[show abstract][hide abstract] ABSTRACT: Objective To determine whether ultraviolet B phototherapy at home is equally safe and equally effective as ultraviolet B phototherapy in an outpatient setting for patients with psoriasis.Design Pragmatic multicentre single blind randomised clinical trial (PLUTO study).Setting Dermatology departments of 14 hospitals in the Netherlands.Participants 196 patients with psoriasis who were clinically eligible for narrowband (TL-01) ultraviolet B phototherapy. The first 105 consecutive patients were also followed for one year after therapy.Intervention Ultraviolet B phototherapy at home using a TL-01 home phototherapy unit compared with standard narrowband ultraviolet B phototherapy in an outpatient setting. Both therapies were done in a setting reflecting routine daily practice in the Netherlands.Main outcome measures The main outcome measure was effectiveness as measured by the proportion of patients with a 50% or more reduction of the baseline psoriasis area and severity index (PASI) or self administered psoriasis area and severity index (SAPASI), called the PASI 50 and SAPASI 50 (relevant treatment effect). Another outcome of effectiveness was the percentage reduction in median scores on the PASI as well as SAPASI. Also the proportions of patients reaching the PASI 75 and SAPASI 75 (successful treatment effect), and the PASI 90 and SAPASI 90 (almost complete clearance) were calculated. Other secondary outcomes were quality of life (SF-36, psoriasis disability index), burden of treatment (questionnaire), patients’ preferences and satisfaction (questionnaire), and dosimetry and short term side effects (diary).Results 82% of the patients treated at home compared with 79% of the patients treated in an outpatient setting reached the SAPASI 50 (difference 2.8%, 95% confidence interval −8.6% to 14.2%), and 70% compared with 73% reached the PASI 50 (−2.3%, −15.7% to 11.1%). For patients treated at home the median SAPASI score decreased 82% (from 6.7 to 1.2) and the median PASI score decreased 74% (from 8.4 to 2.2), compared with 79% (from 7.0 to 1.4) and 70% (from 7.0 to 2.1) for patients treated in an outpatient setting. Treatment effect as defined by the mean decline in PASI and SAPASI scores was significant (P0.3). Total cumulative doses of ultraviolet B light were similar (51.5 v 46.1 J/cm2, difference 5.4, 95% confidence interval −5.2 to 16.0), and the occurrence of short term side effects did not differ. The burden of undergoing ultraviolet B phototherapy was significantly lower for patients treated at home (differences 1.23 to 3.01, all P≤0.001). Quality of life increased equally regardless of treatment, but patients treated at home more often rated their experience with the therapy as “excellent” (42%, 38/90) compared with patients treated in the outpatient department (23%, 20/88; P=0.001).Conclusion Ultraviolet B phototherapy administered at home is equally safe and equally effective, both clinically and for quality of life, as ultraviolet B phototherapy administered in an outpatient setting. Furthermore, ultraviolet B phototherapy at home resulted in a lower burden of treatment and led to greater patients’ satisfaction.Trial registration Current Controlled Trials ISRCTN83025173 and Clinicaltrials.gov NCT00150930.
[show abstract][hide abstract] ABSTRACT: Polymorphous light eruption (PLE) is a very common photodermatosis in which patient history is highly specific. Phototesting is used to confirm the diagnosis and to determine the action spectrum and the severity of this disease. In daily practice and in research studies, it would be convenient to assess disease severity by patient history only.
This study aims to assess PLE disease severity via patient history and compares this with severity assessment via phototesting.
Sixty-one patients with PLE were asked 10 standard questions and all were phototested. The answers to the standard questions were coded with linear scores ranging from 0 to 10. The score of each question was plotted as independent variable in a multiple linear regression model against the score of the phototest (minimal number of irradiations necessary to elicit a positive skin lesion, with a maximum of 6 irradiations) as dependent variable using an enter approach. Furthermore, the scores of the separate questions were added to form a total score, the PLE-severity assessment score (PLE-SAS). The medians of these PLE-SASs were compared with the result scores obtained by phototesting. Phototesting was done with ultraviolet A and ultraviolet B irradiation.
Fifty-seven of the 61 patients had a positive test result (93%). Using the multiple linear regression model, the severity assessment by patient history (PLE-SAS) compared with the result of phototesting showed two significant contributing questions (adjusted PLE-SAS) (P < 0.05) but with a regression coefficient of 0.2. A significant difference in median scores with the severity assessment (PLE-SAS and adjusted PLE-SAS) between patients testing positive after 1-3 irradiations compared with those testing positive after 4-6 irradiations was present (P < 0.05). However, the overlap quartile range between both groups was such that the PLE-SAS and the adjusted PLE-SAS have little predictive value in individual patients.
We showed that in PLE, disease severity as determined using the PLE-SAS or adjusted PLE-SAS did not reliably predict severity as assessed by phototesting. Two significant contributing questions were not discriminating enough to be used as predicting questions to assess severity. Accurate patient history proved to be a reliable method to diagnose PLE. Phototesting is useful to determine the responsible ultraviolet action spectrum and to exclude differential diagnoses like photosensitive eczema, lupus erythematosus or chronic actinic dermatitis. PLE-SAS cannot replace phototesting for determining the severity of PLE.
Journal of the European Academy of Dermatology and Venereology 06/2008; 22(6):675-80. · 2.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects.
However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research
has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage
the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch
acronym for "national trial on home UVB phototherapy for psoriasis").
Methods We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home
UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness.
In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the
patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be
possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the
Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using
several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side
effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and
for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006.
Discussion In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses
the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the
target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also
taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB
Trial registration Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT00150930
[show abstract][hide abstract] ABSTRACT: There is a clear relationship between ultraviolet (UV) radiation (UVR) and the clinical manifestations of patients with lupus erythematosus (LE). Cutaneous lesions are induced or exacerbated by exposure to UVR. Of patients with LE, 24-83% are reported to be photosensitive to UVR. LE tumidus appears to be the most photosensitive subtype of LE, followed by subacute cutaneous LE (SCLE). In general, the history of patients with LE correlates poorly with the presence or absence of photosensitivity, due to a delayed time interval between UV exposure and exacerbation of skin lesions. Phototesting using artificial UVR and visible light is a reliable way of diagnosing photosensitivity.
To investigate the photoreactivity of patients with various subtypes of LE using an individualized phototest protocol. The results of phototests were correlated with the history of photosensitivity, the subtype of LE, the presence of autoantibodies and the use of anti-inflammatory medication by these patients.
Phototesting with UVA, UVB and visible light was performed in 100 patients with LE. The diagnosis of LE was established both on clinical examination and skin histology. Serological studies were also performed in all patients. The phototests were performed on large skin areas of the forearm or trunk; the first dose was twice the minimal erythema dose and the dosage was increased according to the individual reactions of the patients at the test sites. Follow-up of skin reactions at the test sites was performed for up to 2 months. Histological examination of the photoprovoked skin lesions was carried out in 57 patients.
Of the 100 patients included (81 women and 19 men; mean age 41 years, range 17-79), 46 had chronic discoid LE, 30 SCLE and 24 systemic LE. An abnormal reaction to UVR and visible light was found in 93% of our patients with LE. No clinical or histological evidence at the phototest sites of polymorphic light eruption was found. There was no correlation between photosensitivity and LE subtype, presence of autoantibodies or medical history. Concomitant use of anti-inflammatory medication seemed to exert only minimal influence on the results of phototesting.
When using an extended phototesting protocol, almost all patients with LE in this study showed clinical and histological evidence of aberrant photosensitivity. Therefore, patients with LE should receive thorough advice and instruction on photoprotective measures, regardless of their history, LE subtype or presence of autoantibodies.
British Journal of Dermatology 08/2003; 149(1):131-7. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background There is a clear relationship between ultraviolet (UV) radiation (UVR) and the clinical manifestations of patients with lupus erythematosus (LE). Cutaneous lesions are induced or exacerbated by exposure to UVR. Of patients with LE, 24–83% are reported to be photosensitive to UVR. LE tumidus appears to be the most photosensitive subtype of LE, followed by subacute cutaneous LE (SCLE). In general, the history of patients with LE correlates poorly with the presence or absence of photosensitivity, due to a delayed time interval between UV exposure and exacerbation of skin lesions. Phototesting using artificial UVR and visible light is a reliable way of diagnosing photosensitivity.Objectives To investigate the photoreactivity of patients with various subtypes of LE using an individualized phototest protocol. The results of phototests were correlated with the history of photosensitivity, the subtype of LE, the presence of autoantibodies and the use of anti-inflammatory medication by these patients.Methods Phototesting with UVA, UVB and visible light was performed in 100 patients with LE. The diagnosis of LE was established both on clinical examination and skin histology. Serological studies were also performed in all patients. The phototests were performed on large skin areas of the forearm or trunk; the first dose was twice the minimal erythema dose and the dosage was increased according to the individual reactions of the patients at the test sites. Follow-up of skin reactions at the test sites was performed for up to 2 months. Histological examination of the photoprovoked skin lesions was carried out in 57 patients.Results Of the 100 patients included (81 women and 19 men; mean age 41 years, range 17–79), 46 had chronic discoid LE, 30 SCLE and 24 systemic LE. An abnormal reaction to UVR and visible light was found in 93% of our patients with LE. No clinical or histological evidence at the phototest sites of polymorphic light eruption was found. There was no correlation between photosensitivity and LE subtype, presence of autoantibodies or medical history. Concomitant use of anti-inflammatory medication seemed to exert only minimal influence on the results of phototesting.Conclusions When using an extended phototesting protocol, almost all patients with LE in this study showed clinical and histological evidence of aberrant photosensitivity. Therefore, patients with LE should receive thorough advice and instruction on photoprotective measures, regardless of their history, LE subtype or presence of autoantibodies.
British Journal of Dermatology 06/2003; 149(1):131 - 137. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Most clinical studies using photodynamic therapy (PDT) with topical application of delta-aminolaevulinic acid (delta-ALA) use red light because it allows greater depth of penetration. However, given the porphyrin-like spectrum of delta-ALA-induced photosensitivity, violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet light uses less light energy to induce the phototoxic reaction.
To study the efficacy of violet light in combination with topical delta-ALA PDT in the treatment of pre-malignant and malignant skin lesions.
Eight hours after 20% delta-ALA was applied topically, photoirradiation was performed with an incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet light (400-450 nm). Lesions received 10-20 J/cm2 during an exposure time of 30 min. The 38 subjects treated included three with basal cell naevus syndrome with multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject had multiple lesions of Bowen's disease, involving 50% of the scalp, and the remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs, four large solar keratoses and five solitary lesions of Bowen's disease.
Complete remission both clinically and histologically was seen after a single treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of the nodular BCCs, one of the four solar keratosis lesions (partial remission in the other three) and 90-100% of the solitary lesions of Bowen's disease.
delta-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions, especially when there are multiple lesions or large patches comprising a large area of skin.
Journal of the European Academy of Dermatology and Venereology 12/2001; 15(6):550-4. · 2.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the retinal phototoxicity hazards of and to provide safety margins for endoillumination during vitrectomy.
The absolute power and spectral distribution from various light sources and filter combinations that are commercially available for vitreous surgery were measured. The maximal exposure times based on the ICNIRP safety guidelines for photochemical and thermal injury of the aphakic eye were calculated. Additionally, the effect of various measures that reduce the risk of phototoxicity was evaluated.
Measurements of the spectrum and energy indicated that the ICNIRP safety guidelines for photochemical retinal damage are exceeded within 1 minute for nine out of 10 combinations tested. With an additional 475 nm long pass filter, light levels below 10 mW, and a distance from light probe to retina of at least 10 mm, the allowable exposure time can be increased up to 13 minutes. Thermal damage can be anticipated when the light probe touches the retina.
Commercially available light sources for endoillumination during vitrectomy are not safe with respect to photochemical retinal damage. Even with maximal precautions macular phototoxic damage remains a factual danger during vitrectomy.
British Journal of Ophthalmology 01/2001; 84(12):1372-5. · 2.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Polymorphous light eruption is a common chronic idiopathic photodermatosis. The action spectrum and therapy are under debate.
The aim of the study was to analyze the clinical aspects of this dermatosis, the photodiagnostic tests, and the results of therapy in an academic center.
To obtain a reasonable follow-up period, we examined all available data of the patients who underwent diagnostic phototests in the period 1985 through 1991. Our procedure of phototesting included determination of minimal erythema doses, photoprovocation tests, and photopatch tests. The evaluation of the effect of the therapy was based on the patients' experiences, time spent outdoors, and amount of sun exposure.
Our collection included data on 35 men and 75 women. The age at onset differed significantly between men and women (averages 46 and 28 years, respectively; P <.01). The minimal erythema doses for UVB were lowered in 43% of the men and in 4% of the women (P <.01); the minimal erythema doses for UVA were lowered in 37% of the men and in 11% of the women (P <.01). The photoprovocation tests showed a pathologic reaction to both UVB and UVA in 88% of the men and in 52% of the women (P <.01). In the remaining patients we found pathologic reactions to UVB alone (for men 9%, for women 24%; P >.05) or UVA alone (for men 3%, for women 24%; P <.01). The abnormal reactions to visible light were almost exclusively observed in those patients who reacted pathologically to both UVB and UVA (43% of the male patients, 11% of the female patients; P <.01). The photopatch tests showed a large number of positive test results, mainly to skin care products or sunscreens (75% of all patients). The 70 most sensitive patients (64%) were treated with prophylactic UVB therapy 2 or 3 times a week at home or initially in the outpatient department. This treatment was normally done from February to June, but in severe cases throughout the whole year.
Phototests revealed abnormal reactions to UVB as well as UVA and to some extent also to visible light. Prophylactic UVB therapy is a successful treatment for polymorphous light eruption.
Journal of the American Academy of Dermatology 03/2000; 42(2 Pt 1):199-207. · 4.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: After ultraviolet exposure Langerhans cells (epidermal CD1a+ cells) disappear from the healthy skin, and CD11b+ macrophage-like cells, which are reported to produce interleukin-10, appear in a matter of days. These phenomena are related to the ultraviolet-induced local suppression of contact hypersensitivity reactions. A defect in this suppression might allow inadvertent immune reactions to develop after ultraviolet (over)exposure; i.e., it could cause ultraviolet-B-induced polymorphous light eruption. In order to test this we first exposed buttock skin of eight healthy volunteers to six minimal erythema doses from Philips TL12 lamps, and indeed observed a dramatic disappearance of CD1a+ cells 48 and 72 h later, at which time the number of CD11b+ cells increased in the dermis, and some occurred in the epidermis. The epidermis thickened and showed large defects, filled by CD11b+ cells, just below the stratum corneum. In 10 patients with polymorphous light eruption (five with a normal minimal erythema dose and five with a low minimal erythema dose) CD1a+ cells were present in the epidermis as well as in the dermis before exposure. Strikingly, these cells were still present in considerable number at 48 and 72 h after exposure to six minimal erythema doses. CD11b+ cells already present in the dermis before ultraviolet exposure, increased after ultraviolet exposure, and subsequently also invaded the epidermis. Despite the six minimal erythema doses, there were no apparent defects in the epidermis of the polymorphous light eruption patients. This deviant early response to ultraviolet radiation is likely to be of direct relevance to the polymorphous light eruption and is perhaps useful as a diagnostic criterion.
Journal of Investigative Dermatology 08/1999; 113(1):4-10. · 6.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sun exposure has a beneficial effect on acne vulgaris, but it is not clear which wavelengths contribute to the favourable effect.
The aim of the study was to investigate the effect of visible light on acne vulgaris and define the most effective wavelengths.
Thirty patients (15 men and 15 women) with mild to moderate acne vulgaris, involving the face and/or the back and/or the chest, were treated with three different light sources. They were treated 3 times a week, for a total of 7 weeks, each field for 20 min per session.
All the light sources using 'full spectrum', green and violet improved the acne, leading to 14% (p > 0.10), 22% (p < 0.05) and 30% (p < 0.02) improvement, respectively. No statistically significant differences between the three different light sources were found, although there was a tendency that violet light was better than the other light qualities. No side-effects were observed.
Visible light is a moderately effective alternative for treatment of acne vulgaris.
[show abstract][hide abstract] ABSTRACT: UV-induced DNA damage in mononuclear leucocytes can be quantified by flow cytometry of fluorescence from a labelled monoclonal antibody that specifically binds to thymine dimers (T<-->T): specific fluorescence is already detectable after exposures of 1-2 J m-2 of 254 nm radiation and shows a linear relationship with dose. The distribution of UV fluences over an irradiated volume can thus be ascertained by measuring the UV-induced T<-->T loads of the individual cells from that volume. After irradiation of mononuclear cells in a phosphate buffer solution in a Petri dish, most cells showed a similar intensity of specific T<-->T fluorescence, forming a single sharp peak in the fluorescence histogram. This signifies an even distribution of fluences over the cells. It was noticed, however, that a variable minor fraction of mononuclear cells (usually less than 10%) could be resistant to immunostaining; this fraction was rejected from the calculation of the specific fluorescence. The flow cytometric technique was also applied to blood cells exposed in an ISOLDA device, which is in use in Russian clinics for UV irradiation of whole blood for therapeutical purposes. Only a small fraction of mononuclear cells in a sample of whole blood treated in ISOLDA acquired a detectable T<-->T load after exposure to lamps which emit predominantly either UVC or UVB light ((3.6 +/- 1.0)% and (1.8 +/- 0.4)% of all analysed cells respectively). This small fraction had received a large variation in fluences, resulting in differences in nuclear T<-->T loads by a factor of 200.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Photochemistry and Photobiology B Biology 05/1995; 28(1):33-7. · 3.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Exposure of platelet concentrates (PCs) to ultraviolet B radiation (UVB) has been advocated as an alternative method for prevention of the onset of HLA sensitization in recipients. In this study, pooled PCs were irradiated in a Haemonetics UV irradiator (Haemonetics Corp, Braintree, MA) at a dose that did not induce platelet activation. The effect of UVB irradiation on prevention of primary HLA sensitization was evaluated in a prospective controlled clinical study performed in cardiac patients undergoing cardiopulmonary bypass. Patients were treated with filtered red blood cells and a single transfusion of either standard (control group) or UVB-irradiated (UVB group) pooled platelets prepared from 12 donors. Five of 39 patients in the control group and 6 of 62 patients in the UVB group developed allo-antibodies against HLA antigens, which is not significantly different (P = .62). This unexpected finding prompted us to check the efficacy of UVB irradiation. We determined UVB-specific DNA damage in cells by measuring the fluorescence from a labeled specific monoclonal antibody against thymine dimers. With this novel flow cytometer technique, we estimated in UVB-irradiated leukocytes in saline that a mean fluorescence intensity (MFI) of 47 +/- 2 arbitrary units (n = 6) correlated with abolition of alloreactivity in mixed lymphocyte cultures and delayed cell death (within 72 hours). MFI in leukocytes suspended in plasma and exposed to the clinical dose of UVB was sixfold higher (310 +/- 41 arbitrary units) and resulted in early cell death (within 24 hours). We hypothesize that this high level of UVB radiation induces fragmentation of the leukocytes. As a consequence, the poor results of UVB irradiation may be explained by the onset of HLA-alloimmunization induced by soluble donor HLA class I antigens processed and presented by host antigen-presenting cells.
[show abstract][hide abstract] ABSTRACT: Ultraviolet B (UVB) irradiation of platelet concentrates (PCs) has been proposed as a novel technology to prevent HLA sensitization. We have recently reported that 2 J/cm2 of UVB radiation abolishes alloreactive lymphocyte responses in vitro. In order to increase the efficacy of UV irradiation for the prevention of HLA sensitization, we exposed PCs to 4 or 8 J/cm2 of UVB and evaluated the effect of UV radiation on platelet integrity during storage. We report here that UV exposed platelets show a progressive increase in the expression of activation markers P-selectin (GMP-140; CD62) and LIMP-CD63 (GP-53; CD63) on the platelet membrane over time in a dose-dependent manner compared to age-matched controls. Platelet metabolism was also enhanced as evidenced by significant changes in lactate and pH during post-irradiation storage. Based on these findings we transfused PCs within 4 h after UV irradiation. PCs exposed to 4 J/cm2 showed normal post-transfusion recoveries and haemostatic functions, while poor platelet recoveries were found after administration of PCs exposed to 8 J/cm2. We hypothesize that the rapid expression of P-selectin on platelets exposed to the higher dose of UVB leads to an increased binding of these platelets to leucocytes in the circulation resulting in poor platelet recoveries.
British Journal of Haematology 05/1993; 83(4):627-32. · 4.94 Impact Factor