8-Methoxypsoralen cream plus targeted narrowband ultraviolet B for psoriasis

BACKGROUND: Targeted ultraviolet (UV) phototherapy is a recent addition to the therapeutic armamentarium for the treatment of localized psoriasis. Topical psoralens enhance the therapeutic effects of UV-based treatment for various dermatoses, but have never been used in conjunction with targeted UVB. PURPOSE: To compare the efficacy of targeted narrowband UVB phototherapy (NB-UVB) alone with that of the combination of 0.1% 8-methoxypsoralen cream and targeted NB-UVB phototherapy (8-MOP/NB-UVB) for the treatment of plaque-type psoriasis. METHODS: Two areas within the same lesion of stable psoriasis were randomized to receive either targeted NB-UVB alone or 8-MOP/NB-UVB. Fluences of UVB delivered were held constant at four minimal erythema doses. The treatments were continued until lesions cleared or 12 treatments. Follow-ups were done until lesional scores returned to 50% of the baseline values. RESULTS: Ten patients completed this study. Four lesions were cleared by 8-MOP/NB-UVB while three were cleared by NB-UVB alone. The improvement in disease activity as reflected by psoriasis severity index score during treatment was statistically significantly better in the combination group (P=0.005). Mean remission time of lesions which were cleared by 8-MOP/NB-UVB was 8 weeks while that for lesions that were cleared by NB-UVB alone was 4.67 weeks. CONCLUSION: We concluded that addition of 0.1% 8-MOP cream to targeted narrowband UVB significantly enhances the therapeutic effects of the light treatment without increasing the incidence of adverse effects.     

Topical 8-methoxypsoralen increases the efficacy of narrowband ultraviolet B in psoriasis

Background: A combination of oral psoralen with narrowband ultraviolet B (UVB), defined as 'psoralen-narrowband UVB', was shown to have a superior efficacy than UVB alone and even a comparable efficacy to psoralen and ultraviolet A in psoriasis.
Objective: To find out whether topical psoralen-narrowband UVB provides any additional benefit to narrowband UVB alone in psoriasis.
Methods: Nineteen patients with plaque psoriasis were included. Phototherapy was given three times per week. Two symmetrical lesions were selected as target lesions. In the first 12 sessions of phototherapy, the target lesion on one side was treated with 1% 8-methoxypsoralen (MOP) gel 30 min before UVB radiation whereas the target lesion on the other side served as a control. Target lesion scores were assessed at baseline, third, sixth, ninth and 12th sessions. Side effects were recorded.
Results: Sixteen patients completed the study. Target lesion scores decreased significantly on both sides ( P <0.0001). The mean percentage of decreases was greater on the 8-MOP-applied sides compared with the control sides for all assessments, but the difference was statistically significant only at the ninth session (37.7% vs. 58.6%, P =0.043). Pigmentation was frequently seen in 8-MOP gel-applied lesions.
Conclusion: Topical 8-MOP gel plus narrowband UVB has greater efficacy than narrowband UVB alone in psoriasis.     

Comparison of weekly and daily incremental protocols of narrowband ultraviolet B phototherapy for psoriasis

BACKGROUND: Different protocols have been used for narrowband ultraviolet B (UVB) therapy, commonly used in the treatment of psoriasis; however, more effective and reliable protocols are still required. OBJECTIVE: The aim of this study was to compare the weekly and daily dose increment protocols of narrowband UVB phototherapy in psoriasis patients. METHODS: Thirty patients with plaque psoriasis underwent narrowband UVB treatment three times a week and 15 patients selected consecutively among these patients underwent a weekly (once in three treatments) dose increment whereas the remaining 15 patients underwent a daily dose increment. Patients were monitored for 10 weeks and evaluated by the Psoriasis Area Severity Index (PASI). RESULTS: When the two groups were evaluated according to median PASI scores prior to the treatment and during 10 weeks of treatment, there was no statistically significant difference between the groups (P > 0.05). During the treatment lasting for 10 weeks, four patients in the group with a weekly dose increment and three patients in the group with a daily dose increment recovered and no statistically significant difference was detected between the groups (P > 0.05). The groups were also evaluated according to the median cumulative dose. The median cumulative dose was higher in the group with a daily dose increment and the difference between the groups was statistically significant (P = 0.002). CONCLUSION: The application of daily dose increments was no better than that of weekly dose increments in narrowband UVB treatment for psoriasis. Therefore, although our results may need to be supported by large-series studies, we conclude that application of weekly dose increments with a lower cumulative dose having the same efficacy is preferred in narrowband UVB treatment of psoriasis.     

Remission period in psoriasis after multiple cycles of narrowband ultraviolet B phototherapy

The aim of this study was to investigate the duration of remission periods in psoriasis after narrowband ultraviolet B (NB‐UVB) phototherapy, especially during multiple cycles of treatment. We analyzed 63 patients (101 cases) demonstrating marked improvement after NB‐UVB phototherapy. The remission period was defined as the duration of time from the end of phototherapy until treatment using either phototherapy or systemic treatments was required again. It was found that an age of 60 years or older, history of systemic therapy within 6 months and three or more phototherapy cycles were significantly associated with shorter remission periods. Furthermore, multivariate analysis confirmed that three or more phototherapy cycles (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.73–9.33; P = 0.001) and a history of systemic therapy (OR, 2.2; 95% CI, 1.27–3.95; P = 0.005) were independently associated with the shorter remission period. In conclusion, when planning NB‐UVB phototherapy for psoriatic patients who have undergone multiple phototherapy cycles, clinicians should consider the possibility of shorter remission periods.     

A comparison of three times vs. five times weekly narrowband ultraviolet B phototherapy for the treatment of chronic plaque psoriasis

Background: Narrowband ultraviolet B (NB-UVB) phototherapy is an effective treatment for psoriasis.
Objectives: To compare the effects of three and five times weekly NB-UVB phototherapy in the treatment of chronic plaque psoriasis.
Methods: Sixty-five patients with chronic plaque psoriasis were allocated to receive three or five times weekly NB-UVB, starting at low dose.
Results: Among the patients who completed the study, clearance was achieved in 18 out of 23 patients (78%) in the three times weekly group and in 15 out of 22 patients (68%) in the five times weekly group. The difference was not statistically significant ( P =0.44).
No statistically significant differences were found between the two groups in the number of treatments ( P =0.95), cumulative UVB dose ( P =0.51), and rate of side-effects. Length of the treatment period was significantly shorter in the five times weekly group ( P <0.001). At the end of treatment, the mean psoriasis area and severity index score was lower in the three times weekly group ( P =0.02).
Conclusions: We recommend three times weekly NB-UVB for chronic plaque psoriasis; however, the more rapid clearance of psoriasis with five times weekly phototherapy may justify using this method in some patients.     

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.     

A reappraisal of the use of 5-methoxypsoralen in the therapy of psoriasis

5-methoxypsoralen (5-MOP) is considered an alternative to 8-methoxypsoralen (8-MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy and tolerability of 5-MOP (1.2 mg/kg)-UVA versus 8-MOP (0.6 mg/kg)-UVA therapy in 25 patients of skin type III and IV, affected by relapsing plaque-type psoriasis of similar body involvement; indeed, the same patients were given 8-MOP during 1 year and 5-MOP during the subsequent year after relapsing. Both treatments cleared psoriatic lesions with a comparable number of exposures, but 5-MOP required significantly higher cumulative UVA doses. The difference was due to the lower phototoxicity of 5-MOP, as assessed by the determination of the minimal phototoxic dose, and to its higher tanning activity, as assessed by the weekly grading of pigmentation. Nevertheless, therapy by 5-MOP-UVA seemed particularly interesting in that it showed a higher tolerability since only 1 patient experienced nausea, whereas during therapy with 8-MOP-UVA nausea and/or vomiting occurred in 7 patients, sunburn in 6 and itching in 3. Since we have treated the same patients with the two drugs, our results were not influenced by interindividual variations of phototoxic responses, tanning ability and susceptibility to develop psoralen-induced short-term side-effects. It was concluded that, although long-term side-effects of the 5-MOP-UVA treatment have still to be determined, such treatment of psoriasis should be reappraised due to its higher tolerability in comparison to 8-MOP-UVA treatment.     

Successful use of acitretin in conjunction with narrowband ultraviolet B phototherapy in a child with severe pustular psoriasis, von Zumbusch type

Severe pustular psoriasis von Zumbusch type is a therapeutic challenge not only in adults, but even more in children. We report a 3(1/2)-year-old boy who developed a generalized flare of diffusely scattered pustules on erythematous skin which rapidly progressed to large exuding areas. The clinical presentation and investigations including histopathological examination of a biopsy and negative bacterial cultures were consistent with the diagnosis of pustular psoriasis von Zumbusch type. Upon initial treatment with methylprednisolone, acitretin and antibiotics the extent of the disease declined. However, several attempts to reduce the dose of the oral corticosteroid were followed by immediate severe flares. Additional treatment with narrowband ultraviolet B (NB-UVB, 311-313 nm UVB) resulted in a rapid arrest of disease activity and allowed the corticosteroid to be tapered off. After 10 irradiations the patient was both off steroid and disease free. NB-UVB therapy was subsequently reduced to twice-weekly exposures and acitretin gradually diminished to a maintenance dose of 0.3 mg kg(-1) daily. We conclude that NB-UVB in conjunction with acitretin is a potent therapeutic regimen for the treatment of severe pustular psoriasis von Zumbusch type in childhood.     

Comparison of clinical effects of psoriasis treatment regimens among calcipotriol alone,narrowband ultraviolet B phototherapy alone,combination of calcipotriol and narrowband ultraviolet B phototherapy once a week,and combination of calcipotriol and narrowband ultraviolet B phototherapy more than twice a week

We compared the clinical efficacy of various psoriasis treatments among: (i) topical application of calcipotriol ointment twice daily (group I); (ii) topical application of calcipotriol ointment twice daily and narrowband ultraviolet B NB‐UVB phototherapy once a week (group II); (iii) topical application of heparinoid ointment twice daily and NB‐UVB phototherapy more than twice a week (group III); and (iv) topical application of calcipotriol ointment twice daily and NB‐UVB phototherapy more than twice a week (group IV). Ten patients were randomly selected for each group and treated by the indicated regimens for 12 weeks. All treatments were effective and significantly improved Psoriasis Area and Severity Index (PASI) scores, self‐administered PASI scores and visual analog scale scores of pruritus. Group IV showed most marked and rapid reduction in PASI and self‐PASI scores among the four regimens. Although the serum levels of interleukin (IL)‐17, IL‐20 and IL‐22 and psoriasis disability index were significantly decreased after the treatments, no significant difference was detected among the four groups. Our study indicates that combination of calcipotriol ointment plus NB‐UVB more than twice a week is superior to other treatment regimens, rapidly improving psoriasis lesions.     

The challenge of follow-up in narrowband ultraviolet B phototherapy

BACKGROUND: The use of narrowband ultraviolet (UV) B phototherapy to treat psoriasis and other disorders has increased markedly since the TL-01 lamps were introduced in the 1980s. While broadband UVB phototherapy has generally been considered to be a relatively safe treatment, some concern has been raised about the potential increased skin cancer risk with narrowband UVB. OBJECTIVES: The likelihood of a patient who is free of nonmelanoma skin cancer (NMSC) at the start of phototherapy developing a malignancy after a certain follow-up period will be dependent not only on the carcinogenic potential of the treatment but also on the age-conditional probability of natural occurrence. We were interested to explore the potential difficulty of designing studies to separate these two events. Methods Mathematical models were developed that combined age-conditional probabilities of developing NMSC due to natural causes with the risk of inducing these cancers from narrowband UVB phototherapy in order to estimate the excess number of cancers resulting from this therapeutic intervention in a cohort of patients. RESULTS: Within-department studies will be most unlikely to demonstrate that the number of NMSCs observed in follow-up studies is significantly different from that expected in an untreated population, even for a follow-up period of 20 years. CONCLUSIONS: Determination of the carcinogenic potential associated with narrowband UVB will require large multicentre studies typically involving several thousand new patients per year and followed up for 10 years or more.     

Disseminated superficial actinic porokeratosis in a patient undergoing treatment with long-term narrowband ultraviolet B for psoriasis

Disseminated superficial actinic porokeratosis (DSAP) is a subtype of porokeratosis, thought to be clonal disorder of keratinization. Chronic exposure to ultraviolet (UV) light might be an etiological cause of DSAP, of which frequent sites are sun-exposed areas. We report a case of DSAP that occurred on the trunk of a 79-year-old man with psoriasis treated with narrowband ultraviolet B (NB-UVB) for clearing and maintenance therapies. DSAP has been reported to associate with psoralen and ultraviolet A therapy and broadband UVB, but not NB-UVB. This may be the first case of DSAP after repeated exposure to NB-UVB.     

Bexarotene and narrowband ultraviolet B phototherapy combination treatment for mycosis fungoides

Combination therapy for mycosis fungoides (MF) has the potential to be synergistic, improve therapeutic efficacy and reduce toxicities. We present a patient with MF who improved on combination therapy with bexarotene and narrowband ultraviolet B (NB-UVB) therapy. The patient is an 81-year-old Caucasian male who initially presented with stage IB MF. After temporary improvement with NB-UVB phototherapy, he progressed to develop plaques and tumors. Psoralen and ultraviolet A therapy was contraindicated because of ophthalmologic disease. Addition of bexarotene 300 mg daily led to rapid clinical improvement in combination with NB-UVB. Interruption of NB-UVB during a prolonged hospitalization led to a clinical flare of lesions, despite continued treatment with bexarotene. Reinitiating NB-UVB was associated with clinical improvement. This report demonstrates that combination treatment with oral bexarotene and NB-UVB therapy may represent a safe alternative for the treatment of plaque-stage MF.     

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 randomized,observer-blinded trial of twice vs. three times weekly narrowband ultraviolet B phototherapy for chronic plaque psoriasis

BACKGROUND: The optimum treatment frequency for narrowband (TL-01) ultraviolet B (NB-UVB) in psoriasis is not yet known. We have previously found three times weekly to be preferable to five times weekly treatment in our population. OBJECTIVES: To compare twice weekly with three times weekly NB-UVB phototherapy in chronic plaque psoriasis. METHODS: In an observer-blinded, randomized comparison, patients with chronic plaque psoriasis referred from dermatology out-patient clinics in Tayside for NB-UVB phototherapy received either twice weekly (Monday and Friday) or three times weekly (Monday, Wednesday and Friday) whole-body NB-UVB phototherapy following our standard departmental treatment protocol. Treatment was continued to clearance or until the fourth treatment after minimal residual activity (MRA) was first documented. Number of days in treatment, number of treatments, total dose and time to relapse were recorded. RESULTS: In total, 113 patients were recruited, skin phototypes I-III: 58 in the twice weekly and 55 in the three times weekly group. Forty patients in the twice weekly group reached clearance/MRA, as did 44 in the three times weekly group. It took 1.5 (95% confidence interval 1.3-1.7) times longer to reach clearance/MRA with twice weekly therapy, a geometric mean of 88 vs. 58 days (P < 0.0001). Small differences in numbers of treatments and total dose to reach clearance tended to favour three times weekly therapy, but these were not significant. CONCLUSIONS: Three times weekly NB-UVB clears psoriasis significantly faster than twice weekly treatment, and therefore is preferable for most patients.     

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.     

Development of cutaneous tolerance to ultraviolet B during ultraviolet B phototherapy for psoriasis

During a schedule of multiple exposures to ultraviolet B radiation (UVB, 280–320 nm), skin develops a reduced sensitivity, variously called tolerance, photoadaptation, accomodation or acclimatization. In this study we have investigated the development of tolerance in the normal skin of a group of psoriatic patients during the course of UVB therapy Tolerance was assessed by phototests carried out on non-lesional skin as frequently as possible throughout the treatment. Maximum tolerance was developed by the group of individuals most sensitive to UVB, which was twice that of the least sensitive group. The minimal perceptible erythema dose (MPE) increased rapidly in the first 2 weeks (220% per week) and reached a plateau by the eighth week of 800% above the baseline MPE dose. For the more sensitive patients there was a further increase in sensitivity (decrease in MPE dose) after the ninth week of continuous treatment. Tolerance to UVB also involves pigmentation in the first few weeks, but in these patients there was no evidence of hyperpigmentation by the end of treatment. While epidermal hyperplasia is most likely to play a leading role in the development of tolerance to UV, there is no reason to expect this protection to decrease under conditions of continuous exposure. Thus, accommodation to ultraviolet radiation (UVR) is not a monotonically increasing process but appears to alter the accepted reactions of human skin to UVR.     

Calcipotriol vs. tazarotene as combination therapy with narrowband ultraviolet B (311 nm): efficacy in patients with severe psoriasis

BACKGROUND: Phototherapy has been shown to be one of the most effective treatment modalities for patients with psoriasis. Nevertheless, photocombination therapies capable both of reducing cumulative ultraviolet (UV) doses and of accelerating clearance of skin lesions are important and of high interest. There have been no published studies comparing the effect of narrowband UVB irradiation in combination with topical application of tazarotene vs. calcipotriol. OBJECTIVES: To determine, in a half-side manner, whether a combination of UVB (311 nm) and tazarotene is superior to UVB (311 nm) plus calcipotriol or vice versa. METHODS: Ten patients suffering from widespread symmetrical psoriasis were treated for at least 4 weeks with topical calcipotriol and tazarotene in a half-side distribution. Additionally, the whole body was irradiated with narrowband UVB (311 nm) four times a week. Before treatment and once weekly during therapy a modified Psoriasis Area and Severity Index was estimated for each body half. The total treatment time, number of treatment sessions and cumulative UVB dose necessary for clearance of skin lesions were determined in an observer-blind fashion for each patient. Furthermore, all patients completed a quality of life questionnaire. RESULTS: Clearance of psoriasis was observed after a median of 19 treatment sessions (range 14-28) and a median cumulative UVB dose of 22.98 J cm-2 (range 9.24-58.22) simultaneously for both body halves. On the side treated with topical tazarotene gel, four patients complained of itching and dryness of the skin, and skin irritation was observed in three of them. Six patients preferred the application of tazarotene gel, while four preferred calcipotriol. CONCLUSIONS: Our clinical comparison of narrowband UVB with either topical calcipotriol or topical tazarotene revealed no significant therapeutic difference between both regimens. Although these results need to be confirmed in larger patient groups, we feel that both photocombination therapies can broaden the therapeutic options for moderate to severe psoriasis vulgaris and may reduce the cumulative UVB dose during therapy.