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.     

Cutaneous carcinoma and PUVA lentigines in Thai patients treated with oral PUVA

A total of 113 Thai patients who were treated with oral PUVA from 1979 to 1992 were examined for long-term cutaneous side effects of PUVA. Two psoriatic patients developed PUVA keratosis on non-sun-exposed areas. Both were skin type IV and had had phototherapy with UVB and sunlight previously. The total doses of UVA were 909 J/cm² and 242 J/cm² respectively. One psoriatic patient developed Bowen's disease. He had had a cumulative dose of UVA 2207 J/cm². He also had a past history of arsenic intake and phototherapy with UVB and sunlight. PUVA lentigines were seen in 58 patients (51.4%). It was associated with older age at starting PUVA, higher cumulative UVA dose and greater number of PUVA treatment. This study suggests that previous exposure to other risk factors is important for inducing skin cancer in populations with skin phototype III, IV and V treated with oral PUVA.     

Efficacy of topical PUVA soaks for palmoplantar dermatoses: an audit

Background: With a lack of evidence base for individual topical PUVA protocols, treatment is presently based on the consensus of current practice. This audit was designed to investigate the effectiveness of topical PUVA for palmoplantar dermatoses. Methods: Phototherapy notes were reviewed on all patients who received hand and/or foot PUVA 2002–2007 in the Northern Health and Social Care Trust (NHSCT), Northern Ireland. Results: Thirty patients met the inclusion criteria for the study. The mean number of treatments, maximum single UVA dose, and cumulative dose, were 18.4, 4.2 J/cm², and 48.3 J/cm², respectively. A positive response to treatment occurred in 51.3% of patients, which fell short of the 70% standard set. In a multivariate logistic regression analysis, number of treatments (P=0.04) and maximum single UVA dose (P=0.03) were the only variables associated with positive treatment outcome. The response was not influenced significantly by skin type, concurrent topical treatments, or cumulative UVA dose. Limitations to the study: Small patient numbers may have prevented the statistical significance of individual variables. Conclusions: UV dose increments should be clearly defined to avoid excess caution at the expense of an adequate patient response, and a minimum of 20 treatments administered to all patients, if tolerated.     

Response of psoriasis to twice weekly PUVA

In the U.K., PUVA treatment for psoriasis is usually given three times weekly, with the starting dose of UVA chosen according to the skin type of the patient. Observations on the time-course and dose response characteristics of PUVA erythema suggest that larger doses of UVA could be used safely, provided that the frequency of PUVA treatment is reduced. We have examined this by treating 100 patients with chronic plaque-type psoriasis with a PUVA protocol in which treatment using oral 8-methoxypsoralen was given twice weekly, with the starting dose of UVA based on each patient's minimal phototoxic dose, and with weekly UVA dose increments calculated as a percentage of the dose used in the previous treatment.
Clearance of psoriasis was achieved in 92% of patients. The median number of treatments required for clearance was 12, and the median cumulative UVA dose for clearance was 52 J/cm² Although erythema occurred at some stage during the course of PUVA in 48% of patients, in only 16% of cases was the erythema of sufficient intensity to result in more than one treatment being missed.
These results compare favourably with previous studies in which treatment was given three or four times weekly. Thus, twice weekly PUVA treatment for psoriasis is at least as effective as treatment given more frequently, and may be safer, as lower cumulative UVA doses are required for clearance. It also allows for more efficient operation of a PUVA unit and is more convenient for patients.     

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.     

Combination therapy of oral methoxypsoralen: photochemotherapy (PUVA) and an aromatic retinoid (etretinate, tigason) in the treatment of psoriasis

RePUVA is the combination of an oral aromatic retinoid, etretinate, with oral photochemotherapy, PUVA. This combination therapy has the advantage of faster clearance with fewer side effects. In Middle Road Hospital, we treated 29 patients with extensive psoriasis (more than 30% involvement) with a total 32 RePUVA treatments. There was complete clearance in 69% of patients with an average of 19 irradiations and an average total ultraviolet A (UVA) dose of 183 J/cm². This compared well with standard PUVA which needed 25 radiations and a total UVA dose of 346 J/cm². The main side effects were cheilitis, exfoliation of skin and pruritus. Biochemically, 41% of the patients showed elevations of serum triglyceride.     

Retrospective long‐term follow‐up in patients with chronic palmoplantar dermatoses after good response to bath PUVA therapy

Background: Numerous studies have confirmed the short‐term effectiveness of 8‐methoxypsoralen bath PUVA therapy in patients with chronic palmoplantar dermatoses; however, little is known about long‐term results. Patients and methods: In this retrospective study we examined the long‐term results in 79 patients (mean age: 48 years) with chronic palmoplantar dermatoses who were treated with bath PUVA three times a week over an 8‐year period. A good clinical response (a reduction of more than 50% of the skin lesions) occurred after a mean of 23 treatments and a mean cumulative UVA dose of 39 J/cm² in 51 patients (65%). In 2007 a questionnaire was sent to these 51 patients to assess the long‐term outcome. Results: With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%). Thirty‐four patients (67%) answered the questionnaire after a mean follow‐up interval of 4.3 years (10–87 months). Among these patients, 36% reported an improved course of disease after PUVA therapy with reduced frequency and/or intensity of the skin rash, and 29% of patients reported continued complete clearance. 79% of our patients reported a long‐term reduction in the use of topical corticosteroids during the follow‐up period (mean: 4.3 years). In addition, 67% of patients reported a lasting improvement in quality of life. Conclusions: These data show that bath PUVA may have a long‐term, beneficial influence on the course of disease in a majority of patients with recalcitrant chronic palmoplantar dermatoses.     

Efficacy and safety of bexarotene combined with psoralen-ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB-IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial (NCT00056056)

Background Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies. Objective To assess disease response and to compare the response rates of patients treated with PUVA alone or PUVA and bexarotene. Methods EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin^®) and PUVA vs. PUVA alone in patients with stage IB and IIA mycosis fungoides (MF). The primary endpoint was the overall response rate [complete clinical response (CCR) plus partial response (PR)]. Results The study was prematurely closed due to low accrual after 93 of 145 required patients (65%) were randomized. Of the 93 randomized patients, 87 started treatment, 41 received PUVA and 46 received PUVA + bexarotene. Total UVA doses received were 107 J cm^?2 (range 1·4–489·9) in the PUVA arm vs. 101·7 J cm^?2 (0·2–529·9) in the combination arm. The safety profile was acceptable with few grade 3–4 toxicities observed in either arm. More drop‐outs due to toxicity were observed in the combination arm compared with the PUVA‐alone arm. The best overall response (CCR + PR) rate was 71% for PUVA alone and 77% for the combination arm (P = 0·57). The median duration of response was 9·7 months for PUVA vs. 5·8 months for the combination arm (P = 0·33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P = 0·45). CCR was sustained in 25% of patients regardless of therapy. There was a trend towards fewer PUVA sessions needed to achieve CCR in the combination arm (median 22) compared with the PUVA arm (median 27·5) (P = 0·11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55·8 J cm^?2) compared with the PUVA arm alone (median 117·5 J cm^?2) (P = 0·5) was observed. Conclusions No significant difference in response rate or response duration was observed in this study. However, there was a trend towards fewer PUVA sessions and lower UVA dose required to achieve CCR in the combination arm (PUVA + bexarotene) but this did not achieve statistical significance due to insufficient power.     

Effects of in vitro PUVA treatment on adenylate cyclase responses of epidermis

We investigated the effect of 8-methoxypsoralen (8-MOP) plus long wave ultraviolet irradiation (PUVA) on the pig skin epidermal cyclic AMP (cAMP) system. Following PUVA treatment in vitro, pig skin squares were incubated in RPMI 1640 medium, and the cAMP accumulation by various adenylate cyclase stimulators was determined. A significant increase of the beta-adrenergic adenylate cyclase response was observed as early as 6-h following PUVA treatment; the maximal effect was reached at 24-h and lasted at least for 72-h. This augmentation effect of PUVA treatment was potentiated by increasing the 8-MOP concentration (0.5–160 μg/ml) and UVA irradiation dose (0.05–1.4 J/cm²). At higher irradiation doses (2.1–2.8 J/cm²), the beta-adrenergic augmentation effect was less marked. There were no significant differences in the adenosine-and histamine-adenylate cyclase response up to 1.4 J/cm² irradiation; however, the latter was decreased at a higher irradiation dose (2.8 J/cm²). Although UVA irradiation alone had no effect on the beta-adrenergic response, 8-MOP treatment alone increased this receptor response at higher concentrations; this effect was much weaker than that induced by PUVA treatment. Cyclic AMP phosphodiesterase activities were not affected by PUVA treatment. These results indicate that epidermal adenylate cyclase response is affected by in vitro PUVA treatment.     

Comparison of the relative therapeutic efficacy of 7-methyl pyridopsoralen and 8-methoxypsoralen in photochemotherapy in psoriasis treatment

A newly-synthesized, monofunctional psoralen derivative, 7-methyl pyrido (3,4-C) psoralen (MPP) was compared with 8-methoxypsoralen (8MOP) with respect to their therapeutic efficacy in photochemotherapy of psoriasis. Psoriatic lesions of six patients were treated with topical application of MPP plus UVA (MPP PUVA) or with 8MOP plus UVA (8MOP PUVA). The UVA doses used in each treatment were 7.5 or 10 J/cm² with MPP and from 1.2 to 3.6 J/cm² with 8MOP. In every patient, marked improvement was observed after 2 to 6 treatments with MPP PUVA or 8MOP PUVA. Three patients showed clearance of each psoriatic lesion treated 9 to 17 times with MPP or 8MOP PUVA. Althought MPP required much higher UVA doses than 8MOP, MPP PUVA was as effective as 8MOP PUVA in treating psoriasis. When irradiating with identical doses of UVA, MPP PUVA appeared to be less active than 8MOP PUVA. None of the patients developed any severe dermatitis reactions during 20 exposures to MPP PUVA, indicating that the probability of inducing allergic contact and photocontact dermatitis may be extremely low. Erythemogenic and pigmentogenic activities of MPP and 8MOP were also compared. The data demonstrated that 8MOP is more than 8 times as effective as MPP for both activities. With the UV doses used in this study, however, every patient produced marked pigmentation after MPP PUVA therapy. Finally, the UVA dose-dependency of MPP PUVA was studied with an additional patient. Both therapeutic and pigmentogenic effects increased as a function of the UVA dose; it appeared impossible to clear psoriasis without producing pigmentation.     

A trial of accelerated PUVA in psoriasis

Ten psoriatic patients were treated with an accelerated PUVA regimen. Nine patients cleared in an average of 13·7 treatments (range 4-24) after an average total UVA dose of 83 J/cm² (range 18-186). One patient had to withdraw due to pruritus and burning and six others had burning problems. The high incidence of burning may limit the routine use of this irradiation regimen.     

Comparison of trioxsalen bath and oral methoxsalen PUVA in psoriasis

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

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.     

Topical PUVA Therapy for Chronic Hand Eczema

Seventeen patients with persistent chronic hand eczema were treated with topical 0.1% 8-methoxypsoralen and UVA (PUVA) for 8 weeks. Significant improvement was achieved in 5 cases (29%), moderate improvement in 9 (53%), and little improvement in 3 (18%). The mean number of PUVA treatments was 22.2, and the mean total UVA dose was 63.5 J/cm². There was no association between clinical response and duration of hand eczema, positive patch test reaction, or atopic status. Since topical PUVA has no risk of systemic side effects, it should be considered as an alternative treatment for patients with chronic hand eczema who are resistant to other topical medications.     

In vivo PUVA and UVB sensitivity of various human epidermal Langerhans cell markers (ATPase, HLA-DR and T6)—Dose-response and time-sequence studies

To form a comprehensive view of the UV-sensitivity of human epidermal Langerhans cells (LC), the time-sequence and close response effects of single doses of UVB or 8-methoxypsoralen plus UVA (PUVA) radiation on three different LC surface markers were studied with histochemical and immunohistochemical staining. An increasing PUVA dose from 1 to 10 J/cm² caused an almost linear decrease in the surface enzyme (ATPase) positive LC count, whereas the cell surface antigens (HLA-DR and T6) were rather more resistant, up to a PUVA dose of 5 J/cm². A single dose of 5 J/cm² of PUVA induced an LC depletion that was similar during the 21 days of observation, irrespective of whether the cells were visualized with ATPase staining or with monoclonal antibodies against the cell surface antigens HLA-DR or T6. In each case, the nadir was reached 14 days after irradiation; the average residual LC count was then 57%. The cell counts 21 days after PUVA irradiation were still only approximately 74% of the nontreated skin counts. Langerhans cell depletion induced by an erythemagenic dose of UVB irradiation was swifter and more pronounced than that induced by 5 J/cm² of PUVA but, again, a similar time schedule was recorded with ATPase, HLA-DR and T6 staining.     

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.     

Low-dose PUVA maintenance in psoriasis following Ingram therapy

Following the initial treatment of severe psoriasis with conventional Ingram therapy, it is shown that PUVA maintenance at a mean dose-rate of 28·6 J/cm²/month increases the average period of remission from 7 weeks to more than a year. Surprisingly, the patients who withdrew from maintenance therapy whilst still in remission have so far continued (10 months) to show an extremely low relapse rate.     

The efficacy of localized PUVA therapy for chronic hand and foot dermatoses

The response to treatment of all patients enrolled over an 18-month period for localized oral or topical psoralen photochemotherapy (PUVA) of chronic hand and foot dermatoses was retrospectively reviewed. There were broadly similar success rates for the two groups for complete clearance: 61.5% (eight of 13 patients who completed therapy)—oral PUVA, 47.8% (11 of 23 patients who completed therapy)—topical PUVA, and for significant improvement: 23.1% (three of 13 patients)—oral PUVA, 30.4% (seven of 23 patients)—topical PUVA; there were no significant differences in response when diagnostic subgroupings of the hand dermatoses were taken into account. The mean number of treatments (22 for oral PUVA and 24 for topical), treatment durations (122 and 129 days), maximum UVA doses (11.2 and 12.3J/cm²) and to a lesser extent cumulative UVA doses (189.3 and 237.0 J/ cm²) for the therapies were similar in the two groups; adverse effects were minimal for both treatment protocols. However, at least five of the eight patients in the oral PUVA group and five of the 11 in the topical group who cleared completely relapsed after a mean 86 (range 19.245) and 174 (range 23-596) days, respectively. These findings are in broad agreement with those of previous studies. Therefore to avoid generalized photo-sensitivity and a higher likelihood of adverse effects with systemic therapy, as well as a possible slower relapse rate, topical therapy seems preferable.     

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.