Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis

Background Narrowband ultraviolet B (NB‐UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. Objectives To examine whether NB‐UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB‐UVB on antimicrobial peptide and cytokine expression in the skin. Methods Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB‐UVB exposures on the whole body, given three times a week. Serum calcidiol (25‐hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real‐time quantitative polymerase chain reaction. Results At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L^?1). NB‐UVB treatment significantly increased (P < 0·001) serum calcidiol. The increase was 59·9 nmol L^?1 (95% confidence interval, CI 53·5–66·9) in psoriasis, 68·2 nmol L^?1 (95% CI 55·4–80·1) in AD and 90·7 nmol L^?1 (95% CI 63·8–123·4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0·001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human β‐defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB‐UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB‐UVB caused a marked but nonsignificant decrease of interleukin (IL)‐1β and IL‐17 in psoriasis lesions. Conclusions The present study shows that in addition to a significant improvement of psoriasis and AD, NB‐UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.     

Heliotherapy improves vitamin D balance and atopic dermatitis

Background Vitamin D insufficiency during winter is common in the Nordic countries. Heliotherapy (HT) may heal atopic dermatitis (AD) but its effect on vitamin D balance has not been examined. Objectives To study the effect of HT on serum calcidiol (25‐hydroxyvitamin D) concentration and on healing of AD. Methods Twenty‐three adult patients with AD received a 2‐week course of HT in the Canary Islands in either January or March 2005. Daily solar ultraviolet (UV) radiation was measured and personal UV exposure calculated as standard erythema doses (SED). Blood samples were taken during HT and during a 1–2 month follow‐up. Serum calcidiol concentration was measured by radioimmunoassay. Healing of AD was examined by SCORAD index. Results Before HT 17 (74%) AD patients had vitamin D insufficiency (calcidiol < 50 nmol L^?1) and four patients high (> 80 nmol L^?1) serum calcidiol values. The median personal UV dose during the 2‐week HT course was 60 SED in the January group and 109 SED in the March group. Serum calcidiol concentration increased significantly in both groups, by 13·4 and 24·0 nmol/L^?1, respectively, and after HT only four (17%) patients had vitamin D insufficiency. SCORAD improved from 34 to 9 in the January HT group and from 30 to 9 in the March group. Conclusions A 2‐week course of HT significantly improved vitamin D balance by increasing serum calcidiol concentration, and caused a marked healing of AD. These parallel positive responses should be taken into account when the benefits of HT are considered.     

Narrowband ultraviolet B irradiation increases the serum level of vitamin D3 in patients with neurofibromatosis 1

The serum vitamin D₃ levels in patients with neurofibromatosis 1 has been reported to be significantly lower than that in control subjects, and the level of vitamin D₃ reversely correlates with the severity of neurofibroma formation. We found that narrowband ultraviolet B (NB‐UVB) irradiation increased the serum level of 1,25(OH)₂ vitamin D₃ in patients with neurofibromatosis 1. The difference in the 1,25(OH)₂ vitamin D₃ levels between patients who had received irradiation for more than 18 months and those who had no irradiation was highly significant. Time‐course analyses of the serum vitamin D₃ levels in the patients who were enrolled after informed consent revealed that the levels became higher significantly after 6 months of irradiation. It is suggested that NB‐UVB irradiation is effective for increasing the serum level of vitamin D₃ in patients with neurofibromatosis 1, which may be of benefit for skin symptoms such as pigmented macules or neurofibromas.     

The effect of ultraviolet B-induced vitamin D levels on host resistance to Mycobacterium tuberculosis: a pilot study in immigrant Asian adults living in the United Kingdom

Asian immigrants to the United Kingdom demonstrate much higher tuberculosis rates than the indigenous population. This is postulated to be because of their low vitamin D levels, consequent upon a combination of diet and their reduced ultraviolet (UV) exposure in the United Kingdom, because vitamin D enhances antimycobacterial activity in in vitro systems. The aim of this study was to examine the relationship between UVB exposure, vitamin D levels and tuberculo-immunity in Asian immigrants in the United Kingdom. Suberythemal UVB treatments were given to eight subjects on 3 consecutive days, using broadband UVB fluorescent lamps. Blood was sampled for 25-hydroxyvitamin D (25-OH D) and whole blood functional assays were performed for antimycobacterial immunity. The mean 25-OH D level increased from a baseline of 11.23 ng/ml (95% CI 6.7-20.39) to 20.39 ng/ml (95% CI 16.6-20) following UVB treatment, P<0.01. However, no significant change in antimycobacterial immunity occurred following UVB exposure. This pilot study in Asian subjects with good baseline tuberculo-immunity has not supported a role for UVB-induced 25-OH D in the immune response to Mycobacterium tuberculosis.     

Does chronic sunscreen use reduce vitamin D production to insufficient levels?

Exposure to ultraviolet B radiation in sunlight provides the mechanism for more than 90% of the vitamin D production in most individuals. Concern has been expressed in recent years that the widespread use of sunscreens, particularly those with high sun protection factors, may lead to a significant decrease in solar-induced previtamin D₃ in the skin, resulting in a vitamin D level which is considered insufficient for protection against a wide range of diseases. In this article the published evidence to support and to question this view is presented. It is concluded that, although sunscreens can significantly reduce the production of vitamin D under very strictly controlled conditions, their normal usage does not generally result in vitamin D insufficiency.     

Incidence of skin cancers in 3867 patients treated with narrow-band ultraviolet B phototherapy

Background  Narrow‐band ultraviolet B (NB‐UVB) phototherapy is a widely used treatment. Psoralen‐UVA photochemotherapy (PUVA) increases skin cancer risk and some animal studies have raised the possibility of an increased risk with NB‐UVB. The risk of skin cancer in humans following treatment with NB‐UVB is unknown. Objectives  This current analysis forms part of an ongoing study ultimately aiming to define the long‐term carcinogenic risk of NB‐UVB treatment in humans. Methods  Details of all patients receiving NB‐UVB treatment until 31/12/2002 in Tayside, Scotland, were accessed from a treatment database and linked to the Scottish Cancer Registry. Indirect standardization was used to compare skin cancer incidence in the study population with age and sex matched cancer registry data for the Tayside population. We also assessed the effect of NB‐UVB exposure treatment numbers on the risk of developing skin cancer. Results  Of 4690 records reviewed, 4665 were suitable for analysis with 3886 records linked with the cancer registry and 3867 followed‐up for at least 6 months before 31/12/02 (the date at which cancer registration was deemed to be complete). The median number of NB‐UVB treatments was 29 with 352 patients receiving ≥ 100 treatments. The study gave 24 753 person‐years of follow up. First skin cancers recorded in study patients were 27 basal cell carcinomas (BCC), seven squamous cell carcinomas (SCC) and six melanomas. No association was found between NB‐UVB exposure alone (without PUVA) and any skin cancer. For NB‐UVB and PUVA treated patients there was an association with BCC, with 27 BCCs found compared with 14·1 expected in the matched population. Conclusion  We found no significant association between NB‐UVB treatment and BCC, SCC or melanoma. There was a small increase in BCCs amongst those also treated with PUVA. These reassuring results do not demonstrate the early increase in skin cancers that was found associated with PUVA treatment. However, cautious interpretation is required as the cohort contained relatively few patients who had a high treatment number and because the slow evolution of skin cancers may result in a delayed incidence peak. Ongoing risk assessment is therefore essential.     

Topical riboflavin attenuates ultraviolet B‐ and ultraviolet A‐induced immunosuppression in humans

Background: Riboflavin (vitamin B₂) plays a key role in cellular energy metabolism. We have observed previously that nicotinamide (vitamin B₃), which is also centrally involved in cellular energy restoration after UV irradiation, is highly immune protective in humans. We thus hypothesized that riboflavin might also confer immune protection. Methods: We irradiated healthy, nickel‐allergic volunteers with narrowband UVA (385 nm) and UVB (300 nm) at separate sites on the lower back. These areas were treated with riboflavin solution or vehicle at 24 h and again at 30 min before UV exposure. Forty‐eight hours after irradiation, volunteers were patch tested with nickel‐containing Finn chambers, at both irradiated and nonirradiated sites, with and without prior riboflavin treatment. The resulting contact hypersensitivity reactions at each site were then measured 72 h later with a reflectance erythema meter in order to determine and compare the immune suppressive effects of each intervention. Results: We observed that low doses of both UVB and longwave UVA1 were immune suppressive in humans. Topical riboflavin conferred immune protection against both wavebands. Conclusions: Riboflavin is immune protective in humans, and this may reflect the role of the B group vitamins in cellular energy restoration after UV exposure.     

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.     

Modelling the seasonal variation of vitamin D due to sun exposure

Background The current interest in vitamin D as a preventive agent in many chronic diseases has led to a reappraisal of adequate sun exposure. Yet just what constitutes adequacy remains to be clearly defined and validated. To do this requires an understanding of how behaviour outdoors during the year translates into seasonal changes in vitamin D status. Objectives To develop a model for estimating the changes in serum 25‐hydroxyvitamin D [25(OH)D] levels as a consequence of sun exposure throughout the year. Methods A novel mathematical model is described that incorporates the changes in serum 25(OH)D following a single, whole‐body exposure to solar ultraviolet radiation with daily sun exposure in order to estimate the annual variation in serum 25(OH)D. Results The model yields results that agree closely with measured data from a large population‐based study. Application of the model showed that current advice about 10–20 min of daily sun exposure during the summer months does little in the way of boosting overall 25(OH)D levels, while sufficient sun exposure that could achieve a worthwhile benefit would compromise skin health. Conclusions There is little in the way of public health advice concerning the benefits of sun exposure that can be given as an effective means of maintaining adequate vitamin D levels throughout the year. Instead it would seem safer and more effective to fortify more foods with vitamin D and/or to consider the use of supplements during the winter months. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and should avoid giving specific advice on what might be ‘optimal’ sun exposure.     

Narrowband (TL-01) ultraviolet B phototherapy for pruritus in polycythaemia vera

BACKGROUND: There are several reports of the efficacy of broadband ultraviolet (UV) phototherapy in the treatment of pruritus associated with polycythaemia vera. OBJECTIVES: To evaluate whether narrowband (TL-01) UVB phototherapy is also effective in treating this condition. METHODS: Ten patients with pruritus associated with polycythaemia vera were treated with narrowband (TL-01) UVB phototherapy. The first irradiation dose was 2/3 of the minimal erythema dose; the treatment schedule consisted of three irradiation sessions per week, with dose increments of 10% each session for skin types I and II, and 15% for skin types III and IV. RESULTS: Patients reported a marked relief of symptoms after an average of six treatments (median cumulative dose 1851.52 mJ cm-2, range 1180.4-2468.4). A complete remission of the pruritus occurred within 2-10 weeks of treatment (median cumulative dose 5371.46 mJ cm-2, range 3271.2-7336.3) in eight of 10 patients. Two patients had only a partial and temporary relief of pruritus after two cycles of treatment and a cumulative dose of 3271.2 mJ cm-2. CONCLUSIONS: Narrowband UVB phototherapy is effective for treatment of pruritus associated with polycythaemia vera, and has the advantage of being less erythemogenic than broadband UVB.     

Narrowband ultraviolet B phototherapy for alopecia areata

Although narrowband ultraviolet B (NB UVB) phototherapy is a well-established treatment in many dermatosis, there is little evidence of efficacy of this method for alopecia areata (AA) treatment in the literature. We undertook a retrospective review of the 25 AA patients treated with NB UVB. Intramuscular triamcinolone acetonide injections per month were used as concomitant treatment in some patients who did not have any contraindication. Eight patients (32%) received monthly intramuscular corticosteroid injections. Four (22.2%) and two (20%) patients achieved excellent response in extensive patchy hair loss patients and entire scalp hair loss patients, respectively. Four of six patients who achieved excellent response also received monthly intramuscular corticosteroid injections. When patients receiving systemic corticosteroid injections were compared with patients given only NB UVB with respect to the treatment responses, a statistically significant difference was seen in patients who achieved excellent response. NB UVB is not an effective treatment with only 20% excellent treatment responses in patients with severe AA, most of whom were also treated with systemic corticosteroids.     

Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: a case series

BACKGROUND: Cystic fibrosis (CF) and short bowel syndrome (SBS) patients are unable to absorb vitamin D from the diet and thus are frequently found to be severely vitamin D deficient. We evaluated whether a commercial portable ultraviolet (UV) indoor tanning lamp that has a spectral output that mimics natural sunlight could raise circulating 25-hydroxyvitamin D [25(OH)D] levels in subjects with CF and SBS. METHODS: In initial pilot studies, two SBS subjects came to the outpatient clinic twice weekly for 8 weeks for UV light sessions of 6 min each. In a follow-up study, five CF subjects exposed their lower backs in a seated position to the sunlamp at a distance of 14 cm for 5-10 min depending on the skin type five times a week for 8 weeks. Blood samples for 25(OH)D and parathyroid hormone (PTH) measurements were performed at baseline and at the end of the study. RESULTS: In our study, with two SBS subjects, the indoor lamp increased or maintained circulating 25(OH)D levels during the winter months. We increased the UV lamp frequency and found an improved response in the CF patients. Serum 25(OH)D levels in CF subjects at baseline were 21 +/- 3 ng/ml, which increased to 27 +/- 4 ng/ml at the end of 8 weeks (P=0.05). PTH concentration remained largely unchanged in both population groups. CONCLUSION: A UV lamp that emits ultraviolet radiation similar to sunlight and thus produces vitamin D(3) in the skin is an excellent alternative for CF, and SBS patients who suffer from vitamin D deficiency due to fat malabsorption, especially during the winter months when natural sunlight is unable to produce vitamin D3 in the skin. This UV lamp is widely available for commercial home use and could potentially be prescribed to patients with CF or SBS.     

The role of sunlight exposure in determining the vitamin D status of the U.K. white adult population

Background Vitamin D is necessary for bone health and is potentially protective against a range of malignancies. Opinions are divided on whether the proposed optimal circulating 25‐hydroxyvitamin D [25(OH)D] level (≥ 32 ng mL^?1) is an appropriate and feasible target at population level. Objectives We examined whether personal sunlight exposure levels can provide vitamin D sufficient (≥ 20 ng mL^?1) and optimal status in the U.K. public. Methods This prospective cohort study measured circulating 25(OH)D monthly for 12 months in 125 white adults aged 20–60 years in Greater Manchester. Dietary vitamin D and personal ultraviolet radiation (UVR) exposure were assessed over 1–2 weeks in each season. The primary analysis determined the post‐summer peak 25(OH)D required to maintain sufficiency in wintertime. Results Dietary vitamin D remained low in all seasons (median 3·27 μg daily, range 2·76–4·15) while personal UVR exposure levels were high in spring and summer, low in autumn and negligible in winter. Mean 25(OH)D levels were highest in September [28·4 ng mL^?1; 28% optimal, zero deficient (<5 ng mL^?1)], and lowest in February (18·3 ng mL^?1; 7% optimal, 5% deficient). A February 25(OH)D level of 20 ng mL^?1 was achieved following a mean (95% confidence interval) late summer level of 30·4 (25·6–35·2) and 34·9 (27·9–41·9) ng mL^?1 in women and men, respectively, with 62% of variance explained by gender and September levels. Conclusions Late summer 25(OH)D levels approximating the optimal range are required to retain sufficiency throughout the U.K. winter. Currently the majority of the population fails to reach this post‐summer level and becomes vitamin D insufficient during the winter.     

Skin colour and vitamin D: An update

Homo sapiens evolved in East Africa and had dark skin, hair, and eyes, in order to protect against deleterious consequences of intensive UV radiation at equatorial latitudes. Intensive skin pigmentation was thought to bear the risk of inefficient vitamin D₃ synthesis in the skin. This initiated the hypothesis that within the past 75 000 years, in which humans migrated to higher latitudes in Asia and Europe, the need for vitamin D₃ synthesis served as an evolutionary driver for skin lightening. In this review, we summarize the recent archeogenomic reconstruction of population admixture in Europe and demonstrate that skin lightening happened as late as 5000 years ago through immigration of lighter pigmented populations from western Anatolia and the Russian steppe but not primarily via evolutionary pressure for vitamin D₃ synthesis. We show that variations in genes encoding for proteins being responsible for the transport, metabolism and signalling of vitamin D provide alternative mechanisms of adaptation to a life in northern latitudes without suffering from consequences of vitamin D deficiency. This includes hypotheses explaining differences in the vitamin D status and response index of European populations.     

Measurements of the upper body ultraviolet exposure to golfers: non-melanoma skin cancer risk, and the potential benefits of exposure to sunlight

Background: Geographically, Queensland presents an extreme ultraviolet exposure climate to members of the public engaged in outdoor recreational activity. The risk of developing a skin cancer or an eye disease as a result of incidental exposure to naturally occurring ultraviolet radiation in the outdoor environment is proportionately high in a Queensland population compared with fair‐skinned population groups residing in comparable Northern Hemisphere latitudes. In contrast to these risks, elderly members of this high growth population group have been reported to be vitamin D deficient. The risks and potential benefits of exposure to sunlight in southern Queensland are assessed in this study with respect to recreational golfing. This sport is a popular recreational activity for the Queensland population and must be played during daylight hours. Methods: The erythemal and vitamin D effective ultraviolet exposure measured to the forearm, upper back and vertex are presented for individuals playing golf under various atmospheric conditions in a 7‐month period extending from summer to winter. Results: Mean summertime exposures were measured in the 2008 study period as be 1.4, 2.2 and 3.2 standard erythema doses (SED) at forearm, upper back and vertex sites, respectively, compared with respective wintertime forearm, upper back and vertex exposures of 0.2, 0.3 and 0.5 SED, where summertime exposures were recorded in the mean solar zenith angle (SZA) ranges of 56–59° and wintertime exposures were recorded in the mean SZA range 74–83°. Vitamin D₃ effective exposures were determined to vary from between 225, 325 and 475 J/m² during summer and 48, 59 and 88 J/m² during winter for the respective forearm, upper back and vertex body sites measured in the above mean SZA ranges. Conclusion: Exposures to ambient ultraviolet during winter on the golf course between 15:00 and 17:30 hours could be beneficial for office workers for the production of vitamin D. Optimizing exposure periods to late afternoon in the winter months and taking adequate sun protection measures in the summer months are important strategies that golfers can utilize for long‐term preventative health.     

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.