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.     

Coal tar phototoxicity: kinetics and exposure parameters

We examined two manifestations of coal tar phototoxicity: delayed erythema and skin pain (tar smarts) by quantifying the amount (dose) of UVA and exposure conditions required to induce these phenomena in normal human skin. The minimal UVA dose required to induce delayed erythema (minimal phototoxic dose or MPD) and the minimal UVA dose required to induce an immediate smarting reaction (minimal smarting dose or MSD) were recorded in 32 subjects in a variety of settings. A log-log dose-response model described the relation between the interval of time tar was left on the skin and lowering of MPD. We examined 4 different methods of tar removal and showed that several methods using more than water alone were equally effective--judging by resultant phototoxicity. The time between tar removal and UVA irradiation is important. Even 30 min was sufficient for the MPD to increase from 3.77 +/- 1.55 to 6.1 +/- 4.0 J/cm2 (p less than 0.02). The smarting reaction shows a similar dependence on the time interval between tar removal and exposure. The mean MSD was less than the mean MPD at all times tested. Both manifestations of coal tar phototoxicity, reduced delayed erythema threshold and susceptibility to the smarting reaction, persisted at least 30 h after tar removal.     

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.     

Phototesting in bath-PUVA: marked reduction of 8-methoxypsoralen (8-MOP) activity within one hour after an 8-MOP bath

It is not known how long after 8-MOP bath-PUVA administration erythema can be induced. Therefore, after determination of dose-dependence and kinetics of bath-PUVA erythema, we investigated the development of erythema using an erythematogenic UVA-dose (3 J/cm²) in time course experiments. Our results show that there is a loss of biological 8-MOP activity already 1 h after 8-MOP bath. This has important consequences for clinical practice with bath-PUVA, concerning the optimum time interval between the 8-MOP bath and irradiation as well as the persistence of photosensitivity in normal skin after bath-PUVA.     

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.     

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.     

Comparison of minimal phototoxic dose and skin type for determining initial UVA dose in oral liquid methoxsalen photochemotherapy for the treatment of psoriasis.

Twenty-five patients with extensive psoriasis were randomly assigned into one of three groups, each receiving 0.5 mg/kg of oral liquid methoxsalen photochemotherapy followed 1 h later by exposure to long-wave ultraviolet light (UVA). The sole difference between the three groups was the method used to determine the initial UVA dose, which was either based on skin type, 25% of the minimal phototoxic dose (MPD), or 50% of the MPD. All patients were treated in the Phototherapy Unit at the Massachusetts General Hospital. Data were obtained until reaching the endpoint of clearance. At clearance, the results of the number of treatments required to clear, final UVA dose, cumulative UVA dose, and side effects were tabulated, compared, and analyzed for each of the three groups. The 25% and 50% MPD groups required a mean of 15.0 +/- 1.7 and 13.4 +/- 1.9 treatments to clear, respectively, as compared to the skin type group, which needed an average of 17.6 +/- 2.5 treatments. The mean final UVA dose was 7.4 +/- 0.9 J/cm2 and 8.4 +/- 1.4 J/cm2 for the 25% and 50% MPD groups, respectively, in contrast to 11.6 +/- 1.4 J/cm2 for the skin type group. The mean cumulative UVA dose at clearance for the 25% and 50% MPD groups was 79 +/- 16 J/cm2 and 87 +/- 27 J/cm2, respectively, versus 136 +/- 30 J/cm2 for the skin type group. The comparisons between the individual MPD groups and the skin type group did not achieve statistical significance with the exception of a marginally significant difference in final dose between the skin type group and the 25% MPD group (p = 0.06). However, the results of the two MPD groups were then pooled and the mean final (7.9 +/- 0.8 J/cm2) and cumulative (83 +/- 15 J/cm2) UVA doses were significantly (p = 0.04) and marginally significantly (p = 0.07) lower than the respective means of the skin type group. The number of treatments to clear, although lower in the pooled MPD groups (14.2 +/- 1.3) than in the skin type group, did not attain statistical significance (p = 0.19). Our data suggest that the MPD measurement may be superior to the skin-typing system when calculating the initial UVA dose in oral liquid methoxsalen photochemotherapy for the treatment of psoriasis.     

The time course of topical PUVA erythema following 15- and 5-minute methoxsalen immersion

BACKGROUND: Limited data exist in the literature concerning the characteristics of erythema following psoralen UV-A (PUVA) treatment using topical methoxsalen. To optimize the phototherapeutic regimen and reduce short- and long-term risks, knowledge of such basic information is essential. OBSERVATIONS: The characteristics of PUVA erythema following 15- and 5-minute immersion in methoxsalen was determined. The PUVA erythema after 15-minute methoxsalen immersion exhibited a broad peak, with the lowest median minimal phototoxic dose (MPD) at 96, 120, and 144 hours after UV-A irradiation. Seventy-three percent of subjects experienced peak erythema at 120 hours compared with only 45% at 72 hours. From the dose-response data, an increase in the erythema index of 0.025 (equivalent to the MPD) was significantly lower when determined at 120 hours after UV-A irradiation than at 72 hours (P =.03). The median maximum slope of the dose-response curve occurred at 144 hours. After 5-minute immersion, PUVA erythema displayed a broad peak from 72 hours. Erythema summation scores followed a trend similar to that of 15-minute immersion, but the intensity was significantly reduced. CONCLUSIONS: Methoxsalen-UV-A erythema exhibited a broad plateau between 96 and 144 hours, with most subjects at peak erythema at 120 hours. Reduction of methoxsalen immersion time significantly lowered the erythemal intensity. Minimum phototoxic dose reading at 72 hours underestimates the phototoxic effect of topical methoxsalen PUVA, and a change in the MPD assessment time should be considered.     

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.     

Does the minimal phototoxic dose after 8‐methoxypsoralen baths correlate with the individual’s skin phototype?

BACKGROUND/AIMS: Up to now no data have been available concerning whether there is a significant correlation between skin phototypes and the minimum phototoxic dose (MPD) after bath water delivery of 8-MOP. METHODS: The skin phototype of each of 46 patients was determined based on the individual past history of solar-induced burning and tanning. In addition, the MPD of each patient was assesed after photosensitization with a warm water bath (37 degrees C, 98.6 degrees F) containing 1.0 mg/l 8-methoxypsoralen (8-MOP). Statistical analysis was performed using a Mann-Whitney U-test and Spearman rank order correlation. RESULTS: The median MPD in patients with skin phototype II was 2.0 J/cm2 (range < or =0.5 to > or =3.5) versus 1.5 J/cm2 (range 1.0 to > or =3.5) in patients with skin phototype III. There was a considerable overlap between both groups. No significant difference was detected comparing both groups (P=0.7326) and Spearman rank order correlation revealed no correlation between skin phototype and MPD. CONCLUSION: Erythemal sensitivity in PUVA bath therapy, measured as MPD, is not correlated with sun-reactive skin phototype in skin types II and III. Thus skin phototype is not a suitable indicator for the initial UVA dose in PUVA bath photochemotherapy.     

Skin photosensitizing and Langerhans' cell depleting activity of topical (bath) PUVA therapy: comparison of trimethylpsoralen and 8-methoxypsoralen

The skin photosensitizing and Langerhans' cell (LC) depleting effects of a single bath PUVA exposure were studied in 22 healthy young volunteers. The photosensitizing effect of bathing for 15 min in a 0.2 mg/1 trioxsalen-water solution was about 30 times as great as a similar treatment in an equipotent methoxsalen solution. The skin erythema induced by methoxsalen bath PUVA peaked on day 2 and diminished thereafter, whereas the trioxsalen reaction showed a broad plateau on days 2-5 after the irradiation. A reduction in LC density to about 30-40% of the starting value was seen in both trioxsalen and methoxsalen bath PUVA treated skin sites on day 4 after irradiation, and low or diminishing LC counts prevailed until day 10-11. The amount of UVA needed to produce a similar degree of LC depletion was 15-30 times as great in the case of methoxsalen, compared with trioxsalen. A perceptible erythema reaction, however, was, not a prerequisite for a reduction in LC density.     

Alopecia areata treatment with a phototoxic dose of UVA and topical 8-methoxypsoralen

Twenty-five patients with alopecia totalis (AT) or alopecia universalis and 124 patients with alopecia areata (AA) were treated with photochemotherapy, combining topical 8-methoxypsoralen (8-MOP) with UV irradiation of the scalp at a phototoxic dose. The mean energy required was 15 J/cm2 for AA and 42 J/cm2 for AT. Ninety-four patients had multiple bald patches and 12 with AT had complete or > 50% hair regrowth. Positive treatment results did not seem to depend on the age of onset or the duration of the disease. Few side-effects of topical psoralens plus UVA (PUVA) treatment were noted, except a for few days of slight erythema caused by the high dose of UV.     

The effect of methoxsalen dose on ultraviolet-A-induced erythema

There is considerable interindividual variation in bioavailability of Methoxsalen (8-methoxypsoralen) after ingestion of the standard dose used in photochemotherapy (psoralen plus ultraviolet A). A dose change may be used to alter the degree of photosensitivity, although there is limited information on the effect of 8-methoxypsoralen dose alterations on phototoxicity within individuals. We studied the effect of changes of 8-methoxypsoralen dose over a narrow range in 15 subjects with psoriasis. Two hours after ingestion, serum 8-methoxypsoralen concentration was determined and phototesting was performed at 350 +/- 30 nm (0.45-14 J per cm2). The minimal phototoxic dose at 72 h was recorded, erythema was measured using a reflectance instrument, and dose-response curves were constructed. Each subject was tested on three occasions using doses of 25 mg per m2 (conventional dose) or conventional dose +/- 10 mg. Median serum 8-methoxypsoralen concentration increased from 96 to 143 to 229 ng per ml with dose increases from conventional dose - 10 mg to conventional dose and conventional dose + 10 mg, respectively (p < 0.001). The median minimal phototoxic dose and D0.025 (the objective equivalent of the minimal phototoxic dose derived from the dose-response curve) were significantly reduced with increasing 8-methoxypsoralen dose from conventional dose minus 10 mg (minimal phototoxic dose 1.7 J per cm2; D(0.025) 2.8 J per cm2) to conventional dose (1.2; 1.4 J per cm2) and conventional dose plus 10 mg (0.9; 1.0 J per cm2) (p < 0.001). Change in 8-methoxypsoralen dose had no detectable effect on the maximum slope of the psoralen plus ultraviolet A erythema dose-response curve. Thus, 8-methoxypsoralen dose changes within individuals, over a narrow but clinically relevant range, significantly altered the threshold response to psoralen plus ultraviolet A erythema but not the rate of increase in erythema with increasing ultraviolet A dose.     

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.     

Determination of the minimal phototoxic dose and colorimetry in psoralen plus ultraviolet A radiation therapy

BACKGROUND: The use of an adequate initial dose of ultraviolet A (UVA) radiation for photochemotherapy is important to prevent burns secondary to overdosage, meanwhile avoiding a reduced clinical improvement and long-term risks secondary to underdosage. The ideal initial dose of UVA can be achieved based on the phototype and the minimal phototoxic dose (MPD). The objective measurement of constitutive skin color (colorimetry) is another method commonly used to quantify the erythematous skin reaction to ultraviolet radiation exposure. The aim of this study was to determine variations in MPD and constitutional skin color (coordinate L(*)) within different phototypes in order to establish the best initial dose of UVA radiation for photochemotherapy patients. METHODS: Thirty-six patients with dermatological conditions and 13 healthy volunteers were divided into five groups according to phototype. Constitutional skin color of the infra-axillary area was assessed by colorimetry. The infra-axillary area was subsequently divided into twelve 1.5 cm(2) regions to determine the MPD; readings were performed 72 h after oral administration of 8-methoxypsoralen (MOP) followed by exposure of the demarcated regions to increasing doses of UVA. Results: The majority of the participants were women (73.5%) and their mean age was 38.8 years. The MPD ranged from 4 to 12 J/cm(2) in phototypes II and III; from 10 to 18 J/cm(2) in type IV; from 12 to 24 J/cm(2) in type V and from 18 to 32 J/cm(2) in type VI. The analysis of colorimetric values (L(*) coordinate) and MPD values allowed the definition of three distinctive groups of individuals composed by phototypes II and III (group 1), types IV and V (group 2), and phototype VI (group 3). CONCLUSIONS: MPD and L(*) coordinate showed variation within the same phototype and superposition between adjacent phototypes. The values of the L(*) coordinate and the MPD lead to the definition of three distinct sensitivity groups: phototypes II and III, IV and V and type VI. Also, the MPD values bear a strong correlation to coordinate L(*) values. Mean MPD values described for each of the three major sensitivity groups were higher than the values commonly used in clinical settings for the different phototypes. Therefore, phototype alone is not a good parameter to define the initial UVA dose. MPD and colorimetry could be used in pre-treatment evaluation of patients who are to be submitted to photochemotherapy, in a non-invasive and more accurate way when compared with the classical phenotype clinical criteria.     

Concentration-dependent phototoxicity in trimethylpsoralen bath psoralen ultraviolet A

BACKGROUND: Long-term use of topical trimethylpsoralen (TMP) psoralen bath plus ultraviolet A (bath PUVA) is considered safe with regard to the risk of skin cancer. However, the potential for severe phototoxicity limits its use. OBJECTIVES: To study the effect of dilution of the TMP bath on the minimal phototoxic dose (MPD). METHODS: Fifteen volunteers participated in the study. The MPD tests were performed for three TMP concentrations: 0.33 mg L-1, 0.1 mg L-1 and 0.033 mg L-1 at 2-week intervals. Geometric UVA dose series increasing by a factor of radical2 were used for the testing on the previously unexposed buttock skin. The MPD72 h was assessed at 72 h from the bath. RESULTS: For the highest TMP concentration of 0.33 mg L-1, the median MPD72 h was 0.14 J cm-2 (95% confidence interval (CI), 0.10-0.14 J cm-2). For the diluted TMP bath concentration of 0.1 mg L-1, the median MPD72 h increased to 0.29 J cm-2 (95% CI, 0.2-0.41 J cm-2) and for 0.033 mg L-1 to 0.81 J cm-2 (95% CI, 0.57-1.15 J cm-2), respectively. Thus, diluting the labelled concentration of 0.33 mg L-1 1 : 10 increased the median MPD72 h 5.6-fold. CONCLUSIONS: With regard to the safety and practicality of the TMP bath PUVA, the lower concentrations of TMP may be of clinical importance, and this needs to be validated in future controlled clinical trials.     

Inefficacy of topical methoxalen plus UVA for palmoplantar pustulosis

The effect of local application of 8-methoxypsoralen (8-MOP) and subsequent UVA irradiation on palmoplantar pustulosis (PPP) was studied in 10 patients. In 8 patients 8-MOP baths were used, and in 5 patients an 8-MOP ointment was applied, 3 patients receiving both forms of treatment. The number of treatment sessions varied from 15 to 128, with maximal UVA doses of 1.2 to 12 J/cm2, and total cumulative doses of 8 to 348 J/cm2. Two patients experienced a brisk phototoxic erythema and one patient developed a bullous reaction. Only 3 patients responded favourably to the treatment, 2 with moderate and 1 with good clearing of the lesions. In the remaining 7 patients either no effect (5 patients) or an exacerbation of the disease (2 patients) was seen.     

The optimal time to determine the minimal phototoxic dose in skin photosensitized by topical 8 methoxypsoralen

BACKGROUND: We recently investigated the characteristics of psoralen plus ultraviolet (UV) A erythema in skin photosensitized by topical 8-methoxypsoralen (8-MOP) in three independent studies. OBJECTIVES: In order to determine the optimal time to read the minimal phototoxic dose (MPD) after treatment with topical 8-MOP and irradiation with UVA, we assessed the overall data. METHODS: One forearm of each subject was immersed in 8-MOP solution for 15 min and test sites on the flexor surface of the forearm were immediately exposed to a UVA dose series. Erythema was assessed visually and objectively using a reflectance instrument at 24-h intervals for 7 days. RESULTS: Results were obtained from 44 subjects (predominantly Fitzpatrick skin phototype II). A broad erythemal plateau was evident beyond 72 h and the visual MPD was significantly lower at 96, 120 and 144 h than at 72 h (P < 0.01). Only 30% of subjects were at peak erythema at the conventional MPD assessment time of 72 h. The median time to reach maximal erythema was 96 h (range 48-144). Objectively, 85% of subjects were at peak erythema at or beyond 96 h. CONCLUSIONS: We recommend that (i) the optimal time to read the topical 8-MOP MPD is 4 days after UVA exposure as readings beyond this time may be difficult to interpret because of the development of pigmentation, and (ii) 40% of the topical 8-MOP MPD should be considered for the first treatment.     

Does smoking influence the efficacy of bath‐PUVA therapy in chronic palmoplantar eczema?

Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema. However, our own observations showed that patients with palmoplantar eczema of the dyshidrotic or hyperkeratotic type responded only partially to bath-PUVA therapy. In order to evaluate environmental influences possibly having an impact on the efficacy of this therapy, smokers and non-smokers suffering from palmoplantar eczema treated with bath-PUVA therapy were compared. A retrospective study was conducted involving 62 patients, 39 non-smokers and 23 smokers, with palmar and/or plantar eczema resistant to local corticosteroids. Bath-PUVA therapy was performed according to the European standard regimen for oral PUVA therapy. The total number of treatments and the cumulative UVA-dose were similar in smokers and non-smokers (smokers 24+/-17.7 (mean+/-SD) and 67.6+/-51.3 J/cm2 vs. non-smokers 25.7+/-16.3 and 68.5+/-49.3 J/cm2). In the group of non-smokers, 31% showed complete remission (CR; 100% clearance), 33% partial remission (PR; more than 50% clearance) and 36% no change after treatment (NC; less than 50% clearance). In contrast, the group of smokers showed only 13% CR and 22% PR, whereas 65% exhibited NC. The differences regarding complete or partial remission between the groups were statistically significant (Student t-test for paired samples; P<0.05). Regarding the different type of eczema, bath-PUVA proved to be more successful in the dyshidrotic type of eczema as compared to the hyperkeratotic type in non-smokers (P<0.05). In the group of smokers no CR was achieved in patients suffering from the dyshidrotic form of eczema. Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.