Sodium Intake and Atopic Dermatitis.

Importance: The association of diet with atopic dermatitis (AD) remains poorly understood and could help explain heterogeneity in disease course. Objective: To determine the extent to which a higher level of dietary sodium intake, estimated using urine sodium as a biomarker, is associated with AD in a large, population-based cohort. Design, Setting, and Participants: This cross-sectional study of adult participants (aged 37-73 years) from the UK Biobank examined 24-hour urine sodium excretion, which was estimated using a single spot urine sample collected between March 31, 2006, and October 1, 2010, and calculations from the sex-specific International Cooperative Study on Salt, Other Factors, and Blood Pressure equation, incorporating body mass index; age; and urine concentrations of potassium, sodium, and creatinine. The data were analyzed between February 23, 2022, and March 20, 2024. Exposure: The primary exposure was 24-hour urinary sodium excretion. Main Outcome and Measure: The primary outcome was AD or active AD based on diagnostic and prescription codes from linked electronic medical records. Multivariable logistic regression models adjusted for age, sex, race and ethnicity, Townsend Deprivation Index, and education were used to measure the association. Results: The analytic sample comprised 215 832 participants (mean [SD] age, 56.52 [8.06] years; 54.3% female). Mean (SD) estimated 24-hour urine sodium excretion was 3.01 (0.82) g per day, and 10 839 participants (5.0%) had a diagnosis of AD. Multivariable logistic regression revealed that a 1-g increase in estimated 24-hour urine sodium excretion was associated with increased odds of AD (adjusted odds ratio [AOR], 1.11; 95% CI, 1.07-1.14), increased odds of active AD (AOR, 1.16; 95% CI, 1.05-1.28), and increased odds of increasing severity of AD (AOR, 1.11; 95% CI, 1.07-1.15). In a validation cohort of 13 014 participants from the National Health and Nutrition Examination Survey, a 1 g per day higher dietary sodium intake estimated using dietary recall questionnaires was associated with a higher risk of current AD (AOR, 1.22; 95% CI, 1.01-1.47). Conclusions and Relevance: These findings suggest that restriction of dietary sodium intake may be a cost-effective and low-risk intervention for AD.

Urinary lipid profile of atopic dermatitis in murine model and human patients.

Atopic dermatitis (AD) is the most common inflammatory skin disease in children. The serum level of thymus and activation-regulated chemokine (TARC) is a useful AD index to reflect disease severity; however, it requires blood collection from young children. In comparison, urine samples are easier to collect in a pediatric clinical setting. Here, we analyzed the lipids excreted in urine to identify a diagnostic biomarker for AD. We generated a murine dermatitis model by repeated topical application of 2,4-dinitrofluorobenzene (DNFB) or tape-stripping the dorsal skin. Lipid metabolites excreted in the urine were comprehensively analyzed using liquid chromatography-tandem mass spectrometry. To corroborate our findings, we also analyzed urine samples from patients with AD. DNFB application induced AD-like skin lesions, including epidermal thickening, infiltration of eosinophils and T cells, and an increase in Th2 cytokine levels. Assessment of lipids excreted in urine showed a dominance of prostaglandins (PGs), namely, a PGF2α metabolite (13,14-dihydro-15-keto-tetranor-PGF1α ), a PGE2 metabolite (13,14-dihydro-15-keto-tetranor-PGE2 ), and a PGD2 metabolite (13,14-dihydro-15-keto PGJ2 ). mRNA and protein expression of PGF2α , PGE2 , and PGD2 synthase was upregulated in DNFB-treated skin. The tape-stripping model also caused dermatitis but without Th2 inflammation; urine PGF2α and PGD2 metabolite levels remained unaffected. Finally, we confirmed that the urinary levels of the aforementioned PG metabolites, as well as PGI2 metabolite, 6,15-diketo-13,14-dihydro-PGF1α and arachidonic acid metabolite, 17-hydroxyeicosatetraenoic acid (17-HETE) increased in patients with AD. Our data highlights the unique urinary lipid profile in patients with AD, which may provide insight into novel urinary biomarkers for AD diagnosis.

Prostaglandin D2 metabolite is not a useful clinical indicator for assessing atopic dermatitis.

Prostaglandin D2 (PGD2 ) plays an important role in atopic dermatitis (AD), and 11,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioicacid (PGDM) is a major metabolite of PGD2 . We investigated the relationship between urinary PGDM levels and severity of paediatric AD. In total, 31 patients with AD and 21 healthy controls (HCs) without AD were recruited, and urinary PGDM levels were measured. Of the 31 patients with AD, 14 were reassessed for urinary PGDM after topical steroid therapy. There was no difference in urinary PGDM levels between patients with AD and HCs. Although there was a significant positive correlation between the SCORing Atopic Dermatitis (SCORAD) index and the serum level of thymus and activation-regulated chemokine (TARC), the urinary PGDM levels did not correlate with either SCORAD or serum TARC. Moreover, both SCORAD and serum TARC were significantly improved by topical steroid therapy; however, urinary PGDM levels were not changed. In conclusion, the level of urinary PGD2 metabolites in children with AD is substantially the same as that in HCs even if the disease is severe.

The Connection between Urinary Equol Levels and the Prevalence of Atopic Dermatitis.

BACKGROUND: Soy isoflavones and their metabolites such as equol have been associated with a reduced risk of hormone-sensitive tumors and metabolic syndromes. However, individual soy isoflavones and equol levels in atopic dermatitis remain uninvestigated. OBJECTIVE: The aim of this study is to compare the levels of urinary daidzein, genistein, and equol between atopic dermatitis patients and normal subjects and to examine the correlation between equol concentration and the severity of clinical symptoms. METHODS: A cross-sectional study was conducted at Akita University Hospital and Aso Iizuka Hospital in Japan. Fifty patients with confirmed atopic dermatitis diagnosis and 67 healthy controls were recruited. Daidzein, genistein, and equol in urine were measured by using a high-performance liquid chromatography-mass spectrometry system. RESULTS: Urinary equol levels were significantly lower in the atopic dermatitis patients than in the healthy controls (p = 0.002). The difference was particularly noticeable in young people (6-19 years, p < 0.001). No correlations were found between urinary equol levels and the severity of clinical symptoms and laboratory data in the atopic dermatitis patients. CONCLUSION: Equol levels in childhood might be involved in the development of atopic dermatitis.

Associations between urine iodine and allergic diseases in the Korean National Health and Nutrition Examination Survey 2013-2015: A STROBE-compliant article.

BACKGROUND: The associations between excessive iodine intake and allergic diseases have not been evaluated. PURPOSE: We aimed to investigate the associations of allergic diseases with urinary iodine concentration (UIC). STUDY DESIGN: A nation-wide population-based survey conducted by the the Korean Centers for Disease Control and Prevention METHODS: In total, 5598 participants older than 19 years who participated in the Korean National Health and Nutrition Examination Survey 2013-2015 were enrolled for analysis. Multiple logistic regression analysis was used to determine the odds ratios for allergic diseases according to UIC. RESULTS: Allergic diseases were associated with the highest UIC quartile. Compared with subjects in lower UIC quartiles, subjects in the highest UIC quartile were at greater risk for atopic dermatitis (OR = 1.471, 95% CI, 1.028-2.107) and allergic rhinitis (OR = 1.362, 95% CI, 1.129-1.644) after adjustment for age and sex. CONCLUSION: This study revealed that the highest UIC quartile is associated with allergic diseases. Further laboratory and clinical studies are needed to evaluate the associations between excessive iodine intake and allergic diseases.

Prostaglandin D2 metabolite in urine is an index of food allergy.

Food allergy is immediate hypersensitive reactions to ingested foods. Since early diagnosis is effective for disease control, development of an objective diagnostic index is required. Using mediator-lipidomics, we found that levels of the urinary prostaglandin D2 (PGD2) metabolite, tetranor-PGDM, reflected the severity of the allergic symptoms and intestinal mast cell hyperplasia in mice. Repeated oral challenges with ovalbumin promoted allergic symptoms in sensitized mice. Particularly, the allergic mice presented with increased numbers of intestinal mast cells, which strongly expressed hematopoietic PGD synthase (H-PGDS). The levels of urinary tetranor-PGDM increased as the disease progressed. Treatment with a mast cell inactivator or an anti-inflammatory steroid attenuated these symptoms and decreased the tetranor-PGDM urinary levels. The levels of urinary tetranor-PGDM did not correlate with the disease severity in murine models of colitis, asthma, or allergic dermatitis. Furthermore, we have shown that urinary levels of tetranor-PGDM were significantly higher in patients with food allergy than those in healthy volunteers and patients with other types of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. These findings suggest that urinary tetranor-PGDM is a useful diagnostic index of food allergy in both mice and humans.

Exposure to phthalates and bisphenol A are associated with atopic dermatitis symptoms in children: a time-series analysis.

BACKGROUND: Despite increasing evidence on the relationship between exposure to phthalates and bisphenol A with allergies and asthma, reports on atopic dermatitis (AD) with these chemicals are few. We assessed the association between AD symptoms and the exposure to phthalates and bisphenol A and in children. METHODS: We surveyed 18 boys with AD (age 3-7 years) in a day care center in Seoul between May 2009 and April 2010. AD symptoms were recorded by using a daily symptom diary. We collected 460 series of pooled urine twice a day, in the morning and afternoon, over 230 working days and measured the concentrations of mono-2-ethyl-5-oxohexyl phthalate (5-oxo-MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (5-OH-MEHP), mono-isobutyl phthalate (MnBP) and bisphenol A glucuronide (BPAG) in the pooled urine. Logistic regression was used for statistical analysis. RESULTS: Most phthalate metabolite levels were higher in the morning than in the afternoon (p < 0.0001). There was seasonal variation in the levels of phthalates and bisphenol A metabolites. Levels of 5-OH-MEHP, MnBP, and BPAG were highest in summer (p < 0.0001). Manifestation of AD symptoms was associated with an increase in urinary levels of MnBP (adjusted odds ratio, aOR = 2.85, 95% CI: 1.12-7.26 per 1 µg/L of MnBP) and BPAG (aOR = 1.79, 95% CI: 0.91-3.52 per 1 µg/L BPAG) on the same day. The levels of MnBP and BPAG in the previous day increased AD symptoms (aOR = 2.74, 95% CI: 1.21-6.20, for 1 µg/L of MnBP and aOR = 2.01, 95% CI: 1.08-3.74 for 1 µg/L BPAG). CONCLUSION: Our results suggest that exposure to phthalates and bisphenol A is associated with aggravation of AD symptoms in children.

Percutaneous penetration of silver from a silver containing garment in healthy volunteers and patients with atopic dermatitis.

Human data on dermal absorption of silver under "in use" scenario are scarce which hampers health risk assessment. The main objective of the present study was to determine percutaneous penetration of silver after dermal exposure to silver containing garment in healthy individuals and atopic dermatitis (AD) patients. Next to assess pro-inflammatory effect of silver in the skin. Healthy subjects (n=15) and patients with AD (n=15) wore a sleeve containing 3.6% (w/w) silver on their lower arms for 8h during 5 consecutive days. The percutaneous penetration parameters were deduced from the silver concentration-depth profiles in the stratum corneum (SC) collected by adhesive tapes. Furthermore, silver was measured in urine samples collected before and after exposure. Inflammatory response was assessed by measuring IL-1α and IL-1RA in the exposed and non-exposed skin sites. Dermal flux of silver in healthy subjects and AD patients was respectively 0.23 and 0.20 ng/cm(2)/h. The urine silver concentrations showed no increase after exposure. Furthermore, exposure to silver did not lead to the changes in the profiles of IL-1α and IL-1RA. Dermal absorption of silver under "real life scenario" was lower than the current reference dose. Furthermore, dermal exposure did not lead to altered expression of inflammatory IL-1 cytokines in the skin.

Profiling of serum and urinary microRNAs in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in children characterized by dermatitis and pruritus. MicroRNAs (miRNAs) have been shown as great potential biomarkers for disease fingerprints to predict prognostics. We aimed to identify miRNA signature from serum and urine for the prognosis of AD patient by genome-wide miRNA profiling analysis. METHODS: Serum and urine from 30 children with AD and 28 healthy children were collected and their genome-wide miRNA expression profiles were measured by TaqMan-based array and confirmed by quantitative real-time PCR. Inflammatory factors in serum were detected by Antibody Array System. RESULTS: miR-203 and miR-483-5p were significantly up-regulated in serum of children with AD compared with healthy children. The level of miR-483-5p in serum was significantly associated with other atopic conditions, such as rhinitis and/or asthma. However, miR-203 was markedly decreased in urine of children with AD compared with healthy children. Down-regulated miR-203 in urine was significant associated with abnormal level of serum IgE in AD patients. 7 inflammatory factors in serum were altered in children with AD compared with healthy children. Up-regulated miR-203 in serum was significantly associated with increased sTNFRI and sTNFRII. CONCLUSIONS: Up-regulated miR-483-5p in serum may be indicative of other atopic conditions in children with AD. Down-regulated miR-203 in urine may serve as a biomarker for the severity of inflammation in children with AD.

Functional interpretation of metabolomics data as a new method for predicting long-term side effects: treatment of atopic dermatitis in infants.

Topical steroids are used for the treatment of primary atopic dermatitis (AD); however, their associated risk of serious complications is great due to the presence of vulnerable lesions in young children with AD. Topical calcineurin inhibitors (TCIs) are steroid-free, anti-inflammatory agents used for topical AD therapy. However, their use is prohibited in infants <2 years of age because of their carcinogenic potential. We conducted a randomized, double-blind trial to evaluate the efficacy of TCIs as a secondary AD treatment for children <2 years of age by comparing 1% pimecrolimus cream with 0.05% desonide cream. We performed urinary metabolomics to predict long-term side effects. The 1% pimecrolimus cream displayed similar efficacy and exceptional safety compared with the 0.05% desonide cream. Metabolomics-based long-term toxicity tests effectively predicted long-term side effects using short-term clinical models. This applicable method for the functional interpretation of metabolomics data sets the foundation for future studies involving the prediction of the toxicity and systemic reactions caused by long-term medication administration.

Positive Effects of hydrogen water on 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice.

Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation. AD is triggered by oxidative stress and immune imbalance. In the present study, we investigated the effect of drinking hydrogen water (HW) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in NC/Nga mice and found that HW ameliorated DNCB-induced AD-like clinical symptoms. In line with this, the level of reactive oxygen species in the HW group was significantly inhibited compared with that in the purified water (PW) group. In parallel, HW enhanced glutathione peroxidase activity in DNCB-induced AD as compared with the PW group. Accordingly, the levels of thymus and activation-regulated chemokine and cytokines were significantly decreased in the HW group compared with the PW group. Notably, the levels of Th2 cytokine, interleukin-5 (IL-5), and proinflammatory cytokines such as tumor necrosis factor-α and IL-6 in HW-fed mice were significantly lower than in control and PW-fed mice. The total serum immunoglobulin E level was also markedly reduced in the HW group. The collective results indicate that HW suppresses DNCB-induced AD in NC/Nga mice via redox balance and immune modulation and could be a safe clinical fluid treatment for AD.

Elevated urinary levels of cystatin C and neutrophil gelatinase-associated lipocalin in Henoch-Schönlein purpura patients with renal involvement.

Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis in childhood. The long-term prognosis of HSP is determined by the degree of renal involvement. The aim of this study is to search novel clinically applicable biomarkers to evaluate renal involvement in HSP patients. 20 bio-indexes in urine samples were simultaneously screened by antibody array assay. We indicated that urinary levels of cystatin C (Cys C) and neutrophil gelatinase-associated lipocalin (NGAL) in HSP patients with renal involvement were significantly higher than those without renal involvement and healthy controls. Furthermore, ELISA was used to analyze urinary Cys C and NGAL levels in HSP patients with or without renal involvement, atopic dermatitis (AD) patients and healthy controls. Our results demonstrated that urinary Cys C and NGAL levels in HSP patients with renal involvement were significantly elevated, when compared with those without renal involvement, AD patients and control subjects. In addition, by receiver operating characteristic (ROC) curve analysis, we demonstrated that the area under the ROC curve of NGAL (0.789) was larger than that of Cys C (0.692). Taken together, we show firstly that urinary Cys C and NGAL levels is abnormally elevated in HSP patients with renal involvement. We suggest that urinary Cys C and NGAL are novel useful biomarkers of renal involvement in HSP patients.

Phthalate metabolites in urine and asthma, allergic rhinoconjunctivitis and atopic dermatitis in preschool children.

Phthalate esters are among the most ubiquitous of indoor pollutants and have been associated with various adverse health effects. In the present study we assessed the cross-sectional association between eight different phthalate metabolites in urine and allergic disease in young children. As part of the Danish Indoor Environment and Children's Health study, urine samples were collected from 440 children aged 3-5 years, of whom 222 were healthy controls, 68 were clinically diagnosed with asthma, 76 with rhinoconjunctivitis and 81 with atopic dermatitis (disease subgroups are not mutually exclusive; some children had more than one disease). There were no statistically significant differences in the urine concentrations of phthalate metabolites between cases and healthy controls with the exception of MnBP and MECPP, which were higher in healthy controls compared with the asthma case group. In the crude analysis MnBP and MiBP were negatively associated with asthma. In the analysis adjusted for multiple factors, only a weak positive association between MEP in urine and atopic dermatitis was found; there were no positive associations between any phthalate metabolites in urine and either asthma or rhinoconjunctivitis. These findings appear to contradict earlier studies. Differences may be due to higher exposures to certain phthalates (e.g., BBzP) via non-dietary pathways in earlier studies, phthalates serving as surrogates for an agent associated with asthma (e.g., PVC flooring) in previous studies but not the present study or altered cleaning habits and the use of "allergy friendly" products by parents of children with allergic disease in the current study in contrast to studies conducted earlier.

Urinary biomarker of oxidative stress in patients with psoriasis vulgaris and atopic dermatitis.

BACKGROUND: The involvement of oxidative stress in the pathogenesis of various skin disorders has been suggested for decades. However, few clinical studies have assessed oxidative stress in skin diseases. The easiest and least invasive method to assess oxidative stress in patients may be the measurement of oxidation products in urine. OBJECTIVE: This study aims to assess oxidative stress in psoriasis and atopic dermatitis patients. METHODS: Urine samples were collected from 29 psoriasis patients (25 males and 4 females), 21 atopic dermatitis patients (14 males and 7 females) and 20 healthy controls (16 males and 4 females). The severity and extent of psoriasis and atopic dermatitis was assessed by their area and severity index. We measured nitrate as a metabolite of nitric oxide, malondialdehyde as a major lipid oxidation product, and 8-hydroxydeoxyguanosine (8-OHdG) as a DNA oxidation marker. RESULTS: Urinary nitrate and 8-OHdG levels, but not malondialdehyde, were significantly higher in psoriasis patients than those in healthy controls. On the contrary, only urinary nitrate level was significantly higher in atopic dermatitis patients than those in healthy controls. The severity and extent of both psoriasis and atopic dermatitis significantly correlated with urinary nitrate level and malondialdehyde level, but it did not correlate with urinary 8-OHdG level. CONCLUSIONS: Measurement of these three urinary oxidative products is non-invasive. Above all, measurement of urinary nitrate may be most useful in the clinical assessment of oxidative stress in both psoriasis and atopic dermatitis patients. There is a possibility that urinary 8-OHdG level may indicate the different pathogenesis between psoriasis and atopic dermatitis.

The relationship between infantile atopic dermatitis and urinary tract infection.

Atopic dermatitis (AD) is one of the most common infantile diseases. Immunological dysfunctions in AD patients may predispose them to infections. The aim of this study was to evaluate the relationship between infantile AD and urinary tract infection (UTI).In this cross sectional study, we enrolled 57 patients with AD aged 1 to 24 months that referred to dermatology clinic, and 57 healthy controls who were referred to pediatric clinic. The groups were matched according to age and gender. Urine samples were collected by clean-voided bag method. If a single organism was cultured at concentration of > or = 105 organisms per millimeter and the existence of white blood cells more than 10 per microscopic field was seen the patients underwent suprapubic aspiration. The presence of one organism in suprapubic aspiration sample was regarded as positive culture. Data were analyzed using SPSS version 15 software. P value <0.05 was considered as the level of significance. Twelve (21.1%) of AD patients and 1(1.8%) of normal controls had positive urine culture tests. The difference between two groups was statistically significant (p = 0.001). The most common bacteria was E-coli. Infants with AD showed a higher frequency of UTI in this study. So, we suggest screening all AD infants for urinary tract infection.