Kinetics and dose-response of photosensitivity in cream psoralen plus ultraviolet A photochemotherapy: comparative in vivo studies after topical application of three standard preparations

BACKGROUND: Topical photochemotherapy with bath psoralen plus ultraviolet (UV) A irradiation (PUVA) has been developed to reduce possible side-effects of oral PUVA therapy. Although the efficacy of bath PUVA therapy appears to be similar to oral PUVA therapy, provision of bathing facilities has obvious economic, logistic and sanitary implications. Cream PUVA therapy has recently been developed as a variation of topical PUVA. OBJECTIVES: To understand the photobiological effects and to increase the safety and effectiveness of this novel topical PUVA therapy, we assessed the kinetics and dose-response of phototoxicity of 8-methoxypsoralen (8-MOP) cream in order to develop a treatment schedule for this treatment option. METHODS: Ninety-eight patients (63 men and 35 women) undergoing cream PUVA therapy were studied. The phototoxic properties of topically applied 8-MOP in three different water-in-oil creams as vehicles were assessed. In a dose-response study, four concentrations of 8-MOP cream (0.0006-0.005%) were used for determination of the minimal phototoxic dose (MPD). The kinetics of photosensitization were tested by determination of MPDs after different application times of 8-MOP cream (10, 20, 30 and 60 min). The persistence of phototoxicity was assessed by UVA exposure at defined time intervals after application of 8-MOP cream (0, 30, 60 and 120 min). RESULTS: The concentration required to produce sufficient but not undue photosensitization of the skin was 0.001% 8-MOP. The duration of application leading to the lowest MPD was 30 min. Greatest photosensitization was achieved when UVA irradiation was performed between 0 and 30 min after 8-MOP removal. These findings showed no significant difference between the three vehicles used. CONCLUSIONS: Based on our data we recommend application of 0.001% 8-MOP in a water-in-oil cream for 30 min. Irradiation with UVA should be performed within 30 min after removal of 8-MOP cream, as there is a rapid decrease in photosensitivity thereafter.     

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.     

Reduction in 8-methoxypsoralen immersion time alters the erythemal response to bath PUVA

Topical psoralen plus ultraviolet A (PUVA) using 8-methoxypsoralen (8-MOP) bath solution is a well established and effective treatment in dermatology. The standard immersion time in the UK is 15 min, but a shorter bathing period could potentially increase treatment convenience. In order to examine the effect of reduction in immersion time on skin phototoxicity, we compared the erythemal response to UVA following 5 min and 15 min psoralen baths. The study was performed on the forearm skin of 7 healthy volunteers using an 8-MOP psoralen concentration of 2.6 mg/l. One forearm of each volunteer was soaked for 15 min and the other for 5 min, followed by immediate irradiation with a series of 10 doses of broadband UVA ranging from 0.1 J/cm2 to 6.9 J/cm2. At 72 h, the minimal phototoxic doses (MPDs) were noted and erythema readings (erythema index) were taken in triplicate with a reflectance instrument. The median MPD following 5 min immersion was 1.7 (range 0.7-2.7) J/cm2 compared with 1.0 (range 0.4-1.7) J/cm2 after 15 min treatment, with no significant difference. However, the mean slope of erythema dose-response on the 15-min treated side was significantly steeper than on the 5-min treated side, 0.036 and 0.021 respectively, P < 0.05. Hence, this preliminary work shows that reducing 8-MOP immersion time to 5 min reduces the erythemal response to UVA. It will clearly be necessary to examine the effect of a shortened immersion period on disease clearance before considering such a change to the topical PUVA regime.     

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.     

Kinetics of phototoxicity in trioxysalen bath psoralen plus ultraviolet A photochemotherapy

A trioxysalen bath is a safe alternative to systemic 8-methoxypsoralen in long-term psoralen plus ultraviolet A (PUVA) treatment. The kinetics of its main side-effect, the strong phototoxicity, has not been thoroughly studied. This study determined the degree and persistence of phototoxicity after a single 10 min bath at a trioxysalen concentration of 0.33 mg/l. The buttock skin of 16 healthy volunteers was irradiated with UVA 10 min, and 1, 3, 9 and 24h after the bath. The minimal phototoxic dose (MPD) was assessed 48, 72 and 96h after the bath. In general, the 96 h reading showed the lowest values of MPD; for example, a median of 0.14 J/cm2 (95% confidence interval 0.10-0.14 J/cm2) at sites irradiated 10 min after the bath. The values increased progressively with later irradiation, and the maximum dose applied, 18.32 J/cm2, failed to produce any redness when irradiation was given 24 h after the bath. Substantial phototoxicity persists up to at least 9h after the trioxysalen bath, making it wise for patients to avoid sunshine for at least the rest of the day.     

Eficacia terapéutica del baño-PUVA en psoriasis

IntroductionThe use of psoralen baths with long-wave UV radiation, known as PUVA bath therapy, is useful in the treatment of psoriasis. The therapy is not associated with systemic adverse effects and the dose of UV-A radiation administered is lower. The objectives of this study aimed to identify the variables that influence the effectiveness of PUVA bath therapy and the duration of remission, as well as to determine factors that predict relapse. It also aimed to assess the effectiveness of a protocol using the minimal phototoxic dose and to compare two concentrations of 8-methoxypsoralen.Patients and methodsTwo hundred nine patients with moderate-severe plaque psoriasis attended between 1994 and 2000 were included in the study. The characteristics and therapeutic outcomes of the sample were recorded. Survival curves were plotted for the disease-free interval after a good response to treatment. A proportional hazard model was used to assess the factors that influence the duration of remission.ResultsTherapeutic outcomes were better in patients with greater photosensitivity (p = 0.03). Application of the minimal phototoxic dose protocol was not associated with greater phototoxicity during treatment. The median duration of remission was 7 months. Those patients who had previously undergone oral PUVA therapy and those who did not achieve a substantial reduction in the psoriasis area and severity index (PASI) score were at greater risk of relapse.ConclusionsA lower final PASI extended the lesion-free period.     

Can the immersion time of PUVA bath therapy be shortened?

Up to now, there are only a few data available concerning the influence of bathing time on skin phototoxicity. We compared the erythemal responses of normal skin to bath PUVA with 8-methoxypsoralen (8-MOP) after 5, 10 and 20 min immersion time. Currently, 20 min is the routinely performed immersion time in many European countries, including Germany, while in other countries bathing times are shorter. The minimal phototoxic dose (MPD) following immersion times of 5 min and 10 min in a warm water bath (37 degrees C) containing 1 mg/l 8-MOP was compared to the MPD following 20 min immersion time in a half-sided manner in a total of 24 patients. Our results revealed that an immersion time of 5 min did not yield a detectable erythema after 72 h. In contrast, both 10 and 20 min PUVA baths induced visible erythemas with a significantly higher median MPD following 10 min immersion (2.25 J/cm2) compared to 20 min baths (1.5 J/cm2). As an erythemal response of 8-MOP PUVA bath seems reduced after shorter immersion times, comparative studies on the clinical efficacy using shorter time regimens have to be conducted before conclusive recommendations for clinical PUVA-bathing time can be given.     

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

BACKGROUND: 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. Methods: 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. RESULTS: 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. CONCLUSION: 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 modified dosage schedule for increased efficiency in PUVA treatment of psoriasis

Ten patients with chronic widespread plaque psoriasis, all of whom had previously completely cleared and suffered a subsequent widespread relapse after conventional PUVA therapy, were treated with a modified UVA dosage schedule, with psoralen formulation and dosage unchanged. Initial and incremental UVA doses were maximized to near-erythemogenic levels as determined by weekly testing for minimal phototoxic dose (MPD), treatment being given three times a week. A comparison of complete psoriasis clearing between the modified treatment and the last PUVA course showed a geometric mean reduction in treatment duration of 55% (P less than 0.001) for a similar number of treatments each week, and a cumulative UVA dose of 31% (P less than 0.05), representing a reduction in treatment duration from 9.1 to 4.1 weeks and cumulative UVA dose reduction of 100.8 to 69.9 J/cm2. Such an improvement in efficiency permits a marked increase in treated patient numbers for the same cost, and is more convenient. The reduction in the total cumulative UVA dose given as larger individual doses also seems likely to lead to a lower incidence of cutaneous long-term, especially carcinogenic, adverse effects.     

Effects of water temperature on photosensitization in bath-PUVA therapy with 8-methoxypsoralen

The pharmacokinetic aspects of bath-PUVA are not completely clarified. Therefore, we determined the phototoxic response of human skin following psoralen baths at temperatures ranging from 32°C to 42°C (71.6–107.6°F) and UVA doses ranging from 0.5 to 5.5 J/cm². The highest therapeutical photosensitization (i.e., lowest minimal phototoxic dose) was assessed at temperatures of 37°C (98.6°F) and above. Photosensitization was significantly decreased at lower temperatures. These data indicate that a bath temperature of 37°C (98.6°F) should be used to gain optimal therapeutic efficiency in a clinical setting. Furthermore, in order to minimize the risk of adverse phototoxic effects in bath-PUVA, it is important to use a constant temperature during the psoralen bath.     

A polychromatic action spectrum for photosensitivity to orally administered 8-methoxypsoralen in humans

The action spectrum for producing minimal phototoxic erythema after oral administration of 8-methoxypsoralen (8-MOP) was determined in the range of 312-368 nm in 12 human volunteers using six different UV radiation sources. The peak sensitivity was found to be at 343 nm. The 8-MOP photosensitivity was at a high level (1.75 of maximum) between 336 and 355 nm. Conventional UVA radiation sources, like the Philips TL/09R tube, have a high energy output within 335 and 355 nm, and are therefore highly recommended in oral psoralen plus UVA radiation treatment.     

Prophylactic PUVA and UVB therapy in polymorphic light eruption—a controlled trial

A double-blind controlled trial of low-dose prophylactic oral psoralen photochemotherapy (PUVA) and ultraviolet-B (UVB) irradiation therapy was undertaken from April to September 1983 in 42 patients with polymorphic light eruption (PLE). Patients were randomly allocated to three groups, PUVA with oral 8-methoxypsoralen (8-MOP), UVB with oral placebo, and control low-dose UVA with oral placebo. The initial dose given to each active treatment group was a third of the predetermined minimal phototoxic or erythema dose, followed three times weekly for 6 weeks by doses incremented by an eighth on each occasion in the PUVA group and by a seventh in the UVB group. Ultraviolet radiation exposure was monitored throughout with polysulphone film lapel badges. Patients recorded their symptoms on a visual analogue scale. Symptoms of rash and itch in patients treated with PUVA and UVB were significantly less affected by increasing exposure to ultraviolet radiation than were these symptoms in control patients.     

Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. In 14 patients, an area of psoriasis and adjacent uninvolved skin were exposed to a series of UVA doses (350 ± 30 nm, 1–16 J/cm²), using an irradiation monochromator. Six other patients were similarly phototested with a series of UVB doses (300 ± 5 nm, 20–112 mJ/cm²) to both uninvolved and lesional skin. Erythema was judged visually at 72 h for psoralen–UVA, and at 24 h for UVB, and measured using a scanning laser–Doppler velocimeter. In 10 patients, PUVA therapy using high-dose UVA was subsequently given to lesional skin (8–16 J/cm² twice weekly) in addition to conventional whole-body PUVA. For psoralen–UVA, the minimal phototoxic dose within psoriasis was increased by a factor of 4 compared with non-lesional skin (P < 0.01, Wilcoxon signed-rank test). For UVB, the minimal erythema dose within psoriasis was higher than that for non-lesional skin (medians > 112 and 28 respectively, P < 0.05). Laser–Doppler measurements confirmed that the reduced erythemal sensitivity was not due to masking of response by pre-existing increased blood flux within psoriasis. In six patients, the sites subsequently treated twice weekly with PUVA, using high-dose UVA, cleared faster (median number of treatments 3), but with a similar cumulative UVA dose, compared with adjacent lesional skin treated with conventional PUVA (median number of treatments 12). This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease.     

An intraindividual comparative study of psoralen-UVA erythema induced by bath 8-methoxypsoralen and 4, 5', 8-trimethylpsoralen

BACKGROUND: Limited work has been conducted on the characteristics of topical trimethylpsoralen (TMP) psoralen-UVA (PUVA) erythema. OBJECTIVE: We sought to determine the time-course and dose-response characteristics of erythema induced by topical TMP, and to compare these parameters with those for topical 8-methoxypsoralen (MOP) within patients. METHODS: After photosensitization of one forearm with topical TMP, test sites were exposed to a UVA dose series. The procedure was repeated on the other forearm using 8-MOP solution. Erythema was assessed visually and with a reflectance instrument every 24 hours for 7 days. RESULTS: TMP PUVA erythema followed a similar time course to 8-MOP PUVA erythema. The majority of patients were at maximal erythema at or beyond 96 hours. TMP PUVA had a significantly steeper dose-response curve at 48, 72, and 96 hours compared with 8-MOP PUVA. CONCLUSION: On the basis of these data, the optimal time to read the TMP minimal phototoxic dose is 96 hours. In view of the steeper dose-response curve for TMP PUVA, a lower UVA incremental regimen should be considered compared with that for 8-MOP PUVA.     

Assessment of minimal phototoxic dose following 8-methoxypsoralen bath: maximal reaction on average after 5 days

An essential procedure before starting bath psoralen ultraviolet (UV) A (PUVA) photochemotherapy is the evaluation of the minimal phototoxic dose (MPD), which is traditionally assessed 3 days after irradiation. However, there are no controlled studies supporting the 72 h peak of bath-PUVA erythema. The aim of this study was therefore to determine the exact time course of the erythematous reaction in human skin following bath-PUVA. For this purpose, the skin of 10 volunteers was exposed to 0.5-3.0 J/cm2 UVA directly after a 20-min 8-methoxypsoralen bath (0.5 mg/L, 37 degrees C). At 24, 48, 72, 96, 120 and 144 h (1-6 days) after irradiation, the MPD and the erythema sum score (ESS) were determined in each subject. The results showed a maximal erythematous reaction on average 5 days after irradiation. The mean MPD gradually decreased from day 2 (> 3.0 J/cm2) to day 5 (mean +/- SD 1.15 +/- 0.63 J/cm2) and started to increase at day 6 (mean +/- SD 1.6 +/- 0.52 J/cm2). The mean +/- SD ESS correspondingly increased from day 2 (0 +/- 0) to day 5 (10.5 +/- 3. 7) with a decrease at day 6 (7.5 +/- 3.1) (difference between day 3 and beyond statistically significant at P < 0.05). As our study indicates a maximal erythematous reaction to the bath-PUVA up to 5 days after irradiation, the traditional MPD assessment at 3 days generates a risk of phototoxic side-effects within the phototherapy course by underestimating the phototoxic effect in some patients. These findings contribute towards a more defined understanding of the kinetics of the phototoxic reaction in bath-PUVA therapy.     

Childhood Vitiligo Successfully Treated with Bath PUVA

Abstract: A significant proportion of vitiligo patients are children. Systemic PUVA therapy, the most consistently effective and practical therapy for this disease, has not been recommended in pediatric patients because of concerns regarding potential long-term side effects. We report a 9-year-old Caucasian girl with progressive vitiligo who was successfully treated with bath PUVA. This form of PUVA therapy may provide a wider margin of safety, in that less exposure to ultraviolet A (UVA) radiation is required and systemic absorption of psoralen is minimal.     

Large increments in psoralen-ultraviolet A (PUVA) therapy are unsuitable for fair-skinned individuals with psoriasis

The ideal psoralen-ultraviolet A (PUVA) regimen for chronic plaque psoriasis has yet to be established. There are four components to a PUVA regimen: the dose of psoralen, the starting dose of UVA, the frequency of treatment and the incremental UVA dose protocol. Recent studies have been directed at trying to optimize the efficacy of PUVA while minimizing acute side-effects and the risk of cutaneous carcinogenesis, believed to be independently related to the cumulative dose of UVA and the total number of treatments. The British Photodermatology Group recommends two twice-weekly PUVA regimens: one starts with 50% of the minimal phototoxic dose (MPD) and uses weekly increments of 40%, 30%, 25%, 20%, 15%, 10% and 5% of the previous dose to a maximum of 14.5 J/cm2; the other starts with a fixed dose based on skin type and uses weekly dose increments of 40%, decreasing to 20% once erythema develops. We undertook a prospective randomized controlled trial comparing these regimens in 85 Irish patients. The clearance rate with the MPD regimen was lower than with the skin type regimen, 67.5% vs. 95% (P < 0.05). The reasons for treatment failure were grade 3 erythema and severe PUVA itch. There was a trend suggesting that patients with skin types I and II, but not skin type III, required a higher cumulative UVA dose and fewer exposures to clear with the MPD regimen than the skin type regimen, although this did not reach statistical significance. Grades 2 or 3 erythema were very common in both treatment groups (52. 5% of the skin type group and 45% of the MPD group). This is the third study to suggest that patients with skin types I and II receive a higher total UVA dose when the starting dose is 50-70% of the MPD (rather than 0.5 J/cm2 for skin type I and 1.0 J/cm2 for skin type II) and when large dose increments are used. We suggest that smaller dose increments should be used in patients with skin types I and II.     

8-MOP PUVA for psoriasis: a comparison of a minimal phototoxic dose-based regimen with a skin-type approach

Summary Two ultraviolet A (UVA) regimens for oral S-methoxypsoralen (8-MOP) photochemotherapy (PUVA) for moderate/severe chronic plaque psoriasis using a half body study technique were compared. Each patient received both regimens. A higher-dose regimen based on minimal phototoxic dose (MPD) within percentage incremental increases was given to one-half of the body. The other half received a lower dose regimen based on skin type with fixed incremental UVA increases. Patients were treated twice weekly. Symmetrical plaques were scored to determine the rate of resolution with each regimen. In addition, the number of treatments, cumulative UVA dose and number of days in treatment to achieve overall clearance were recorded. Patients were reviewed monthly for 1 year to record remission data. Thirty-three patients completed the study. Both regimens were effective and well tolerated. With the MPD-based approach, the number of exposures was significantly less for patients with skin types I and II but not III. Although the cumulative UVA dose was higher with the MPU regimen for all skin types studied, the reduced number of exposures required for clearance for skin types I and II but not III, combined with thesecurity of individualized MPD testing, has practical attractions. MPD testing also identified live patients who required an increased psoralen dose and six patients who required a reduction of the initial UVA dose with the skin type regimen. Forty-two per cent were still clear 1 year after treatment and there was no significant difference in the number of days in remission between the regimens for those whose psoriasis had recurred. The reduction in the number of exposures required lor clearance with the MPD-based regimen may be safer and more cost effective in the long term.     

Relationship between minimal phototoxic dose and skin colour plus sun exposure history: a neural network approach

Before beginning PUVA-therapy it is important to accurately gauge an individual's degree of psoralen photosensitivity. This determination is usually based on an individual's skin phototype or minimal phototoxic dose. Since minimal phototoxic dose is technically complex and time consuming to measure, sun reactivity skin phototype is often used instead; however, it has recently been shown that skin phototype lacks specificity as a predictor of an individual's minimal phototoxic dose. In this study, an artificial neural network was developed to attempt to predict the minimal phototoxic dose from skin colour measurements combined with skin phototype. Our results showed that minimal phototoxic dose was predicted with an error less than 1 J/cm² in only about half the subjects. In conclusion, minimal phototoxic dose probably cannot be predicted with sufficient accuracy on the basis of skin colour and skin phototype alone.     

Successful treatment of resistant alopecia areata with a phototoxic dose of ultraviolet A after topical 8-methoxypsoralen application

Background: The efficacy of a phototoxic dose of ultraviolet A (UVA) after topical application of 8‐methoxypsoralen (8‐MOP) in the treatment of alopecia areata (AA) was evaluated previously in only one study. However, the possibility of spontaneous regrowth of hair cannot be excluded as sessions were carried out every 3 months. Objective: To determine the efficacy of a phototoxic dose of UVA after topical application of 8‐MOP in the treatment of AA resistant to other lines of treatment. Subjects/Methods: Thirty‐five patients with AA were treated by topical 8‐MOP application to the lesions followed by UVA irradiation using a phototoxic dose every 3 months for a maximum of four sessions. Severity grading of AA was carried out using the Severity of Alopecia Tool (SALT) score before and after treatment. Results: Fifty‐seven percent of patients showed a positive treatment response (40% showed complete and 17% showed partial response) with significant improvement of SALT score. The mean cumulative UVA dose was 22±8.3 J/cm². Mild reversible side effects were observed in 63% of patients after the first session. Conclusion: Phototoxic psoralen and ultraviolet A therapy after topical application of 0.1% 8‐MOP is an effective treatment option for resistant AA, with low total cumulative UVA dose, few treatment sessions, and minimal reversible side effects.