Carl-Fredrik Wahlgren

The antipruritic effect of a sedative and a non‐sedative antihistamine in atopic dermatitis

A double‐blind, randomized, cross‐over study was carried out on the effect of a sedative and a non‐sedative antihistamine on 25 adults with atopic dermatitis. Intensity of itch was recorded using a computerized method for self‐assessment (Pain‐Track®) and using conventional visual analogue scales. The antipruritic effect of 3 days of treatment with the non‐sedative H, antagonist terfenadine (60 mg b.i.d.) and with the sedative antihistamine, clemastine (2 mg b.i.d.) did not differ from that found with the placebo. Our findings support the view that histamine is not of importance in the pathogenesis of itch in atopic dermatitis.

Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence‐based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence‐based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long‐term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.

The prevalence of Malassezia yeasts in patients with atopic dermatitis, seborrhoeic dermatitis and healthy controls

Cultures for Malassezia yeasts were taken from both normal-looking skin and lesional skin in 124 patients with atopic dermatitis, 16 patients with seborrhoeic dermatitis and from normal skin of 31 healthy controls. Positive Malassezia growth was found in fewer patients with atopic dermatitis (56%) than in patients with seborrhoeic dermatitis (88%) or in healthy controls (84%, p<0.01). In the patients with atopic dermatitis, fewer positive cultures were found in lesional (28%) than in non-lesional skin (44%, p<0.05), while positive cultures were found in 75% of both lesional and non-lesional skin of patients with seborrhoeic dermatitis (not significant). M. sympodialis dominated in patients with atopic dermatitis (46%) and in healthy controls (69%). In patients with seborrhoeic dermatitis both M. sympodialis and M. obtusa were cultured in 43%. A Malassezia species extract mixture would increase the possibility of detecting IgE sensitization to Malassezia in patients with atopic dermatitis.

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients.

Summary Background The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD).

Clinical features of atopic dermatitis at two years of age: a prospective, population-based case-control study.

While atopic dermatitis (AD) usually presents early in life, few prospective studies focus on young children with AD. The objective of this study was to characterize, phenotypically and prospectively, young children with AD. From a community birth cohort of 2,256 children, consecutive children with AD (n = 221) were followed to 2 years of age, when they were re-examined and screened for atopic sensitization (skin-prick test to foods; Phadiatop). Ninety-nine controls were also examined. AD debuted during the first year in 88% of cases. At the 2-year examination, when the children had already undergone topical treatment, 157/221 (71%) had ongoing eczema ranging among mild (45%), moderate (53%) and severe (2%). Airway problems indicating asthma had occurred in 9% of cases and 6% of controls (not significant), and allergic rhinoconjunctivitis in 5% and 0%, respectively (p<0.05). The skin-prick test to common food allergens was positive in 27% of cases and Phadiatop was positive in 15%. In 67% both tests were negative. Eczema severity did not differ between sensitized and non-sensitized children. Positive Phadiatop was more common in boys than in girls with ongoing AD (22% vs 3%, p<0.01), and more boys than girls had ongoing AD (82% vs 59%, p<0.001); otherwise, no differences attributable to gender were found.

Atopic dermatitis and concomitant disease patterns in children up to two years of age.

There are few prospective studies of atopic dermatitis and co-existing diseases such as respiratory infections in children up to 2 years of age. Using annual questionnaires, we studied the cumulative incidence of atopic dermatitis and concomitant symptoms indicating other atopic diseases and respiratory infections in 0-2-year-old children in a prospective birth cohort of 4089 children. We found associations between atopic dermatitis and asthma (ratio of proportion 1.45, 95% CI 1.16-1.80), allergic rhinoconjunctivitis (RP 2.25, CI 1.77-2.85), adverse reactions to foods (RP 3.20, CI 2.83-3.62), urticaria (RP 2.04, CI 1.80-2.31), acute otitis media (RP 1.13, CI 1.05-1.21), more than one pneumonia during the first and/or second year of life (RP 2.17, CI 1.14-4.15), and use of antibiotics at least twice yearly (RP 1.29, CI 1.07-1.56). The association between atopic dermatitis and respiratory infections persisted after stratification for asthma. There was a higher proportion of atopic disease manifestations, but not respiratory infections, in children with onset of atopic dermatitis during the first year of life than during the second. The study shows that during the first 2 years of life there is a significant association not only between atopic dermatitis and other atopic disease manifestations, but also between atopic dermatitis and respiratory infections manifested in an increased rate of acute otitis media, pneumonia and use of antibiotics.

Global Expression Profiling in Atopic Eczema Reveals Reciprocal Expression of Inflammatory and Lipid Genes

Background Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Methodology/Findings We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusions/Significance Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. The full data set is available at http://microarray-pubs.stanford.edu/eczema.

Family history and risk of atopic dermatitis in children up to 4 years

Background The aetiology of atopic dermatitis (AD) is presumably multi‐factorial, with interactions between genetic and environmental factors.

Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis

Background  Filaggrin is a key protein involved in maintaining skin barrier function and hydration. Mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and are a major predisposing factor for atopic dermatitis (AD) in individuals of European and Asian descent. It has been proposed that FLG mutations are population specific and a difference in the spectra of mutations between different ancestral groups has been described. However, it is unknown whether FLG mutations in the African population are a causative genetic factor for IV and predispose to AD, or whether other mechanisms are more prominent.

The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey.

There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management.