Shifts in the Skin Microbiota after UVB Treatment in Adult Atopic Dermatitis.

BACKGROUND: The pathophysiology in atopic dermatitis (AD) is not fully understood, but immune dysfunction, skin barrier defects, and alterations of the skin microbiota are thought to play important roles. AD skin is frequently colonized with Staphylococcus aureus (S. aureus) and microbial diversity on lesional skin (LS) is reduced compared to on healthy skin. Treatment with narrow-band ultraviolet B (nb-UVB) leads to clinical improvement of the eczema and reduced abundance of S. aureus. However, in-depth knowledge of the temporal dynamics of the skin microbiota in AD in response to nb-UVB treatment is lacking and could provide important clues to decipher whether the microbial changes are primary drivers of the disease, or secondary to the inflammatory process. OBJECTIVES: To map the temporal shifts in the microbiota of the skin, nose, and throat in adult AD patients after nb-UVB treatment. METHODS: Skin swabs were taken from lesional AD skin (n = 16) before and after 3 treatments of nb-UVB, and after 6-8 weeks of full-body treatment. We also obtained samples from non-lesional skin (NLS) and from the nose and throat. All samples were characterized by 16S rRNA gene sequencing. RESULTS: We observed shifts towards higher diversity in the microbiota of lesional AD skin after 6-8 weeks of treatment, while the microbiota of NLS and of the nose/throat remained unchanged. After only 3 treatments with nb-UVB, there were no significant changes in the microbiota. CONCLUSION: Nb-UVB induces changes in the skin microbiota towards higher diversity, but the microbiota of the nose and throat are not altered.

Glove-related hand urticaria. / Hanskerelatert håndurtikaria.

BACKGROUND: Glove-related hand urticaria is probably underdiagnosed and is an important differential diagnosis in suspected cases of contact allergy. CASE PRESENTATION: A nurse in her twenties presented with recurrent immediate-onset erythematous eruption with burning sensation on the dorsal hands after wearing disposable gloves. This occurred irrespective of the type of disposable gloves used. Patch testing, serological analysis for latex IgE and prick tests with latex and different glove materials all gave negative results. Dermographism was demonstrated on her back, and symptoms were reproduced after wearing disposable gloves. Symptoms were less severe when a looser-fitting glove was worn. She was treated with antihistamines and intensified barrier cream, and was recommended to wear loose-fitting gloves at work. She experienced no effect from antihistamines but some improvement from barrier protection. INTERPRETATION: Glove-related hand urticaria should be suspected in healthcare workers with immediate-onset urticarial reaction to multiple glove types, negative allergy tests and the presence of dermographism. Symptoms may be reproduced when wearing a tight-fitting glove.

Morning Salivary Cortisol in Young Children: Reference Values and the Effects of Age, Sex, and Acute Bronchiolitis.

OBJECTIVE: To identify morning salivary cortisol reference values in infancy and at 2 years of age and to investigate the influence of age, sex and acute bronchiolitis. STUDY DESIGN: In this South-East Norwegian cohort study, 308 children hospitalized with moderate to severe acute bronchiolitis in infancy in 2010-2011 were compared with 223 healthy controls included in 2012 by measuring morning salivary cortisol levels at inclusion and at 2 years of age. Samples were collected shortly after awakening after 6 am. The influences of age, sex, and acute bronchiolitis were assessed by regression analysis. RESULTS: In infancy, cortisol values were higher in acute bronchiolitis, with an age- and sex-adjusted weighted mean group difference of 13.9 nmol/L (95% CI 8.1-19.7; P < .0001). The median level in reference group was 23.7 nmol/L (95% CI 9.7-119.6). At 2 years of age, sex but not inclusion groups differed, with significantly higher values in girls. The weighted mean of all boys' cortisol levels was 32.4 nmol/L, (95% CI 30.5-34.3), and all girls' levels were 36.9 nmol/L (95% CI 34.7-39.2; P < .003). CONCLUSIONS: Salivary cortisol levels were higher at 2 years of age than in infancy in the reference group, were higher in girls than in boys at 2 years of age, and were higher in infants at the time of acute bronchiolitis than in healthy infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00817466.

Weight-for-length, early weight-gain velocity and atopic dermatitis in infancy and at two years of age: a cohort study.

BACKGROUND: Overweight and atopic dermatitis (AD) are major health problems in most industrialised countries, but the relationship between overweight and AD in infants and young children is unclear. We investigated if weight-for-length at birth, in infancy and at two years, as well as early weight-gain velocity, are associated with the development of AD in early life. METHODS: Cohort study of infants (n = 642), all living in south-east Norway, hospitalized with acute bronchiolitis (n = 404) or recruited from the general population (n = 238), examined at mean age 5.1 months (enrolment) and at a two-year follow-up visit (n = 499; 78%) at mean age 24.6 months. Exposures were weight-for-length (g/cm) at birth, enrolment and two-year follow-up, and early weight-gain velocity (gram/month from birth to enrolment). Excessive weight-for-length was defined as weight-for-length >95th percentile of WHO child-growth standards. Data on weight-for-length at the three time points were obtained for 435, 428 and 473 children. AD was diagnosed according to the Hanifin & Rajka criteria or from a history of physician-diagnosed AD. We performed multivariate analyses with weight-for-length at birth, at enrolment and at the two-year follow-up visit and with early weight gain velocity for the endpoint AD at each visit. RESULTS: In adjusted analyses, excessive weight-for-length at enrolment was associated with concurrent AD (OR 3.03; 95% CI 1.23-7.50) and with AD at two years (OR 2.40; 1.11-5.17). In infants without AD, weight-for-length at enrolment increased the risk of AD at two years, with OR being 1.02 (95% CI 1.00-1.04) per increased gram/cm. AD at two years was not associated with concurrent excessive weight-for-length, nor was AD at any time associated with weight-for-length at birth or with early weight-gain velocity. CONCLUSIONS: The results suggest that overweight in infancy may contribute to the development of AD in early life, highlighting the need for child health-care professionals to address potential overweight and atopic disease when advising infants' caregivers. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00817466 , EudraCT number, 2009-012667-34.

Topical treatment with fresh human milk versus emollient on atopic eczema spots in young children: a small, randomized, split body, controlled, blinded pilot study.

BACKGROUND: Public health nurses report on effects of fresh human milk as treatment for conjunctivitis, rhinitis and atopic eczema (AE), the latter being highly prevalent in early childhood. Emollients and topical corticosteroids are first line treatment of AE. As many caregivers have steroid phobia, alternative treatment options for mild AE are of interest. The aim of this small pilot study was to assess the potential effects and risks of applying fresh human milk locally on eczema spots in children with AE. METHODS: This was a split body, controlled, randomized and physician blinded pilot study, of children with AE with two similar contralateral eczema spots having a mother breastfeeding the child or a sibling. Fresh expressed milk and emollient was applied on the intervention spot and emollient alone on the control area, three times a day for four weeks. The severity and area of the eczema spots was evaluated weekly, and samples from milk and the spots were analysed weekly with respect to bacterial colonisation. RESULTS: Of nine patients included, six completed the study. Mean age at inclusion was 18.5 months. The spots examined were localized on the arms, legs or cheeks. The spots were similar in severity, but differed in area. In one patient the eczema ceased after inclusion. In four patients both control and intervention areas increased during the intervention. The relative change in eczema area compared to baseline showed less increase in the intervention spots in two patients, whereas the opposite was observed in three. In four children Staphylococcus aureus was found in their eczema once or more. In three of the 28 human milk samples, Staphylococcus aureus, alfa haemolytic streptococci or coagulase negative staphylococci were detected. Staphylococcus aureus was found once both in human milk and in the eczema spots, no clinical signs of infection were however observed. No secondary infection due to milk application was detected. CONCLUSION: In this small pilot study, no effect was found on eczema spots treated with topical application of fresh human milk. (ClinicalTrials.gov Identifier, NCT02381028 ).

Virus, allergic sensitisation and cortisol in infant bronchiolitis and risk of early asthma.

BACKGROUND: Acute bronchiolitis during infancy and human rhinovirus (HRV) lower respiratory tract infections increases the risk of asthma in atopic children. We aimed to explore whether specific viruses, allergic sensitisation or cortisol levels during acute bronchiolitis in infancy increase the risk of early asthma, using recurrent wheeze as a proxy. METHODS: In 294 children with a mean (range) age of 4.2 (0-12) months enrolled during hospitalisation for acute infant bronchiolitis, we analysed virus in nasopharyngeal aspirates, serum specific immunoglobulin E against food and inhalant allergens, and salivary morning cortisol. These factors were assessed by regression analyses, adjusted for age, sex and parental atopy, for risk of recurrent wheeze, defined as a minimum of three parentally reported episodes of wheeze at the 2-year follow-up investigation. RESULTS: At 2 years, children with, compared to without, recurrent wheeze had similar rates of respiratory syncytial virus (RSV) (82.9% versus 81.8%) and HRV (34.9% versus 35.0%) at the acute bronchiolitis, respectively. During infancy, 6.9% of children with and 9.2% of children without recurrent wheeze at 2 years were sensitised to at least one allergen (p=0.5). Neither recurrent wheeze nor incidence rate ratios for the number of wheeze episodes at 2 years were significantly associated with specific viruses, high viral load of RSV or HRV, allergic sensitisation, or morning salivary cortisol level during acute bronchiolitis in infancy. CONCLUSION: In children hospitalised with acute infant bronchiolitis, specific viruses, viral load, allergic sensitisation and salivary morning cortisol did not increase the risk of early asthma by 2 years of age.

Predicting Skin Barrier Dysfunction and Atopic Dermatitis in Early Infancy.

BACKGROUND: Dry skin is associated with increased transepidermal water loss (TEWL), which has been found to precede atopic dermatitis (AD) in childhood. OBJECTIVE: We aimed to identify parental, prenatal, and perinatal predictive factors of dry skin, high TEWL, and AD at 3 months of age, and to determine if dry skin or high TEWL at 3 months can predict AD at 6 months. METHODS: From the Preventing Atopic Dermatitis and Allergies in children prospective birth cohort study, we included 1150 mother-child pairs. Dry skin, TEWL, and eczema were assessed at 3- and 6-month investigations. Eczema, used as a proxy for AD, was defined as the presence of eczematous lesions, excluding differential diagnoses to AD. High TEWL was defined as TEWL >90th percentile, equaling 11.3 g/m2/h. Potential predictive factors were recorded from electronic questionnaires at 18- and 34-week pregnancy and obstetric charts. RESULTS: Significant predictive factors (P < .05) for dry skin at 3 months were delivery >38 gestational weeks and paternal age >37 years; for high TEWL, male sex, birth during winter season, and maternal allergic disease; and for eczema, elective caesarean section, multiparity, and maternal allergic diseases. Dry skin without eczema at 3 months was predictive for eczema at 6 months (adjusted odds ratio: 1.92, 95% confidence interval: 1.21-3.05; P = .005), whereas high TEWL at 3 months was not. CONCLUSION: In early infancy, distinct parental- and pregnancy-related factors were predictive for dry skin, high TEWL, and AD. Dry skin at 3 months of age was predictive for AD 3 months later.

[Graze with unusual progress]. / Skrubbsår med uvanlig forløp.

There is a high incidence of traumatic wounds. Such wounds often become infected which prolongs the wound healing process. Many patients will contact a pharmacy for antiseptic treatment. Various over-the-counter drugs can help as antiseptic treatment; Brulidine is a cream which is widely used for treating local skin infections. Its active component is dibrompropamidine. Some incidences of contact allergy have been reported after use of dibrompropamidine. As dibrompropamidine is sold as an over-the-counter drug, the incidence of contact allergy caused by it may be underreported. This article presents two case reports of patients with contact allergy to dibrompropamidine. The article also describes a diagnostic procedure with Users test and patch testing for diagnosising contact dermatitis.

Quality of life, salivary cortisol and atopic diseases in young children.

BACKGROUND: Children with atopic disease may have reduced health-related quality of life (QoL) and morning cortisol. Possible links between QoL, morning cortisol and atopic disease are unclear. We aimed to determine if QoL was associated with morning salivary cortisol at two years of age, and if asthma, atopic dermatitis and/or allergic sensitisation influenced this association. Secondarily, we aimed to determine if QoL at one year of age was associated with salivary cortisol one year later. METHODS AND FINDINGS: The Bronchiolitis All SE-Norway study included infants during hospitalisation for acute bronchiolitis in infancy (bronchiolitis group) and population-based control infants (controls). The present study included all 358 subjects with available Infant Toddler Quality of Life Questionnaire (ITQOL) from parents, consisting of 13 domains and morning salivary cortisol at two years of age. Answers from the same 0-100 score questionnaire, with optimal score 100 nine months after enrolment, was also available for 289 of these children at about one year of age. Recurrent bronchial obstruction was used as an asthma proxy. Atopic dermatitis was defined by Hanifin and Rajka criteria and allergic sensitisation by a positive skin prick test. Due to different inclusion criteria, we tested possible interactions with affiliation groups. Associations between QoL and cortisol were analysed by multivariate analyses, stratified by bronchiolitis and control groups due to interaction from affiliation grouping on results. At two years of age, QoL decreased significantly with decreasing cortisol in 8/13 QoL domains in the bronchiolitis group, but only with General health in the controls. The associations in the bronchiolitis group showed 0.06-0.19 percentage points changes per nmol/L cortisol for each of the eight domains (p-values 0.0001-0.034). The associations remained significant but diminished by independently including recurrent bronchial obstruction and atopic dermatitis, but remained unchanged by allergic sensitisation. In the bronchiolitis group only, 7/13 age and gender adjusted QoL domains in one-year old children were lower with lower cortisol levels at two years of age (p = 0.0005-0.04). CONCLUSIONS: At two years, most QoL domains decreased with lower salivary cortisol among children who had been hospitalised for acute bronchiolitis in infancy, but for one domain only among controls. Recurrent bronchial obstruction and to a lesser extent atopic dermatitis, weakened these associations that nevertheless remained significant. After bronchiolitis, lower QoL in one-year old children was associated with lower salivary cortisol at two years.

Skin Barrier Function and Staphylococcus aureus Colonization in Vestibulum Nasi and Fauces in Healthy Infants and Infants with Eczema: A Population-Based Cohort Study.

Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants.

Allergic diseases and the effect of inhaled epinephrine in children with acute bronchiolitis: follow-up from the randomised, controlled, double-blind, Bronchiolitis ALL trial.

BACKGROUND: Although use of inhaled bronchodilators in infants with acute bronchiolitis is not supported by evidence-based guidelines, it is often justified by the belief in a subgroup effect in individuals developing atopic disease. We aimed to assess if inhaled epinephrine during acute bronchiolitis in infancy would benefit patients with later recurrent bronchial obstruction, atopic eczema, or allergic sensitisation. METHODS: In the randomised, double-blind, multicentre Bronchiolitis ALL trial, 404 infants with moderate-to-severe acute bronchiolitis were recruited from eight hospitals in Norway to receive either inhaled epinephrine or saline up to every second hour throughout the hospital stay. Randomisation was done centrally, and the two study medications (20 mg/mL racemic epinephrine or 0.9% saline) were prepared in identical bottles. The dose given depended on the infant's weight: 0.10 mL, less than 5 kg; 0.15 mL, 5-6.9 kg; 0.2 mL, 7-9.9 kg; and 0.25 mL, 10 kg or more; all dissolved in 2 mL of 0.9% saline before nebulisation. The primary outcome was the length of hospital stay. In this follow-up study, 294 children were reinvestigated at 2 years of age with an interview, a clinical examination, and a skin prick test for 17 allergens, determining bronchial obstruction, atopic eczema, and allergic sensitisation, on which subgroup analyses were done. Analyses were done by intention to treat. The trial has been completed and is registered at ClinicalTrials.gov (number NCT00817466) and EUDRACT (number 2009-012667-34). FINDINGS: Length of stay did not differ between patients who received inhaled epinephrine versus saline in the subgroup of infants who developed recurrent bronchial obstruction by age 2 years (143 [48.6%] of 294 patients; p(interaction)=0.40). However, the presence of atopic eczema or allergic sensitisation by the age of 2 years (n=77) significantly interacted with the treatment effect of inhaled epinephrine (p(interaction)=0.02); the length of stay (mean 80.3 h, 95% CI 72.8-87.9) was significantly shorter in patients receiving inhaled epinephrine versus saline in patients without allergic sensitisation or atopic eczema by 2 years (-19.9 h, -33.1 to -6.3; p=0.003). No significant differences were found in length of hospital stay in response to epinephrine or saline in children with atopic eczema or allergic sensitisation by 2 years (+16.2 h, -11.0 to 43.3; p=0.24). INTERPRETATION: Contrary to our hypothesis, hospital length of stay for bronchiolitis was not reduced by administration of inhaled epinephrine in infants who subsequently developed atopic eczema, allergic sensitisation, or recurrent bronchial obstruction. The present study does not support an individual trial of inhaled epinephrine in acute bronchiolitis in children with increased risk of allergic diseases. FUNDING: Medicines for Children Network, Norway.