treatment (P = 0.48). No serious adverse reactions to either of the two regimens were observed. Our data confirm the high efficacy of bath-PUVA and narrow-band UVB phototherapy in the treatment of patients with chronic severe AD. Both regimens appear to be equally effective when administered in equi-erythemogenic doses.

Narrowband UV-B phototherapy vs photochemotherapy in the treatment of chronic plaque-type psoriasis: a paired comparison study.

OBJECTIVE: To compare the therapeutic efficacy of narrowband (TL-01) UV-B phototherapy vs photochemotherapy (psoralen-UV-A [PUVA]) in patients with chronic plaque-type psoriasis. DESIGN: Open, nonrandomized, intraindividually controlled paired comparison study. SETTING: Phototherapeutic unit in a university hospital. PATIENTS: Twenty-five patients with chronic plaque-type psoriasis. INTERVENTIONS: Paired irradiations with threshold erythemogenic doses of narrowband UV-B and PUVA were given to the patients' dorsal aspect including the arms and legs. Treatment was performed 3 times weekly until complete or almost complete clearing with one or both regimens or over a maximum period of 18 exposures. MAIN OUTCOME MEASURES: Assessment of the Psoriasis Area and Severity Index (PASI) in each half of the patient's dorsal aspect before and after treatment with the 2 regimens. RESULTS: The median pretreatment PASI score of 16 (range, 6.2-23.4) was reduced by 84% to 2.5 (range, 0-12.6) by the narrowband UV-B treatment and by 89% to 1.8 (range, 0-8.2) by the PUVA treatment. Statistical analysis of these data showed a tendency for PUVA being superior to narrowband UV-B although the difference remained below the level of significance (P = .17). However, a clear effect of the pretreatment PASI score on the therapeutic outcome was found. Patients with higher baseline PASI scores responded significantly better to PUVA than to narrowband UV-B (P = .03). CONCLUSIONS: Our data demonstrate that in many patients with plaque-type psoriasis, narrowband UV-B is comparably as effective as PUVA and, given the lack of photosensitizer-related adverse reactions and the possibly lower long-term cancer risk, can be considered as first-line treatment. Treatment with PUVA, on the other hand, remains the mainstay for patients with high PASI scores who do not respond or whose psoriasis cannot be controlled adequately by narrowband UV-B.

Bullous pemphigoid induced by PUVA therapy.

An 80-year-old psoriatic patient developed a blistering eruption during oral PUVA therapy. The diagnosis of bullous pemphigoid (BP) was established by routine histopathology, which demonstrated subepidermal blistering, and direct immunofluorescence, which revealed linear deposits of IgG, IgM and C3 along the basement membrane zone. Indirect immunofluorescence using normal human split skin revealed binding of IgG antibodies to the epidermal side, thus confirming a subepidermal blistering disorder. These proteins were identified by the immunoblotting technique as BP antigens I and II. Clinically, the lesions could be reproduced by phototesting using topical 8-methoxypsoralen. Again, the histopathological and immunopathological findings were consistent with the diagnosis of PUVA-induced BP. To the best of our knowledge, this is the first report demonstrating psoriasis-associated BP, in which the clinical diagnosis of BP is confirmed by immunoblotting analysis. The exact role of UV light in precipitating bullous lesions, particularly the question whether UV light may represent an unspecific epidermal injury leading to further attraction of autoantibodies to the basement membrane zone, as suggested recently by an experimental study in rodents, remains to be clarified in future studies.

Skin tumors in photochemotherapy for psoriasis: a single-center follow-up of 496 patients.

BACKGROUND: The significance of oral psoralen photochemotherapy (PUVA) for the development of nonmelanoma skin cancers (NMSC) is still controversial. OBJECTIVE: We evaluated 496 psoriatics, who received PUVA treatment according to the European PUVA protocol in order to reassess the influence of the cumulative UVA dose on the development of NMSC and to answer the question if there is a UVA threshold dose above which the carcinogenic risk is increased. METHODS: The study was conducted as a retrospective investigation. All patients were seen personally. Age, sex, skin type, cumulative UVA dose and carcinogenic risk factors (arsenic, X-rays, tar, UVB, methotrexate) were recorded and investigated by marginal (MA) and partial effects analyses (PA) according to the Cox regression model. RESULTS: In 14 patients (2.8%), one or multiple histologically confirmed NMSC were diagnosed. Nine patients (1.8%) had squamous cell carcinoma (SCC), 5 patients (1.0%) had basal cell carcinoma (BCC). No patient had both types of NMSC. None of the SCC had metastasized. By taking the appearance of BCC and SCC as the endpoint, arsenic [MA: relative risk (RR) = 7.62; PA:RR = 5.36], tar (MA:RR = 4.51; PA:RR = 3.83) and methotrexate (MTX; MA:RR = 4.97; PA:RR = 4.07) appear to produce strong and significant effects (p < 0.05), both in MA and PA. Using the endpoint SCC only, the effect of the natural logarithm of UVA (ln UVA; RR = 2.47), arsenic (RR = 11.2), tar (RR = 9.92) and MTX (RR = 7.1) is significant (p < 0.05) in MA. In PA, only the effect of arsenic (RR = 5.19) is strong and significant (p < 0.05) while the effects of tar (RR = 7.85), MTX (RR = 3.22) and ln UVA (RR = 2.77) are strong but of borderline significance (p = 0.05-0.11). Nonlinear effects of ln UVA on the risk of SCC were far from significant (p > 0.2). CONCLUSION: PUVA with the European treatment protocol appears to be only a weak carcinogen by itself for SCC with a linear increase in tumor risk but not for BCC development.

Safety and effectiveness of an aggressive and individualized bath-PUVA regimen in the treatment of psoriasis.

BACKGROUND: The optimal therapeutic regimen of bath-PUVA therapy of psoriasis is still under debate. OBJECTIVE: We investigated the safety and efficacy of an aggressive and individualized bath-PUVA regimen. METHODS: Two closely matched groups of 22 psoriatic patients were treated either with 30-min baths in 0.0003% 8-methoxypsoralen (8-MOP) aqueous solution or oral administration of the drug. According to the standard European regimen, treatments were delivered 4 times a week starting with the minimal phototoxic dose. RESULTS: Complete clearing or marked improvement was observed in all the patients. However, with bath-PUVA, the same therapeutic effect required smaller cumulative UVA doses (39.3 +/- 15.8 vs. 123.8 +/- 39.9 J/cm2) and lower numbers of exposures (15.2 +/- 4.4 vs. 20.6 +/- 4.2). Both differences were significant at the 0.01 level (Student's t test). Gastro-intestinal side-effects were of course restricted to oral 8-MOP. The incidences of burns and pruritus were similar. CONCLUSION: Using an aggressive and individualized schedule, bath-PUVA therapy showed a greater efficacy than oral PUVA therapy while being just as safe.

Comparison of narrow-band (311 nm) UVB and broad-band UVA after oral or bath-water 8-methoxypsoralen in the treatment of psoriasis.

BACKGROUND: There is a disparity between the absorption spectrum of 8-methoxypsoralen and the action spectrum for psoralen-sensitized erythema. In an action spectrum corrected for unsensitized reaction 313 and 365 nm have similar efficacies. OBJECTIVE: We evaluated the relative erythemogenic and antipsoriatic efficacy of narrow-band (311 nm) UVB with and without prior psoralen exposure. We also compared the effects of narrow-band UVB and broad-band UVA after oral and bath-water psoralen exposure. METHODS: Patients with psoriasis underwent half-side comparison studies. In one group the therapeutic efficacy of 311 nm UVB with and without oral psoralen was assessed. The second group received UVA and 311 nm UVB after oral psoralen. The third group was exposed to both radiation sources after bath-water exposure. RESULTS: The erythemogenic, pigmentogenic, and therapeutic efficacy of 311 nm was increased by oral psoralen. With systemic 8-methoxypsoralen, UVA was comparable to 311 nm UVB. After bath-water exposure, 311 nm was clearly superior to broad-band UVA. CONCLUSION: The efficacy of narrow-band 311 nm UVB can be enhanced by psoralen. Narrow-band 311 nm UVB is also effective after psoralen bath-water delivery.