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.     

Evaluation of time-dependent response to psoralen plus UVA (PUVA) treatment with topical 8-methoxypsoralen (8-MOP) gel in palmoplantar dermatoses

BACKGROUND: Topical psoralen plus UVA (PUVA) is an effective treatment for localized forms of eczema, psoriasis, and palmoplantar pustulosis, which avoids some of the undesirable side-effects of systemic psoralens. Aims In this study, the efficacy of topical PUVA treatment with 8-methoxypsoralen (8-MOP) gel was compared with placebo plus UVA in chronic recurrent palmoplantar dermatoses. METHODS: Twenty-two patients with palmoplantar disease (11 with psoriasis vulgaris, six with eczema, and five with pustulosis) were enrolled in the study. The study design was a left-right comparison: one hand or foot was treated with 8-MOP 0.01% gel plus UVA, whilst the contralateral hand or foot received placebo and UVA for 6 weeks. Twenty minutes after application of the gel, both sides were exposed to UVA. The treatment regimen was three times a week, and the UVA dose was increased weekly by 20%. RESULTS: A comparison of the pre- and post-treatment scores with regard to the severity of the clinical picture and the infiltration of plaques showed a significant decrease (from 7.5 +/- 2.0 to 2.5 +/- 2.1 and from 2.0 +/- 0.7 to 0.3 +/- 0.5, respectively) in the sites treated with 8-MOP gel compared with placebo after 6 weeks. CONCLUSION: The results of the study indicate that at least 18 courses of local PUVA within 6 weeks, with a cumulative dose of 87 J/cm(2), are required to induce a significant decrease in the disease severity and an improvement in the infiltration of plaques due to 8-MOP gel at a concentration of 0.01% when treating chronic recurrent palmoplantar dermatoses.     

Topical psoralen photochemotherapy (PUVA) and superficial radiotherapy in the treatment of chronic hand eczema

The therapeutic efficacy of conventional superficial radiotherapy and topical psoralen photochemotherapy (topical PUVA) administered over a 6 week period was compared in a double-blind study of 21 patients with chronic bilateral constitutional hand eczema. One hand was treated with conventional superficial radiotherapy and the other with topical 8-methoxy-psoralen and long-wave ultraviolet light (topical PUVA). Significantly better clinical improvement was seen in superficial radiotherapy treated hands over topical PUVA treated hands after 6 weeks of treatment, but this difference was not maintained at 9 or 18 weeks. There was no significant difference in symptom severity between the two treatments after 6 weeks, but superficial radiotherapy produced significantly more symptomatic improvement at 9 and 18 weeks. Superficial radiotherapy is a less time consuming procedure than topical PUVA and leads to more rapid improvement.     

Comparison of topical PUVA with UVA for chronic vesicular hand eczema.

Topical PUVA was compared with UVA for the treatment of chronic vesicular hand eczema in a double-blind randomized within-patient trial. Twelve of 15 patients completed 8 weeks' treatment and were followed up for 8 weeks. Both sides improved over the 8-week treatment period (p less than 0.05) and both remained substantially better objectively and subjectively at 8 weeks' follow-up. There was no statistical difference between assessments of the treated hands at any stage. Nine of the patients who completed the study answered a questionnaire up to 18 months later. In 4, eczema was healed, 3 were better on the PUVA-treated hand and 1 on the UVA-treated hand. It is possible that UVA alone is beneficial for chronic hand eczema.     

A new psoralen-containing gel for topical PUVA therapy: development,and treatment results in patients with palmoplantar and plaque-type psoriasis,and hyperkeratotic eczema

Summary Topical photochemotherapy with psoralen and its derivatives 4.5′,8-trimethylpsoralen (TMP) and 8-methoxypsoralen (8-MOP), with UVA irradiation, was evaluated with regard to minimum phototoxic dose, concentration, timing of UVA irradiation and systemic and local side-effects, in healthy volunteers. Psoralen (0.005%) in aqueous gel was found to be superior to TMP and 8-MOP in aqueous gel. No hyperpigmentation was seen after topical PUVA treatment with psoralen in aqueous gel. Patients with plaque-type psoriasis (n = 7), palmoplantar psoriasis (n = 7) and hyperkeratotic eczema (n = 2) were treated. Topical PUVA therapy was effective in most psoriasis patients, without the occurrence of local or systemic side-effects. Moreover, hyperkeratotic eczema patients who did not respond to conventional therapy showed partial remission. These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.     

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.     

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.     

Comparison of localized high-dose UVA1 irradiation versus topical cream psoralen-UVA for treatment of chronic vesicular dyshidrotic eczema

BACKGROUND: Vesicular dyshidrotic palmoplantar eczema is a common disorder but treatment is difficult. Localized photochemotherapy (cream psoralen-UVA [PUVA]) has widely been used for therapy. Although the efficacy of cream PUVA therapy is well known, potential side effects may occur. Therefore, a more standardized safe and effective UV therapy should be carried out. OBJECTIVE: This study compared the effects of localized high-dose UVA1 irradiation versus topical cream PUVA for treatment of chronic vesicular dyshidrotic eczema. METHODS: On the basis of the assessment of the Dyshidrotic Area and Severity Index, the decrease of score points on the UVA1-treated side was compared with the decrease on the cream PUVA-treated side in 27 patients. In addition, analysis of serum markers was performed. RESULTS: Of 27 patients, 24 showed a good response to localized UVA1 irradiation or cream PUVA. Dyshidrotic Area and Severity Index scores significantly decreased on both sides and were reduced to half of the pretreatment values. No statistically significant differences between localized UVA1 irradiation or cream PUVA could be detected. CONCLUSION: This study demonstrates that localized UVA1 phototherapy is easy to perform and appears to be an effective and safe treatment for vesicular dyshidrotic eczema.     

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.     

Long-term results of topical PUVA in necrobiosis lipoidica

The aim of our study was to evaluate the long-term results of topical psoralen ultraviolet A (PUVA) in patients with necrobiosis lipoidica (NL), in whom conventional methods (pentoxifylline, vitamin E, tretinoin, and topical or intralesional corticosteroids) had failed. The study comprised 10 women (age range 17-44 years), six of whom were insulin-dependent diabetics and four were diabetes-free. Duration of NL ranged from 3 to 10 years. The patients were treated with a 0.005% aqueous solution of 8-methoxypsoralen, applied topically for 30 min, and subsequently irradiated with UVA three times weekly. All the patients experienced almost complete remission (softening of skin lesions, no hyperpigmentation, lack of lesion progression) after a mean of 47 sessions (mean UVA cumulative dose 69.5 J/cm2). They were followed up for 12-24 months, during which time two recurrences, both in diabetic patients, were observed after 8 and 12 months of treatment cessation, which further resolved after another course of topical PUVA. We conclude that topical PUVA is well tolerated by NL patients and may serve as an alternative therapeutic regimen.     

Topical photochemotherapy for alopecia areata

Twenty-two patients with alopecia areata were treated with a combination of topical 0.1% 8-methoxypsoralen and UVA (PUVA). Eight of the twenty-two patients (36.3%) responded with excellent regrowth (terminal hair in at least 75% of the treated scalp), and two patients (9.1%) showed good regrowth (terminal hair in 50% to 75% of the treated scalp). The mean total UVA exposure and the mean total number of treatments for the entire treatment course for these responders was 171.7 joules/cm2 and 47.4 treatments, respectively. Eight of the nine responders available for follow-up experienced some degree of relapse when PUVA treatments were tapered or during a follow-up period (mean, 8.3 months) after treatment was discontinued. Despite the failure of topical PUVA to change the long-term course of alopecia, the combination of PUVA with other therapeutic modalities may result in the prolongation of the beneficial effect in selected patients. The mechanism of action of PUVA in alopecia areata might involve an immunomodulatory effect.     

Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema: an open-label randomized controlled trial of efficacy

OBJECTIVE: To study whether oral psoralen-UV-A (PUVA) with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. DESIGN: Open-label randomized controlled trial, with a 10-week treatment period and an 8-week follow-up period. SETTING: Two university hospital dermatology departments in the Netherlands, specializing in hand eczema. PATIENTS: One hundred fifty-eight patients with moderate to severe chronic hand eczema (more than 1 year in duration). INTERVENTIONS: Oral PUVA using methoxsalen capsules and a simple portable commercial facial tanning unit, or hospital-administered bath PUVA with trioxsalen. MAIN OUTCOME MEASURES: The primary outcome was clinical assessment by a hand eczema score (evaluation of desquamation, erythema, vesiculation, infiltration, fissures, itch, and pain, each on a 4-point scale) after 10 weeks of treatment. The secondary outcome was hand eczema score at 8 weeks of follow-up, after completion of treatment. The tertiary outcome was travel cost and time off work. RESULTS: Both groups showed a comparable and substantial decrease in hand eczema score (meaningful clinical improvement). This decrease was maintained during the follow-up period. Patients treated with oral PUVA at home had lower travel costs and less time off work. CONCLUSIONS: Oral PUVA at home has a clinically relevant efficacy, similar to that of hospital-administered bath PUVA. This effect was maintained during an 8-week follow-up period. It resulted in lower travel costs and less time off work.     

Treatment of chronic urticaria with PUVA or UVA plus placebo: A double-blind study

Summary Chronic urticaria is a disease for which the available range of treatment modalities is limited. Ultraviolet radiation has recently been shown to affect histamine release from mast cells. We therefore studied the effects of PUVA and UVA on chronic urticaria. Nineteen patients took part in the study, which was designed as a randomized double-blind study. Eleven patients received PUVA, and 8 received UVA plus a placebo. In the PUVA group, 7 patients showed improvement, 3 noticed no change, and 1 became worse. In the group that received UVA plus placebo, 5 patients experienced an improvement, whereas the other 3 showed no change. The differences between the groups were not statistically significant. However, the probability of achieving this degree of improvement in both groups just by chance is less than 1%. Consequently, the improvement noted could have been due to either UVA alone or a placebo effect. It is concluded that PUVA is not better than UVA in the treatment of chronic urticaria.     

Image Gallery: A case of malignant syphilis in an HIV‐infected patient mimicking fungal infection

Hand eczema is one of the most common skin diseases with some studies estimating that up to 10% of the European population has some degree of hand eczema at any one time. There are various causes with some people having a genetic tendency and others developing hand eczema due to their jobs, often a result of hand washing in healthcare or hospitality sectors. The initial treatment of hand eczema is to avoid obvious triggers and use plenty of moisturising creams. If problems continue steroid creams are prescribed. These measures are often enough but if the eczema continues patients are then offered either ultraviolet (UV) light based treatments or tablets. This research study investigated two different forms of UV light treatment which are used to treat eczema. PUVA involves soaking the hands in a water‐based solution of a photosensitising drug before receiving UVA light for 5‐15 minutes whereas NBUVB involves a 1‐2 minute exposure to UVB light. PUVA is the traditional treatment and has been used for 30 years. It is time consuming. There are some concerns that excessive PUVA use could increase the risk of skin cancers and indefinite repeated treatment is not used. The research study invited patients with hand eczema not improving with steroid creams to receive either PUVA or UVB treatment. The severity of their eczema was scored before, during and after treatment. Due to difficulties in recruiting enough patients it was not possible to say which treatment was better. However, the study did show that both treatments improved the eczema severity. There were more side effects with the NBUVB treatment mainly due to mild episodes of skin redness. This research has provided new information. We now know that NBUVB is a safe and acceptable treatment for hand eczema. It does lead to improvement in hand eczema severity. It takes less time but does produce more side effects than PUVA. We have measured the improvement in patients’ eczema with both treatments using official scoring systems which means we are now in a position to design a larger clinical trial to determine which treatment is more effective.     

Hand and foot PUVA soaks: An audit of the Massachusetts General Hospital''s experience from 1994 to 1998

Palmoplantar psoriasis and eczema can be chronic recalcitrant dermatoses. Oral psoralen plus ultraviolet A (PUVA) has proven effective for these, but has a number of unwanted side effects. Previous studies have shown that regional PUVA therapy using the 8-methoxypsoralen (8-MOP) soak method followed by immediate UVA irradiation is also beneficial and well tolerated. The purpose of this audit was to determine the efficacy of hand and foot PUVA soaks by reviewing the experience of the Massachusetts General Hospital's Phototherapy Unit with this treatment modality. Phototherapy records of all patients who underwent hand and foot PUVA soaks from 1994 to 1998 were reviewed. Details regarding the treatment procedure, patient compliance, patient response and incidence of side effects were noted and summarized. Of the 56 patients who underwent at least 20 treatments, 29% had excellent response, 42% had minimal to moderate response, and 29% had poor response. The average number of treatments to induce clearing was 41. The average maximum treatment dose at clearing was 5.85 J/cm2, while the average cumulative dose to achieve clearing was 267.17 J/cm2. 8-MOP PUVA soak therapy is quite useful for chronic hand and foot dermatoses. Patient compliance must be emphasized to obtain favorable results.     

Ultravioletttherapie des chronischen Handekzems

Treatment of hand eczema is dominated by the administration of topical glucocorticosteriods. If topical treatment fails, the best second-line option is ultraviolet (UV) therapy alone or as combination therapy. UVB and PUVA (psoralen plus UVA) therapy is effective and has relatively few side effects. Due to the localized nature of the disease, topical PUVA therapy is preferable to systemic PUVA treatment. Among the topical methods, cream PUVA therapy is simple, safe and highly effective. Recent clinical studies have demonstrated the therapeutic efficacy of a new retinoid called alitretinoin, a 9-cis-retinoic acid. However, even this form of treatment does not lead to a complete cure in all patients. Under the primacy of multimodal treatment, UV therapy should be administered as combination therapy if oral retinoids are not sufficiently effective.     

Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo‐controlled double‐blind study

BACKGROUND: Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A (PUVA) therapy in patients with vitiligo. OBJECTIVES: We performed a placebo-controlled double-blind study to investigate whether the effectiveness of PUVA treatment could be enhanced by combination with topical calcipotriol in the treatment of vitiligo. METHODS: Thirty-five patients with generalized vitiligo enrolled in the study. Symmetrical lesions of similar dimensions and with no spontaneous repigmentation on arms, legs or trunk were selected as reference lesions. In this randomized left-right comparison study, calcipotriol 0.05 mg g(-1) cream or placebo was applied to the reference lesions 1 h before PUVA treatment (oral 8-methoxypsoralen and conventional UVA units) twice weekly. Patients were examined at weekly intervals. The mean number of sessions and the cumulative UVA dosage for initial and complete repigmentation were calculated. RESULTS: Twenty-seven patients (nine women, 18 men; mean +/- SEM age 29.8 +/- 13.5 years) were evaluated. The mean +/- SEM cumulative UVA dose and number of UVA exposures for initial repigmentation were 52.52 +/- 6.10 J cm(-2) and 9.33 +/- 0.65 on the calcipotriol side, and 78.20 +/- 7.88 J cm(-2) and 12.00 +/- 0.81 on the placebo side, respectively (P < 0.001). For complete repigmentation, respective values were 232.79 +/- 14.97 J cm(-2) and 27.40 +/- 1.47 on the calcipotriol side and 259.93 +/- 13.71 J cm(-2) and 30.07 +/- 1.34 on the placebo side (P = 0.001). Treatment with calcipotriol and PUVA resulted in significantly higher percentages of repigmentation for both initial (81%) and complete pigmentation (63%), compared with placebo and PUVA (7% and 15%, respectively). CONCLUSIONS: Our results have shown that concurrent topical calcipotriol potentiates the efficacy of PUVA in the treatment of vitiligo, and that this combination achieves earlier pigmentation with a lower total UVA dosage.     

Oral vs. bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema

Background: Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema. However, most studies were retrospective and did not include longer follow-up periods.
Aim: To compare the therapeutic efficacy, tolerability and duration of remission after oral vs. bath PUVA using 8-MOP in patients with chronic palmoplantar eczema.
Methods: Twenty-nine patients were randomly allocated to treatment with oral or bath PUVA. Treatment was given thrice weekly for a maximum of 20 weeks. The primary outcome measure was the improvement in eczema score at the end of treatment. After clearing patients were followed up until relapse or up to 40 months.
Results: Overall, both PUVA modalities appeared comparably effective. However, after stratifying according to eczema type, significant differences in therapeutic outcome in general as well as in response to the two regimes were found. Dyshidrotic eczema responded better to both treatments ( P =0.048) and remained longer in remission than hyperkeratotic eczema. Hyperkeratotic eczema cleared significantly better with oral than with bath PUVA ( P =0.03).
Conclusion: Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.     

Cutaneous carcinoma and 8-methoxypsoralen and ultraviolet A (PUVA) lentigines in Japanese patients with psoriasis treated with topical PUVA: a follow-up study of 214 patients

A total of 214 Japanese patients with psoriasis, under treatment with topical 8-methoxypsoralen and ultraviolet A (PUVA), were examined for malignant skin tumors and pigmented lesions during a follow-up period of up to 17 years (mean 5.8 years). One patient had developed multiple superficial basal cell carcinomas, and the remaining 213 patients had neither cutaneous carcinomas nor actinic keratoses. PUVA lentigines were seen in 89 patients (42%) and the incidence of lentigines increased as the number of PUVA treatments and the cumulative UVA dose increased. Melanocytic atypia was not observed histologically in 24 pigmented lesions examined. This report suggests that this topical PUVA regimen may not be highly carcinogenic in the Asian population.