A feasibility study of a novel low-level light therapy for digital ulcers in systemic sclerosis.

BACKGROUND: Locally acting, well-tolerated treatments for systemic sclerosis (SSc) digital ulcers (DUs) are needed. OBJECTIVES: Our primary aim was to investigate the safety, feasibility, and tolerability of a novel low-level light therapy (LTTT). A secondary aim was to tentatively assess efficacy. METHODS: A custom-built device comprising infrared (850 nm), red (660 nm), and violet (405 nm) LEDs was utilized. DUs were irradiated with 10 J/cm2 twice weekly for 3 weeks, with follow-up at weeks 4 and 8. Any safety concerns were documented. Patient opinion on time to deliver, feasibility, and pain visual analogue score (VAS; 0-100, 100 most severe) was collected. Patient and clinician DU global assessment VAS were documented. DUs were evaluated by laser Doppler perfusion imaging pre- and post-irradiation. RESULTS: In all, 14 DUs in eight patients received a total of 46 light exposures, with no safety concerns. All patients considered LTTT 'took just the right amount of time' and was 'feasible', with a low associated mean pain VAS of 1.6 (SD: 5.2). Patient and clinician global DC VAS improved during the study (mean change: -7.1 and -5.2, respectively, both p < .001). DU perfusion significantly increased post-irradiation. CONCLUSIONS: LTTT for DUs is safe, feasible, and well tolerated. There was an early tentative suggestion of treatment efficacy.

Sunlight exposure behaviour and vitamin D status in photosensitive patients: longitudinal comparative study with healthy individuals at U.K. latitude.

BACKGROUND: Low vitamin D status is prevalent in wintertime in populations at northerly latitudes. Photosensitive patients are advised to practise sun avoidance, but their sunlight exposure levels, photoprotective measures and resulting vitamin D status are unknown. OBJECTIVES: To examine seasonal vitamin D status in photosensitive patients relative to healthy individuals and to assess quantitatively behavioural and demographic contributors. METHODS: This was a longitudinal prospective cohort study (53·5°N) examining year-round 25-hydroxyvitamin D [25(OH)D] levels, sun-exposure behaviour and oral vitamin D intake in photosensitive patients diagnosed at a photoinvestigation unit (n = 53), compared with concurrently assessed healthy adults (n = 109). RESULTS: Photosensitive patients achieved seasonal 25(OH)D variation, but insufficient (< 20 ng mL(-1); 50 nmol L(-1)) and even deficient (< 10 ng mL(-1); 25 nmol L(-1)) levels occurred at the summer peak in 47% and 9% of patients, respectively, rising to 73% and 32% at the winter trough. Adjusting for demographic factors, the mean values were lower than for healthy volunteers by 18% [95% confidence interval (CI) 4-29] in summer (P = 0·02) and 25% (95% CI 7-39) in winter (P = 0·01). Behavioural factors explained 25(OH)D differences between cohorts. Patients demonstrated lower weekend ultraviolet B doses (P < 0·001), smaller skin surface area exposure (P = 0·004) and greater sunscreen use (P < 0·001), while average oral vitamin D intake was low in both groups (photosensitive: 2·94 µg per day). Supplementation and summer surface area exposure predicted summer peak and winter trough 25(OH)D levels. A 1 µg per day increment in supplementary vitamin D raised summer and winter 25(OH)D by 5% (95% CI 3-7) and 9% (95% CI 5-12), respectively (both P < 0·001). CONCLUSIONS: Photosensitive patients are, through their photoprotective measures, at high risk of year-round low vitamin D status. Guidance on oral measures should target this patient group and their physicians.

Lifestyle factors including less cutaneous sun exposure contribute to starkly lower vitamin D levels in U.K. South Asians compared with the white population.

BACKGROUND: Long-standing concerns over the vitamin D status of South Asian adults in the U.K. require studies using statistically valid sample sizes to measure annual variation and contributory lifestyle factors. OBJECTIVES: To measure annual variation in the vitamin D status of U.K. South Asians, to determine the associated lifestyle influences, and to compare these with a similar study of white adults. METHODS: A single-centre, prospective cohort study measuring circulating 25-hydroxyvitamin D [25(OH)D], sunlight exposure levels and lifestyle factors for 1 year in 125 ambulant South Asian adults with sun-reactive skin type V, aged 20-60 years, in Greater Manchester, U.K. (53·5°N). RESULTS: The 25(OH)D levels of South Asians were alarmingly low. In summer, their median 25(OH)D level was 9·0 ng mL(-1) , [interquartile range (IQR) 6·7-13·1], falling to 5·8 ng mL(-1) (IQR 4·0-8·1) in winter. This compared with values in the white population of 26·2 ng mL(-1) (IQR 19·9-31·5) in summer and 18·9 ng mL(-1) IQR (11·6-23·7) in winter. Median daily dietary vitamin D was lower in South Asians (1·32 µg vs. 3·26 µg for white subjects) and was compounded by low supplement use. Despite similar times spent outdoors, ultraviolet (UV) dosimeters recorded lower personal UV exposure among South Asians, indicating sun avoidance when outside, while sun exposure diaries recorded lower amounts of skin surface exposure. CONCLUSIONS: The majority of South Asians never reached sufficiency in vitamin D status. Lifestyle differences, with lower oral intake, sun exposure and rates of cutaneous production due to darker skin, indicate that standard advice on obtaining sufficient vitamin D needs modification for the South Asian community in the U.K.

Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial.

BACKGROUND: Previous epidemiological, animal and human data report that lycopene has a protective effect against ultraviolet radiation (UVR)-induced erythema. OBJECTIVES: We examined whether tomato paste--rich in lycopene, a powerful antioxidant--can protect human skin against UVR-induced effects partially mediated by oxidative stress, i.e. erythema, matrix changes and mitochondrial DNA (mtDNA) damage. METHODS: In a randomized controlled study, 20 healthy women (median age 33 years, range 21-47; phototype I/II) ingested 55 g tomato paste (16 mg lycopene) in olive oil, or olive oil alone, daily for 12 weeks. Pre- and postsupplementation, UVR erythemal sensitivity was assessed visually as the minimal erythema dose (MED) and quantified with a reflectance instrument. Biopsies were taken from unexposed and UVR-exposed (3 × MED 24 h earlier) buttock skin pre- and postsupplementation, and analysed immunohistochemically for procollagen (pC) I, fibrillin-1 and matrix metalloproteinase (MMP)-1, and by quantitative polymerase chain reaction for mtDNA 3895-bp deletion. RESULTS: Mean ± SD erythemal D(30) was significantly higher following tomato paste vs. control (baseline, 26·5 ± 7·5 mJ cm(-2); control, 23 ± 6·6 mJ cm(-2); tomato paste, 36·6 ± 14·7 mJ cm(-2); P = 0·03), while the MED was not significantly different between groups (baseline, 35·1 ± 9·9 mJ cm(-2); control, 32·6 ± 9·6 mJ cm(-2); tomato paste, 42·2 ± 11·3 mJ cm(-2)). Presupplementation, UVR induced an increase in MMP-1 (P = 0·01) and a reduction in fibrillin-1 (P = 0·03). Postsupplementation, UVR-induced MMP-1 was reduced in the tomato paste vs. control group (P = 0·04), while the UVR-induced reduction in fibrillin-1 was similarly abrogated in both groups, and an increase in pCI deposition was seen following tomato paste (P = 0·05). mtDNA 3895-bp deletion following 3 × MED UVR was significantly reduced postsupplementation with tomato paste (P = 0·01). CONCLUSIONS: Tomato paste containing lycopene provides protection against acute and potentially longer-term aspects of photodamage.

Systemic photoprotection in solar urticaria with α-melanocyte-stimulating hormone analogue [Nle4-D-Phe7]-α-MSH.

BACKGROUND: Solar urticaria is a rare photosensitivity disorder demonstrating a range of action spectra, which can inflict a very large impact on life quality despite available treatments. Melanin broadly reduces skin penetration by ultraviolet-visible wavelengths, thus increased melanization may protect in solar urticaria. OBJECTIVES: To examine quantitatively for impact of the potent α-melanocyte stimulating hormone analogue afamelanotide ([Nle(4)-D-Phe(7)]-α-MSH, Scenesse(®); Clinuvel Pharmaceuticals Ltd, Melbourne, Vic., Australia) on the solar urticaria response and skin melanization. METHODS: Five patients with solar urticaria received a single dose of 16 mg subcutaneous afamelanotide implant in winter time. Melanin density was assessed spectrophotometrically from day 0 to day 60. Detailed monochromated light testing to geometric dose series (increment ) of wavelengths 300-600 nm was performed at 0, 30 and 60 days, with assessment of weal and flare area and minimum urticarial dose (MUD). Data were analysed by repeated-measures anova. RESULTS: Mean melanin density increased by day 7, peaked at day 15 and remained elevated at day 60 (P=0·03, 0·01, 0·02 vs. baseline, respectively). Baseline phototesting revealed action spectra of 320-400 (n=1), 320-500 (n=2), 300-600 (n=1) and 370-500 nm (n=1), and on afamelanotide mean rises in MUD of 1-12 and 1-3 dose increments were seen at the individual wavelengths tested, at 30 and 60 days, respectively. A significant fall in weal area occurred across responding wavelengths from 300 to 600 nm at 60 days postimplant (P=0·049 vs. baseline), accompanied by greater than twofold overall increase in MUD (P=0·058 vs. baseline). CONCLUSIONS: Melanization following afamelanotide is accompanied by reduction in solar urticaria response across a broad spectrum of wavelengths. Further study is warranted to assess clinical benefit under ambient conditions in summer.

The impact of photosensitivity disorders on aspects of lifestyle.

BACKGROUND: Photosensitivity disorders involve an abnormal skin reaction to sunlight exposure and affect a substantial percentage of the population. No previous studies have directly compared lifestyle attributes between photosensitive and healthy individuals. OBJECTIVES: To assess the impact of photosensitivity on time spent outdoors in the U.K., holiday behaviour, use of sunscreens and vitamin D supplements, and employment status. METHODS: Questionnaires were completed by ambulant photosensitive and healthy adults aged 18-60 years residing in Greater Manchester. RESULTS: Forty-five adults with moderate-severe photosensitivity and 124 healthy adults completed the questionnaire. This revealed that photosensitive subjects spent significantly less time outdoors in the U.K. on both summer weekdays (P < 0·01) and summer weekends (P < 0·0001) than healthy subjects, took fewer holidays per year (P < 0·05), and spent less time outdoors on a sunny holiday (P < 0·0001). They wore clothing that covered a wider skin area (P < 0·0001), and use of sunscreen was greater (both frequency of application and area covered) in the photosensitive group outside of holiday time (P < 0·0001), but not when on a sunny holiday, as healthy people increased their sunscreen use at this time. Despite the reduced sun exposure, photosensitive subjects were no more likely to take vitamin D supplements than healthy subjects were; they also exhibited a significantly higher rate of unemployment (P < 0·05). CONCLUSIONS: Photosensitivity disorders negatively influence lifestyle including employment status; more attention is required to the socioeconomic impact of these conditions.

Photoaggravated pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous condition with an estimated incidence of one in 35,000 to one in 50,000. Psoralen and ultraviolet A (UVA) therapy has been used in its treatment but some patients are reported to be clinically photosensitive. We describe the photoinvestigation of a patient with PRP in whom sensitivity to broadband UVA was demonstrated.

An update and guidance on narrowband ultraviolet B phototherapy: a British Photodermatology Group Workshop Report.

Summary These guidelines for use of narrowband (TL-01) ultraviolet B have been prepared for dermatologists by the British Photodermatology Group on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment of patients with a variety of dermatoses and photodermatoses, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of background photobiology.

UVR-induced oxidative stress in human skin in vivo: effects of oral vitamin C supplementation.

Previous studies of cultured skin cells and murine skin in vivo have indicated that UVR-induced damage involves the generation of reactive oxygen species and depletion of endogenous antioxidant systems. In order to explore the relevance of this to UVR-induced damage to human skin, we have undertaken a detailed examination of the time-course of changes in markers of oxidative stress in human skin following exposure to physiological amounts of UVR in vivo. In addition, we have examined the skin bioavailability of a common nutritional antioxidant, vitamin C, and have assessed the effects of supplementation on markers of oxidative stress. Our hypothesis was that acute exposure of human skin to UVR in vivo would lead to oxidation of cellular biomolecules that could be prevented by prior vitamin C treatment. A UVR-challenge of 120 mJ/cm2 of broadband UVB (peak 310 nm, range 270-400 nm) was applied to buttock skin of 8 healthy volunteers. This caused a rapid and significant rise in activity of skin catalase at 1 h and an increase in the oxidized/total glutathione ratio at 6 h post-UVR. AP-1 DNA binding also peaked at 1-6 h post-UVR, then declined rapidly to baseline levels. No significant changes were seen in skin malonaldehyde content. Oral vitamin C supplements (500 mg/day) were taken by 12 volunteers for 8 weeks resulting in significant rises in plasma and skin vitamin C content. Supplementation had no effect on the UVR-induced erythemal response. The skin malonaldehyde content was reduced by vitamin C supplementation, but surprisingly, reductions in the skin content of total glutathione and protein thiols were also seen. We speculate that this apparently paradoxical effect could be due to regulation of total reductant capacity by skin cells, such that vitamin C may have been replacing other reductants in these cells. No evidence was obtained for an effect of the supplementary vitamin C on the mild oxidative stress seen in human skin following UVR exposure.

Effects of micronutrient supplements on u.v.-induced skin damage.

Development of an orally-administered systemic agent that could reduce the effects of u.v. exposure on skin could potentially have a major effect on the incidence of skin cancers and photo-ageing. A number of micronutrients have been suggested to have metabolic properties that could induce this protection, and our data indicate that n-3 polyunsaturated fatty acids are particularly effective in this role. The mechanisms of action of n-3 polyunsaturated fatty acids appear to depend on their anti-inflammatory properties, acting to reduce the u.v.-induced release of cytokines and other mediators from a variety of skin cell types.

Cholesterol supplementation objectively reduces photosensitivity in the Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz (SLO) affected children have multiple congenital physical and mental abnormalities; photosensitivity to ultraviolet A (UVA) has recently become a recognized feature. We present a patient with SLO and prominent photosensitivity in whom detailed phototesting has been performed at baseline and following 6 months of cholesterol supplementation. There was significant improvement in the symptoms of photosensitivity, confirmed objectively by phototesting and accompanied by partial correction of the biochemical abnormalities seen in SLO. This case report is the first to show that cholesterol supplementation in SLO can lead to an objective improvement in the associated photosensitivity.

Reduction in 8-methoxypsoralen immersion time alters the erythemal response to bath PUVA.

Topical psoralen plus ultraviolet A (PUVA) using 8-methoxypsoralen (8-MOP) bath solution is a well established and effective treatment in dermatology. The standard immersion time in the UK is 15 min, but a shorter bathing period could potentially increase treatment convenience. In order to examine the effect of reduction in immersion time on skin phototoxicity, we compared the erythemal response to UVA following 5 min and 15 min psoralen baths. The study was performed on the forearm skin of 7 healthy volunteers using an 8-MOP psoralen concentration of 2.6 mg/l. One forearm of each volunteer was soaked for 15 min and the other for 5 min, followed by immediate irradiation with a series of 10 doses of broadband UVA ranging from 0.1 J/cm2 to 6.9 J/cm2. At 72 h, the minimal phototoxic doses (MPDs) were noted and erythema readings (erythema index) were taken in triplicate with a reflectance instrument. The median MPD following 5 min immersion was 1.7 (range 0.7-2.7) J/cm2 compared with 1.0 (range 0.4-1.7) J/cm2 after 15 min treatment, with no significant difference. However, the mean slope of erythema dose-response on the 15-min treated side was significantly steeper than on the 5-min treated side, 0.036 and 0.021 respectively, P < 0.05. Hence, this preliminary work shows that reducing 8-MOP immersion time to 5 min reduces the erythemal response to UVA. It will clearly be necessary to examine the effect of a shortened immersion period on disease clearance before considering such a change to the topical PUVA regime.

Guidelines for topical PUVA: a report of a workshop of the British photodermatology group.

Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions.1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.

Home phototherapy: report on a workshop of the British Photodermatology Group, December 1996.

Phototherapy is a popular and effective treatment for many patients with skin diseases. However, repeated journeys to hospital for phototherapy can be inconvenient and expensive. If it were available, many patients might prefer home-based phototherapy as long as it was safe and effective. Indeed, many psoriasis patients already self-treat with ultraviolet A sunbeds at home. This report represents a consensus view from a British Photodermatology Group workshop held in December 1996, the purpose of which was to examine the potential role of home-based phototherapy in dermatological practice. We conclude that home-based therapy represents a suboptimal treatment with greater attendant risks than phototherapy in a hospital environment. The level of medical supervision of the home treatment is crucial to its safety and effectiveness. Until further studies are forthcoming, home phototherapy should be largely restricted to those with overwhelming difficulties in attending hospital.

Dietary fish oil as a photoprotective agent in hydroa vacciniforme.

Hydroa vacciniforme is a troublesome and scarring photosensitivity disorder for which treatment is unsatisfactory. Dietary fish oil rich in omega-3 polyunsaturated fatty acids reportedly increases the resistance to ultraviolet-induced erythema and rash provocation in polymorphic light eruption. We report for the first time the response of hydroa vacciniforme to dietary fish oil. Three Caucasian boys with the condition were placed on MaxEPA, five capsules daily. Phototesting was performed at baseline and after 3 months supplementation. At baseline, low erythemal thresholds were seen to monochromated UVA at 350 and 370 nm in all three boys, while one also had a low threshold to 320 nm (UVA) and another showed a low threshold to 300 nm (UVB). Broad-band UVA provocation challenge produced typical skin lesions in all the subjects. Following fish oil, all the boys showed reduced erythemal sensitivity to UVA and one also showed reduced sensitivity to UVB. Provocation challenge revealed a reduced response in all three children. Clinically, these changes were accompanied by pronounced improvement in one child, mild improvement in the second child, but no improvement in the third. The third boy subsequently showed good clinical response to azathioprine.

Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels in skin and increases the threshold to provocation of polymorphic light eruption.

The sunburn response is markedly reduced by dietary fish oil rich in omega-3 polyunsaturated fatty acids. Because prostaglandins mediate the vasodilatation, we examined the effect of fish oil on ultraviolet (UV) B-induced prostaglandin metabolism. In addition we assessed the potential photoprotective effect of fish oil in light-sensitive patients. Thirteen patients with polymorphic light eruption received dietary supplements of fish oil rich in omega-3 polyunsaturated fatty acids for 3 months. At baseline and 3 months, the minimal erythema dose of UVB irradiation was determined, and a graded UVA challenge given to a forearm to assess the threshold dose for papule provocation. Suction blisters were raised on the other forearm, on control skin, and on skin irradiated with four times the minimal erythema dose of UVB 24 h previously, and blister fluid prostaglandin E2 was measured by radioimmunoassay. Following 3 months of fish oil, the mean minimal erythema dose of UVB irradiation increased from 19.8 +/- 2.6 to 33.8 +/- 3.7 mJ/cm2 (mean +/- SEM), p < 0.01. The UVA provocation test was positive in 10 patients at baseline, and after 3 months nine of these showed reduced sensitivity to papule provocation, p < 0.001. Before fish oil, PGE2 increased from 8.6 (SEM 2.1) ng/ml in control skin to 27.2 (11) ng/ml after UVB, p < 0.01. Following 3 months of fish oil, PGE2 decreased to 4.1 (1) and 9.6 (2.4) ng/ml in control and irradiated skin, respectively, p < 0.05. Reduction of UV-induced inflammation by fish oil may be due, at least partially, to lowered prostaglandin E2 levels. The photoprotection against UVA-provocation of a papular response suggests a clinical application for fish oil in polymorphic light eruption.

Dietary fish-oil supplementation in humans reduces UVB-erythemal sensitivity but increases epidermal lipid peroxidation.

Ultraviolet radiation (UVR)-induced erythema may be mediated in part by free radical-generated tissue damage, including lipid peroxidation. We have examined the effect of dietary fish oil rich in omega-3 fatty acids upon susceptibility to UVB-induced erythema and epidermal lipid peroxidation. Fifteen volunteers took 10 g fish oil, containing 18% eicosapentaenoic acid and 12% docosahexaenoic acid, daily for 3 or 6 months. Sensitivity to UVB was assessed at intervals on fish oil, and 2.5 months after stopping treatment. Paired skin shave biopsies were taken from six subjects, at baseline and 3 months, from both irradiated and control skin. Fatty acid composition was analyzed and thiobarbituric acid-reactive substances measured as an index of lipid peroxidation. With increasing time on fish oil the minimal erythema dose rose progressively, from 18.9 +/- 13.9 mJ/cm2 (mean +/- SD) at baseline to 41.1 +/- 16.6 mJ/cm2 at 6 months, p < 0.01. Ten weeks after stopping fish oil the minimal erythema dose fell to 23.1 +/- 4.9 mJ/cm2, p < 0.05. Epidermal total omega-3 fatty acids rose from 1.8 +/- 0.4% total fatty acids (mean +/- SEM) to 24.2 +/- 3.9% at 3 months, p < 0.01. This was accompanied by a rise in thiobarbituric acid-reactive substances in irradiated skin from 6 +/- 0.3 (mean +/- SEM) to 18.5 +/- 2.6 A532/g skin, p < 0.01. Hence dietary omega-3 fatty acids produce a pronounced reduction in UVB-erythemal sensitivity, although susceptibility of skin to lipid peroxidation is increased. Thus, omega-3 fatty acids may act as an oxidizable buffer, protecting more vital structures from free radical damage.

PUVA and methotrexate therapy of psoriasis: how closely do dermatology departments follow treatment guidelines? Psoriasis Audit Workgroup of the British Association of Dermatologists.

Following publication of treatment guidelines for patients with psoriasis, a six-centre audit was undertaken to assess current therapeutic practice for two second-line treatments, PUVA and methotrexate. The audit consisted of random sampling of casenotes by external auditors from a paired dermatology department, and assessment by questionnaire. One hundred and eight PUVA and 118 methotrexate casenotes were audited. The commonest indications for treatment were: (a) failure of tropical therapy--PUVA (mean 81% of casenotes), methotrexate (84%); (b) repeated hospital admissions--PUVA (16%), methotrexate (25%). For both PUVA and methotrexate, some aspects of treatment were well documented: PUVA--psoralen dosage (91%), response to PUVA (89%), cumulative lifetime UVA dosage (81%); methotrexate--pretreatment assessment of full blood count (91%), urea and electrolytes (85%), liver function tests (84%). For other aspects documentation was less complete: PUVA--no documentation of presence/absence of skin cancer history (66%), note of photoactive drugs (32%); methotrexate--concurrent medication (69%), history of presence/absence of liver disease (36%). Another aspect which was poorly documented in both PUVA and methotrexate notes was whether advice on contraception/fertility had been given. There was no indication in 29 of 32 casenotes of females of child-bearing age receiving PUVA, and 52 of 63 case notes of relevant patients on methotrexate. This project has demonstrated that formal, multicentre audit based on published guidelines is a practical proposition.