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Background: Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs), and leukotrienes with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. This study aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease., Methods: This study quantified the levels of 21 eicosanoids in urine from children from the COPSAC 2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) (age 1 year, n = 450) and VDAART (Vitamin D Antenatal Asthma Reduction Trial) (age 3 years, n = 575) mother-child cohorts and analyzed the associations with development of wheeze/asthma, atopic dermatitis, and biomarkers of type-2 inflammation, applying false discovery rate of 5% (FDR5%) multiple testing correction., Results: In both cohorts, analyses adjusted for environmental determinants showed that higher TXA 2 eicosanoids in early life were associated with increased risk of developing atopic dermatitis (P < FDR5%) and type-2 inflammation (P < .05). In VDAART, lower PGE 2 and PGI 2 eicosanoids and higher isoprostanes were also associated with increased risk of atopic dermatitis (P < FDR5%). For wheeze/asthma, analyses in COPSAC 2010 showed that lower isoprostanes and PGF 2 eicosanoids and higher PGD 2 eicosanoids at age 1 year associated with an increased risk at age 1-10 years (P < .05), whereas analyses in VDAART showed that lower PGE 2 and higher TXA 2 eicosanoids at age 3 years associated with an increased risk at 6 years (P < FDR5%)., Conclusions: This study suggests that early life perturbations in the eicosanoid metabolism are present before the onset of atopic disease in childhood, which provides pathophysiological insight in the inception of atopic diseases., Competing Interests: Disclosure Statement COPSAC is funded by private and public research funds, which are all listed on www.copsac.com. The Lundbeck Foundation, Danish State Budget, Danish Council for Strategic Research, Danish Council for Independent Research, and The Capital Region Research Foundation have provided core support for COPSAC. The study is further supported by the following National Institutes of Health grants: R01HL129735, R01HL141826, and UH3OD023268. C.E.W. acknowledges support from the Swedish Heart Lung Foundation (HLF 20200693 and HLF 20210519) and the Swedish Research Council (2022-00796). This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 946228). R.S.K. was supported by the National Heart, Lung, and Blood Institute (HKL146980). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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 PGF 2α metabolite (13,14-dihydro-15-keto-tetranor-PGF 1α ), a PGE 2 metabolite (13,14-dihydro-15-keto-tetranor-PGE 2 ), and a PGD 2 metabolite (13,14-dihydro-15-keto PGJ 2 ). mRNA and protein expression of PGF 2α , PGE 2 , and PGD 2 synthase was upregulated in DNFB-treated skin. The tape-stripping model also caused dermatitis but without Th2 inflammation; urine PGF 2α and PGD 2 metabolite levels remained unaffected. Finally, we confirmed that the urinary levels of the aforementioned PG metabolites, as well as PGI 2 metabolite, 6,15-diketo-13,14-dihydro-PGF 1α 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., (© 2021 Federation of American Societies for Experimental Biology.)

Prostaglandin D 2 (PGD 2 ) 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 PGD 2 . 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 PGD 2 metabolites in children with AD is substantially the same as that in HCs even if the disease is severe., (© 2020 British Association of Dermatologists.)

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., (© 2020 S. Karger AG, Basel.)

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., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

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 D 2 (PGD 2 ) 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.

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.

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., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

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.

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.

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., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

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.

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.

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.

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.

Atopic children have an increased risk for asthma, which is preceded by bronchial inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess alveolar NO concentration and bronchial NO flux, which reflect inflammation in lung periphery and central airways, respectively. Exhaled breath condensate is another non-invasive method to measure lung inflammation. The purpose of the present study was to find out if the severity of atopic eczema is associated with lung inflammation that can be observed with these non-invasive tests. We studied 81 patients (7-22 yr old) with atopic eczema and increased wheat-specific IgE (>or=0.4 kUA/l) and no diagnosis of asthma. Exhaled NO was measured at multiple exhalation flow rates, and bronchial NO flux and alveolar NO concentration were calculated. Cysteinyl-leukotriene concentrations were measured in exhaled breath condensate. The patients were divided into two groups according to the severity of atopic eczema. Patients with severe atopic eczema had enhanced bronchial NO output as compared with patients with mild eczema (2.1 +/- 0.5 vs. 0.9 +/- 0.1, p = 0.003). No statistically significant differences in alveolar NO concentrations were found between the groups. In the whole group of patients, the bronchial NO output correlated positively with serum eosinophil protein X (r(s) = 0.450, p < 0.001), serum eosinophil cationic protein (r(s) = 0.393, p < 0.001), serum total IgE (r(s) = 0.268, p = 0.016) and with urine eosinophil protein X (r(s) = 0.279, p = 0.012), but not with lung function. Alveolar NO concentration correlated positively with serum eosinophil protein X (r(s) = 0.444, p < 0.001) and with serum eosinophil cationic protein (r(s) = 0.362, p = 0.001). Measurable cysteinyl-leukotriene concentrations in exhaled breath condensate were found only in one-third of the patients, and there were no differences between the two groups. The results show that increased bronchial NO output is associated with eosinophilic inflammation and severe atopic eczema in patients without established asthma.

Background: It has been reported that measurements of eosinophil-derived neurotoxin (EDN) may be useful for identifying eosinophil activities in allergic diseases including atopic dermatitis., Methods: EDN concentrations in the urine were measured by enzyme-linked immunosorbent assay, and the number of eosinophils in the peripheral blood was counted in 30 patients with atopic dermatitis. The severity of atopic dermatitis was graded on the criteria proposed by Rajka and Langeland. The disease activity was assessed by each patient on a visual analogue scale (VAS)., Results: Urinary concentrations of EDN in patients with atopic dermatitis showed a significant positive correlation with disease severity. Urine EDN concentrations also correlated with VAS scores for itching, skin condition, overall skin symptoms and total VAS score, but not with the VAS score for skin dryness. Urinary EDN concentrations did not correlate with the number of eosinophils in the peripheral blood., Conclusions: The urinary EDN concentration in patients with atopic dermatitis is a useful clinical marker for monitoring disease activity.

It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of neopterin. Thus, the determination of neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary neopterin concentrations at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic and recurrent course, beginning primarily in early childhood. The etiopathogenesis of AD has not yet been fully understood, although various types of inflammatory cells including eosinophils may be involved in its pathomechanism. The basic aim of the study was to evaluate the usefulness of selected eosinophil proteins in serum and urine of AD patients, as markers of disease severity. The study also aimed to analyze correlations between the level of examined proteins and parameters such as skin prick test (SPT) results, serum concentration of total IgE, and coexistence of symptoms of other atopic diseases. The study included 30 AD patients and two control groups: 30 patients suffering from chronic urticaria and 30 healthy individuals. The mean level of eosinophil proteins measured in serum and urine of AD patients was higher than that in controls, although a significant difference was only recorded for serum and urine level of eosinophil protein X (EPX). Patients with very severe/severe AD presented higher levels of eosinophil proteins than patients presenting with mild/moderate AD, although no significant difference was found between these two groups. AD patients with positive SPT results and detectable specific IgE in serum, and with coexisting symptoms of other atopic diseases presented with higher mean levels of serum and urine eosinophil proteins than AD cases with negative SPT results and without any symptoms of other atopic diseases. In children suffering from AD, serum eosinophil cationic protein level, EPX level and urine EPX level were higher than those in healthy children, however, without statistical significance. Study results suggested a significant role of eosinophils in the etiopathogenesis of AD. Serum and urine levels of selected eosinophil proteins may serve as an important part of diagnostic approach to AD patients, especially in differentiation of allergic and non-allergic forms of AD. The results are also promising for the usefulness of selected eosinophil proteins in the diagnosis of AD in children, however, thorough analysis on a larger group of patients is needed.

Background: Leukotrienes are thought to play a role in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS). Urinary leukotriene E4 (U-LTE4) is a marker of whole-body cysteinyl-leukotriene production., Aims of the Study: To evaluate the role of leukotrienes in children with AEDS by measuring levels of U-LTE4, and to evaluate whether levels of U-LTE4 may reflect disease activity and allergic sensitization in AEDS., Methods: U-LTE4 was measured by enzyme-linked immunosorbent assay in 87 children with mild (n=32), moderate (n=34) and severe (n=21) AEDS, as well as in 72 nonatopic healthy controls. Fifty-eight of the children with AEDS were sensitized to common allergens, and 29 were not., Results: Levels of U-LTE4 were higher in children with severe AEDS (140; 66-166 microg/mmol creatinine, median; quartiles) than in controls (52; 30-90, P <0.05), whereas levels of U-LTE4 in moderate and mild disease were similar to controls. U-LTE4 levels were similar in children with or without sensitization to common allergens, but severe AEDS children with sensitization had higher levels of U-LTE4 than those without sensitization., Conclusion: The results suggest a role for leukotrienes in the pathogenesis of severe AEDS, and may support a role for leukotriene-antagonists in the treatment of this disorder. Levels of U-LTE4 may reflect the disease severity and sensitization to allergens in AEDS.

Background: Atopic dermatitis (AD) affects infants, children, and adults with a wide degree of severity; several scoring systems have been used in trials and clinical practice. Infants and young children have a typical distribution of the lesions, but a correlation among skin surface involvement, intensity and subjective symptoms has not been reported in age groups., Aims of the Study: To evaluate the clinical features of AD in infants and young children, by using the SCORAD index. A simplified scoring method for clinical practice is also discussed., Methods: The SCORAD index was assessed in 63 infants and young children with AD [mean age (+/-SD) 17.5 +/- 11.15 months]; the single parameters of the index were evaluated, and compared with each other. Serum eosinophil cationic protein (s-ECP) and urinary eosinophil protein X (u-EPX) levels were determined and correlated with the SCORAD index., Results: The presence of erythema, edema/papulation, and oozing/crust was significantly high in these patients. A strong positive correlation resulted among the three SCORAD index parameters (extent-intensity: P <0.001; extent-subjective symptoms: P <0.001; intensity-subjective symptoms: P <0.001). S-ECP and u-EPX levels positively correlated to almost every single parameter of the SCORAD index as well as to its total., Conclusions: Distinctive intensity items were found in infants and young children with AD. A strong correlation resulted among the extent, intensity, and subjective symptoms; each of the three parameters was positively correlated with the total SCORAD. Immunologic parameters positively correlated to each of the SCORAD index items, which remains the gold standard for assessing disease severity in clinical trials.

Leukotriene E4 (LTE(4)) is elevated in adults with atopic dermatitis (AD). We evaluated whether urinary LTE(4) as a noninvasive marker correlates with clinical indices of disease activity in children with AD. AD patients aged 18 years or younger were eligible for inclusion in the study. Disease severity over the preceding 3 days was evaluated by the SCORing Atopic Dermatitis (SCORAD) index. Severity of AD over the past 12 months was evaluated by the Nottingham Eczema Severity Score (NESS) in Chinese. Urinary LTE(4) concentration was measured by competitive enzyme immunoassay. One hundred and twenty-six children with AD (82 boys and 44 girls) and 45 controls were recruited. The mean +/- SD urinary log-transformed LTE(4) concentration in AD patients and controls was 2.94 +/- 0.32 and 2.62 +/- 0.20 pg/mg creatinine, respectively (P < 0.0001). SCORAD significantly correlated with NESS (r = 0.681, P < 0.0001). There were significant correlations between urinary LTE(4) concentration and overall SCORAD score (r = 0.270, P = 0.002) and its extent (r = 0.185, P = 0.038) and intensity components (r = 0.247, P = 0.005), but not with NESS. When compared with mild AD, urinary LTE(4) concentrations were higher in patients with moderate-to-severe disease (P = 0.049). Urinary LTE(4) measurement is noninvasive and may be useful in supplementing the SCORAD for following longitudinal changes in AD severity in children. However, the practical value of this assay in a clinical setting remains to be determined.

To study the role of mast cell activation in children with atopic eczema/dermatitis syndrome (AEDS), we measured levels of urinary 9alpha,11beta-prostaglandin F(2) (U-9alpha,11beta-PGF(2)) by enzyme-linked immunoassay in 88 children (mean age 44 months, range 3-135) with mild (n=32), moderate (n=34) or severe (n=22) AEDS, as well as in 72 non-atopic healthy controls. Fifty-eight of the children with AEDS were sensitized to common allergens (atopics) and 30 were not (non-atopics). Levels of U-9alpha,11beta-PGF(2) were higher in children with severe AEDS (median 324 microg/mmol creatinine, quartiles 220-593) than in controls (198, 102-389, p<0.001), whereas levels of U-9alpha,11beta-PGF(2) in moderate and mild disease were similar to controls. U-9alpha,11beta-PGF(2) levels were similar in atopic and non-atopic children, but in severe AEDS those with atopy had higher levels than those without atopy (p<0.05). The results suggest a role for mast cell activation in children with severe AEDS. Exacerbation of AEDS caused by allergen triggering may involve mast cell activation, and U-9alpha,11beta-PGF(2) may serve as a marker of this process.

Pentosidine is an advanced glycation end product formed by sequential glycation and oxidation. The formation of pentosidine is increased in diseases associated with oxidative stress, such as inflammatory conditions. The aim of the present study was to determine the urinary concentration of pentosidine in atopic dermatitis (AD) and its relationship to the inflammatory status of AD. Urine samples of 32 children with AD and 30 age-matched healthy control subjects were assayed for pentosidine, pyrraline (another advanced glycation end product formed by nonoxidative glycation), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) (an established marker of oxidative stress). Of these 3 markers, urinary concentrations of pentosidine were significantly higher in patients with acute exacerbation of AD than in healthy controls and patients with stable AD. Urinary concentrations of 8-OHdG were significantly higher in AD patients with and without acute exacerbation than in healthy controls. Urinary pentosidine levels correlated significantly with those of 8-OHdG when all data of healthy controls and AD patients were plotted. In patients with acute exacerbation of AD, both urinary pentosidine and 8-OHdG significantly decreased after 7 to 9 days of treatment. Our findings in patients with acute exacerbation of AD suggest that pentosidine levels are partly determined by the prevailing oxidative stress in these patients.

Coal tar preparations, as used in dermatological practice, contain numerous polycyclic aromatic hydrocarbons of which many are proven animal carcinogens. Increased urinary 1-hydroxypyrene excretion in patients with atopic dermatitis treated with topical coal tar preparations has been demonstrated. Little is known about the relationship between the dermal uptake of polycyclic aromatic hydrocarbons on the one hand and the amount of tar applied to the skin, the total body area affected, the condition of the epidermal barrier and the severity of the dermatitis on the other. We compared urinary 1-hydroxypyrene excretion rate with these variables. The urinary 1-hydroxypyrene excretion rate was highly dependent on the total amount of tar applied to the skin and the total body area affected, and less on the severity of the atopic dermatitis or the condition of the epidermal barrier. Exposure to therapeutic doses of coal tar leads to much higher rates of urinary 1-hydroxypyrene excretion than occupational exposure. Because of the potential carcinogenicity of coal tar, as clearly demonstrated both in animal studies and from occupational exposure, careful consideration should be given to the use of coal tar preparations in dermatological practice. However, the risk of short-term high exposure is unknown. Restriction of the use of coal tar should be based on epidemiological studies and/or appropriate risk models taking into account its relative safety established over many years of clinical use.

Background: Eosinophils are important effector cells in several atopic diseases. The levels of eosinophil granule-derived mediators (ECP, EPX) in serum and body fluids have been proven to be correlated with disease activity in atopic respiratory diseases and atopic dermatitis. The study aimed to demonstrate an interrelationship between urine EPX and disease activity in adult patients with atopic dermatitis., Methods: We determined urine EPX concentration, serum ECP concentration, and peripheral blood eosinophil count in 40 adult patients with mild to severe atopic dermatitis and compared it with the disease activity as assessed with the SCORAD index., Results: Urine EPX and serum ECP concentrations were significantly higher in patients with severe atopic dermatitis than in patients with mild or moderate disease (median values 123.5 vs 78.3 microg/mmol creatinine, P<0.0001; 25.4 vs 14.9 microg/l, P<0.0001, respectively). We found a significant correlation between urine EPX levels, serum ECP levels, and the SCORAD (r=0.36, P<0.0001 and 0.34, P<0.0001, respectively)., Conclusion: Urine EPX is a useful in vitro parameter of inflammation in atopic dermatitis of the adult age.

We measured both urinary 17-hydroxycorticosteroids(17-OHCS) and 17-ketosteroid sulfates(17-KS-S) in normal children and in children with some diseases to evaluate adaptation to stress in children. 17-OHCS and 17-KS-S values were measured in morning urine from 60 normal children(3-18 years old) and 24 children with atopic dermatitis or renal disease. In normal children, the 17-OHCS/creatinine showed no difference by age, but both 17-KS-S/creatinine and 17-KS-S/17-OHCS showed significant positive correlation with age. No sex differences were significant. In children with atopic dermatitis or with renal disease treated with cyclosporine A, 17-OHCS/creatinine was significantly higher and the 17-KS-S/17-OHCS ratio was significantly lower than in age-matched controls. These values returned to normal as the conditions improved or as treatment ended. In patients who underwent renal biopsy, both 17-OHCS/creatinine and 17-KS-S/creatinine values were significantly higher after biopsy than before because of the stress caused by pain and complete bed rest. Measurement of urinary 17-OHCS and 17-KS-S in children can be useful for evaluation of adaptation to stress as well as in adults.

Background: Synthesis of cysteinyl leukotrienes (LTs) is known to play a part in the pathogenesis of inflammatory diseases., Objectives: To define the involvement of cysteinyl LTs in atopic dermatitis (AD)., Methods: Synthesis of cysteinyl LTs was assessed in patients with AD and healthy volunteers by measuring urinary LTE4, a useful index of systemic cysteinyl LT synthesis, using liquid chromatography/tandem mass spectrometry., Results: Mean +/- SD urinary LTE4 levels in patients with AD (125 +/- 69 pg mg(-1) creatinine, n = 20) were significantly higher (P < 0.01) than in healthy volunteers (60 +/- 19 pg mg(-1) creatinine, n = 17). A significant correlation between urinary LTE4 and total serum IgE levels in patients with AD was observed (r = 0.643, P < 0.05)., Conclusions: Our findings demonstrate an enhanced synthesis of cysteinyl LTs in patients with AD and suggest that cysteinyl LTs are involved in the pathophysiology of AD.

Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EPX) are cytotoxic molecules involved in helminth infections and allergic reactions. Hitherto most clinical chemical studies have been concerned with the analysis of serum ECP in allergic diseases. The aim of this study was to examine whether serum as well as urine levels of these proteins are useful clinical chemical parameters in helminthiases and allergic diseases such as atopic dermatitis. Comparing these diseases under the same methodological conditions, levels of ECP and EPX were generally higher in helminthiases than in atopic dermatitis and non-helminth, non-allergic diseases. The highest levels of both proteins occurred in tropical worm diseases, in particular hookworm disease and onchocerciasis. When comparing helminthiases with allergic disorder, only hookworm disease (ECP and EPX) and onchocerciasis (EPX) exhibited significantly higher eosinophil cationic protein serum levels than atopic dermatitis. In patients with schistosomiasis mansoni and egg loads of > 1000-10 000 eggs/g stool (epg) EPX serum levels were significantly higher than in patients exhibiting loads < 1000 epg. Urinary analyses revealed only EPX to be present in measurable amounts. Levels of this protein were much higher in urine of patients with hookworm disease and onchocerciasis than in those with atopic dermatitis and in healthy controls. The results suggest that besides serum EPX, urinary EPX may be a useful clinical chemical parameter in eosinophilia of helminth and allergic aetiology.

Background: Parameters of eosinophil inflammation have been suggested as markers of disease activity in atopic dermatitis (AD), but the value of urinary eosinophil protein X (U-EPX) in children with AD, as well as the influence of allergic sensitization, is not known., Methods: We measured U-EPX in 59 atopic and 29 nonatopic children with mild (n = 32), moderate (n = 34), and severe (n = 22) AD, as well as in 64 controls., Results: U-EPX was increased in children with AD (110; 67-164 microg/mmol creatinine, median; quartiles) compared to controls (62; 41-95, P<0.001). Children with mild (97; 63-164, P < 0.01), moderate (108; 67-157, P < 0.01), and severe disease (152; 99-202, P < 0.001) had levels of U-EPX higher than controls. U-EPX was significantly higher in children with severe AD than in mild and moderate disease (P < 0.05 for both). Children with AD and a positive skin prick test (120; 81-176) had higher levels of U-EPX than children with a negative skin prick test (87; 56-155, P<0.05)., Conclusions: U-EPX is significantly increased in children with AD and may reflect disease activity. U-EPX may also reflect differences in eosinophil activation between those sensitized and those not sensitized to common allergens.

Background: Adrenocortical suppression is a potential complication of the use of topical corticosteroids in patients with atopic dermatitis (AD)., Objectives: To determine whether or not the adrenocortical suppression observed in patients with severe AD is a sole result of the application of topical steroids., Methods: A total of 45 patients with severe AD that required hospitalization for treatment were enrolled. These patients were divided into two groups according to the treatment received before hospitalization: group 1 had not used topical corticosteroids for at least three months (n = 17), while group 2 had used topical corticosteroids daily (n = 28). Otherwise, these two groups were matched to clinical characteristics. A rapid ACTH test was performed upon hospital admission. Topical corticosteroids were then applied to both groups. The second ACTH test was performed just before discharge, an average of 23 days after the first test., Results: The basal serum cortisol levels as well as the response to ACTH stimulation in the first examination were significantly lower in the AD patients than in the controls (P < .001), although there were no significant differences in the results between groups 1 and 2. The followup study of adrenocortical function at hospital discharge showed that morning basal serum cortisol levels were significantly increased in group 1 (P < .01), despite their topical corticosteroid treatment, while no significant increase or decrease was seen in group 2., Conclusion: Our findings suggest that the adrenocortical suppression seen in patients with AD may be caused by the percutaneous absorption of topical corticosteroids as well as by other factors related to the disease.

Background: Staphylococcus aureus has been identified as a possible trigger factor in atopic dermatitis (AD). Some 30-60% of S. aureus strains isolated from patients with AD are able to produce exotoxins with superantigenic properties, mostly staphylococcal enterotoxins A, B, C, and D (SEA-D) and toxic shock syndrome toxin-1 (TSST-1). Recently, it was demonstrated that the presence of IgE antibodies to SEA and SEB is correlated with the severity of skin lesions in children with AD. To determine the relevance of staphylococcal enterotoxins in adult patients with AD, we investigated the relationship between the severity of skin lesions and sensitization to SEA and SEB., Methods: Clinical severity was determined by the SCORAD index. Circulating IgE antibodies to SEA and SEB, serum eosinophil cationic protein (ECP) levels, and urine eosinophil protein X (EPX) levels were measured., Results: The skin condition was significantly worse in patients sensitized to SEB than in unsensitized patients. Serum ECP and urine EPX levels were found to be significantly higher in SEB-sensitized patients, confirming the higher degree of cutaneous inflammation., Conclusions: Our results demonstrate a relationship between severity of skin lesions and sensitization to SEB in adult patients with AD, but a relationship between disease activity and sensitization to SEA could not be shown.

Background: Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) or eosinophil-derived neurotoxin (EDN) are released by eosinophil granulocytes in allergic diseases. Serum ECP (s-ECP) levels have been correlated with disease activity in atopic dermatitis (AD) in adults and young patients, and high urinary EPX (u-EPX) levels in asthmatic patients seem to reflect active disease. A relationship between AD severity and u-EPX concentration in young children has not been previously studied., Objective: This study was performed to evaluate whether the severity of AD in infants and young children was correlated with s-ECP and u-EPX levels., Methods: Fifty-four infants and children (mean age, 17.7 months; range, 4-48 months) with AD and without other allergic conditions were evaluated. The severity of AD was measured by using the SCORAD index. S-ECP, serum total IgE, serum-specific IgE for common allergens, and peripheral blood eosinophil counts (PBECs) were determined. In forty-two children u-EPX was also measured. Seven age-matched control patients underwent the same determinations., Results: S-ECP and u-EPX were significantly higher in children with AD than in control children (mean, 23.9 vs 3.5 microg/dL [P <.001] and 57.7 vs 6.0 microg/mmol creatinine [P <.001]). A significant correlation was found between SCORAD and s-ECP (P =.002), u-EPX (P =.01), and PBECs (P =.01) and between symptom index and uEPX (P =.0004). PBECs were strongly correlated to s-ECP and u-EPX (P <.0001). However, 5 patients with moderate and severe AD (11.9%) showed low levels of s-ECP, u-EPX, and PBECs., Conclusion: S-ECP and u-EPX were useful markers of AD activity in infants and young children. When taken together, the two determinations could give more information about the clinical course of the illness. Some patients seemed to have clinical exacerbations without an involvement of eosinophils and their products.

The content of medium molecular weight (MMW) substances in the blood and urine was studied in patients with chronic dermatoses (psoriasis and atopic dermatitis). Intoxication was detected in all these patients, which was confirmed by clinical symptoms and a high level of plasma MMW substances, indicating pronounced catabolic processes in this condition. The distribution of MMW substances in biological media and the absence of positive changes after treatment in patients with atopic dermatitis in comparison with psoriasis patients may be indicative of different mechanisms of biochemical homeostasis and different adaptation potential, which should be taken into consideration when prescribing correction.

8-hydroxydeoxyguanosine (8-OHdG) is one of the products which are excreted in urine as a result of oxidative damage to DNA. We investigated the feasibility of using 8-OHdG in urine as an index for oxidative damage to DNA in atopic dermatitis (AD). Seventeen patients with long-standing AD and 17 healthy volunteers were enrolled in this study. The severity of AD was evaluated by SCORAD index. Eosinophils, total IgE and lactate dehydrogenase-5 in peripheral blood were measured as clinical parameters for AD. A newly developed enzyme-linked immunosorbent assay method was used to measure urine 8-OHdG. The AD patients showed significantly higher levels (P < 0.0001) of 8-OHdG in their urine than corresponding controls. Urine 8-OHdG levels showed as strong a positive correlation as other haematological parameters did using the SCORAD index. Thus, we conclude that the urine 8-OHdG levels can also serve as a biochemical index of tissue damage and can act as a useful tool in the clinical evaluation of AD.

Leukotriene synthesis may be increased in a variety of inflammatory diseases. Urinary leukotriene E4 is a stable metabolite of leukotrienes C4 and D4 which has previously been found to be increased in exacerbations of severe asthma and after antigen inhalation. Levels of urinary LTE4 in seven patients during and after a severe flare of atopic dermatitis were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Mean urinary LTE4 levels (+/- SEM) were not increased during (16.7 +/- 3.7 pg/mumol) or after (16.9 +/- 4.8 mumol) the acute exacerbation of atopic dermatitis when compared with the normal range (mean = 23.8 [95% confidence interval 19.9-28.2] pg/mumol creatinine). These findings do not provide evidence of cysteine leukotriene involvement in the pathogenesis of atopic dermatitis.

To study the usefulness of urinary 1-methylhistamine and serum tryptase concentration as monitoring parameters in clinical settings, we investigated 32 children with atopic dermatitis and suspected food allergy during oral food challenges with eggs and cow's milk. Urinary 1-methylhistamine (MH) excretion increased significantly within 1 h after positive oral food challenges (p < 0.006), but showed considerable variation in negative challenges. MH seems to be a sensitive parameter (92.8%), but its specificity is insufficient (37.7%). In the group of 16 positive oral food challenges serum tryptase concentration increased significantly (p < 0.02) directly after provocation and remained elevated up to 2 h after provocation. No variation was observed in negative challenges or nonatopic controls. Serum tryptase concentration seems to be specific for marked clinical reactions after oral food challenges (100%), but its sensitivity was low (25%) and not superior to evaluation by clinical means. We conclude that, despite positive results for the group of children, MH and serum tryptase concentrations are not useful parameters for monitoring oral food challenges in an individual child due to insufficient sensitivity and specificity.

Background: Infants under evaluation for atopic dermatitis (AD) at our clinic undergo a battery of examinations that include urinalysis and urine culture tests with antibiograms. The prevalence of cases with significant bacteriuria and leukocyturia (SBL) appeared to be unexpectedly high., Objective: This study attempts to establish whether infants with AD should be suspected of having a higher prevalence of urinary tract infections (UTI)., Methods: A retrospective analysis of urine and urine culture tests was performed in 131 infants (84 males and 47 females) aged 1-24 months with untreated AD and in 1,327 control subjects (621 male, 706 female) aged 1-24 months., Results: SBL was present in 27.5% of cases versus 3% of controls (p < 10(-5)). After routine treatment for AD and antibiotic treatment on the basis of a urine antibiogram, the recurrence rate of SBL, evaluated monthly over a 6-month period, was only 8.3%., Conclusion: Infants with AD might be at a greater risk for developing UTI, and when treated for AD this risk might be reduced.

Synthesis of cysteinyl leukotrienes was assessed in patients with atopic dermatitis (AD; n = 8) and healthy volunteers (n = 8) by measuring urinary excretion of leukotriene E4 (LTE4), the main index metabolite of cysteinyl leukotrienes in man. Using this non-invasive method we demonstrated a significant (P < 0.05) 4.5-fold increase in excretion of LTE4 compared with healthy volunteers. The identity of LTE4 was unequivocally demonstrated by gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS). LTE4 was routinely measured by radioimmunoassay (RIA), and quantitative measurement of LTE4 by RIA was validated by GC-MS/MS. There was a linear correlation between LTE4 measured by RIA and by GC-MS/MS (r = 0.994). In representative samples, LTE4 was also quantitatively assessed by GC-MS/MS. In these samples, LTE4 values obtained by GC-MS/MS differed < 10% from those obtained by RIA. The present findings suggest that cysteinyl leukotrienes play a role in AD.

We measured small intestinal permeability to lactulose and rhamnose in 18 healthy children and in 15 children with atopic eczema, before and after a 14-day elimination diet. The children with atopic eczema had higher initial urinary lactulose/rhamnose ratios than the controls. After dietary restriction, there was no overall change in permeability. Dietary therapy did however result in a large reduction in permeability in three of the nine children whose skin disease was improved, but a statistically significant decrease in permeability was not observed in the diet-responsive group as a whole. Larger studies would be required to confirm that dietary restrictions can reduce intestinal permeability in some children with atopic eczema.

Absorption of lactulose and mannitol was measured in eleven patients with atopic eczema and lactulose/mannitol excretion ratios were calculated. Mean lactulose absorption was increased in the patients with exzema and their excretion ratios were higher than those of controls. There was no correlation between either eczema extent or severity and the excretion ratio. We conclude that small intestinal passive permeability is increased in some patients with atopic eczema.

Passive intestinal permeability was measured in 15 adult patients with atopic eczema. Values in the patients did not differ significantly from those in 12 healthy control subjects. These results suggest that altered intestinal permeability is not important in the pathogenesis of atopic eczema in adults.