Skinformatics: Navigating the big data landscape of dermatology.

Big data and associated approaches to analyse it are on the rise, especially in healthcare settings. This growth is also seen with unique applications in the field of dermatology. While big data offer a plethora of opportunity for improving our current understanding of disease and ability to deliver care, as with any technology innovation, the potential pitfalls should be addressed. In this piece, we highlight opportunities and challenges associated with big data in dermatology. Opportunities include large and novel data sources that may offer a wealth of information, automated detection, classification and diagnostics and improved public health monitoring. Challenges include data quality, issues of interpretability and disparities within artificial intelligence (AI) training data sets. Clinicians and researchers in the field should be aware of these developments within the field of big data to understand how best it may be used toward improving patient care and health outcomes, particularly in the field of dermatology.

Exploring Skin Pigmentation Adaptation: A Systematic Review on the Vitamin D Adaptation Hypothesis.

Understanding the genetic adaptations that occurred as humans migrated out of Africa to higher latitudes helps explain on a population-wide level how UV radiation (UVR) exposure will have varying consequences and benefits in patients of different skin pigmentations. It has been hypothesized that the need for efficient vitamin D synthesis was the primary driver for the skin-lightening process that evolutionarily occurred as humans migrated to higher latitudes. This review analyzes the level of support for the hypothesis that skin lightening occurred to enable adequate vitamin D synthesis in populations that migrated to areas with less UVR. Our literature search supported the hypothesis that through natural selection and intricate genetic adaptations, humans who migrated to areas with lower levels of UVR underwent a skin-lightening process to avoid the consequences of vitamin D deficiency. Our review includes an analysis of migration patterns out of Africa and how these affected pigmentation genes that are found in certain ethnic populations can be used to better understand this critical adaptation process when counseling patients on the need for sun protection.

Sex-Specific Associations Between Serum Lipids, Antinuclear Antibodies, and Statin Use in National Health and Nutrition Examination Surveys 1999-2004.

Lipid metabolism contributes to the regulation of leukocyte activity and immune responses, and may serve as a therapeutic target in the pathophysiology and clinical management of autoimmune disorders. In addition to lipid-lowering properties, statins have been shown to exert anti-inflammatory and immunomodulatory effects within the context of autoimmunity. Importantly, autoimmune incidence and lipid markers differ between men and women, suggesting that the relationship between lipid metabolism and immune function may vary by sex. Therefore, we investigated whether a predictive, sex-specific relationship exists between serum lipids, statin use, and antinuclear antibodies (ANA)-a routine clinical marker of autoimmunity and immune dysfunction-in U.S. men and women (>20 years old; n = 1,526) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Within this population, a greater proportion of women were positive for ANA (ANA+) and had higher ANA titers, as compared to men. While we did not observe statistical differences in average total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), or triglyceride levels in ANA positive (ANA+) vs. ANA negative (ANA-) men or women, we observed that a greater proportion of ANA+ women had high total cholesterol levels (>240 mg/dL) when compared to ANA+ men (13.0 vs. 9.0%), and that a greater percentage of ANA+ women had low HDL-C as compared to ANA+ men (29.2 vs. 19.6%). However, in logistic regression models, total cholesterol, LDL-C, and HDL-C levels were not able to predict ANA status, whereas elevated serum triglycerides (150 to < 200 mg/dL) were significantly less likely to be ANA+ vs. ANA- (OR 0.33; 95% CI 0.11-0.92) in men only. Interestingly, women who reported taking statins have significantly lower odds of being ANA+ (OR 0.25; 95% CI 0.09-0.76), whereas no significant association between statin use and ANA status was observed in men. Together, our findings provide novel insight into the relationship between lipid metabolism and autoimmunity by elucidating the limited, albeit sex-specific utility of routine clinical serum lipid levels to predict ANA status at the population level, while further identifying a sex-specific and protective role for statins in predicting ANA status in women.

Fish intake and risk of melanoma in the NIH-AARP diet and health study.

PURPOSE: Prior epidemiological studies evaluating the association between fish intake and melanoma risk have been few and inconsistent. Few studies distinguished different types of fish intake with risk of melanoma. METHODS: We examined the associations between intake of total fish and specific types of fish and risk of melanoma among 491,367 participants in the NIH-AARP Diet and Health Study. We used multivariable-adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 6,611,941 person-years of follow-up with a median of 15.5 years, 5,034 cases of malignant melanoma and 3,284 cases of melanoma in situ were identified. There was a positive association between higher total fish intake and risk of malignant melanoma (HR = 1.22, 95% CI = 1.11-1.34 for top vs. bottom quintiles, ptrend = 0.001) and melanoma in situ (HR = 1.28, CI = 1.13-1.44 for top vs. bottom quintiles, ptrend = 0.002). The positive associations were consistent across several demographic and lifestyle factors. There were also positive associations between tuna intake and non-fried fish intake, and risk of malignant melanoma and melanoma in situ. However, fried fish intake was inversely associated with risk of malignant melanoma, but not melanoma in situ. CONCLUSIONS: We found that higher total fish intake, tuna intake, and non-fried fish intake were positively associated with risk of both malignant melanoma and melanoma in situ. Future studies are needed to investigate the potential biological mechanisms underlying these associations.

A randomized trial of diphenylcyclopropenone (DPCP) combined with anthralin versus DPCP alone for treating moderate to severe alopecia areata.

BACKGROUND: Alopecia areata (AA) is a chronic autoimmune disorder. Finding the best treatment regimen for it remains a challenge. Currently, one of the best documented treatment modalities for AA is topical immunotherapy. AIM: To evaluate the safety and efficacy of combined DPCP and anthralin versus standard protocol (DPCP alone). METHODS: A prospective randomized clinical trial was conducted on 50 patients with Alopecia areata who received DPCP alone (group D) or in combination with anthralin (group D/A). Percentage of hair regrowth after 6 months of treatment and the incidence of drug-related adverse effects were evaluated and compared between the two groups. RESULTS: Complete hair regrowth was observed among three patients in each group (18.75% in Group D and 15.79% in Group D/A) after 6 months. Moreover, 25% and 31% of patients in group D and 21% and 47% of patients in group D/A had > 75% and > 50% hair regrowth respectively at the end of the study (P-value: 0.696). In addition, earlier age of onset, chronicity of lesions, nail involvement, facial hair loss and extensive lesions at baseline were associated with poor clinical outcome. CONCLUSION: DPCP and anthralin was as effective as DPCP alone and anthralin did not add to the effect of DPCP in treating AA.

Rituximab exhibits a better safety profile when used as a first line of treatment for pemphigus vulgaris: A retrospective study.

BACKGROUND: Pemphigus is an autoimmune disease that is challenging to treat and has few available therapeutic options. Recently, several studies have demonstrated that rituximab may be an efficacious first-line treatment in newest guidelines. AIM: To compare the side effect profiles of rituximab administered after a course of immunosuppressant agents versus as a first-line therapy and evaluate the impact of patient characteristics and disease severity indices on occurrence of adverse effects. METHODS: A retrospective cross-sectional study was conducted on 999 patients with pemphigus vulgaris who received rituximab either as a first-line treatment or after conventional adjuvant therapies. The occurrence of partial or complete remission as well as the incidence of drug-related adverse effects were evaluated and compared between the two groups. RESULTS: Smoking, pulmonary comorbidity, and mucocutaneous phenotype were associated with an increased risk of developing infectious complications by 12.49, 5.79, and 2.37 fold, respectively. These associations were more prominent among those who received rituximab after immunosuppressant agents. CONCLUSIONS: Early use of rituximab benefits pemphigus patients, especially those with a mucocutaneous phenotype, pulmonary comorbidity, or history of smoking, and reduces their risk of infectious adverse events.

Vitiligo: Targeted Therapies Add Color to Disease Pathophysiology.

There is excitement in the air for patients with vitiligo. For the first time in decades, we have early case studies showing that targeted therapies can repigment vitiliginous skin, and well-powered clinical trials are underway. However, at the time of this writing, there is no Food and Drug Administration-approved drug for vitiligo. In a randomized clinical trial by Khemis et al. report negative results on a randomized clinical trial testing the combination of apremilast, a phosphodiesterase 4 inhibitor, and narrowband-ultraviolet B versus placebo and narrowband-ultraviolet B in patients with nonsegmental vitiligo. The results of this trial are a reminder that clinical management of vitiligo is challenging at best, even when combining anti-inflammatory and/or immunomodulating agents with repigmenting agents. However, these negative trials are critical in improving our understanding of this complex and disfiguring disease.

Effective use of oral tofacitinib and phototherapy in a patient with concomitant alopecia areata, vitiligo, and plaque and inverse psoriasis.

This case presentation suggests that tofacitinib combined with phototherapy may be an effective treatment option for patients with concomitant alopecia areata, vitiligo, and different phenotypes of psoriasis including plaque and inverse psoriasis.

Gender Dictates the Relationship between Serum Lipids and Leukocyte Counts in the National Health and Nutrition Examination Survey 1999⁻2004.

Dyslipidemias and leukocytosis are associated with cardiovascular disease and immune disorders. Mechanistic studies have shown lipoprotein metabolism to play a significant role in the regulation of atherosclerosis development and leukocyte activation, whereas lipid-lowering treatments have been shown to exert beneficial anti-inflammatory and immunomodulatory effects in clinical trials. However, the relationship between clinical markers of lipid metabolism and leukocyte counts has not been extensively evaluated at the population level. We aimed to determine whether clinical blood lipid measures are associated with leukocyte counts in the general U.S. population represented in the National Health and Nutrition Examination Survey (NHANES) 1999⁻2004, and whether differences exist between men and women (n = 5647). We observed a strong positive linear trend between serum triglycerides vs. blood lymphocyte and basophil counts in both men and women, whereas a positive trend between monocytes vs. triglycerides and lymphocytes vs. total cholesterol and LDL-cholesterol (LDL-C) was only detected in women. Conversely, HDL-C was inversely associated with a greater number of leukocyte subsets in men, whereas inverse trends between HDL-C vs. lymphocytes were observed in both men and women. In multiple regression models, a 10% increase in total cholesterol, LDL-C, and triglycerides was associated with a predicted 1.6%, 0.6%, and 1.4% increase in blood lymphocyte counts in women, respectively, whereas no relationship was observed in men. In both men and women, a 10% increase in triglycerides was additionally associated with higher lymphocyte, neutrophil, and basophil counts, whereas 10% increases in HDL-cholesterol were associated with significantly lower lymphocyte, neutrophil, eosinophil, and basophil counts in men, in addition to lower lymphocyte and monocyte counts in women. These findings suggest that clinical lipid markers may be used to predict blood leukocyte distributions, and that a gender-specific relationship exists between distinct classes of serum lipids and immune cell subsets.

The relationship between zinc intake and cadmium burden is influenced by smoking status.

A preliminary study by our group suggested that the absorption and accumulation of cadmium may be affected by zinc intake. Tobacco smoke is one major source of cadmium exposure that highly influences cadmium burden among smokers, but it is unclear whether this zinc-cadmium relationship differs by smoking status. The objective of this study was to examine whether the association between zinc intake and cadmium burden differs by smoking status using data from 3900 US adults in the National Health and Nutrition Examination Survey 2007-2012. In an adjusted regression model, dietary cadmium was positively associated with blood and urinary cadmium. There was a significant interaction between zinc intake and smoking status, so we analyzed associations within smoking status subgroups. In an adjusted regression model, zinc intake was inversely associated with urinary cadmium only among non-smokers. Failure to meet the Recommended Dietary Allowance (RDA) for zinc was more common among current smokers than non-smokers, and among those in the highest quintile of blood and urinary cadmium than those in lower quintiles. Zinc intake was inversely associated with urinary cadmium only among subjects meeting the zinc RDA, suggesting that the relationship between zinc intake and cadmium burden differs by smoking status.

Dietary Cadmium Intake and Sources in the US.

Cadmium (Cd) is a toxic heavy metal that can contribute to numerous diseases as well as increased mortality. Diet is the primary source of Cd exposure for most individuals, yet little is known about the foods and food groups that contribute most substantially to dietary Cd intake in the US. Therefore, the objective of this study was to estimate dietary Cd intake and identify major food sources of Cd in the US population and among subgroups of the population. Individuals aged 2 years and older from the National Health and Nutrition Examination Survey (NHANES) 2007⁻2012 were included in this study (n = 12,523). Cd intakes were estimated from two days of 24-h dietary recalls by matching intake data with the Cd database of the Food and Drug Administration (FDA)'s Total Diet Study 2006 through 2013. The average dietary Cd consumption in the population was 4.63 µg/day, or 0.54 µg/kg body weight/week, which is 22% of the tolerable weekly intake (TWI) of 2.5 µg/kg body weight/week. Greater daily Cd intakes were observed in older adults, males, those with higher income, higher education, or higher body mass index. The highest Cd intakes on a body weight basis were observed in children 10 years and younger (38% of TWI), underweight individuals (38% of TWI), and alcohol non-consumers (24% of TWI). The food groups that contributed most to Cd intake were cereals and bread (34%), leafy vegetables (20%), potatoes (11%), legumes and nuts (7%), and stem/root vegetables (6%). The foods that contributed most to total Cd intake were lettuce (14%), spaghetti (8%), bread (7%), and potatoes (6%). Lettuce was the major Cd source for Caucasians and Blacks, whereas tortillas were the top source for Hispanics, and rice was the top contributor among other ethnic subgroups including Asians. This study provides important information on the dietary Cd exposure of Americans, and identifies the groups with the greatest dietary Cd exposure as well as the major sources of dietary Cd among sociodemographic subgroups.

Dietary total antioxidant capacity is inversely associated with all-cause and cardiovascular disease death of US adults.

PURPOSE: Although evidence strongly supports that antioxidant-rich diets reduce risk of chronic disease and mortality, findings from the previous studies on the effect of individual antioxidants on mortality have been inconsistent. The aim of this study was to assess the relationship between dietary total antioxidant capacity (TAC) and all-cause and disease-specific mortality in a representative sample of the US population. METHODS: A total of 23,595 US adults aged 30 years and older in NHANES 1988-1994 and 1999-2004 were selected for this study. Dietary TAC was calculated from 1-day 24-h diet recall data at baseline and all-cause, cancer and cardiovascular disease (CVD) mortality was assessed through December 31, 2011. RESULTS: During a mean follow-up of 13 years, deaths from all-cause, cancer and CVD were 7157, 1578, and 2155, respectively. Using cause-specific Cox proportional hazards models, inverse associations and linear trends were observed between dietary TAC and all-cause mortality [highest quartile (Q4) versus Q1 ref. HR 0.78; 95% CI 0.71-0.86], cancer mortality (Q4 versus Q1 ref. HR 0.75; 95% CI 0.60-0.93), and CVD mortality (Q4 versus Q1 ref. HR 0.83; 95% CI 0.69-0.99), respectively, after adjusting for age, sex, ethnicity, and total energy intake. The inverse association and linear trend still remained between dietary TAC and all-cause mortality (Q4 versus Q1 ref. HR 0.79; 95% CI 0.71-0.87) and CVD mortality (Q4 versus Q1 ref. HR 0.74; 95% CI 0.61-0.89) when further adjusted for relevant covariates. CONCLUSIONS: These findings support that antioxidant-rich diets are beneficial to reducing risk of death from all-cause and CVD.

Furocoumarin Kinetics in Plasma and Urine of Healthy Adults Following Consumption of Grapefruit (Citrus paradisi Macf.) and Grapefruit Juice.

Furocoumarins are a class of organic compounds found in a variety of vegetables and fruits. Relatively little is known about the absorption and excretion of these compounds following ingestion. The objective of this study was to identify furocoumarins in grapefruit and grapefruit juice and observe their kinetics in blood and urine. The furocoumarins detected in grapefruit using UPLC-MS/MS were bergamottin, 6',7'-dihydroxybergamottin (6',7'-DHB), epoxybergamottin, and bergaptol. Bergamottin, 6',7'-DHB, bergaptol, and bergapten were detected in grapefruit juice. In this study of 6 males and 3 females, only bergamottin and 6',7'-DHB were detected in plasma, whereas in urine, four distinct furocoumarin metabolites as well as bergaptol, 6',7'-DHB, 8-methoxypsoralen (8-MOP), bergamottin, and psoralen were identified. Following grapefruit ingestion, furocoumarins were detectable in plasma as early as 15 min and in urine within 1 h. They remained in plasma for up to 3 or more hours and in urine as late as 24 h.

Aronia berry polyphenol consumption reduces plasma total and low-density lipoprotein cholesterol in former smokers without lowering biomarkers of inflammation and oxidative stress: a randomized controlled trial.

Former smokers are at increased risk for cardiovascular disease. We hypothesized that dietary aronia polyphenols would reduce biomarkers of cardiovascular disease risk, inflammation, and oxidative stress in former smokers. We also determined the extent these effects were associated with polyphenol bioavailability. A 12-week, randomized, placebo-controlled trial was conducted in 49 healthy adult former smokers (n = 24/placebo, n = 25/aronia) to evaluate if daily consumption of 500 mg aronia extract modulated plasma lipids, blood pressure, biomarkers of inflammation and oxidative stress, and lipid transport genes of peripheral blood mononuclear cells. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C) from baseline, and multivariate correlation analysis was performed to determine if changes in lipids were associated with urinary polyphenol excretion. Aronia consumption reduced fasting plasma total cholesterol by 8% (P = .0140), LDL-C by 11% (P = .0285), and LDL receptor protein in peripheral blood mononuclear cells (P = .0036) at 12 weeks compared with the placebo group. Positive changes in the urinary polyphenol metabolites peonidin-3-O-galactoside, 3-(4-hydroxyphenyl) propionic acid, and unmetabolized anthocyanin cyanidin-3-O-galactoside were associated with lower plasma total cholesterol and LDL-C in the aronia group. Aronia consumption did not change blood pressure or biomarkers of inflammation and oxidative stress. Aronia polyphenols reduced total and LDL-C in former smokers but did not improve biomarkers of oxidative stress and chronic inflammation. The cholesterol-lowering activity of aronia extract was most closely associated with urinary levels of cyanidin-3-O-galactoside and peonidin-3-O-galactoside, its methylated metabolite. This trial was registered at ClinicalTrials.gov as NCT01541826.

Validation of Analytical Methods for Plasma Total Antioxidant Capacity by Comparing with Urinary 8-Isoprostane Level.

Although several analytical methods for measuring total antioxidant capacity (TAC) have been applied to biological samples, there were often dissimilar results due to the different principles of methods applied. Thus, this study aimed to validate four conventional analytical methods for measuring plasma TAC, including the ABTS assay, DPPH assay, FRAP assay, and ORAC assay, by comparing with urinary 8-isoprostane concentration. In addition, TAC results were compared with antioxidant enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase in erythrocyte, and catalase in plasma. Plasma TAC measure by ABTS assay was strongly correlated with the result by FRAP assay. Plasma TAC by FRAP and ORAC assays were negatively correlated with erythrocyte SOD activity. The agreement among the four TAC assay methods and 8-isoprostane was determined using 95% prediction limits of linear regression, expressed as the mean of 8-isoprostane ± 95% prediction limits. The ABTS method better agreed with 8-isoprostane than the other methods, demonstrating narrow prediction of limits. Furthermore, only plasma TAC determined by the ABTS assay was inversely correlated with urinary 8-isoprostane (r = -0.35, p < 0.05). In summary, the ABTS assay would be an appropriate method to measure overall plasma antioxidant capacity and predict the body's antioxidant status.

Development of a comprehensive analytical method for furanocoumarins in grapefruit and their metabolites in plasma and urine using UPLC-MS/MS: a preliminary study.

To develop a comprehensive analytical method for photoactive furanocoumarins, grapefruit (whole, flesh, peel and juice) was extracted using QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method. Seven furanocoumarins: bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6',7'-dihydroxybergamottin (6',7'-DHB), epoxybergamottin and bergamottin were determined in grapefruit using UPLC-MS/MS. The concentrations of furanocoumarins in the plasma and urine of six healthy young adults before and after ingestion of grapefruit or grapefruit juice were also determined. Recovery rates of furanocoumarins by QuEChERS method from matrix spike sample and laboratory calibrate sample were 125.7 ± 25.4% and 105.7 ± 6.3%, respectively. Bergamottin and 6',7'-DHB were predominant compounds in grapefruit flesh, juice and plasma, while bergaptol and 6',7'-DHB were major compounds detected in the urine. The results demonstrated that bergamottin and 6',7'-DHB were metabolized to bergaptol. Overall, the analytical methods developed in the present study can be applied to the analysis of various furanocoumarins in plant sources and biological samples.