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

BACKGROUND: Both bath psoralen plus ultraviolet A (PUVA) and oral PUVA with 8-methoxypsoralen (8-MOP) have been successfully used for the treatment of recalcitrant palmoplantar psoriasis. This trial was designed to assess the efficacy and side effects of the different treatment modalities in a randomized half-side comparison. Methods: Eight patients with moderate-to-severe psoriasis on soles (n = 6) and/or palms (n = 8) were randomly assigned to receive bath PUVA treatment on one side and oral PUVA on the other. Initial treatment dose was 50% of the minimal phototoxic dose evaluated for bath PUVA and oral PUVA. Treatment was given three times a week for 4 weeks. Before treatment and every week a severity index (SI) was assessed by summing the scores of erythema, infiltration, scaling and vesicles evaluated on a scale from 0 to 4. After 4 weeks of treatment the half-side trial was finished and the treatment was continued on both sides with the more effective treatment regimen. RESULTS: Both bath PUVA and oral PUVA achieved a reduction of the mean initial SI from 5.9 (95% confidence intervals (CI) 4.5-8.0) to 3.3 (1.8-6.0) (44% SI reduction, P < 0.005, Student's paired t-test) and 6.0 (5.0-7.8) to 2.9 (1.8-4.0) (52% SI reduction; P < 0.005), respectively. The statistical comparison of the entire 4-week study period revealed a significant better effect in lesions treated with oral PUVA compared with bath PUVA (P = 0.033). However, at 4 weeks, there was no significant difference between the achieved SI reduction of oral PUVA and bath PUVA. Systemic side effects (nausea and/or dizziness) were only observed after oral PUVA. CONCLUSION: This study gives evidence that in the first 4 treatment weeks oral PUVA is slightly more effective than bath PUVA but the former has more systemic side effects.     

Comparison of crude coal tar and topical methoxsalen in treatment of psoriasis.

Fluorescent sunlamp bulbs have been an effective light source for treatment of psoriasis when they are used in combination with crude coal tar. In addition to their ultraviolet B (UVB) emission, the spectral output of these bulbs contains a substantial amount of ultraviolet A (UVA). Prior testing with this light source and topically applied methoxsalen achieved excellent results in psoriasis. This study compared topically applied methoxsalen to crude coal tar in 16 patients who had plaque-type psoriasis, using the same fluorescent sunlamp source of irradiation. Fourteen of 16 patients had complete clearing of plaques when they were treated with methoxsalen, compared with six patients who had complete clearing with the tar treatment. These results indicate that the use of methoxsalen and ultraviolet light may be more effective than tar, when used as they were in this study. The advantages of a clean, white, nonstaining topical agent also makes outpatient therapy more cosmetically acceptable.     

Comparison of the efficacy of local narrowband ultraviolet B (NB-UVB) phototherapy versus psoralen plus ultraviolet A (PUVA) paint for palmoplantar psoriasis

Palmoplantar psoriasis is an idiopathic disabling condition, often resistant to conventional therapies. The purpose of this study was to evaluate the efficacy and safety of local narrowband ultraviolet B (NB-UVB) phototherapy and to compare it with local psoralen plus ultraviolet A (PUVA) paint in patients with palmoplantar psoriasis unresponsive to conventional therapies other than phototherapy. A cohort of 25 patients with palmoplantar psoriasis were included in this study, which was based on a left-to-right comparison pattern. The treatments were administered with local narrowband UVB irradiation on one side and local PUVA on the other side three times a week over 9 weeks. Clinical assessments were performed at baseline and every 3 weeks during the 9-week treatment. There was a statistically significant decrease in the mean clinical scores at the third, sixth and ninth week with both treatments. The difference in clinical response between the two treatment modalities was statistically significant at the end of the treatment period, with the percentage reduction in severity index scores with the PUVA-paint-treated side being 85.45% compared with 61.08% for the NB-UVB treated side (t = 5.379, P = 0.0001, Student's t-test for unpaired samples). Our results show that, although some clinical improvement was achieved with local NB-UVB phototherapy, the results were better with local PUVA, and such a treatment option may be reserved for patients with palmoplantar psoriasis who experience phototoxic reaction to psoralens.     

Treatment of necrobiosis lipoidica with topical psoralen plus ultraviolet A

BACKGROUND: Necrobiosis lipoidica (NL) is a rare skin disease, mostly seen on the legs and often occurring in patients with diabetes mellitus. The disease belongs to the idiopathic cutaneous palisading granulomatous dermatitides associated with a degeneration of collagen, thus leading to skin atrophy. Application of topical corticosteroids is the most widely used treatment but the results are not always satisfactory and may worsen skin atrophy. Preliminary studies in patients with NL have shown a clinical response with psoralen plus ultraviolet (UV) A (PUVA). Objectives To study the effect of topical PUVA on NL in a multicentre prospective study. METHODS: Thirty patients (27 women and three men) including 13 with insulin-dependent diabetes mellitus, with a diagnosis of NL proven by histopathology, were included. All patients had been unsuccessfully treated with topical and/or intralesional corticosteroids. Patients were treated twice weekly with an aqueous gel containing 0.005% psoralen followed by irradiation with UVA. Clinical photographs were taken for evaluation. In addition, 20-MHz high-frequency ultrasound analysis was performed in 10 patients to evaluate the thickness and density of the dermis during topical PUVA therapy. RESULTS: Five patients (17%) showed complete clearing (healing of ulceration and disappearance of erythema) after a mean of 22 exposures (range 15-30). Eleven patients (37%) showed improvement, defined as healing of ulceration and/or reduction of erythema, after a mean of 23 exposures (range 11-42). Ten patients (33%) showed no effect and four patients (13%) worsened during topical PUVA therapy. The treatment results of the patients who suffered from diabetes mellitus were not different from those who did not have diabetes mellitus. No difference was seen in mean dermal thickness (1666 vs. 1706 micro m) and density (17 vs. 16 units) before and after topical PUVA therapy. Side-effects were seen in 10 patients: hyperpigmentation (n = 4), blistering (n = 4) and bacterial infection (n = 2). CONCLUSIONS: Topical PUVA may be a useful treatment modality for NL in patients not responding to topical or intralesional corticosteroids.     

Narrowband ultraviolet B versus psoralen plus ultraviolet A therapy for severe plaque psoriasis: an Indian perspective

There is a dearth of studies comparing the efficacy of psoralen ultraviolet A (PUVA) and narrowband (NB)‐UVB in psoriasis in South Asian patients. Patients having plaque psoriasis with > 20% body surface area involvement were randomly assigned to one of two groups (group A: NB‐UVB, group B: PUVA). The response to treatment was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and every 2 weeks thereafter. The maximum possible treatment duration was 16 weeks. In total, 43 patients (21 NB‐UVB, 22 PUVA) completed the study. Marked improvement was seen in 80.9% of the patients in group A and 81.8% in group B (NS: P > 0.05). The mean ± SD time taken to achieve marked improvement was 9.9 ± 3.3 and 9.9 ± 3.5 weeks, respectively. In total, 29 patients were available for the analysis of the remission data at 6 months after treatment completion; 26.7% of the patients in group A and 42.8% in group B were in remission (NS: P > 0.05). Both methods seem to be equally effective in achieving clearance and maintaining remission of severe chronic plaque psoriasis in patients with Fitzpatrick skin type 4 and 5.     

A study of psoralen photochemotherapy with topical tar in the management of psoriasis vulgaris

In a random study of 150 patients with psoriasis vulgaris, oral psoralen photochemotherapy using natural sunlight (PUVASOL) used alone was compared to PUVASOL plus adjunctive topical therapy with tar. The combined PUVASOL and topical therapy with tar in 75 patients (group-I) with 30 minutes sunlight exposure done in every alternate day showed complete clearing of lesions in 68 (90.6%) patients. The average rate of clearance of lesions started to appear 12-24 days with a mean of 18 days. Group I patients who received topical therapy in conjunction with PUVASOL, their skin lesions cleared more quickly with fewer treatments at a lower final 15 PUVASOL doses as compared to 22 PUVASOL doses in the control patients. Ninety percent of 51 patients using topical therapy on their scalp cleared their psoriasis in this area by the time their body psoriasis had cleared. Only 2 of the 45 (4.4%) patients with scalp involvement cleared receiving PU VASOL alone. All 7 patients with psoriatic arthritis cleared their psoriasis, but none of them noted any symptomatic alteration in the severity of their arthritis during the course of treatment in both the groups.     

The epidermal Langerhans' cell population in psoriasis during topical coal tar therapy

We have studied the effect on the Langerhans' cell (LC) population of topical 3% coal tar therapy. Biopsies were taken from psoriatic plaques and from controls with no skin disease before and after the application of 3% coal tar for one week; LC were identified by immunofluorescence using monoclonal antibody. LC counts expressed per unit epidermal surface length were similar in untreated psoriasis plaques and in normal skin. Differences in the LC population in paired biopsies from both patients and controls showed considerable variation following coal tar treatment but no consistent effect could be demonstrated.     

Topical tazarotene vs. coal tar in stable plaque psoriasis

Background. The efficacy of topical tazarotene has not previously been compared with the conventional topical treatment of crude coal tar (CCT) in stable plaque psoriasis. Aim. To assess the comparative efficacy and tolerability of topical tazarotene 0.1% gel and CCT 5% ointment in stable plaque psoriasis. Methods. In this nonblinded side‐to‐side comparison study, patients with chronic stable plaque psoriasis, who had bilaterally symmetrical plaques on the limbs, applied 0.1% tazarotene gel on the right side and 5% CCT ointment on the left side once daily for 12 weeks followed by an 8‐week treatment‐free follow up period. Severity of psoriatic lesions and response to treatment was evaluated by scoring erythema, scaling and induration (ESI). Results. Of 30 patients recruited, 27 could be assessed. In the per‐protocol analysis, the mean percentage reduction in ESI score at the end of the treatment period was 74.15% ± 9.43 and 77.37% ± 10.93 with tazarotene and CCT, respectively (P > 0.05). A reduction in ESI score of > 75% was seen in 11 (40.74%) and 16 (59.26%) patients with tazarotene and CCT, respectively, at the end of 12 weeks. Side‐effects were seen in 48.14% of patients treated with tazarotene, but in no patient treated with CCT. Conclusions. Tazarotene 0.1% gel has comparable clinical efficacy to CCT 5% ointment. CCT ointment remains a cost‐effective therapy for plaque psoriasis.     

Efficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry

Background Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis. Objectives To compare the clinical efficacy of PUVA and biologic therapies for psoriasis under daily life conditions. Methods Data from a psoriasis registry ( http://www.psoriasis‐therapieregister.at ) of 172 adult patients with moderate to severe chronic plaque psoriasis treated between 2003 and 2010 were analysed retrospectively. These patients had received oral PUVA [118 treatment courses including 5‐methoxypsoralen (5‐MOP; n = 32) and 8‐methoxypsoralen (8‐MOP; n = 86)] and/or biologic agents [130 treatment courses including adalimumab (n = 18), alefacept (n = 32), efalizumab (n = 17), etanercept (n = 38), infliximab (n = 7) and ustekinumab (n = 18)]. Treatment responses were analysed in terms of Psoriasis Area and Severity Index (PASI) improvement, including complete remission (CR) and reduction of PASI by at least 90% (PASI 90) or 75% (PASI 75), at treatment completion for PUVA (median time 10·3 and 9·2 weeks, for 8‐MOP and 5‐MOP, respectively) and at week 12 for biologics. Results Intention‐to‐treat–as observed CR, PASI 90 and PASI 75 rate was 22%, 69% and 86% for PUVA compared with 6%, 22% and 56% for adalimumab (P = 0·0034 by adapted Wilcoxon test), 3%, 3% and 25% for alefacept (P = 0·000000002), 6%, 6% and 59% for efalizumab (P = 0·000053), 6%, 29% and 39% for etanercept (P = 0·0000086), 29%, 71% and 100% for infliximab (P = 0·36) and 6%, 39% and 67% for ustekinumab (P = 0·028). When applying a more conservative post‐hoc modified worst‐case scenario analysis, with CR of 15%, PASI 90 of 58% and PASI 75 of 69%, PUVA was superior only to alefacept (P = 0·000013), efalizumab (P = 0·015) and etanercept (P = 0·0037). There were no statistically significant differences in PASI reduction rates between PUVA and infliximab. Conclusions Retrospective analysis of registry data revealed that the primary efficacy of PUVA was superior to that of certain biologics. Prospective head‐to‐head studies of PUVA and biologics are warranted to confirm these observations.     

Calcitriol ointment and clobetasol propionate cream: a new regimen for the treatment of plaque psoriasis

For psoriasis therapy, topical derivatives of vitamin D3 represent a versatile option: they can be used either alone or in combination with other agents such as topical corticosteroids. In this two-phase parallel-group study, the naturally occurring vitamin D3 analogue, calcitriol, was compared with the vitamin D analogue calcipotriol in 125 patients with chronic plaque-type psoriasis. The proposed treatment regimen was an initial bitherapy for 2 or 4 weeks, with clobetasol propionate 0.05% cream, a super potent topical corticosteroid applied in the morning and either calcitriol 3 mug/g ointment or calcipotriol 50 mug/g ointment applied in the evening, followed by monotherapy with either calcitriol or calcipotriol applied twice daily until endpoint week 12. Efficacy evaluations (global assessment of improvement, PASI and body surface area (BSA) affected) showed no significant differences between the two regimen groups at the primary endpoints (week 2 and week 12) or at any interim points. At week 2 the investigator's global assessment showed clinical success (psoriasis markedly improved, almost clear or clear) for more than 50% of the patients in both groups and for 48 (79%) and 56 (88%) patients, respectively in the calcitriol and calcipotriol regimen group at week 12. Least-square means analysis of PASI indicated the calcitriol regimen to be equivalent to the calcipotriol regimen. There were no significant differences between the two groups with regards to cutaneous safety or to incidence of adverse events. The present study shows that for the treatment of mild to moderate plaque psoriasis calcitriol 3 mug/g ointment can provide a safe and effective alternative to calcipotriol 50 mug/g ointment while being administered within a regimen based on a bitherapy with corticosteroids followed by a vitamin D3 maintenance monotherapy.     

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.     

Epidermal dystrophy. Occurrence after psoriasis therapy with psoralen and long-wave ultraviolet light.

Focal dystrophy of epidermal cells has been recognized in about half of 37 patients treated with psoralen and long-wave ultraviolet radiation (PUVA) for psoriasis. This lesion appeared in many patients by the end of the clearing phase of therapy and was present to a similar degree one year after the beginning of the treatment. It is probable that most such changes are transient, but the appearance suggests the possibility that cells have undergone somatic mutation that potentially could be dangerous.