The role of phototherapy in the surgical treatment of vitiligo: a systematic review.

Vitiligo is frequently treated with the combination of phototherapy and melanocyte transplantation. However, the additional benefit of phototherapy is unclear. Moreover, the optimal type and regimen of phototherapy are unknown. The objective of this systematic review was to identify whether phototherapy improves the outcome of melanocyte transplantation in vitiligo. We searched and screened for eligible studies in the databases of MEDLINE, EMBASE and CENTRAL. We included all clinical studies investigating melanocyte transplantation combined with phototherapy. After screening and selection of abstracts and full-texts, we found 39 eligible clinical studies with 1624 patients. The eligible studies investigated several phototherapy modalities, such as NBUVB (n = 9), PUVA (n = 19), UVA (n = 1), MEL (n = 4) and active sunlight exposure (n = 9). Four studies directly compared phototherapy versus no phototherapy and two studies confirmed the benefit of phototherapy for melanocyte transplantation. We found no significant differences in repigmentation in studies directly comparing phototherapy modalities. The overall quality of the studies was moderate to poor and high heterogeneity between studies was found. We found limited evidence that phototherapy improves the outcome of melanocyte transplantation in vitiligo. There is insufficient evidence to recommend a specific type or regimen of phototherapy. More studies should be performed investigating the additional benefit of different phototherapies and the preferred moment of phototherapy.

Vitiligo Area Scoring Index and Vitiligo European Task Force assessment: reliable and responsive instruments to measure the degree of depigmentation in vitiligo.

BACKGROUND: Vitiligo is a common skin disorder causing depigmented macules that can impair a patient's quality of life. Currently, there are no standardized outcome measures to assess the degree of depigmentation. Moreover, there is limited knowledge on the measurement properties of outcome measures in vitiligo. OBJECTIVES: To assess the reliability and responsiveness of the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force assessment (VETFa), two well-described clinician-reported outcomes. METHODS: We included three vitiligo patient groups. In one group of 31 patients, the interobserver reliability was assessed by three observers. In 27 patients the intraobserver reliability was assessed by two repeated measures by one of the observers. To assess the responsiveness the repigmentation was calculated after 6 months of phototherapy in 33 patients and tested against hypotheses. RESULTS: The interobserver reliability was high for VASI [intraclass correlation coefficient (ICC) 0·93] and VETFa depigmentation (ICC 0·88). The intraobserver reliability was high for VASI (ICC 0·93) and VETFa depigmentation (ICC 0·97). The smallest detectable changes (SDCs) were 7·1% and 10·4% for interobserver reliability and 4·7% and 2·9% for intraobserver reliability in VASI and VETFa depigmentation, respectively. All four responsiveness hypotheses formulated a priori were confirmed. CONCLUSIONS: VASI and VETFa are reliable and responsive instruments to assess the degree of depigmentation in vitiligo. VASI and VETFa for depigmentation are potential instruments for vitiligo research in the future. However, for use in individual patient care, caution is needed when interpreting score changes in individual patients because of the relatively large SDC.

Satisfaction with treatment among patients with psoriasis: a web-based survey study.

BACKGROUND: Various psoriasis treatments are currently available: topical therapy, photo(chemo)therapy, oral agents and biologics. Little is known about patients' satisfaction with these treatment options. Moreover, the few available studies show methodological shortcomings. OBJECTIVES: To answer the following questions: firstly, how satisfied are patients with psoriasis with their current treatment and does patients' satisfaction significantly differ between treatment types when controlling for demographic and clinical factors? Secondly, how important are specific domains of satisfaction to patients, and when taking perceived importance into account, which domains merit the most attention in improving quality of care? METHODS: Members of the two existing Dutch associations for patients with psoriasis were invited to complete a web-based survey, which included a study-specific satisfaction questionnaire. RESULTS: A total of 1293 patients completed the survey (response rate 32%). Overall, patients were moderately satisfied with their current treatment. Patients receiving topical treatment were significantly least satisfied; patients receiving biologic treatment were significantly most satisfied. Overall, patients rated 'treatment effectiveness' as most important, followed by 'treatment safety' and 'doctor-patient communication'. Domains with the highest 'room for improvement' scores were effectiveness of topical therapy, phototherapy and oral agents (but not biologic treatment), convenience of topical treatment and safety of systemic treatments (both oral agents and biologics). CONCLUSIONS: From the perspective of patients, biologic treatment is promising. To improve further the quality of psoriasis care, the effectiveness and convenience of topical therapies, the safety of systemic therapies, and doctors' communication skills need to be addressed.

A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: quality-of-life outcomes of a randomized controlled trial of supervised treatment of psoriasis in a day-care setting.

BACKGROUND: Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease. OBJECTIVES: To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). RESULTS: At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36. CONCLUSIONS: The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.

Patients with moderate-to-severe plaque psoriasis preferred oral therapies to phototherapies: a preference assessment based on clinical scenarios with trade-off questions.

OBJECTIVE: The importance of validly identifying and incorporating patients' views for improving health care is generally acknowledged. Common approaches to assess patients' preferences are based on the quality adjusted life year (QALY) framework, but this ignores a number of aspects that may be relevant. As an alternative, we assessed patients' treatment preferences and trade-offs for five common systemic therapies for psoriasis. STUDY DESIGN AND SETTING: Twenty-nine patients with moderate-to-severe psoriasis expressed treatment preferences for five oral and phototherapies and indicated the relative importance of various treatment attributes, such as adverse effects, discomforts, and safety measures. In a structured interview, they were presented with clinical scenarios that contained descriptions of process and outcome characteristics and illustrations of the anticipated treatment benefit. RESULTS: Over all paired comparisons, methotrexate (33%), cyclosporin (30%), acitretin (15%), UV-B (14%), and PUVA (8%) were preferred to the other treatment. Patients were willing to trade-off their initial preference for more improvement of psoriasis. CONCLUSIONS: Psoriasis patients generally prefer oral to phototherapies and consider most adverse effects and several discomforts important for selecting treatment. Our scenario-based structured interview approach to treatment preferences allowed us to incorporate a broad spectrum of potentially relevant decision components in a clinically meaningful way.

Treatment of poikiloderma of Civatte with the pulsed dye laser: a series of patients with severe depigmentation.

BACKGROUND: Pulsed dye laser (PDL) treatment is widely used for poikiloderma of Civatte. Some adverse events in small numbers of patients have been reported. Guidelines for treatment of poikiloderma of Civatte do not exist. OBJECTIVE: To report the occurrence of persistent depigmentation as a late adverse event in a series of patients with poikiloderma of Civatte after treatment with PDL. METHODS: Eight patients (seven women and one man, mean age 48 years) with poikiloderma of Civatte were treated with PDL using a 585-nm wavelength and a fixed pulse duration of 450 micros. In all patients one or two test PDL patches were performed and reviewed after 3 months. All of the patients tolerated the testing without complications. Subsequent treatments were undertaken at intervals of 3 months. RESULTS: All patients were treated with fluences between 3.5 and 7 J/cm2, using a 7- or 10-mm spot size. All patients had a good result with respect to clearing of the vascular component. Nevertheless, six of them, treated with 5-7 J/cm2, reported severe depigmentation 4-11 months after treatment. Two patients treated with lower fluences (3.5-5.5 J/cm2) did not report this depigmentation. CONCLUSIONS: Great care is needed when PDL treatment is used for poikiloderma of Civatte. Pigment changes have been incidentally mentioned as late complications but have not been well documented as the late depigmentation has been in this series. It is advisable to use fluences as low as possible, and not exceeding an upper limit of 5 J/cm2, on a 10-mm spot size. More research is needed to define an optimal pulse duration.

[The practice guideline 'Photo(chemo)therapy and systemic therapy in severe chronic plaque-psoriasis']. / Richtlijn 'Foto(chemo)therapie en systemische therapie bij ernstige chronische plaque-psoriasis'.

The guideline for the treatment of adults with moderate to severe chronic plaque-type psoriasis vulgaris is based on published scientific evidence. The efficacy of the treatment, its safety, the side effects, the patients' discomfort, the patients' preference and the costs of treatment and follow-up are listed as criteria that play a role in the choice of treatment. Photo(chemo)therapy is the treatment of choice for severe forms of psoriasis. Phototherapy with ultraviolet-B light (UVB), especially narrow-band UVB, is preferred above photochemotherapy with ultraviolet-A light and psoralenes (PUVA). Of the oral treatments, methotrexate and ciclosporin are preferred above retinoids and fumarates because they yield a higher percentage of patients with partial or nearly complete remission. Fumarates are not officially registered in The Netherlands and Belgium.

Evaluation of medium-dose UVA1 phototherapy in localized scleroderma with the cutometer and fast Fourier transform method.

PURPOSE: To evaluate the efficacy of medium-dose UVA1 phototherapy in patients with localized scleroderma. METHOD: A controlled pilot study with medium-dose UVA1 (48 J/cm2) was performed. The results were evaluated by means of a skin score and two objective methods for quantifying sclerosis (cutometer and fast Fourier transform method). Patients were treated 4 times a week for 5 weeks. The follow-up period was 12 weeks. RESULTS: All patients responded to therapy. Skin score and cutometer results showed improvement of skin elasticity of treated skin compared to control skin. Fast Fourier transform measurements showed no change in bundle orientation ratio and spacing. CONCLUSION: We concluded that treatment for 12 weeks 4 times a week with medium-dose UVA1 may be a beneficial therapy and a well-tolerated treatment modality for localized scleroderma (morphea). After 12 weeks, improvement of skin sclerosis can be detected by skin score and cutometer measurements but not by the fast Fourier transform method.

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.

[Photo dermatology]. / Fotodermatologie.

Photodermatology has become an important part of the dermatologist's area of focus. This subspeciality is not only involved with studying basic biological processes such as the effects of ultraviolet (UV) irradiation on the skin's immune system (photo-immunology), melanocytes or DNA (carcinogenesis), but also with clinical issues such as photoprotection, photosensitive skin diseases (photodermatoses) and phototherapy. Increasing knowledge about the effects of UV irradiation on the skin, with or without photosensitising agents, has led to the development of new forms of photo(chemo)therapy. These allow good therapeutic results to be achieved in the treatment of not only psoriasis, but also other chronic inflammatory skin diseases, with minimal side effects. DNA can absorb UV irradiation. This can lead to irreversible DNA damage and mutations in genes responsible for cell cycle control. These events can lead to skin cancer. The presence of pheomelanin, which is an inferior type of UV light-absorbing melanin, can add to this process of DNA damage. The three most important types of skin cancer are basal cell carcinoma (more than 30,000 new patients per year in the Netherlands), squamous cell carcinoma and melanoma.

Pharmacoeconomic evaluation of calcipotriol (Daivonex/Dovonex) and UVB phototherapy in the treatment of psoriasis: a Markov model for The Netherlands.

BACKGROUND: The high prevalence and chronic nature of psoriasis leads to high costs in relation to the treatment and control of the disease. A number of clinical trials have shown that a combination therapy of calcipotriol cream (Daivonex/Dovonex), Leo Pharmaceutical Products) and ultraviolet B phototherapy (UVB) decreases the total number of UVB exposures required compared to UVB treatment alone. From a societal point of view, the addition of calcipotriol to UVB therapy could achieve cost savings due to the fewer UVB treatments needed and the reduced travelling and time off work for patients. Fewer UVB exposures may also have other beneficial effects, i.e., shortened waiting lists and less risk to patients of developing cancer or photoaging of the skin. OBJECTIVE: To compare the cost-effectiveness of treating psoriatic patients in the Netherlands with calcipotriol cream used daily combined with twice weekly UVB treatments to emollient used daily combined with UVB given 3 times weekly. METHODS: Based on the clinical results from a Canadian trial, a decision-analytical model was constructed to simulate treatment outcomes and estimate the costs of managing psoriatic patients in the Netherlands over a period of 20 weeks from initiation of therapy. Unit costs and details of standard treatment protocols were collected from Dutch dermatology centres in hospitals and the community for use in the model. Other therapies, such as topical corticosteroids, tar or dithranol were not investigated in this analysis. RESULTS: The total cost of managing psoriatic patients in the Netherlands over a 20-week period is estimated as EUR 1,175.90 for those treated with calcipotriol and UVB and EUR 1,212.14 for patients treated with emollient and UVB. Thus, the former treatment, adding calcipotriol to UVB phototherapy, provides a minor cost saving of EUR 36.24 (3%) compared to the cost of UVB treatment alone. Sensitivity analyses demonstrated that these results are sensitive to changes in the cost of UVB treatment. CONCLUSION: Calcipotriol treatment combined with UVB phototherapy is a cost-neutral alternative to UVB phototherapy used with an emollient. The patients achieve treatment success in the same time on both treatments but the former, with calcipotriol, requires less exposure to UVB radiation. The additional drug costs from using calcipotriol are offset by savings from the fewer UVB sessions required. Essential beneficial effects for patients are less inconvenience, less risk of developing photoaging of the skin and less exposure to potentially carcinogenic radiations.

Calcipotriol ointment and cream or their vehicles applied immediately before irradiation inhibit ultraviolet B-induced erythema.

Results of ultraviolet (UV) B phototherapy can be improved by the application of calcipotriol, but studies are needed to decide how the two treatments should be combined. We studied the effect of UVB after application of calcipotriol ointment (50 microg g-1) and calcipotriol cream (50 microg g-1) and determined the optimal time of application of calcipotriol when combined with UVB phototherapy (280-350 nm), in a single-blinded randomized vehicle-controlled study of 37 healthy adult volunteers. Calcipotriol ointment or cream was applied randomly on five areas on the back at different time intervals from UVB irradiation. One area was left untreated as the control. Application times were the evening before, the morning before, 2 h before, immediately before, and immediately after irradiation. UVB irradiation was administered by TL20W/12 fluorescent tube lamps at increasing doses (20, 25, 32, 40, 50 and 64 mJ cm-2) to six subunits of each test area. Clinical assessment was performed 24 h after UVB irradiation by a blinded investigator. Calcipotriol ointment and cream were applied in 19 and 18 subjects, respectively, and erythema was measured for each application time quantified. We found that erythemal reactions were significantly smaller when calcipotriol ointment or cream was applied immediately before irradiation compared with all other application times. To explain these findings, a vehicle control study was performed. No difference in erythema was seen between calcipotriol medication and the vehicle controls. Spectrophotometric analysis of the calcipotriol cream and ointment showed no UV absorbance in the UVB range. No signs of photosensitization were noted. In conclusion, the vehicles of the calcipotriol ointment and cream inhibit the induction of erythema by UVB irradiation if applied immediately before phototherapy. Consequently, calcipotriol ointment and cream should not be applied directly before UVB irradiation; however, they may be applied at any time up to 2 h prior to or immediately after UVB irradiation. Possible explanations for this sunscreen activity are discussed.

No additional effect of calcipotriol ointment on low-dose narrow-band UVB phototherapy in psoriasis.

BACKGROUND: Broad-band UVB phototherapy has appeared to be effective in clearing psoriatic lesions. After the advent of calcipotriol ointment, promising results have been obtained by combining these two therapeutic modalities. Also, an additional effect of narrow-band UVB phototherapy on treatment with calcipotriol ointment has been demonstrated. OBJECTIVE: Our purpose was to compare treatment with low-dose narrow-band UVB phototherapy both with and without calcipotriol ointment. METHODS: We included 53 patients suffering from plaque-type psoriasis. All patients underwent low-dose narrow-band UVB phototherapy. Nearly half of the patients were randomized to apply calcipotriol ointment (50 microg/g) twice daily on the affected skin. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic lesions. RESULTS: In this study we showed that low-dose narrow-band UVB phototherapy is effective in the treatment of psoriasis and that calcipotriol ointment does not improve treatment outcome. CONCLUSION: Calcipotriol ointment does not improve treatment with low-dose narrow-band UVB phototherapy.

Low-dose narrow-band UVB phototherapy combined with topical therapy is effective in psoriasis and does not inhibit systemic T-cell activation.

BACKGROUND: Psoriasis is a chronic T-cell-mediated inflammatory skin disease which can be treated with topical medication, phototherapy or systemic medication. A subgroup of psoriatic patients does not respond to monotherapy and needs combination therapy. We used low-dose narrow-band UVB phototherapy, combined with balneotherapy, short-contact anthralin, liquor carbonis detergens and calcipotriol for treatment of psoriatic patients in our day care centre. OBJECTIVE: Our purpose was to study the efficacy, induction of erythema and effect on systemic T-cell activation of this combination therapy. METHODS: Skin reflectance spectrophotometry was used to measure skin erythema. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic patients. Serum soluble IL-2 receptor (sIL2-R) levels were measured by an ELISA. RESULTS: The possible erythematogenic effect of low-dose narrow-band UVB irradiation was studied (skin reflectance spectrophotometer) in a control group of psoriatic patients (n = 11). No induction of skin erythema was seen. Subsequently, this low-dose irradiation regimen was used in combination with topical medication in 26 psoriatic patients. A 90% decrease in the PASI was seen after a mean number of 35 treatment sessions. Seventeen patients (65%) remained in remission during the following 6 months. Serum sIL-2R levels were elevated in all patients (mean 913 U/ml) and did not change during treatment. CONCLUSION: Our data indicate that low-dose narrow-band UVB can be used successfully, in combination with topical treatment, in a day care setting to treat psoriatic patients. Since sIL-2R serum levels were not decreased, it can be speculated that this treatment does not induce systemic immunosuppression.

Photoisomerization spectrum of urocanic acid in human skin and in vitro: effects of simulated solar and artificial ultraviolet radiation.

Ultraviolet (UV) irradiation of trans-urocanic acid (UCA), a major UV absorbing component of the epidermis, leads to the formation of cis-UCA, which mediates immunosuppressive effects. In this study, the net yield of cis-UCA was measured after the photoisomerization of urocanic acid by narrow UV wavebands (spectral range 295-405 nm), with the irradiation doses related to solar irradiance at sea level. The formation of cis-UCA in Caucasian skin (in vivo), as well as in aqueous solution (in vitro), was determined by HPLC analysis. The same irradiation conditions were met in both components of the study. The in vivo experiments showed high efficiency of cis-UCA formation in the spectral region of 305-341 nm, whereas high efficiency in vitro was found at 305 and 326 nm. At 350 and 363 nm, cis-UCA was formed in vivo, but not in vitro. At longer test wavelengths up to 405 nm, no significant formation of cis-UCA was detectable. The established partition between UVB and UVA at 320 nm is not relevant for the isomerization pattern of UCA. Additional studies revealed substantial cis-UCA formation in human skin by UVA phototherapy lamps. Furthermore, raised levels of 295 nm irradiation doses, a possible effect of stratospheric ozone depletion, were found to increase the cis-UCA yield. Our results demonstrate that the formation of cis-UCA in the skin with common exposures takes place over a broad spectrum range of UVB and UVA, up to at least 363 nm. These findings emphasize the potency of UVA to isomerize UCA, and they may contribute to further elucidation of the effects of phototherapy and sunbathing.

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

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.