Phototherapy in the perspective of the chronicity of psoriasis.

According to the guidelines for the treatment of psoriasis, phototherapy is given in courses of UVB exposure starting at 50-70% of the minimal erythema dose, MED, with subsequently incremental dosages, but keeping erythemal skin reactions to a minimum by restraining the dosages when necessary. In this review, this classical principle of short-term near erythematogenic UVB therapy without further UVB maintenance therapy is challenged as it is evidently not optimal for psoriasis as a chronic condition. There is old experimental evidence supplemented with growing knowledge on the mode of action of phototherapy and more recent data on low-level UVB regimens as maintenance therapy that should urge us to revisit our guidelines on phototherapy to address psoriasis for what it is: a chronic condition.

Human health in relation to exposure to solar ultraviolet radiation under changing stratospheric ozone and climate.

The Montreal Protocol has limited increases in the UV-B (280-315 nm) radiation reaching the Earth's surface as a result of depletion of stratospheric ozone. Nevertheless, the incidence of skin cancers continues to increase in most light-skinned populations, probably due mainly to risky sun exposure behaviour. In locations with strong sun protection programs of long duration, incidence is now reducing in younger age groups. Changes in the epidemiology of UV-induced eye diseases are less clear, due to a lack of data. Exposure to UV radiation plays a role in the development of cataracts, pterygium and possibly age-related macular degeneration; these are major causes of visual impairment world-wide. Photodermatoses and phototoxic reactions to drugs are not uncommon; management of the latter includes recognition of the risks by the prescribing physician. Exposure to UV radiation has benefits for health through the production of vitamin D in the skin and modulation of immune function. The latter has benefits for skin diseases such as psoriasis and possibly for systemic autoimmune diseases such as multiple sclerosis. The health risks of sun exposure can be mitigated through appropriate sun protection, such as clothing with both good UV-blocking characteristics and adequate skin coverage, sunglasses, shade, and sunscreen. New sunscreen preparations provide protection against a broader spectrum of solar radiation, but it is not clear that this has benefits for health. Gaps in knowledge make it difficult to derive evidence-based sun protection advice that balances the risks and benefits of sun exposure.

Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2017.

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low-level summer sunlight exposures.

BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.

Predicted increased risk of squamous cell carcinoma induction associated with sunbed exposure habits.

BACKGROUND: Solar ultraviolet radiation (UVR) is recognized as the principal environmental cause of skin cancer. In particular, the risk of induction of squamous cell carcinoma (SCC) has been shown to increase with cumulative exposure to UVR. Models of risk of SCC induction have been developed but these do not include the use of sunbeds. OBJECTIVES: To explore the links between sunbed exposure and risk of SCC induction. METHODS: To this end, the values of published on-site UVR levels emitted from sunbeds were used to provide real measured sunbed exposure levels to inform the model. The model incorporated three conditions of exposure: day-to-day, holiday and sunbed exposure. The risks associated with different exposure scenarios were implemented in the model. Baseline exposure comprised day-to-day and holiday exposure. Relative risk (RR) was defined as the risk of SCC induction from (sunbed + baseline dose)/baseline dose. RESULTS: The RR of SCC induction from estimated median sunbed exposure output [176 standard erythemal dose (SED) per year; 20-35 years of age] in addition to median baseline sun exposure level (166 SED year + 85.5 SED per year holiday) was 1.9 (90% risk increase) up to 55 years of age. A higher sunbed exposure (302 SED per year; 20-35 years of age) produced an RR value of 2.8 (180% increase) at 55 years of age. CONCLUSIONS: This is the first time that a risk model for SCC of the skin has been developed that includes estimated sunbed doses derived from measured irradiance data. The model demonstrates that the additional risk associated with sunbed use may be significant, particularly when high-output, fast-tan sunbeds are used.

The consequences for human health of stratospheric ozone depletion in association with other environmental factors.

Due to the implementation of the Montreal Protocol, which has limited, and is now probably reversing, the depletion of the stratospheric ozone layer, only modest increases in solar UV-B radiation at the surface of the Earth have occurred. For many fair-skinned populations, changing behaviour with regard to exposure to the sun over the past half century - more time in the sun, less clothing cover (more skin exposed), and preference for a tan - has probably contributed more to greater levels of exposure to UV-B radiation than ozone depletion. Exposure to UV-B radiation has both adverse and beneficial effects on human health. This report focuses on an assessment of the evidence regarding these outcomes that has been published since our previous report in 2010. The skin and eyes are the organs exposed to solar UV radiation. Excessive solar irradiation causes skin cancer, including cutaneous malignant melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma, and contributes to the development of other rare skin cancers such as Merkel cell carcinoma. Although the incidence of melanoma continues to increase in many countries, in some locations, primarily those with strong sun protection programmes, incidence has stabilised or decreased over the past 5 years, particularly in younger age-groups. However, the incidence of non-melanoma skin cancers is still increasing in most locations. Exposure of the skin to the sun also induces systemic immune suppression that may have adverse effects on health, such as through the reactivation of latent viral infections, but also beneficial effects through suppression of autoimmune reactivity. Solar UV-B radiation damages the eyes, causing cataracts and pterygium. UV-B irradiation of the skin is the main source of vitamin D in many geographic locations. Vitamin D plays a critical role in the maintenance of calcium homeostasis in the body; severe deficiency causes the bone diseases, rickets in children and osteomalacia in adults. Although many studies have implicated vitamin D deficiency in a wide range of diseases, such as cancer and cardiovascular disease, more recent evidence is less compelling, with meta-analyses of supplementation trials failing to show a beneficial effect on the health outcomes that have been tested. It continues to be difficult to provide public health messages to guide safe exposure to the sun that are accurate, simple, and can be used by people with different skin types, in different locations, and for different times of the year or day. There is increasing interest in relating sun protection messages to the UV Index. Current sun protection strategies are outlined and assessed. Climatic factors affect the amount of UV radiation received by the skin and eyes, separately from the effect of ozone depletion. For example, cloud cover can decrease or increase the intensity of UV radiation at Earth's surface and warmer temperatures and changes in precipitation patterns may alter the amount of time people spend outdoors and their choice of clothing. The combination of changes in climate and UV radiation may affect the number of pathogenic microorganisms in surface waters, and could have an impact on food security through effects on plant and aquatic systems. It remains difficult to quantify these effects and their possible importance for human health.

Skin hardening effect in patients with polymorphic light eruption: comparison of UVB hardening in hospital with a novel home UV-hardening device.

BACKGROUND: An effective prophylactic treatment of patients with polymorphic light eruption (PLE) consists of repeated low, gradually increasing exposures to UVB radiation. This so-called UV(B) hardening induces better tolerance of the skin to sunlight. OBJECTIVE: SunshowerMedical company (Amsterdam) has developed an UV (B) source that can be used during taking shower. The low UV fluence of this apparatus makes it an interesting device for UV hardening. In a group of PLE patients, we compared the effectiveness of the irradiation with SunshowerMedical at home with that of the UVB treatment in the hospital. METHODS: The PLE patients were randomized for one of the treatments. The hospital treatment consisted of irradiations with broad-band UVB (Waldmann 85/UV21 lamps) twice a week during 6 weeks. The home UV-device was used each day with the maximal irradiation time of 6 min. The outcome assessment was based on the information obtained from patients' dermatological quality of life (DLQI) questionnaires, the ability of both phototherapies to reduce the provocation reaction and from the patients' evaluation of the long-term benefits of their phototherapies. RESULTS: Sixteen patients completed treatment with SunshowerMedical and thirteen completed treatment in hospital. Both types of phototherapy were effective. There was a highly significant improvement in DLQI with either treatment. In most cases, the hardening reduced or even completely suppressed clinical UV provocation of PLE. The patients using SunshowerMedical at home were, however, much more content with the treatment procedure than the patients visiting the dermatological units. CONCLUSIONS: Both treatments were equally effective in the induction of skin tolerance to sunlight in PLE patients. However, the home treatment was much better accepted than the treatment in the hospital.

UV-induced ablation of the epidermal basal layer including p53-mutant clones resets UV carcinogenesis showing squamous cell carcinomas to originate from interfollicular epidermis.

Chronic ultraviolet (UV) exposure induces clones of cells overexpressing mutant p53 in the interfollicular (IF) epidermis and subsequently squamous cell carcinomas (SCCs) with similar p53 mutations. Mutated p53 may give cells growth advantage over neighbouring cells by impaired apoptosis. We tested this by UV overexposure of skin laden with p53-mutant clones and assessed the impact on subsequent tumour development. P53-mutant clones were induced in two groups of hairless SKH1 mice by daily exposures (500 J/m(2) UV from TL12 lamps) for 28 days. On day 29, one group was overexposed (to 10 kJ/m(2) UV), whereas the control group received the regular daily dose. After 1 week of recovery, the daily exposures were resumed in both groups to induce SCCs. UV overexposure forced the entire IF basal layer into caspase-3-driven apoptosis while leaving overlying layers with sunburn cells intact. No apparent regions were spared from apoptosis. Pulse-chase BrdU labelling showed the IF epidermis to be repopulated from the hair follicles (remaining p63 positive). One week after overexposure, the p53-mutant clones had virtually disappeared (0.6, 95% confidence interval 0.5-0.8 per mouse versus 102, 59-179, without overexposure). Tumour development was significantly delayed after UV overexposure (P < 0.0001) by an average of 27 days (standard error of the mean 3); a period matching that of daily exposures preceding the overexposure. Thus, we found that UV-induced ablation of the IF epidermal basal layer eliminates p53-mutant clones and resets UV carcinogenesis. Furthermore, and in contrast with earlier reports, our data show that UV-induced p53-mutant clones and SCCs originate from the IF epidermis.

Rapamycin impairs UV induction of mutant-p53 overexpressing cell clusters without affecting tumor onset.

Because of its antitumor effect, the immunosuppressant rapamycin holds great promise for organ transplant recipients in that it may lower their cancer risk. In a mouse model, we showed previously that rapamycin inhibits the outgrowth of primary skin carcinomas induced by UV radiation. However, the tumors that did grow out showed an altered p53 mutation spectrum. Here, we investigated whether this shift in p53 mutations already occurred in the smallest tumors, which were not affected in onset. We found that rapamycin did not alter the mutational spectrum in small tumors and in preceding microscopic clusters of cells expressing mutant-p53. However, rapamycin did reduce the number of these cell clusters. As this reduction did not affect tumor onset, we subsequently investigated whether rapamycin merely suppressed expression of mutated p53. This was not the case, as we could demonstrate that switching from a diet with rapamycin to one without, or vice versa, did not affect the number of existing mutant-p53 expressing cell clusters. Hence, rapamycin actually reduced the formation of mutant-p53 cell clusters. In wild-type and p53-mutant mice, we could not measure a significant enhancement of UV-induced apoptosis, but we did observe clear enhancement in human skin equivalents. This was associated with a clear suppression of HIF1α accumulation. Thus, we conclude that rapamycin reduces the formation of mutant-p53-expressing cell clusters without affecting tumor onset, suggesting that tumors grow out of a minor subset of cell clusters, the formation of which is not affected by rapamycin.

The human health effects of ozone depletion and interactions with climate change.

Depletion of the stratospheric ozone layer has led to increased solar UV-B radiation (280-315 nm) at the surface of the Earth. This change is likely to have had an impact on human exposure to UV-B radiation with consequential detrimental and beneficial effects on health, although behavioural changes in society over the past 60 years or so with regard to sun exposure are of considerable importance. The present report concentrates on information published since our previous report in 2007. The adverse effects of UV radiation are primarily on the eye and the skin. While solar UV radiation is a recognised risk factor for some types of cataract and for pterygium, the evidence is less strong, although increasing, for ocular melanoma, and is equivocal at present for age-related macular degeneration. For the skin, the most common harmful outcome is skin cancer, including melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma. The incidence of all three of these tumours has risen significantly over the past five decades, particularly in people with fair skin, and is projected to continue to increase, thus posing a significant world-wide health burden. Overexposure to the sun is the major identified environmental risk factor in skin cancer, in association with various genetic risk factors and immune effects. Suppression of some aspects of immunity follows exposure to UV radiation and the consequences of this modulation for the immune control of infectious diseases, for vaccination and for tumours, are additional concerns. In a common sun allergy (polymorphic light eruption), there is an imbalance in the immune response to UV radiation, resulting in a sun-evoked rash. The major health benefit of exposure to solar UV-B radiation is the production of vitamin D. Vitamin D plays a crucial role in bone metabolism and is also implicated in protection against a wide range of diseases. Although there is some evidence supporting protective effects for a range of internal cancers, this is not yet conclusive, but strongest for colorectal cancer, at present. A role for vitamin D in protection against several autoimmune diseases has been studied, with the most convincing results to date for multiple sclerosis. Vitamin D is starting to be assessed for its protective properties against several infectious and coronary diseases. Current methods for protecting the eye and the skin from the adverse effects of solar UV radiation are evaluated, including seeking shade, wearing protective clothing and sunglasses, and using sunscreens. Newer possibilities are considered such as creams that repair UV-induced DNA damage, and substances applied topically to the skin or eaten in the diet that protect against some of the detrimental effects of sun exposure. It is difficult to provide easily understandable public health messages regarding "safe" sun exposure, so that the positive effects of vitamin D production are balanced against the negative effects of excessive exposure. The international response to ozone depletion has included the development and deployment of replacement technologies and chemicals. To date, limited evidence suggests that substitutes for the ozone-depleting substances do not have significant effects on human health. In addition to stratospheric ozone depletion, climate change is predicted to affect human health, and potential interactions between these two parameters are considered. These include altering the risk of developing skin tumours, infectious diseases and various skin diseases, in addition to altering the efficiency by which pathogenic microorganisms are inactivated in the environment.

Early and late effects of the immunosuppressants rapamycin and mycophenolate mofetil on UV carcinogenesis.

Increased skin cancer risk in organ transplant recipients has been experimentally emulated with enhanced UV carcinogenesis from administering conventional immunosuppressants. However, newer generation immunosuppressive drugs, rapamycin (Rapa) and mycophenolate mofetil (MMF), have been shown to impair angiogenesis and outgrowth of tumor implants. To ascertain the overall effect on UV carcinogenesis, Rapa and MMF were admixed into the food pellets of hairless SKH1 mice receiving daily sub-sunburn UV dosages. With immunosuppressive blood levels neither of the drugs affected onset of tumors (<2 mm), but in contrast to MMF, Rapa significantly increased latency of large tumors (>or=4 mm, medians of 190 vs 125 days) and reduced their multiplicity (1.6 vs 4.5 tumors per mouse at 200 days). Interestingly, tumors (>2 mm) from the Rapa-fed group showed a reduction in UV-signature p53 mutations (39% vs 90%) in favor of mutations from putative base oxidation. This shift in mutation spectrum was not essentially linked to the reduction in large tumors because it was absent in large tumors similarly reduced in number when feeding Rapa in combination with MMF, possibly owing to an antioxidant effect of MMF. Significantly fewer tumor cells were Vegf-positive in the Rapa-fed groups, but a correspondingly reduced expression of Hif1alpha target genes (Vegf, Ldha, Glut1, Pdk1) that would indicate altered glucose metabolism with increased oxidative stress was not found. Remarkably, we observed no effect of the immunosuppressants on UV-induced tumor onset, and with impaired tumor outgrowth Rapa could therefore strongly reduce skin carcinoma morbidity and mortality rates in organ transplant recipients.

Reduced IL-1Ra/IL-1 ratio in ultraviolet B-exposed skin of patients with polymorphic light eruption.

Polymorphic light eruption (PLE) is a putative delayed-type allergic reaction to (solar) ultraviolet (UV) exposure. Inadequate immune suppression after UVB-induced sunburn appears to be associated with reduced trafficking of Langerhans cells (LCs) out of and neutrophils into the epidermis of patients sensitive to UVB provocation of PLE. Therefore, we investigated whether pro-inflammatory and chemotactic cytokines are differentially expressed in UVB-irradiated skin of UVB-provocable PLE patients (n = 6) and age- and gender-matched healthy controls (n = 6). Interstitial interleukin-1alpha (IL-1alpha), IL-1beta, IL-1Ra, IL-4, IL-8, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein 1-alpha (MIP-1alpha), MIP-1beta and monocyte chemotactic protein-1 (MCP-1) were measured in suction blister fluid raised 16 h after exposure to 0, three and six minimal erythemal UVB doses. In unirradiated skin, the IL-1Ra levels were significantly lower in the PLE patients than in controls (P < 0.05). IL-8 and TNF-alpha levels increased strongly upon UVB irradiation in both groups. No differential shifts in cytokine profiles were found that could explain a reduced trafficking of Langerhans cells and neutrophils in PLE patients. Dose-trend analyses showed that UVB irradiation caused significant increases in IL-1alpha in both groups, and that the levels of IL-1alpha and IL-1beta were on average twofold higher in the PLE group (P = 0.03 and P = 0.004, respectively.). Accordingly, the ratios of IL-1Ra over IL-1alpha and over IL-1beta were overall lower in the skin of PLE patients (P = 0.015 and P < 0.001, respectively.). This shift in cytokines in UVB-irradiated skin of PLE patients reveals an amplified early pro-inflammatory cytokine response, which may contribute to the allergic reaction to UVB radiation.

Molecular and immunologic mechanisms of cancer pathogenesis in solid organ transplant recipients.

The increased risk for the development of malignancies in transplant recipients is generally attributed to the debilitated immune system that results from chronic exposure to potent immunosuppressive drugs required to prevent graft rejection. While impaired immunity is clearly a key determinant, there is strong evidence that a constellation of other factors contribute to the pathogenesis of posttransplant cancers. In this article we discuss the underlying molecular and immunologic mechanisms that contribute to the development of de novo malignancies in transplant recipients, with particular focus on the two leading posttransplant neoplasia, skin cancer and Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (PTLD).

The effects on human health from stratospheric ozone depletion and its interactions with climate change.

Ozone depletion leads to an increase in the ultraviolet-B (UV-B) component (280-315 nm) of solar ultraviolet radiation (UVR) reaching the surface of the Earth with important consequences for human health. Solar UVR has many harmful and some beneficial effects on individuals and, in this review, information mainly published since the previous report in 2003 (F. R. de Gruijl, J. Longstreth, M. Norval, A. P. Cullen, H. Slaper, M. L. Kripke, Y. Takizawa and J. C. van der Leun, Photochem. Photobiol. Sci., 2003, 2, pp. 16-28) is discussed. The eye is exposed directly to sunlight and this can result in acute or long-term damage. Studying how UV-B interacts with the surface and internal structures of the eye has led to a further understanding of the location and pathogenesis of a number of ocular diseases, including pterygium and cataract. The skin is also exposed directly to solar UVR, and the development of skin cancer is the main adverse health outcome of excessive UVR exposure. Skin cancer is the most common form of malignancy amongst fair-skinned people, and its incidence has increased markedly in recent decades. Projections consistently indicate a further doubling in the next ten years. It is recognised that genetic factors in addition to those controlling pigment variation can modulate the response of an individual to UVR. Several of the genetic factors affecting susceptibility to the development of squamous cell carcinoma, basal cell carcinoma and melanoma have been identified. Exposure to solar UVR down-regulates immune responses, in the skin and systemically, by a combination of mechanisms including the generation of particularly potent subsets of T regulatory cells. Such immunosuppression is known to be a crucial factor in the generation of skin cancers. Apart from a detrimental effect on infections caused by some members of the herpesvirus and papillomavirus families, the impact of UV-induced immunosuppression on other microbial diseases and vaccination efficacy is not clear. One important beneficial effect of solar UV-B is its contribution to the cutaneous synthesis of vitamin D, recognised to be a crucial hormone for bone health and for other aspects of general health. There is accumulating evidence that UVR exposure, either directly or via stimulation of vitamin D production, has protective effects on the development of some autoimmune diseases, including multiple sclerosis and type 1 diabetes. Adequate vitamin D may also be protective for the development of several internal cancers and infections. Difficulties associated with balancing the positive effects of vitamin D with the negative effects of too much exposure to solar UV-B are considered. Various strategies that can be adopted by the individual to protect against excessive exposure of the eye or the skin to sunlight are suggested. Finally, possible interactions between ozone depletion and climate warming are outlined briefly, as well as how these might influence human behaviour with regard to sun exposure.

[Retarded excision of pyrimidine dimers in human unstimulated lymphocytes].

Using immuno-labelling of cyclobutane pyrimidine dimers (CPDs) in nuclei of peripheral lymphocytes after their UVC-irradiation and cultivation, we have found that within the first four hours of cultivation the CPD-specific fluorescent signal from cell nuclei increased. Earlier, a similar increase in binding of antibody specific for pyrimidine (6-4) pyrimidone photoproducts to undenatured DNA isolated from UV-irradiated Chinese hamster ovary cells was reported (Mitchell et al., 1986). Our experiments showed that nucleotide excision repair enzyme might induce such of DNA modification in lymphocyte nuclei that increased specific antibody binding to DNA fragments with lesions. We suggest that enzymatic formation of open structures in DNA predominated qualitatively over dual-incision and excision of these fragments, and resulted in the enhanced exposure of the pyrimidine dimers in nuclei to specific antibodies. The results evidence that nucleotid excision repair in unstimualted human lymphocytes being deficient in dual incision and removal of UV-induced DNA lesions appear to be capable of performing chromatin relaxation and pre-incision uncoiling of DNA fragments with lesions.

Normalized ultraviolet (UV) induction of Langerhans cell depletion and neutrophil infiltrates after artificial UVB hardening of patients with polymorphic light eruption.

BACKGROUND: Ultraviolet (UV) B hardening has been widely used as a prophylactic treatment in patients with polymorphic light eruption (PLE). Recent investigations have shown that in patients with PLE Langerhans cells (LCs) and neutrophils display less migration from and to the epidermis after an intense UVB irradiation compared with controls. OBJECTIVES: To investigate the effect of UVB hardening of patients with PLE on their cell migratory responses after intense UVB exposure. METHODS: Thirteen patients with PLE were recruited and UVB provocation testing was performed before entering the study. Among these patients, seven developed PLE rash upon UVB provocation ('UVB-P') and the other six did not respond ('UVB-NP'). Eleven age/sex-matched controls were included. Buttock skin of all included individuals was exposed to 6 minimal erythema doses (MED) of UVB (TL-12 lamps). Biopsies were taken after 24 h and 48 h, together with one control biopsy of unirradiated skin. Patients received total-body UVB hardening therapy consisting of 12 irradiations, on average rising from 10% to 140% of the initial MED in 6 weeks. Subsequently, MEDs were reassessed and biopsies were taken from newly irradiated (6 MED UVB) and unirradiated buttock skin. Skin sections were stained for the presence of LCs, macrophages and neutrophils. The cross-sectional area (in percentage) of positively stained cells within the epidermis was assessed from patients before and after hardening and compared with controls. RESULTS: Before therapy, epidermal LC depletion and neutrophil influx at 48 h after 6 MED were most significantly reduced in 'UVB-P' patients (P = 0.025 and P =0.006, respectively) when compared with controls. 'UVB-NP' patients did not differ significantly from controls. After therapy, there were no longer any significant differences in the cell numbers among these three groups. CONCLUSIONS: UVB hardening significantly improves UV-induced cell migratory responses in patients with PLE. UVB provokability of PLE appears to be most strongly linked to reduced UVB-induced trafficking of LCs and neutrophils, and 'UVB-P' patients show normalization of these responses after UVB hardening.

Predictions of skin cancer incidence in the Netherlands up to 2015.

BACKGROUND: Skin cancer is an important, growing public health problem among white caucasians, causing a heavy burden on dermatologists and general practitioners. OBJECTIVES: To predict the future incidence of skin cancer in the Netherlands up to 2015. METHODS: Expected numbers of skin cancer cases in the Netherlands up to 2015 were calculated by trend modelling of observed rates for melanoma and squamous cell carcinoma (SCC) between 1989 and 2000 obtained from the Netherlands Cancer Registry and for basal cell carcinoma (BCC) obtained from the Eindhoven Cancer Registry; these rates were then multiplied by the predicted age distributions. Incidence rates were fitted to four different models, and predictions were based on the best fitting model. RESULTS: An increase of 80% in the total number of skin cancer patients is expected in the Netherlands: from 20 654 in 2000 to 37 342 in 2015. The total number of melanoma cases is expected to increase by 99%, with the largest increase for males (males aged 35-64, 111%; males aged > or = 65, 139%). Numbers of patients with SCC will increase overall by 80%, mainly among older males and females (increase of 79%) and females aged 35-64 (increase of 93%). The number of cases of BCC will increase by 78%, with the largest increase for the combined groups, those aged 15-64 (males, 66% increase; females, 94% increase), especially for sites other than the head and neck. The contribution of demographic changes (ageing effect) was largest for males with BCC and SCC (35-44%). CONCLUSIONS: If incidence rates for skin cancers in the Netherlands continue to increase and population growth and ageing remain unabated, a rise in annual demand for care of more than 5% could occur, putting a heavy burden on general practitioners and dermatologists. In the absence of marked changes in current ultraviolet radiation exposure, these increases will probably continue after 2015.