Detection of DNA-psoralen photoadducts in mammalian skin

An immunofluorescence (IF) method for the detection of 8-methoxypsoralen (8-MOP) photoadducts to DNA has been developed to assess nuclear damage in keratinocytes and melanocytes after psoralen plus UVA (PUVA) treatment, both under in vitro and in vivo conditions. Cryostat sections of the albino and pigmented guinea pig and human skin were used for in vitro studies to establish minimal and maximal drug concentration and UVA dosimetry for the detection of DNA-8-MOP photoadducts. Limits of detection were as low as 10 ng/cm2 8-MOP and 1 J/cm2 UVA for skin sections and sodium bromide-split epidermal sheets. Guinea pigs treated with topical PUVA revealed positive IF stain in epidermal cell nuclei at a threshold dose of 100 micrograms/cm2 8-MOP and 13 J/cm2 UVA. Pretreatments of cryostat cuts with ethanol and alkali before IF test enhanced the sensitivity of detection in vivo about 10-fold and enabled us to follow the repair of DNA damage after treating normal guinea pig skin with a dose of 50 micrograms/cm2 8-MOP plus 6 J/cm2 UVA. The most interesting findings were as follows: A sensitive method to detect PUVA-induced nuclear damage in epidermal and dermal cells was developed. PUVA treatment induced nuclear DNA damage to melanocytes as well as to adjacent keratinocytes, and melanocytes appeared to be 10 times less vulnerable to photo-damage than keratinocytes. There was a greater propensity for the proliferative cells to be damaged by PUVA. PUVA induced nuclear damage up to 700 micron depth in the dermis. The usefulness of the IF test in detecting DNA damage in microgram and ng amounts in vivo and in following the repair of damaged DNA induced by PUVA.     

Psoralen-containing sunscreen is tumorigenic in hairless mice

Sunscreens containing 5-methoxypsoralen (5-MOP) are currently being marketed to promote tanning by inducing psoralen-mediated ultraviolet (UV) A (320-400 nm) melanogenesis. The rationale is that this may prevent UVB (290-320 nm) radiation-induced skin damage. However, mouse studies have shown that 5-MOP has the same cutaneous photocarcinogenic potential as 8-methoxypsoralen. In addition, the 5-MOP--containing sunscreen Sun System III (SS III), when combined with UVA, induces epidermal ornithine decarboxylase activity, an enzyme associated with tumor promotion. Therefore, we investigated whether SS III had sufficient psoralen concentration to be tumorigenic in hairless mice exposed to chronic, intermittent UVA radiation. SS III was applied to hairless mice 5 days per week for 20 weeks. After each application the mice were exposed to 2.5 to 10 joules/cm2 UVA radiation. All test groups developed atypical squamous papillomas in direct proportion to the dosage of UVA radiation received. A shorter latency period for tumor development was seen with larger UVA doses. Test animals followed up to 1 year developed invasive squamous cell tumors. Control groups (SS III without UVA and UVA without SS III) remained free of tumors. Animals receiving SS III plus UVA developed persistent skin thickening and increased dermal cyst formation similar to that reported with chronic exposure to UVB, a known carcinogenic wavelength. Over-the-counter sunscreens containing 5-MOP do contain sufficient psoralen concentrations to cause cutaneous phototoxicity and photocarcinogenicity in mice, and their use in humans should be discouraged in the interest of preventing further UV-induced skin damage and skin cancer.     

PUVA and PUVB in vitiligo – are they equally effective?

BACKGROUND/AIMS: The combination of psoralens with different types of ultraviolet (UVL) sources in the treatment of vitiligo has led to different reports of success. The purpose of this trial is to compare in a random right-left comparison study the efficacy and side effects of oral 8-MOP plus UVA (PUVA) and oral 8-MOP plus UVB (broadband, 290-320 nm P-UVB) in the treatment of vitiligo. METHODS: The study included 24 cases of extensive vitiligo involving more than 30% of the body surface area in a bilateral symmetrical distribution. Each patient received 0.7 mg/kg 8-MOP orally 2 h before the light session. The right side of the body was exposed to UVA (320-400 nm), while the left half was exposed to UVB (290-320 nm). The patients received 3 sessions/week for a total of 30 sessions. RESULTS: Both PUVA and PUVB produced moderate (50-60%) improvement, with similar incidences of phototoxic reaction and skin thickening. However, the study revealed a significant difference in the number of sessions needed to improve produce erythema and perifollicular pigmentation as well as a moderate response, the response on the UVA side always being earlier. Furthermore, the amount of joules needed to achieve the same response was 10 times greater on the UVA side than on the UVB side. CONCLUSION: The use of psoralen plus broadband UVB is as effective as PUVA in the treatment of vitiligo. However, the long-term side effects of psoralen plus UVB are unknown.     

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.     

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.     

PUVA erythemal sensitivity depends on plasma psoralen concentration and UVA sensitivity

The variation in erythemal sensitivity of the skin during PUVA therapy with oral 8-methoxypsoralen (8-MOP) was examined by measuring both UVA and PUVA erythemal responses, together with plasma 8-MOP concentration, in 27 patients about to start PUVA therapy for psoriasis. The erythema responses were judged visually, and also measured using a reflectance instrument in order to construct dose-response curves. No significant association was found between the UVA and PUVA minimal erythema responses. The plasma psoralen concentration showed significant association with the slope of the PUVA erythema dose-response curve. The slopes of the UVA and PUVA erythema dose-response curves were significantly associated, and this association became much stronger when allowance was made for plasma psoralen concentration. These results show that erythemal sensitivity during PUVA therapy is related to both plasma psoralen concentration and inherent UVA sensitivity, but that this relationship is not apparent when sensitivity is judged visually as the minimal erythema response. The association between PUVA and UVA erythemal sensitivity suggests a common pathway in the vascular response induced hy UVA radiation, with or without psoralen.     

Efficacy of 8-methoxypsoralen vs. 5-methoxypsoralen plus ultraviolet A therapy in patients with mycosis fungoides

BACKGROUND: Psoralen plus ultraviolet (UV) A (PUVA) is the standard treatment for early stage mycosis fungoides (MF). When 8-methoxypsoralen (8-MOP) is used in PUVA therapy, it often produces intolerance reactions such as nausea, vomiting and headache. OBJECTIVES: To investigate whether 5-methoxypsoralen (5-MOP) is a safe and effective alternative to 8-MOP in PUVA therapy for MF. METHODS: A retrospective database search and chart review was done to identify patients with MF who received PUVA with either 5-MOP or 8-MOP as initial monotherapy at our institution. Between 1990 and 2004, 14 patients [seven men and seven women; mean age 70 years, range 51-82; National Cancer Institute disease stages IA (n = 6) and IB (n = 8)] received 5-MOP, and 24 patients [21 men and three women; mean age 58 years, range 28-89; disease stages IA (n = 11), IB (n = 12) and IIB (n = 1)] received 8-MOP. RESULTS: Twelve of 14 patients (86%) in the 5-MOP group and 22 of 24 (92%) in the 8-MOP group had a complete response to PUVA. These two subgroups of complete responders did not differ significantly in terms of PUVA therapy duration, number of treatments or cumulative UVA dose. They also did not differ significantly in terms of relapse-free rate [8% (one of 12) vs. 23% (five of 22)] or time to relapse [17 months (range 4-31) vs. 14 months (range 4-33)]. Moreover, PUVA maintenance therapy with either 5-MOP or 8-MOP in a subset of patients [26% (nine of 34)] did not affect long-term relapse-free status either. CONCLUSIONS: 5-MOP and 8-MOP have comparable therapeutic efficacy when used in PUVA therapy for MF.     

UVB/PUVA-induced suppression of human natural killer activity is reduced by superoxide dismutase and/or interleukin 2 in vitro

We have evaluated the effects of ultraviolet irradiation or PUVA treatment [8-methoxypsoralen (8-MOP) plus long-wave ultraviolet (UVA) irradiation] on natural killer (NK) activity of human peripheral blood mononuclear cells (PBMC). In vitro exposure of PBMC to UVB (280-320 nm, 1-30 mJ/cm2) or PUVA [8-MOP, 0.1 microgram/ml; UVA (320-400 nm), 0.5-5 J/cm2] resulted in a dose-dependent suppression of NK activity, whereas UVA (0.5-5 J/cm2) or 8-MOP (0.1 microgram/ml) treatment alone did not have the inhibitory effects. This suppressive effect of UVB/PUVA irradiation was successfully reduced in the presence of superoxide dismutase (SOD) (100 or 1000 U/ml) during the irradiation. The addition of interleukin 2 (IL-2) (100 U/ml) markedly enhanced the NK activity of both irradiated and nonirradiated PBMC. Combination treatment with both SOD and IL-2 to UVB/PUVA-irradiated PBMC resulted in a more remarkable improvement of NK suppression than with either SOD or IL-2 treatment alone.     

Alteration of lymphocyte functions by 8-methoxypsoralen and longwave ultraviolet radiation. I. Suppressive effects of PUVA on T-lymphocyte migration in vitro

We investigated the influence of 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet radiation (PUVA) on lymphocyte migration in vitro. Nylon wool-purified, mouse splenic T lymphocytes showed locomotive responses to casein, normal mouse serum (NMS), and zymosan-activated mouse serum (ZAS). Migratory responses to casein and NMS, and to ZAS were remarkably suppressed in lymphocytes exposed to 0.5 J/cm2 UVA plus 0.1 micrograms/ml 8-MOP and to 0.8 J/cm2 UVA plus 8-MOP, respectively. The PUVA treatment used in the present study had no effect on random movement and lymphocyte viability. T lymphocytes cultured in the absence of mitogenic agent for 24 h demonstrated a greater increase in their migration activity than noncultured cells, while lymphocytes cultured after 1.0 J/cm2 PUVA pretreatment remained low. These findings suggest that the therapeutic effect of PUVA on inflammatory skin disorders may be due in part to the suppression of lymphocyte migration.     

8-Methoxypsoralen-DNA adducts in patients treated with 8-methoxypsoralen and ultraviolet A light

The combination of 8-methoxypsoralen (8-MOP) plus ultraviolet A light (320-400 nm), termed PUVA, is used in the treatment of psoriasis, a hyperproliferative disease of the skin. This treatment results in the formation of specific 8-MOP adducts with cellular DNA. We have previously developed monoclonal antibodies which recognize these 8-MOP photoadducts. We now report the use of these antibodies in an indirect immunofluorescence technique to study human skin biopsies. Nuclei in 3 of 5 skin biopsies from psoriasis patients undergoing PUVA therapy were positive for adducts. The presence of adducts by immunofluorescence did not correlate with plasma levels of 8-MOP. Enzyme-linked immunosorbent assays, used to determine whether 8-MOP photoadducts could be detected in DNA isolated from the lymphocytes of psoriasis patients after PUVA therapy, were negative.     

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.     

The effect of 8-methoxypsoralen plus long-wave ultraviolet (PUVA) radiation on mast cells: PUVA suppresses degranulation of mouse skin mast cells induced by compound 48/80 or concanavalin A

In order to see whether 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet (UVA) radiation (PUVA) has an influence on immediate-type skin reactions, we have undertaken an animal study. Ears of mice were treated with a 0.5% 8-MOP solution topically plus UVA radiation (1.5-2.5 J/cm2). After PUVA radiation, skin responses to intradermal injection with mast cell liberators, including compound 48/80 (2.5 mg/ml, 10 microliter) and concanavalin A (Con-A) (2.0 mg/ml), or with a mixture of 5-hydroxytryptamine (5-HT) and histamine as vasodilator (1.0 mg/ml and 50 mM, respectively) were examined with time (2 h-14 days). At each time point, an ear swelling response (ESR) was measured with a dial thickness gauge. The rate of mast cell degranulation and mast cell numbers were assessed by light microscopy using toluidine blue-stained semithin (1 micron) sections. ESR induced by compound 48/80 or Con-A was significantly suppressed dose-dependently (greater than 42% inhibition) by PUVA between 2 h-3 days postirradiation as compared with that in nonirradiated control mice, and the value returned to normal levels by 7-14 days. Compound 48/80- or Con-A-induced mast cell degranulation (%) was remarkably decreased between 2 h-3 days (greater than 48% inhibition) in accordance with the suppression in ESR and it was restored to the rates in nonirradiated controls by 7-14 days. Neither ESR nor percent degranulation was affected by UVA radiation only (less than 3.5 J/cm2) or application of 8-MOP only. 5-HT plus histamine-mediated ESR was not altered at all by PUVA throughout the experimental period. Since PUVA radiation itself at given doses did not produce measurable ESR, mast cell degranulation, or a reduction in mast cell numbers, and since PUVA did not affect a normal vascular response to vasodilator, it seemed that decreased skin reactivity to mast cell degranulators by PUVA might be due to a PUVA-induced noncytolytic alteration in mast cell release mechanisms.     

Systemic suppression of contact hypersensitivity in mice by psoralen plus UVA radiation (PUVA)

Treatment of mice with 8-methoxypsoralen plus longwave UV radiation (UVA, 320-400 nm) decreased their response to contact sensitizers applied subsequently to unirradiated skin. This decreased reactivity exhibited a delayed time course, it affected the afferent but not the efferent phase of the reaction, and it was associated with the development of splenic suppressor cells. These suppressor cells were antigen-specific T lymphocytes, and they prevented the induction, but not the elicitation, of contact hypersensitivity in recipient mice. In all of these characteristics, the decreased reactivity induced by treatment with psoralen plus UVA radiation (PUVA) resembled that produced by UV radiation of shorter wavelengths (less than 320 nm). These studies suggest that PUVA treatment may initiate the same sequence of cellular events as does exposure to sunlamp (UVB, 280-320 nm) radiation, leading to preferential activation of the suppressor cell pathway.     

The effect of psoralen plus ultraviolet A in vitro in HUT-78 enhances by 5-aminolevulinic acid

BACKGROUND: Sezary syndrome and mycosis fungoides are forms of cutaneous T-cell lymphoma, and in the early stage of these diseases psoralen plus ultraviolet A (PUVA) is one of the treatments of choice. Photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) is an effective, non-invasive, and safe treatment for most superficial skin cancers. In order to obtain greater efficacy of PUVA, we investigated the synergistic anti-tumor effects of ALA-PDT and PUVA using 8-methoxypsoralen (8-MOP) and a UVA lamp. METHODS: The in vitro effects of PUVA and ALA-PDT and their combination in HUT-78 cell line from human SS were determined by MTT assay. RESULTS: In our results, cell proliferation compared with controls was inhibited to 53.2% with UVA alone, 52.3% with 1 microM 8-MOP, 43.8% with 100 microM ALA, and 19.2% with combined 8-MOP and ALA. CONCLUSION: Combined use of ALA and PUVA using 8-MOP and UVA lamps, which are widespread in Japan, had a strong anti-tumor effect in vitro. Combined treatment with ALA-PDT and PUVA using a UVA lamp appears to have a strong treatment effect.     

Narrowband UVB as an effective substitute for psoralen plus UVA: lessons from a psoralen shortage

From March to August 2010, there was a shortage of encapsulated liquid 8-methoxypsoralen (8-MOP), the psoralen used for bath psoralen plus UVA (PUVA) in Toronto, Canada. Patients were forced to discontinue bath PUVA treatment and were transitioned to other therapeutic modalities, including narrowband UVB (nbUVB). A retrospective chart review was conducted of all patients who discontinued bath PUVA due to the unavailability of 8-MOP, with a focus on those who were switched to nbUVB. Sixty-three patients discontinued PUVA, 39 of whom were switched to nbUVB. Fifteen of 17 patients with mycosis fungoides (MF) who were switched to nbUVB improved, and patients with earlier-stage disease were more likely to improve. Ten of 13 (77%) psoriasis patients improved with nbUVB, including two patients whose psoriasis cleared completely. All three small-plaque parapsoriasis patients who switched to nbUVB had complete clearance of their lesions. In conclusion, nbUVB may be a suitable alternative for patients with MF, small-plaque parapsoriasis and psoriasis who cannot access PUVA therapy.     

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.     

The Role of PUVA in the Treatment of Psoriasis

Photochemotherapy with methoxsalen (8-methoxypsoralen) and long wavelength ultraviolet (UV) radiation (referred to as ‘PUVA’ for psoralen plus UVA) is commonly used to treat psoriasis and vitiligo. These vastly different diseases respond to the therapy by different mechanisms even though the immediate effects of the therapy — the photomodification of cellular biomolecules — is the same for each. Because psoriasis is not cured by PUVA, patients receive many treatments over their lifetime and have a significantly increased risk for the development of skin cancers (primarily squamous cell carcinomas). In this article the basic aspects of psoralen photobiology are reviewed briefly. Several recent studies describing the incidence of skin cancer in UVA treated psoriasis cohorts are comparatively reviewed. In addition the impact of the analysis of mutations in the tumor suppressor gene, p53, are summarized. An unexpected mutation spectrum (very few PUVA type T→A transversions and frequent UVB solar signature C→T transitions) suggest that effects other than direct DNA photoadduct formation may be at play. These analyses suggest that it may be possible to improve the therapeutic efficacy of PUVA by a careful evaluation of the mode of delivery. In this review the science behind PUVA is summarized. In addition, the incidence of skin cancer as a long term consequence of repeated treatments is surveyed. To relate clinical observations to molelcular events, the nature of p53 mutations found in skin cancers from psoriasis patients is also analyzed. Finally some suggestions for improving the delivery of PUVA therapy are presented.     

Spectral effects in activation of the human immunodeficiency virus promoter by psoralens plus ultraviolet A treatment.

The effects of PUVA treatment on HIV promoter activation and cell killing in HIV cat/HeLa cells were studied using two UV sources, a UVASUN sunlamp and a UVAR Photoactivation Chamber. A 4 to 5 times higher dose of ultraviolet radiation was required from the UVASUN lamp than from the UVAR lamps: 1) to activate the HIV promoter in the presence of 0.1 or 1.0 microgram/ml 8-MOP and 2) to reduce cell survival to a level of 10%, in the presence of 0.1 or 1.0 microgram/ml 8-MOP. In addition, exposures performed with a fixed dose of 20 kJ/m2 at varying concentrations of 8-MOP, required a 4.7 times higher combined PUVA dose from the UVASUN lamp than from the UVAR lamps. Two possible sources of these differences were analyzed: (1) the presence of UVB + UVA2 (280-340 nm) in the radiation emitted by the UVAR, but not the UVASUN lamp, and its potential biological activity independent of 8-MOP, and (2) the difference in the overlap of the emission spectra of the two lamps with the absorption spectrum of 8-MOP. The area of overlap was higher for the UVAR lamp than for the UVASUN lamp by a factor of 4.6, which is close to the difference between these two lamps in induction of the HIV promoter and killing HeLa cells. This indicates that the effectiveness of a particular UVA source used in combination with 8-MOP can be predicted by its congruence to the absorption spectrum of the photosensitizing drug.     

UVB 308‐nm excimer light and bath PUVA: combination therapy is very effective in the treatment of prurigo nodularis

Background Prurigo nodularis (PN) is a chronic inflammatory skin disease with nodular itching lesions. UV therapy – both PUVA and NUVB – are known to clear up PN temporarily due to the antipruritic effect of UV light. However, relapse after treatment is common in PN, which means that either long‐term therapy is necessary or the treatment protocols have to be optimized to minimize side‐effects. Objective The aim of this study was to evaluate the effect that combining bath PUVA and targeted UVB 308 nm excimer radiation has on recalcitrant nodular prurigo. Methods In a prospective trial, 22 patients with PN were treated with either PUVA alone or with a combination of PUVA and excimer UVB. The end point was complete or almost complete remission of PN. Results Adding a 308‐nm excimer UVB to the treatment of the pruritic nodules sped up the healing process; 30% less PUVA radiation was needed. Conclusion The combination of PUVA and excimer UVB in PN appears to be very efficacious. Reducing psoralen UVA doses by 30% offered long‐term benefits in phototherapy of chronic recalcitrant diseases like PN.     

Cumulative UV radiation dose and outcome in clinical practice: effectiveness of trioxsalen bath PUVA with minimal UVA exposure

BACKGROUND: The cumulative artificial ultraviolet (UV) exposure dose of dermatological patients was prospectively monitored in clinical conditions for a total of 2 years (August 1997 - July 1999). We focused on whole body UV treatments, i.e. the trioxsalen (TMP) bath PUVA, the broad-band UVB, and the UVA plus UVB phototherapy. METHODS: Irradiance of the UV devices was calibrated with a spectroradiometer. The cumulative UV doses received by the patients were recorded. A visual analog scale scoring system (VAS) was employed to assess the improvement of various skin conditions at the end of the treatment course. RESULTS: The analysis included 265 patients (141 females and 124 males) and a total of 311 UV treatment courses. Treatments consisted of 86 courses of TMP bath PUVA for psoriasis with a mean cumulative UVA dose of 3.54 J/cm2 and an improvement rate of 89%. For other conditions, 30 courses were needed, with a cumulative UVA dose of 1.47 J/cm2 and an improvement rate of 76%. Altogether, 47 UVB courses were undertaken for psoriasis, and the mean cumulative unweighted UV dose was 2.20 J/cm2, equivalent to 85 standard erythema doses (SED), and an improvement rate of 85%. A total of 25 UVB courses was used for other skin conditions with a mean UV dose of 1.05 J/ cm2, equivalent to 40 SED, and an improvement rate of 71%. A total of 123 courses of UVA plus UVB phototherapy were completed, resulting in a mean cumulative dose of 73.01 J/cm2 for UVA and 0.75 J/cm2 for the unweighted UVB, equivalent to 29 SED. The VAS improvement rate was 85%. CONCLUSION: The exceptionally low mean cumulative UVA dose in the TMP bath PUVA, taken together with the previous report showing no increase in the risk of squamous cell carcinoma or cutaneous malignant melanoma after TMP bath PUVA, suggests that TMP bath PUVA is an effective and safe therapeutic option.