Solar urticaria (SU) is a rare, poorly understood photodermatosis characterized by inappropriate mast cell degranulation following cutaneous exposure to sunlight. Based on a lack of Mendelian inheritance in families and its onset in adulthood with limited impact on reproductive fitness, SU is likely a complex trait whose development is determined by genetic and environmental factors. Its rarity and unusual phenotype, which constitutes an extreme aberration of physiological responses to sunlight, imply that its genetic architecture may be underpinned by rare, highly penetrant and deleterious variants. To investigate this, we performed a case–control whole-exome sequencing gene association study in SU. Forty-six patients of European ancestry with phototest-confirmed SU underwent whole-exome sequencing. Healthy control whole exomes (n = 971) were derived from the 1958 British Birth Cohort. Following quality control, joint variant calling and variant filtering to retain rare, high-impact variants, burden testing was performed. Sanger sequencing and bioinformatic resources were used to validate and explore identified genes/variants. Burden testing revealed exome-wide significant enrichment of rare, high-impact variants in ACACA among SU cases (P = 4.7 × 10−7). This gene encodes acetyl-coenzyme A carboxylase alpha, an enzyme that catalyses the rate-limiting step in de novo lipogenesis. Six of 46 SU cases carried rare, heterozygous missense variants in ACACA compared with 3 of 971 controls. Sanger sequencing validated the presence of these variants in ACACA. Structural analyses demonstrated that ACACA variants were predicted to decrease protein stability. Reanalysis of single-cell RNA sequencing data from skin confirmed ACACA expression in all cell types, including mast cells. Enrichment of rare, deleterious ACACA variants among patients with SU suggests a role for altered lipid metabolism, potentially affecting mast cell function, in SU pathogenesis. Characterization of lipid-mediated disease mechanisms in SU should form the basis of future investigations.

Abstract Ultraviolet radiation (UVR) is a major environmental factor affecting human skin, yet the early molecular effects of everyday low-dose exposure remain poorly understood. The objective of this study was to examine the acute molecular and cellular responses to low-dose single and repeated UVR exposure in healthy human skin. Six volunteers (five female, one male; age 28–65 years; skin types II–III) received 10 J cm−2 of solar simulated UVR (290–400 nm), equivalent to around 30 min of UK midday summer sunlight, on an area of upper buttock skin on three consecutive days. Skin biopsies were collected at 30 min, 3 h and 24 h after the first exposure, at 24 h following the third exposure, and from unexposed skin. Biopsies were analysed using immunohistochemistry and RNA sequencing, with predictive analysis from Ingenuity Pathway Analysis software. A single UVR exposure induced only modest transcriptional changes, with 27, 87 and 137 differentially expressed genes (> 1 log2 fold change, q < 0.05) detected at 30 min, 3 h and 24 h, respectively. In contrast, repeated daily exposure induced a pronounced response, with 1498 differentially expressed genes, including 333 long noncoding RNAs. Enriched pathways included cell cycle regulation, melanogenesis, interferon signalling and proinflammatory responses, with predicted activation of upstream regulators ELDR, MITF, VEGF genes, TNF and interferons. Immunohistochemistry after three exposures showed increased epidermal proliferation (Ki-67) and mild immune infiltration (CD4+ and CD8+ T cells, dendritic cells and neutrophils). CIBERSORT also suggested shifts in immune cell proportions after repeated UVR, although these changes were not statistically significant. These findings provide insights into the wide range of transcriptional changes occurring in healthy human skin following low-dose UVR exposure, and indicate that the skin does not return to baseline within 24 h, resulting in cumulative effects with subsequent exposures. Brief UVR exposures as experienced in daily life may profoundly influence skin physiology and health.

Abstract Skin solar ultraviolet radiation (UVR) exposure is a major source of vitamin D synthesis, but UVR concurrently causes skin DNA damage, which may contribute to skin cancer risk. The relationship between these beneficial and hazardous effects may vary by skin phototype. This study aimed to examine the relationship between the vitamin D (UVR-benefit) and skin DNA damage (UVR-harm) concurrently produced following UVR exposure, and to evaluate how this relationship differs across skin phototypes. A systematic review was performed in accordance with the PRISMA guidelines to identify human intervention studies reporting both changes in serum 25-hydroxyvitamin D levels and markers of skin DNA damage following UVR exposure. Literature searches were performed on 26 January 2025 across four databases (PubMed, MEDLINE OVID, MEDLINE Embase and Scopus). Studies were appraised using the National Heart, Lung and Blood Institute quality assessment tools. The findings were synthesized narratively and summarized in tables to inform evidence-based sun-exposure recommendations. The PROSPERO registration number for this study is CRD42025625834. Four studies, comprising data from 158 participants, were included. All studies were assessed as having fair-to-good quality. Two studies on solar-simulated radiation explored the effects of low-level exposure, while two sunlight studies explored the effects of high-level exposures, on 25-hydro­xy­vitamin D gain and cyclobutane pyrimidine dimer (CPD) formation. UVR exposure benefited vitamin D status and generated CPDs across all phototypes. Individuals with darker skin required higher exposure to achieve vitamin D sufficiency, with CPD formation not detected in basal (dividing) epidermal cells where epidermal localization was assessed. In contrast, individuals with the lightest skin phenotypes did not achieve vitamin D gains without concurrent basal cell CPD formation. These findings demonstrate phototype-specific differences in the balance between vitamin D benefit and UVR-induced DNA damage, which have implications for personalized sun-exposure guidance and the role of vitamin D supplementation.

Abstract Introduction and aims The skin and its resident microbiota are routinely exposed to ultraviolet radiation (UVR) from sunlight. Although UVR effects on skin are well described, it is not fully understood how the skin microbiota, an important modulator of skin immunity and barrier integrity, regulates the human cutaneous response to UVR exposure. We aimed to determine whether the human skin microbiota alters keratinocyte apoptosis and proliferation in vivo after UVR exposure. Methods Healthy volunteers [n = 10; Fitzpatrick skin types I–III; mean age 31.6 years (SD 2.47)] participated in a controlled clinical study. The right upper back was disinfected with 70% ethanol (we previously showed this to reduce skin microbiota for up to 6 h), then exposed to 80 mJ cm−2 erythemally weighted solar-simulated UVR. The contralateral nondisinfected sites were similarly exposed. Skin biopsies were collected from irradiated and matched unirradiated sites at 0.5 h and 24 h post-UVR exposure. Gene expression and pathway enrichment at 24 h postexposure was assessed by spatial transcriptomics (Xenium, n = 3). Keratinocyte apoptosis (TUNEL) and proliferation (Ki67) were quantified by immunostaining (n = 10) at 0.5 h and 24 h postexposure. Results At 24 h post-UVR exposure, keratinocytes from UVR-irradiated, disinfected skin showed relatively higher expression of cell-cycle/proliferation-associated genes, whereas keratinocytes from UVR-irradiated, nondisinfected skin showed relatively higher expression of apoptosis effector genes. Compared with nonirradiated skin, ingenuity pathway analysis predicted upregulation of cell-cycle/proliferation signalling in disinfected skin and TP53-related cell-death transcriptional signalling in nondisinfected skin. Consistent with this, UVR-irradiated, disinfected skin had significantly fewer TUNEL+ keratinocytes (P = 0.046) and significantly more Ki67+ keratinocytes (P = 0.042) than UVR-irradiated, nondisinfected skin. Conclusions Reduction of the skin microbiota alters human cutaneous response to UVR exposure at both transcriptomic and protein levels, indicating that the skin microbiota may promote keratinocyte apoptosis and suppress keratinocyte proliferation after UVR exposure. This broadens understanding of microbiota–host interactions in UVR-induced skin responses.

This Assessment Update by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) addresses the interacting effects of changes in stratospheric ozone, solar ultraviolet (UV) radiation, and climate on the environment and human health. These include new modelling studies that confirm the benefits of the Montreal Protocol in protecting the stratospheric ozone layer and its role in maintaining a stable climate, both at low and high latitudes. We also provide an update on projected levels of solar UV-radiation during the twenty-first century. Potential environmental consequences of climate intervention scenarios are also briefly discussed, illustrating the large uncertainties of, for example, Stratospheric Aerosol Injection (SAI). Modelling studies predict that, although SAI would cool the Earth’s surface, other climate factors would be affected, including stratospheric ozone depletion and precipitation patterns. The contribution to global warming of replacements for ozone-depleting substances (ODS) are assessed. With respect to the breakdown products of chemicals under the purview of the Montreal Protocol, the risks to ecosystem and human health from the formation of trifluoroacetic acid (TFA) as a degradation product of ODS replacements are currently de minimis. UV-radiation and climate change continue to have complex interactive effects on the environment due largely to human activities. UV-radiation, other weathering factors, and microbial action contribute significantly to the breakdown of plastic waste in the environment, and in affecting transport, fate, and toxicity of the plastics in terrestrial and aquatic ecosystems, and the atmosphere. Sustainability demands continue to drive industry innovations to mitigate environmental consequences of the use and disposal of plastic and plastic-containing materials. Terrestrial ecosystems in alpine and polar environments are increasingly being exposed to enhanced UV-radiation due to earlier seasonal snow and ice melt because of climate warming and extended periods of ozone depletion. Solar radiation, including UV-radiation, also contributes to the decomposition of dead plant material, which affects nutrient cycling, carbon storage, emission of greenhouse gases, and soil fertility. In aquatic ecosystems, loss of ice cover is increasing the area of polar oceans exposed to UV-radiation with possible negative effects on phytoplankton productivity. However, modelling studies of Arctic Ocean circulation suggests that phytoplankton are circulating to progressively deeper ocean layers with less UV irradiation. Human health is also modified by climate change and behaviour patterns, resulting in changes in exposure to UV-radiation with harmful or beneficial effects depending on conditions and skin type. For example, incidence of melanoma has been associated with increased air temperature, which affects time spent outdoors and thus exposure to UV-radiation. Overall, implementation of the Montreal Protocol and its Amendments has mitigated the deleterious effects of high levels of UV-radiation and global warming for both environmental and human health.

Vitamin D may mitigate bone stress injuries in military training by modulating changes in bone. This cross-sectional observational study (Study 1) and randomized controlled trial (Study 2) investigated associations between vitamin D metabolites and tibial structure and density, and the effect of vitamin D supplementation on tibial adaptations to military training. A total of 343 (Study 1) and 194 (Study 2) male British Army recruits participated. Circulating vitamin D metabolites (biologically "active" and "inactive") and tibial structure were measured in participants during week 1 and week 12 (Study 2 only) of initial military training. Associations between vitamin D metabolites and HRpQCT outcomes at week 1 were tested in Study 1. Participants in Study 2 were randomly assigned to vitamin D (oral pill or simulated sunlight) or placebo (placebo pill or placebo simulated sunlight) supplementation for 12 wk designed to achieve vitamin D sufficiency. There was no association between total 25(OH)D or vitamin D receptor single-nucleotide polymorphisms and any measure of density, geometry, or microarchitecture (p ≥ .063). Higher 1,25(OH)2D was associated with lower cortical porosity and perimeter (p ≤ .040). Higher total 24,25(OH)2D was associated with higher trabecular number and lower trabecular thickness (p = .016). Higher 25(OH)D:24,25(OH)2D (VMR 1) was associated with higher trabecular thickness, trabecular separation, and cortical porosity (p ≤ .034). Higher 1,25(OH)2D:24,25(OH)2D (VMR 2) was associated with lower trabecular number, and higher trabecular spacing and thickness (p ≤ .035). There was no effect of vitamin D supplementation on any tibial outcome. Training decreased trabecular area (-0.1%), thickness (-4.4%), and separation (-2.1%), and increased cortical thickness (0.8%) and area (0.9%) (p ≤ .042). Vitamin D metabolites and their ratios were associated with tibial size and microarchitecture, but vitamin D supplementation had no impact on the adaptive response to military training.

Background: In addition to the well-known vitamin D metabolites 25(OH)D and 1,25(OH)2D, the catabolite 24,25(OH)2D may also reflect vitamin D status and influence biological and skeletal processes. However, the effects of UVR-induced synthesis on 24,25(OH)2D levels and the 25-VMR (24,25(OH)2D3:25(OH)D3 ratio) remain unclear. Objectives: We aimed to assess how a single standardised UVR dose influences the production of 25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3 and 25-VMR, with a comparison between younger and older adults being conducted to explore potential age-related differences in vitamin D metabolism. Methods: A total of 11 young (18-40 years; 7M, 4F) and 10 older (65-89 years; 6M, 4F) skin type I-III volunteers received a single sub-erythemal dose of solar simulated UVR (SSR) (95% UVA: 320-400 nm, 5% UVB: 290-320 nm, 1.3 standard erythemal dose) during winter time in the UK (vitamin D trough season), exposing approximately 35% of the body surface area. The Blood was assayed for 25(OH)D3, 24,25(OH)2D3 and 1,25(OH)2D3 using LC-MS/MS at baseline, 24 h and 7 days following UVR exposure. Results: There was a significant increase in 25(OH)D3 from baseline (44 ± 22 nmoL/L) to 24 h post-UVR (48 ± 22 nmoL/L) in the combined age group (p = 0.044), but no significant differences were found in 24,25(OH)2D3 in the combined group, or between young and older volunteers for both metabolites. 1,25(OH)2D3 concentrations were higher in young groups (163 ± 60 pmoL/L) than in older (105 ± 38 pmoL/L) groups at 7 days post-UVR (p = 0.044). The 25-VMR decreased from baseline (9 ± 3) to 24 h post-UVR (7.5 ± 2.1) in the combined group (p = 0.003). Conclusions: Our data suggest that a single sub-erythemal UVR challenge does not influence 24,25(OH)2D3 concentration in younger and older adults at 24 h and 7 days post-UVR and that the significant difference seen in the 25-VMR between baseline and 24 h post-UVR is due to the increase in 25(OH)D3 concentration post-UVR. This is in line with vitamin D oral supplementation studies, and indicates that low doses of UVR trigger the metabolic pathway, without affecting the catabolic pathway.

Vitamin D3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC concentration differs between younger and older adults and (2) the impact of older age on serum vitamin D3 response to solar simulated UVR. Eleven younger (18–40 years) and 10 older (65–89 years) adults, phototype I–III, received low-dose UVR (95% UVA, 5% UVB, 1.3 SED) to ~35% of the body surface area. Biopsies were taken for 7DHC assay from unexposed skin, skin immediately and 24 h post-UVR, and blood sampled at baseline, 24 h and 7 d post-UVR for vitamin D3 assay. Samples were analysed by HPLC-MS/MS. Baseline skin 7DHC (mean ± SD) was 0.22 ± 0.07 and 0.25 ± 0.08 µg/mg in younger versus older adults (no significant difference). Baseline serum vitamin D3 concentration was 1.5 ± 1.5 and 1.5 ± 1.7 nmol/L in younger versus older adults, respectively, and showed a significant increase in both groups post-UVR (no significant differences between age groups). Thus, skin 7DHC concentration was not a limiting factor for vitamin D3 production in older relative to younger adults. This information assists public health guidance on sun exposure/vitamin D nutrition, with particular relevance to the growing populations of healthy ambulant adults ≥65 years.

Abstract Photoaggravated atopic dermatitis (PAD) is a subtype of atopic dermatitis (AD) that is exacerbated or provoked by exposure to ultraviolet radiation. However, its early pathomechanisms are poorly understood. Our aims were (i) to investigate cutaneous clinical, barrier, cellular and molecular changes in the evolution of PAD following low-dose solar simulated ultraviolet radiation (SSR) exposure, and (ii) to compare the findings in healthy controls exposed to the same SSR challenge. Three consecutive daily low-dose (10 J cm−2) SSR exposures were delivered to upper buttock skin of six patients with PAD and six healthy controls. Biopsies were taken from unexposed skin and from SSR-exposed skin at 30 min, 3 h and 24 h after the first exposure, and at 24 h after the third exposure (4 days from baseline). Biopsies were analysed by RNA sequencing using immunohistochemistry and Ingenuity Pathway Analysis. Baseline (unexposed) comparison of PAD vs. healthy control skin revealed 838 differentially expressed genes including significant upregulation of molecules associated with AD, such as inflammatory cytokines and chemokines (CCL1, CCL13, CCL18; all P < 0.01) and epidermal differentiation and proliferation markers (LCE3A, SPRR2B, S100A7; all P < 0.01), along with functional enrichment of immune cell trafficking, T helper (Th)2 pathway response, and cell signalling. Following SSR, clinically and histologically eczematous responses were provoked in patients with PAD, with histological abnormalities becoming progressively more abnormal from baseline to 4 days. Erythema scores were higher in PAD skin than in healthy controls at 24 h and 4 days (24-h erythema score 11.3 vs. 6.8, P < 0.01). In PAD 3 h post-SSR, transcriptomic analysis indicated activation or recruitment of lymphocytes, neutrophils and antigen-presenting cells (all P < 0.001 vs. unexposed skin). Upregulated cytokine genes included IL22, IL20 and IL6 (all P < 0.01 vs. unexposed skin). Interleukin (IL)-1α, tumour necrosis factor and several Toll-like receptors were identified as activated upstream regulators. These findings were not seen in healthy controls, and indicated that innate, Th1 and Th22 activation was provoked by SSR at an early stage. By 24 h post-SSR, additional upregulation of IL13 and CCL17 was consistent with augmented Th2 responses alongside more histologically eczematous features, including lymphocytic infiltration, acanthosis and spongiosis. The evolving dermal inflammatory infiltrate included dual positive CD4+ GATA3+, as well as CD69+ and CD11c+ cells, suggesting involvement of resident memory cells, myeloid dendritic cells and Th2 lymphocytes. In conclusion, PAD was characterized by a predominant Th2 signature, with the additional early involvement of pattern recognition responses, and innate and adaptive immune cells. These findings may inform treatment strategies for flares of both PAD and AD.

Abstract Solar urticaria (SU) is a rare immunologically mediated photodermatosis caused by abnormal cutaneous mast cell degranulation following exposure to solar radiation. It manifests as the rapid development of erythemal flares, weals and/or angio-oedema following sunlight exposure and is associated with anaphylaxis-like symptoms in severe cases. Unsurprisingly, it has a significant impact on patients’ quality of life. As part of a genetic investigation of SU pathobiology, we have undertaken a descriptive cross-sectional study of the demographic, clinical and photobiological features of patients with SU recruited from six UK tertiary photobiology units. Clinical and genetic material were collected from participants following informed consent (19/EM/0312 and 07/H0802/104). Eligibility criteria were a diagnosis of SU made by a consultant dermatologist and confirmed by phototesting. Patients with comorbid porphyrin disorders were excluded. A standardized case report form was used to collect demographic, clinical and photobiological features. A descriptive and exploratory statistical ana­lysis was performed using the R statistical programme (R Foundation, Vienna, Austria). When data were missing for a participant, they were excluded from the relevant analysis. Of 178 included individuals, 66.9% were female and the mean age of disease onset was 36 years (range 1–82). Reported ethnicity was European in 90.2%, South Asian in 5.7%, East Asian in 1.1%, and African, Afro-Caribbean or mixed in 2.9%. Skin phototype was reported as phototype I (16.6%), phototype II (57.3%), phototype III (14.6%), phototype IV (4.5%), phototype V (5.1%) and phototype VI (1.9%). Photoprovocation was achieved using monochromator phototesting in 94.2%, while 5.8% could only be provoked using a solar simulator. Based on monochromator phototesting, the most common pathogenic waveband was ultraviolet A alone (28.1%). Among individuals with skin phototypes I–III, the most common pathogenic wavebands were ultraviolet A and visible light (29.9%), and among skin phototypes IV–VI, it was ultraviolet A and ultraviolet B (25.0%). Over half of the patients (57.3%) had coexisting atopic disorders (eczema, hay fever or asthma), while 15.2% had another photodermatosis, and 27.0% reported another type of urticaria. Sunscreen was used by 92.1% of patients, as were H1-receptor antagonists (92.1%), while 37.1% used H2-receptor antagonists, 44.4% used montelukast, and 20.2% used omalizumab. Of those treated with H1-receptor antagonists (n = 164), 75.0% reported that they were partially or completely effective. Omalizumab was reported to be completely or partially effective in 29 of 36 (81%) treated patients. In conclusion, this study summarizes the demographic and clinicophotobiological features of SU in the UK, while also highlighting the effectiveness of H1-receptor antagonist and omalizumab treatment in many cases.

Understanding skin health and disease across global populations is of great importance yet the majority of studies focus primarily on individuals with lightly-pigmented skin. We obtained skin biopsies from photoprotected buttock of healthy, young (18-40 years; n = 33) individuals of black African, South Asian, Hispanic and white European ancestries. Our study cohort demonstrated diversity of pigmentation levels, with skin types ranging from lightest to darkest according to Individual Typology Angle (ITA) – an objective spectrophotometric skin colour classification consisting of 6 groups: 'very light'; 'light'; 'intermediate'; 'tan'; 'brown'; and 'dark'. In the 'dark' and 'brown' groups, epidermal thickness and dermal-epidermal junction (DEJ) convolution were significantly increased as compared to those in the 'light' and 'very light' groups, whereas measurements for the 'tan' and 'intermediate' groups were midway (P < 0.001). Fibrillin-rich microfibrils (FRM) are located at the DEJ in candelabra-like cascades, with concentration at the base of rete pegs. The distribution of FRM was assessed across all skin types; for individuals in 'dark' or 'brown' groups FRM were significantly more abundant (44.5% and 40.2%, respectively) than those in 'light' and 'very light' groups (28.6% and 26.9%, respectively), whereas those in the 'tan' or 'intermediate' groups were midway (33.7% and 30.8%, respectively; P < 0.001). A positive correlation exists between DEJ convolution and FRM abundance (r = 0.379; P < 0.001) suggesting that FRM may contribute to DEJ structure and integrity. This study demonstrates that fundamental differences exist in skin structure and composition in individuals of diverse geographical ancestry and suggest a role for FRM in DEJ architecture.

BACKGROUND:Systemic drugs are a potentially reversible cause of photosensitivity. We explore prevalence, impact, phototest findings and culprit drugs. METHODS:Retrospective review of patients was diagnosed with drug-induced photosensitivity in a specialist photoinvestigation centre (2000-2016), using data recorded in standardized pro forma. Patients underwent detailed clinical evaluation. Monochromator phototesting was performed to 300 ± 5 nm, 320 ± 10 nm, 330 ± 10 nm, 350 ± 20 nm, 370 ± 20 nm, 400 ± 20 nm, 500 ± 20nm and 600 ± 20 nm. Broadband UVA and solar-simulated radiation (SSR) testing were performed, and photopatch testing and laboratory tests examined for other causes of photosensitivity. DLQI was evaluated. RESULTS:Prevalence of drug-induced photosensitivity was 5.4% (122/2243) patients presenting with photosensitivity. Patients with drug-induced photosensitivity were 52.5% female; median 62 years (range 11-86); phototype I (17.2%), II (39.3%), III (26.2%), IV (6.5%), V (4.1%). Fifty-five (45.1%) patients had reduced erythemal thresholds on monochromator phototesting: 83.6%% to UVA alone, 14.5% to both UVA and UVB, 1.8% to UVA and visible light; 61.4% (n = 75) showed abnormal response to broadband UVR. Drugs implicated: quinine (11.5%), diuretics (10.7%; thiazide 9.8%), antifungals (9.8%), proton-pump-inhibitors (9.8%), angiotensin-converting enzyme inhibitors (7.4%), anti-inflammatory drugs (6.6%), statins (5.7%), selective serotonin reuptake inhibitors (4.9%), calcium channel antagonists (3.3%), anti-epileptics (3.3%), tricyclic antidepressants (3.3%), beta-blockers (2.5%), antibiotics (2.5%), others (≤1.6% cases each). Emerging culprits included azathioprine (2.5%) and biologics (TNF-α inhibitors, denosumab; 2.5%). Median DLQI was 11 (range 2-27) for the past year. CONCLUSION:Classically described photosensitizing drugs such as thiazides and quinine remain common offenders, while emerging culprits include biologics such as TNF-a inhibitors and proton-pump-inhibitors. There is very large impact on life quality; identification facilitates measures including drug cessation and implementation of appropriate photoprotection.

A 6-year-old boy presented with a 2-year history of recurrent episodes of painful, haemorrhagic vesicles and erythema affecting the face, ears and neck, 2 hours after sun exposure (figures 1 and 2). He had severe ulceration and crusting affecting the helix of his ear (figure 3). Healing was accompanied by residual varioliform, atrophic scarring (figure 4). His rash occurred during spring and summer months and only affected sun-exposed sites. Figure 1 Tender erythematous vesicles and papules …

Linked Article: Passeron et al. Br J Dermatol 2019; 181:916-31.

Public health guidance recommends limiting sun exposure to sub-sunburn levels, but it is unknown whether these can gain vitamin D (for musculoskeletal health) while avoiding epidermal DNA damage (initiates skin cancer). Well-characterized healthy humans of all skin types (I-VI, lightest to darkest skin) were exposed to a low-dose series of solar simulated UVR of 20%-80% their individual sunburn threshold dose (minimal erythema dose). Significant UVR dose responses were seen for serum 25-hydroxyvitamin D and whole epidermal cyclobutane pyrimidine dimers (CPDs), with as little as 0.2 minimal erythema dose concurrently producing 25-hydroxyvitamin D and CPD. Fractional MEDs generated equivalent levels of whole epidermal CPD and 25-hydroxyvitamin D across all skin types. Crucially, we showed an epidermal gradient of CPD formation strongly correlated with skin darkness (r = 0.74, P < 0.0001), which reflected melanin content and showed increasing protection across the skin types, ranging from darkest skin, where high CPD levels occurred superficially, with none in the germinative basal layer, to lightest skin, where CPD levels were induced evenly across the epidermal depth. People with darker skin can be encouraged to use sub-sunburn UVR-exposure to enhance their vitamin D. In people with lighter skin, basal cell damage occurs concurrent with vitamin D synthesis at exquisitely low UVR levels, providing an explanation for their high skin cancer incidence; greater caution is required.