A case-control study: epigenetic age acceleration in psoriasis.

Psoriasis (PsO) is a chronic inflammatory skin condition, often accompanied by psoriatic arthritis (PsA) and linked to various comorbidities and increased mortality rates. This study aimed to explore the relationship between PsO and accelerated biological aging, specifically focusing on epigenetic DNA methylation clocks. Using a matched case-control design, 20 PsO cases were selected along with age, race, and sex-matched 20 controls without PsO from the Skin Disease Biorepository at Brown Dermatology, Inc, Providence, Rhode Island. Blood samples retrieved from both groups were analyzed for DNA methylation, and epigenetic ages were calculated using DNA methylation clocks, including Horvath, Hannum, Pheno, SkinBlood, and Grim ages. Generalized estimation equations were employed to test the differences in epigenetic and chronological ages between PsO cases and controls, as well as within various subgroups in comparison to their respective controls. There were no statistically significant differences in epigenetic ages between PsO cases and controls. However, notably, PsO cases with PsA demonstrated an accelerated PhenoAge, compared to their matched controls. This study represents a pioneering investigation into the potential link between PsO and epigenetic aging, shedding light on the possibility of accelerated epigenetic aging in PsA, possibly associated with heightened inflammatory burden. These findings emphasize the systemic impact of PsA on the aging process, prompting the need for deeper exploration into autoimmune pathways, inflammation, and epigenetic modifications underlying PsO pathogenesis and aging mechanisms. Larger-scale studies with diverse populations are imperative to discern PsO subgroups experiencing accelerated biological aging and decipher the intricate interplay between PsO, inflammation, and aging pathways.

A prospective cohort study exploring the joint influence of sunlight exposure and tanning bed use on basal cell carcinoma, squamous cell carcinoma, and melanoma risk.

Exposure to solar ultraviolet (UV) radiation and use of UV-emitting tanning devices are known risk factors for skin cancer. Few studies have explored the interaction between these risk factors, namely how the risk of skin cancer increases among those who both have been exposed to high levels of natural sunlight and regularly use tanning beds. Nurses' Health Study II followed 116,430 women, aged 25-42, from 1991 to 2011. Cumulative average UV exposure was based on participants' residences at follow-up periods. History of severe sunburn during ages 15-20 was used as a proxy for early-life sunlight exposure. Tanning bed use in early life data was collected. Participants reported melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) diagnoses. We built multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of skin cancer associated with joint effects of sunlight exposure and tanning bed use. Participants with high sunlight exposure and tanning bed use during high school/college had an increased risk of BCC (HR = 1.53, 95% CI 1.37-1.71, Pinteraction=0.01; vs. low sun exposure and no tanning bed use). Participants with a history of severe sunburns and tanning bed use during high school/college were at increased risk of BCC (HR = 1.62, 95% CI 1.47-1.79, Pinteraction=0.02; vs. no sunburns and no tanning bed use). No significant interactions were found between sunlight exposure and tanning bed use on SCC and melanoma risk. We found significant interactions between sunlight exposure and tanning bed use on the risk of BCC.

A Prospective Cohort Study Exploring the Joint Influence of Sunlight Exposure and Tanning Bed Use on Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma Risk.

Exposure to solar ultraviolet (UV) radiation and use of UV-emitting tanning devices are known risk factors for skin cancer. Few studies have explored the interaction between these risk factors, namely how the risk of skin cancer increases among those who both have been exposed to high levels of natural sunlight and regularly use tanning beds. Nurses' Health Study II followed 116,430 women, aged 25-42, from 1991 to 2011. Cumulative average UV exposure was based on participants' residences at follow-up periods. History of severe sunburn during ages 15-20 was used as a proxy for early-life sunlight exposure. Tanning bed use in early life data was collected. Participants reported melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) diagnoses. We built multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of skin cancer associated with joint effects of sunlight exposure and tanning bed use. Participants with high sunlight exposure and tanning bed use during high school/college had an increased risk of BCC (HR=1.53, CI 1.37-1.71, P interaction =0.01; vs. low UV exposure and no tanning bed use). Participants with a history of severe sunburns and tanning bed use during high school/college were at increased risk of BCC (HR=1.62, CI 1.47-1.79, P interaction =0.02; vs. no sunburns and no tanning bed use). No significant interactions were found between sunlight exposure and tanning bed use on SCC and melanoma risk. We found significant interactions between sunlight exposure and tanning bed use on the risk of BCC.

Photosensitizing antihypertensive medication and risk of skin cancer among postmenopausal women.

BACKGROUND: Few prospective studies exist with an evaluation of a dose-response relationship between use of some photosensitizing antihypertensive medications and skin cancer. PATIENT AND METHODS: We used prospective data from the Women's Health Initiative Observational Study to investigate the association between antihypertensive use and risk of non-melanoma skin cancer (NMSC) and melanoma in postmenopausal women aged 50-79 years at baseline (n  =  64,918). Multivariable Cox proportional hazards regression models were used and hazard ratios (HRs) and 95 confidence intervals (CIs) were calculated. RESULTS: 8,777 NMSC and 1,227 melanoma cases were observed. Use of antihypertensives (HR [95% CI]: 1.12 [1.07-1.18]), ACE inhibitors (1.09 [1.01-1.18]), calcium channel blockers (1.13 [1.05-1.22]), diuretics (1.20 [1.12-1.27]), loop diuretics (1.17 [1.07-1.28]), and thiazides (1.17 [1.03-1.33]) were each associated with higher NMSC risk. NMSC risk linearly increased with use of multiple antihypertensives (p-trend  =  0.02) and with longer duration of use (p-trend < 0.01). Antihypertensives (1.15 [1.00-1.31]), angiotensin-II receptor blockers (1.82 [1.05-3.15]), and diuretics (1.34 [1.13-1.59]) were each associated with elevated melanoma risk. Effect modification by solar radiation exposure was found between antihypertensive use and incidence of melanoma (p-interaction  =  0.02). CONCLUSIONS: Use of antihypertensives overall, and several individual classes thereof, were associated with higher incidence of NMSC and melanoma with dose-response relationship.

Association of sun-seeking behaviors with indoor tanning behavior in US white females during high school/college in Nurses' Health Study II.

BACKGROUND: Frequent exposure to ultraviolet light has more detrimental and longer-term effects on the skin in early life than in adulthood. Teenagers with strong sun-seeking behaviors may be more likely to use an indoor tanning bed than those who seek less sun. We aimed to examine associations between sun-seeking behaviors and indoor tanning behavior during high school/college in US females. METHODS: In this cross-sectional study, we used data from The Nurses' Health Study II, a large prospective cohort of US female nurses. We included a total of 81,746 white females who provided responses on the average annual frequency of indoor tanning during high school/college. Our study exposures were number of times/week spent outdoors in a swimsuit and percentage of time wearing sunscreen at the pool/beach as a teenager, weekly hours spent outdoors in direct sunlight during the daytime during high school/college, and number of severe sunburns that blistered between ages 15-20 years. The main outcome was annual frequency of indoor tanning bed usage during high school/college. RESULTS: In multivariable-adjusted logistic regression, we demonstrated positive associations between sun-seeking behaviors and indoor tanning use. Specifically, teenagers who spent 7 times/week outdoors in a swimsuit (adjusted odds ratio [aOR], 95% confidence interval [CI] for daily vs. <1/week: 2.68, 1.76-4.09) were more likely to use indoor tanning beds ≥ 12 times/year. Teenagers with ≥ 10 sunburns (aOR, 95% CI for ≥ 10 vs. never: 2.18, 1.53-3.10) were more likely to use indoor tanning beds ≥ 12 times/year. Also, teenagers/undergraduates who spent ≥ 5 h/week outdoors in direct sunlight (aOR, 95% CI for ≥ 5 h/week vs. <1 h/week: 2.18, 1.39-3.44) were more likely to use indoor tanning ≥ 12 times/year. However, there was not a significant association between average usage of sunscreen at the pool/beach and average usage of indoor tanning beds. Multivariable-adjusted linear regression models also showed similar results. CONCLUSIONS: Teenagers who spent more time outdoors in a swimsuit/direct sunlight or got more sunburns tended to use indoor tanning more frequently. These findings provide evidence that teenagers with stronger sun-seeking behaviors may have more exposure to artificial ultraviolet radiation as well.

Risk of infection in patients with hidradenitis suppurativa on biologics or other immunomodulators: a systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.

Association between plasma L-carnitine levels and mitochondrial DNA copy number.

Mitochondria are key cytoplasmic organelles in eukaryotic cells that generate adenosine triphosphate (ATP) through the electron transport chain and oxidative phosphorylation. Mitochondrial DNA (mtDNA) copy number (mtDNAcn) is considered a biomarker for both mitochondrial quantity and function as well as cellular oxidative stress level. Previous epidemiologic findings revealed that weight gain, higher body mass index (BMI), smoking, and high insulinemic potential of lifestyle were associated with lower leukocyte mtDNAcn. Carnitines are a group of compounds that play a critical role in energy production. We quantified the associations of plasma L-carnitine levels with leukocyte mtDNAcn. We then examined the association between mtDNAcn and L-carnitine (HMDB0000062) in 538 U.S. men without cancers, diabetes, or cardiovascular disease at blood collection from the Health Professionals Follow-Up Study (HPFS). We found a significant inverse association between L-carnitine and mtDNAcn (ρ = -0.1, P = 0.02). This implies that the carnitine metabolic pathway may be associated with mitochondrial function and oxidative stress.

Furocoumarins potentiate UVA-induced DNA damage in skin melanocytes.

Epidemiological studies have found that high citrus fruit consumption was associated with higher risk of skin cancer. Citrus fruits and some vegetables contain furocoumarins, which may interact with ultraviolet radiation to induce skin cancer. We aimed to determine the effects of two furocoumarins, including 8-methoxypsoralen (8-MOP) and 6',7'-dihydroxybergamottin (DHB), on UVA-induced DNA damage in human epidermal melanocytes, the origin of melanoma. Our hypothesis was that these dietary furocoumarins increase UVA-induced DNA damage in melanocytes, compared to cells exposed to UV alone. We incubated melanocytes with 8-MOP or DHB, followed by exposure to physiological doses of UVA radiation. We used Western blots to quantify the UVA-induced DNA damage measured by the fraction of phosphorylated histone variant H2AX (γH2AX), which is a marker of DNA damage, relative to total H2AX (γH2AX/H2AX) in the presence or absence of furocoumarins. To quantify the UVA-induced change in γH2AX/H2AX, we calculated the UVA:Control ratio as the ratio of γH2AX/H2AX in UVA-exposed cells to that in cells without UVA (control). The mean UVA:Control ratios were borderline significantly higher for cells treated with 8-MOP and significantly higher for cells treated with DHB, compared to that of untreated cells. This study suggests that furocoumarins (particularly 8-MOP and DHB) enhance UVA-induced DNA damage in melanocytes, which is a potential novel mechanism for citrus and furocoumarins to elevate the risk of skin cancer.

Off-Label Use of Baricitinib in Dermatology.

The current US Food and Drug Administration (FDA) indications for baricitinib include alopecia areata, rheumatoid arthritis, and COVID-19. However, increasing evidence indicates that baricitinib is effective in treating a variety of dermatological conditions. This review article comprehensively presents the available literature on this topic and will be of interest to practitioners in the field. These disorders may be broadly classified as connective tissue diseases, eczematous dermatoses, alopecias, vascular disorders, granulomatous diseases, neutrophilic dermatoses, vitiligo, psoriasis, lichenoid disorders, and other miscellaneous disorders. Shah A, Yumeen S, Qureshi A, et al. Off-label use of baricitinib in dermatology. J Drugs Dermatol. 2023;22(8):795-801. doi:10.36849/JDD.7360.

Coffee, Citrus, and Alcohol: A Review of What We Drink and How it May Affect our Risk for Skin Cancer.

Climate change and environmental health are closely linked with agriculture and food supply. The environment influences accessibility, quality, and variety of foods and drinks that are available for consumption, which in turn influences population health. A growing area of research is the role of dietary intake of nutrients and how they may influence risk for skin cancer. In recent years, our group has studied dietary nutrients, particularly those found in commonly consumed beverages, such as those containing caffeine, citrus products, and alcohol, in large prospective cohorts to evaluate how their intake may influence risk for skin cancer. Our data suggest that intake of citrus juices, when consumed around once per day or more, or around 5 to 6 times per week, may be associated with increased risk for both keratinocyte carcinomas (KC) and malignant melanoma (MM). With regards to alcohol consumption, we have found that intake of white wine may be associated with increased risk for both KC and MM, while beer and red wine have not shown such associations. Lastly, our work suggests caffeinated beverages, including coffee, tea, and cola, may be associated with decreased risk for basal cell carcinoma (BCC) and MM. While the associations between food intake and skin cancer development are complex, and remain to be further analyzed in future studies, we hope that our summary may help guide individuals to small changes they may make towards potentially reducing their risk for certain skin cancers.

When Surgery Won't Cut It: Successful Management of Eruptive Squamous Atypia With Combination Medical Therapy.

The termeruptive squamous atypia(ESA) is used to describe squamous proliferations that do not present with high-grade histologic features and for which surgical management may exacerbate the condition. Non-surgical management of ESA with radiation, local or systemic chemotherapy, retinoids, or immunotherapy have been reported with variable success. In contrast, combination treatment with retinoids, immunomodulatory or chemotherapeutic agents may result in a more durable response. We report a case of recalcitrant ESA of the lower extremities where complete clinical remission was induced with triple combination medical management with intralesional 5-fluorouracil, field treatment with topical 5-fluorouracil and imiquimod, and oral acitretin. Our case adds to the literature supporting combination medical therapy for challenging cases of ESA.

Host and primary tumor factors for the development of multiple cutaneous squamous cell carcinomas among a retrospective cohort in Rhode Island.

INTRODUCTION: Risk factors for a primary cutaneous squamous cell carcinoma (CSCC) are well-established; however, the host and primary tumor risk factors for subsequent CSCC have not been fully explored. METHODS: We performed a retrospective chart review of patients diagnosed with CSCC in an academic dermatology clinic in Rhode Island from 2016-2019. Logistic regression was used to evaluate the associations between host factors and multiple CSCC and between primary tumor characteristics and the risk of subsequent CSCC. Adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: A total of 1312 patients with CSCC diagnoses were included. Host risk factors significantly associated with multiple CSCCs included: aged >80 years (aOR, 2.18; 95% CI, 1.46-3.31); history of: solid organ transplant (aOR, 2.41; 95% CI, 1.20-4.80); skin cancer (aOR, 1.96; 95% CI, 1.52-2.54); other cancer (aOR, 1.49; 95% CI, 1.11-2.00); family history of skin cancer (aOR, 1.36; 95% CI, 1.03-1.78); and actinic keratosis (aOR, 1.52; 95% CI, 1.18-1.95). Tumor location, diameter, histologic differentiation, and treatment were not significant predictors of subsequent CSCCs. LIMITATIONS: Study patients were predominantly White and from a single institution, limiting the generalizability of results. CONCLUSIONS: Certain host characteristics were associated with the development of subsequent CSCC, which may inform clinical guidelines for follow-up.

Association of omega-3 and omega-6 fatty acid intake with leukocyte telomere length in US males.

BACKGROUND: Omega-3 (n-3) and omega-6 (n-6) fatty acids may contribute to oxidative stress and inflammation, which are related to telomere shortening. Evidence supporting an association between intake of n-3 or n-6 fatty acids and leukocyte telomere length (LTL) in males has been limited. OBJECTIVES: We conducted a cross-sectional study to examine the associations of total or individual n-3 or total n-6 fatty acid intake with LTL in US males. METHODS: We included 2,494 US males with LTL measurement from 4 nested case-control studies within the Health Professionals Follow-Up Study. Individuals with previous histories of cancers, diabetes, and cardiovascular diseases at or before blood collection were excluded. Blood collection was performed between 1993 and 1995, and relevant information including n-3 and n-6 intake was collected in 1994 by questionnaire. The LTL was log-transformed and Z scores of the LTL were calculated for statistical analyses by standardizing the LTL in comparison with the mean within each selected nested case-control study. RESULTS: We found that consumption of DHA (22:6n-3) was positively associated with LTL. In the multivariable-adjusted model, compared with individuals who had the lowest intake of DHA (i.e., first quartile group), the percentage differences (95% CIs) of LTL were -3.7 (-13.7, 7.5), 7.0 (-4.3, 19.7), and 8.2 (-3.5, 21.3) for individuals in the second, third, and fourth quartiles of consumption, respectively (P-trend = 0.0498). We did not find significant associations between total n-3 or total n-6 fatty acid intakes and LTL. In addition, we found that males who consumed canned tuna had longer LTL than those who did not; in the multivariable-adjusted model, the percentage difference of LTL was 10.5 (95% CI: 1.3, 20.4) (P = 0.02). CONCLUSIONS: Our results suggest that higher intakes of DHA and canned tuna consumption are associated with longer LTL.