Childhood atopic dermatitis is associated with cardiovascular risk factors in young adulthood-A population-based cohort study.

BACKGROUND: Studies have indicated that atopic dermatitis (AD) is associated with an increased risk of cardiovascular disease (CVD). However, data are conflicting. Furthermore, the longitudinal effect of childhood AD on cardiovascular risk factors in young adulthood is less investigated. OBJECTIVES: To assess associations between AD in childhood and CVD risk factors in young adulthood. METHODS: The study encompasses longitudinal data from a population-based birth cohort. Participants with data up to age 24 years were included (n = 2270). The primary outcomes were body mass index (BMI), waist circumference (WC), body fat per cent (BF%) and blood pressure (BP) at 24 years. The secondary outcome was blood lipids. Severe AD was defined as AD in combination with sleep disturbance due to itching. RESULTS: In total, 18.6% (n = 420) had AD at 24 years. Males with AD had higher BMI (ßAdj. 0.81, 95% CI 0.15-1.47), BF% (ßAdj. 1.19, 95% CI 0.09-2.29), systolic BP (ßAdj. 1.92, 95% CI 0.02-3.82), total cholesterol (ßAdj. 0.14, 95% CI 0.00-0.28) and LDL cholesterol (ßAdj. 0.15, 95% CI 0.02-0.27) compared with males without AD. No associations were seen in females. Current AD with prepubertal onset was associated with increased BMI in both males (ßAdj. 0.89, 95% CI 0.11-1.67) and females (ßAdj. 0.72, 95% CI 0.11-1.33). At 24 years, 23.1% (n = 97) of all with AD, had severe disease, which was significantly associated with overweight in both sexes, with BMI (ßAdj. 1.83, 95% CI 0.72-2.94), WC (ßAdj. 4.03, 95% CI 1.54-6.52) and BF% (ßAdj. 2.49, 95% CI 0.60-4.39) in females and with BF% (ßAdj. 2.96, 95% CI 0.23-5.69) in males, compared with peers with mild to moderate AD. CONCLUSION: AD in males appears to be associated with CVD risk factors in young adulthood. The duration and severity of AD seem to be of importance in both sexes.

Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE.

BACKGROUND: There is limited knowledge regarding prevalence and characteristics of atopic dermatitis (AD) among young adults in the general population. OBJECTIVES: To study AD among young adults in a Swedish population-based birth cohort, with a particular focus on prevalence, sex differences including risk for AD at different ages, disease course and characteristics of AD at 24 years. METHODS: The BAMSE cohort includes 4089 individuals who have been followed regularly from birth to age 24 years regarding AD and atopic diseases. For this study 3055 individuals who answered questions regarding AD at the 24-year follow-up were included. All were invited to a clinical examination including skin examination, evaluation by William's criteria and collection of blood for analysis of specific IgE, and 2264 individuals chose to participate. RESULTS: At 24 years, the 12-month prevalence of AD was 17.8% and more females than males had AD (20.5% vs. 14.8%), P < 0.0001. The point prevalence of ongoing AD at clinical examination was 8.0%. AD severity as assessed by Patient-Oriented Eczema Measure (POEM) did not differ between sexes. The proportion of adult onset of AD was 16.9% (92 of 543), females 17.3% vs. males 16.4%. More females than males with AD at 24 years reported disturbed sleep due to itch (26.1% vs. 15.5%, P < 0.003). IgE sensitization was less common among females with AD than males with AD (61.3% vs. 79.6%, P < 0.0001). In addition, male sex (female sex being the reference) was associated with increased odds for AD the first year of life (OR: 1.31, 95% CI; 1.10-1.56), and decreased odds of AD in adolescence and young adulthood (OR: 0.66, 95% CI; 0.55-0.80). CONCLUSIONS: Atopic dermatitis is a common disease among young adults, and even though more females than males have AD at 24 years, adult onset of AD seems to be equally prevalent among both sexes in young adulthood.

Association between atopic dermatitis and autoimmune diseases: a population-based case-control study.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder and is well known to be associated with other atopic conditions. There is increasing evidence for an association also with nonatopic conditions, including autoimmune diseases, but data are limited about several autoimmune diagnoses. OBJECTIVES: To investigate the association between AD and autoimmune diseases. METHODS: This case-control study used Swedish national healthcare registers. The source population comprised the entire Swedish population aged ≥ 15 years from 1968 to 2016. Cases, including all those with an inpatient diagnosis of AD (from 1968) and/or a specialist outpatient diagnosis of AD (from 2001), were matched by sex and age to healthy controls (104 832 cases of AD, 1 022 435 controls). RESULTS: AD was significantly associated with one or more autoimmune diseases compared with controls - adjusted odds ratio (aOR) 1·97, 95% confidence interval (CI) 1·93-2·01 - and this association was significantly stronger in the presence of multiple autoimmune diseases compared with only one. The association was strongest for autoimmune disorders involving the skin (aOR 3·10, 95% CI 3·02-3·18), the gastrointestinal tract (aOR 1·75, 95% CI 1·69-1·82) or connective tissue (aOR 1·50, 95% CI 1·42-1·58). In the overall analysis, men with AD had a stronger association with rheumatoid arthritis and coeliac disease than did women with AD. In subanalyses, the findings remained stable in multivariable analyses after adjustment for smoking and parental autoimmune disease. CONCLUSIONS: This large population-based study indicates significant autoimmune comorbidity of adults with AD, especially between AD and autoimmune dermatological, gastrointestinal and rheumatological diseases. Having multiple autoimmune diseases resulted in a stronger association with AD than having only one autoimmune disease.

Atopic dermatitis at preschool age and contact allergy in adolescence: a population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is characterized by an impaired skin barrier, which can allow enhanced penetration of allergens. It is not clear whether AD influences the risk of developing contact allergy. OBJECTIVES: To examine the association between AD at preschool age and contact allergy at 16 years of age. METHODS: At 16 years of age, 2215 adolescents from the population-based cohort BAMSE were included. These adolescents had been followed with repeated questionnaires regarding AD throughout childhood, and contact allergy was assessed by skin patch test at 16 years. RESULTS: AD at preschool age was associated with contact allergy to at least one of the tested substances at 16 years of age among boys [adjusted odds ratio (OR) 1·51, 95% confidence interval (CI) 1·03-2·20] but not among girls (adjusted OR 0·77, 95% CI 0·54-1·10). AD at preschool age was not associated with contact allergy to nickel in either boys or girls. In contrast, AD at preschool age was associated with contact allergy to fragrance mix I (adjusted OR 3·10, 95% CI 1·66-5·80). This association was observed especially for AD at preschool age in combination with IgE sensitization to airborne or food allergens (adjusted OR 3·80, 95% CI 1·67-8·61). CONCLUSIONS: The results suggest that AD in early childhood may be associated with contact allergy to fragrances, but not to nickel, in adolescence.

Use of emollients and topical glucocorticoids among adolescents with eczema: data from the population-based birth cohort BAMSE.

BACKGROUND: Knowledge regarding how adolescents treat their eczema is sparse. OBJECTIVES: To explore the use of emollients and topical glucocorticoids in adolescents with eczema in relation to sex and disease severity, and to study dispensing patterns of topical glucocorticoids. METHODS: Questionnaire-based data on symptoms of eczema, eczema severity and treatment with emollients and topical glucocorticoids were obtained from 3108 adolescents in the Swedish population-based birth cohort BAMSE. Severity of reported eczema was evaluated with the BAMSE Eczema Severity Score (BESS) in a questionnaire and with the Patient-Oriented Eczema Measure in clinically examined patients with current eczema (n = 247). Information on dispensed topical glucocorticoids was obtained from the Swedish Prescribed Drug Register. RESULTS: In all, 10% of the adolescents reported eczema in the preceding year: 73% mild, 17% moderate and 10% severe according to BESS. Almost all used emollients, whereas use of topical glucocorticoids was reported by 55%, with no significant difference between sexes. The likelihood of treatment with emollients and topical glucocorticoids increased when the adolescents had symptoms of current eczema [adjusted odds ratio (OR) 5·95, 95% confidence interval (CI) 1·90-18·8], but not if they had more severe eczema compared with mild eczema (adjusted OR 1·57, 95% CI 0·58-4·25). Among those with reported eczema, 24% had a topical glucocorticoid dispensed in the preceding year, and among those with moderate-to-severe current eczema 24% had a dispensed potent topical glucocorticoid. CONCLUSIONS: This population-based study indicates that adolescents with eczema are undertreated or completely untreated, even those with severe eczema.

The tight junction gene Claudin-1 is associated with atopic dermatitis among Ethiopians.

BACKGROUND: The strong association between epidermal barrier gene variants and Atopic Dermatitis (AD) highlights that impaired skin barrier is a key feature in the pathogenesis of AD. Although the filaggrin (FLG) gene is the major AD risk gene in European and Asian populations, disease-associated variants remain elusive in African populations. OBJECTIVE: A previous study has reported that variants in the tight junction gene CLDN1 have been associated with AD susceptibility and disease severity in African-Americans. Our aim was therefore to investigate the association of CLDN1 with AD in the Ethiopian population. METHODS: To investigate how CLDN1 variants may be involved in increasing the risk of AD in the Ethiopian population, we analysed whole exome sequencing (WES) data for all exons in CLDN1, and in addition, assayed four SNPs (rs17501010, rs9290927, rs9290929 and rs893051) which had previously showed association in African-American AD patients. RESULTS: No damaging variants were detected through WES in 22 Ethiopian samples. Genotyping of disease-associated CLDN1 SNPs in Ethiopian cases and control material showed no overall association. However, significant association was seen for rs893051 in patients who developed AD before the age of 5 years (P < 0.03). CONCLUSION: Taken together, we demonstrate that tight junction genes and, in particular, CLDN1 rather than variants in FLG may be involved in the susceptibility of AD in the Ethiopian population.

IgE antibodies in relation to prevalence and multimorbidity of eczema, asthma, and rhinitis from birth to adolescence.

BACKGROUND: Eczema, asthma, and rhinitis affect a large proportion of children, but their prevalence varies with age. IgE antibodies are also common in the pediatric population. However, the links between IgE, disease, and trajectories are unclear. OBJECTIVE: To better understand the links between sensitization and disease, we studied IgE sensitization ever in relation to eczema, asthma, and rhinitis, in children followed up to 16 years of age. METHODS: From the Swedish population-based birth cohort BAMSE, 2607 children were included. Parental reports from six time points between 1 and 16 years were used to identify children with eczema, asthma, and rhinitis. Blood was collected at 4, 8, and 16 years, and sensitization ever was defined as allergen-specific IgE ≥0.35 kUA /l to common food and/or inhalant allergens at any time point. Odds ratios for eczema, asthma, rhinitis, and multimorbidity in relation to sensitization ever were calculated using generalized estimating equations. RESULTS: Fifty-one percent were sensitized at least once up to 16 years. Almost a quarter of ever-sensitized children did not have any disease. After adjustment for potential confounders, sensitization ever was significantly associated with the following: (i) eczema throughout childhood, (ii) multimorbidity of eczema, asthma, and rhinitis from 1 to 16 years (OR for multimorbidity: 5.11, 95% CI: 3.99-6.55), (iii) asthma and rhinitis from 4 to 16 years of age. CONCLUSIONS: Specific IgE is strongly associated with eczema and allergic multimorbidity throughout childhood and with asthma and rhinitis from age 4 years. However, 23% of the children with IgE sensitization do not develop any disease in childhood.

Hand eczema and atopic dermatitis in adolescents: a prospective cohort study from the BAMSE project.

BACKGROUND: There is a well-known association between atopic dermatitis (AD) and hand eczema but less is known about how age at onset, persistence and severity of AD influence the risk of developing hand eczema. OBJECTIVES: To examine the role of AD in the occurrence of hand eczema in adolescence. In addition, associations between asthma and rhinoconjunctivitis, sensitization to common airborne and food allergens, and hand eczema were studied. METHODS: From the population-based birth cohort BAMSE, 2927 adolescents who had been followed up repeatedly concerning allergy-related disease were included. Questionnaires identified adolescents with hand eczema at 16 years, and their blood was analysed for specific IgE. RESULTS: A total of 152 (5·2%) adolescents had hand eczema at the age of 16 years. Many of these adolescents had a history of AD (n = 111; 73·0%) and asthma and/or rhinitis (n = 83; 54·6%), respectively. Children with AD (aged 0-16 years) had more than threefold increased odds ratios (OR) for having hand eczema; those with persistent or severe AD had a crude OR of 6·1 [95% confidence interval (CI) 4·0-9·1] and 5·3 (95% CI 2·9-9·6), respectively. CONCLUSIONS: We confirm a strong association between AD during childhood and hand eczema in adolescence. Children with persistent or more severe AD are at greater risk of developing hand eczema. Asthma and/or rhinoconjunctivitis, positive specific IgE or age at onset of AD are not associated with hand eczema in adolescence.

Atopic and nonatopic eczema in adolescence: is there a difference?

BACKGROUND: There is limited information on clinical manifestations of atopic eczema (AE) and non-AE in teenagers. OBJECTIVES: To describe the characteristics of adolescent eczema in the general population and to identify potential differences between AE and non-AE in teenagers. METHODS: Overall, 3108 teenagers were included from the population-based BAMSE cohort and 2529 of these teenagers provided blood samples for analysis of specific IgE. At age 16 years, the teenagers answered questionnaires regarding the symptoms of eczema, asthma and rhinitis for the previous year. RESULTS: The prevalence of eczema in adolescence was 9·6% (n = 297). More girls than boys had eczema (12·5% vs. 6·5%; P < 0·001). The age at onset was usually within the first 2 years of life (48·8%), but onset in adolescence was also common (25·6%). Eczema was mild in 72·7% of cases, moderate in 16·8% and severe in 10·4%. Body folds were most frequently affected (73·4%). More than half of the teenagers with eczema had AE (59%). The teenagers with AE had more severe and more chronic eczema. Onset in infancy was most common in AE and onset in adolescence was most common in non-AE. There were no major differences in location or seasonal variance between AE and non-AE in adolescence. CONCLUSIONS: AE is more common than non-AE among teenagers. More than one in four teenagers with eczema has moderate-to-severe disease. Onset in adolescence is common, especially for non-AE. AE in adolescence has an earlier onset and is more chronic and more severe than non-AE.

Prevalence and incidence of hand eczema in adolescence: report from BAMSE--a population-based birth cohort.

BACKGROUND: BAMSE is a Swedish population-based birth cohort. OBJECTIVES: To estimate prevalence proportions and the incidence rate of hand eczema in Swedish adolescents, and to compare information given by adolescents and parents. Further aims were to study sex distribution, age at onset and extension of hand eczema. METHODS: At 16 years of age, 2927 adolescents were included in this study; both adolescent and parental questionnaires were used, as well as clinical examination. RESULTS: The 1-year prevalence of hand eczema was 5·2% (n = 152) and 4·0% (n = 116) (P < 0·03), and lifetime prevalence was 9·7% (n = 284) and 7·0% (n = 206) (P < 0·01), respectively, when adolescents and parents reported. The incidence rate was 573/100 000 person-years according to the adolescent report. The level of agreement between adolescents and parents was fair for 1-year and lifetime prevalence (κ = 0·56 and κ = 0·49, respectively). According to the Hand Eczema Extent Score, 27·0% (n = 36) had moderate-to-severe hand eczema. CONCLUSIONS: At the age of 16 years, the 1-year prevalence of hand eczema was substantial, with an incidence rate of the same magnitude as in adults. Female predominance was seen in adolescence. It is preferable that the occurrence of hand eczema is reported by adolescents themselves, as they are the ones most aware of their symptoms.

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

BACKGROUND: 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. OBJECTIVES: The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey was established to collect data on current prescribing practice, to identify factors influencing the use of specific systemic agents, and to inform the design of a clinically relevant intervention study. METHODS: Consultant physician members of the paediatric dermatology societies and interest groups of eight European countries were invited to participate in a web-based survey. The multiple-response format questionnaire collated data on clinical practice in general, as well as detailed information on the use of systemic agents in refractory paediatric atopic eczema. RESULTS: In total, 343/765 members (44·8%) responded to the invitational emails; 89·2% were dermatologists and 71% initiate systemic immunosuppression for children with severe atopic eczema. The first-line drugs of choice were ciclosporin (43·0%), oral corticosteroids (30·7%) and azathioprine (21·7%). Ciclosporin was also the most commonly used second-line medication (33·6%), with methotrexate ranked as most popular third choice (26·2%). Around half of the respondents (53·7%) replied that they routinely test and treat reservoirs of cutaneous infection prior to starting systemic treatment. Across the eight countries, penicillins were the first-line antibiotic of choice (78·3%). CONCLUSIONS: In the absence of a clear evidence base, the European TREAT survey confirms the wide variation in prescribing practice of systemic immunosuppression in refractory paediatric atopic eczema. The results will be used to inform the design of a randomized controlled trial relevant to patient management across Europe.

Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort.

BACKGROUND: Filaggrin (FLG) mutations are major genetic determinants for eczema, but their role in eczema severity needs further investigation. Children with eczema are at higher risk of having asthma and rhinitis but it is not known if this risk is associated with the severity of eczema. OBJECTIVES: To investigate eczema severity in relation to sex, FLG mutations, asthma, rhinitis and topical treatment among preadolescent children in a population-based cohort. METHODS: Parental questionnaires were used to obtain data on symptoms of eczema, asthma, and rhinitis among 3301 preadolescent children. Eczema severity was evaluated based on sleep disturbance, extent of disease and total time with eczema the previous year. Genotyping was performed in 1854 individuals for three common FLG mutations (R501X, R2447X and 2282del4). Results Eczema was more prevalent among girls (14·5%) than boys (9·4%). FLG mutations were detected in 13·1% of children with mild eczema and 12·5% with moderate-to-severe eczema. Of children with moderate-to-severe eczema, 45·1% had rhinitis and 22·0% had asthma compared with 32·7% and 13·8% of children with mild eczema, respectively. Children with moderate-to-severe eczema used moisturizers and topical glucocorticoids more frequently than children with mild eczema. Boys used moisturizers less frequently than girls. CONCLUSIONS: More preadolescent girls than boys had eczema. FLG mutations did not influence eczema severity in our population-based cohort. Prevalence of rhinitis and asthma was associated with eczema severity, with the highest prevalence among boys with moderate-to-severe eczema.

Lack of association between filaggrin gene mutations and onset of psoriasis in childhood.

BACKGROUND: Atopic dermatitis (AD; OMIM#603165) and psoriasis (OMIM#177900) are two common inflammatory skin disorders. Both are genetically complex, multifactorial and do not follow a Mendelian pattern of inheritance. Both diseases share several genetic susceptibility loci such as the epidermal differentiation complex (EDC) on chromosome 1q21. Within the EDC, mutations in the filaggrin (FLG) gene are strongly associated with AD whereas no association has been replicated with psoriasis. However, reduced levels of filaggrin have been reported in psoriatic skin. Further, filaggrin deficiency was shown to be a modifying factor for the phenotype in another epidermal skin disorder, X-linked recessive ichthyosis. Altogether, this raises the question if FLG mutations may modify the disease course in other epidermal skin diseases such as psoriasis. Psoriasis is a highly heterogeneous disease and so far genetic studies have not taken the distinct sub-phenotype childhood onset into account. OBJECTIVE: To determine if FLG mutations modify the onset of psoriasis. MATERIALS AND METHODS: A total of 241 children with onset of psoriasis below 15 years of age and 314 healthy controls were identified at the Dermatology clinic, Karolinska University Hospital and diagnosed by the same dermatologist (JL). Blood samples were taken and medical history was recorded. FLG was genotyped in all patients and controls using allelic discrimination (n = 555) and sequencing (n = 20). RESULTS AND CONCLUSIONS: No association between FLG mutations and early onset of psoriasis was demonstrated (P = 0.57) and no novel mutations were detected, indicating that FLG loss-of-function variants do not have a strong effect on the onset of psoriasis in childhood.

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. OBJECTIVES: The present aim was to investigate the role of FLG mutations as predisposing factors for IV or AD among individuals from Ethiopia. METHODS: A case series of Ethiopian patients with AD (n = 103) and IV (n = 7) together with controls (n = 103; subjects without past or present history of AD, dry skin or atopic manifestations) was collected at the outpatient dermatology clinics at ALERT Dermatology Hospital, Tikur Anbessa Hospital and Gondar University Hospital, Ethiopia. AD was diagnosed by a dermatologist using the U.K. Working Party's diagnostic criteria. The IV diagnosis was based on clinical examination and genetic testing of the steroid sulphatase gene to exclude X-linked recessive ichthyosis. Patients were studied with direct sequencing (n = 40) and/or allelic discrimination (n = 110). Immunohistochemical analysis was performed for filaggrin expression in the skin of patients (n = 7) and controls (n = 2). RESULTS: The Ethiopian patients and controls were genotyped for the four previously described common European FLG null mutations (R501X, 2282del4, S3247X, R2447X) and no carriers were found. In one patient with AD a novel heterozygous 2-bp deletion, 632del2, leading to a premature stop codon was revealed by direct sequencing. No additional carrier of this deletion or other mutations was found. In addition, no difference in filaggrin expression was detected in AD or IV skin compared with healthy control skin. CONCLUSIONS: Our results indicate that FLG loss-of-function-variants are less common in patients with IV and AD in the Ethiopian population, suggesting that other factors may be of importance in the pathogenesis in this ethnic group.

Parental sun-protective regimens and prevalence of common melanocytic naevi among 7-year-old children in Sweden: changes over a 5-year period.

BACKGROUND: Common melanocytic naevi and cutaneous malignant melanoma share a common risk profile, influenced by ultraviolet radiation exposure. A high density of common melanocytic naevi correlates with an increased lifetime risk of developing cutaneous malignant melanoma. Effective strategies for sun protection, starting in early childhood, are considered of great importance to reduce the steadily rising melanoma trend. OBJECTIVES: To investigate the 5-year changes in sun tanning habits, sun-protective regimens and density of common melanocytic naevi between two age-standardized populations of children. METHODS: Population-based cross-sectional study performed among 7-year-old children in southern Sweden in 2002 and 2007. The parents answered a questionnaire and all children were examined by the same, trained research nurse. RESULTS: In total, 1190 children were enrolled: 681 in 2002 and 509 in 2007. The results showed that sun-protective regimens, such as use of sunscreen (+29%), clothing (+30%), staying in the shade (+123%) or indoors (+136%) during peak sun hours, had all increased significantly (P<0·0001). Travelling to sunny seaside holiday resorts abroad before the age of 2years had almost doubled (P<0·0001). The adjusted mean number of naevi per square metre body surface was significantly (P<0·0001) lower in 2007: 6·6 [95% confidence interval (CI) 5·6-7·6], compared with 11·0 (95% CI 10·0-12·0) in 2002. CONCLUSIONS: This study demonstrates increased self-reported parental actions for sun protection of young Swedish children in recent years; in consistency, lower numbers of common melanocytic naevi were observed. Results support the use of common melanocytic naevi as an objective measure of sun exposure in children.

Responses to intradermal injections of substance P in psoriasis patients with pruritus.

BACKGROUND: Various mediators have been suggested for the pathogenesis of pruritus in psoriasis. METHODS: To investigate cutaneous responses of substance P in pruritic lesional and nonlesional areas of psoriasis patients and in healthy controls, substance P, saline and histamine were injected intradermally. After each injection, pruritus, flare and wheal were recorded. RESULTS: There was no statistical difference in the latency period, duration, area under the curve and maximum intensity of pruritus evoked by substance P (10(-5) and 10(-6) mol/l) between psoriasis and healthy control skin. Substance P (10(-5) mol/l) induced a tendency to a greater intensity of pruritus in lesional compared to nonlesional psoriatic skin (p = 0.08). Histamine produced a shorter itch latency period (p < 0.05) and a lower maximum intensity of pruritus (p = 0.05) in lesional psoriasis skin than in healthy control skin. No significant difference in flare area was observed between the psoriasis patients and healthy controls. The histamine-induced wheal was smaller in psoriasis patients than in healthy individuals (p < 0.05). CONCLUSION: Intradermally injected substance P induced pruritus, flare and wheal in psoriasis patients. However, these responses did not differ significantly from those of the healthy controls.

Cornulin, a marker of late epidermal differentiation, is down-regulated in eczema.

BACKGROUND: Eczema is a common chronic inflammatory skin disorder which shows strong genetic predisposition. To identify new potential molecular determinants of the disease pathogenesis, we performed a gene expression study in an eczema mouse model. This analysis identified a marked down regulation of the cornulin gene (CRNN), a member of the epidermal differentiation complex, in the eczema-like skin. We then investigated CRNN as an eczema candidate gene and studied its polymorphism and the expression in the skin of eczema patients. METHODS: An eczema-like phenotype was induced in mice by allergen (Der p2) patching. Gene expression analysis was performed with the subtractive suppression hybridization method and validated by real time PCR and the transmission disequilibrium test was used to test for genetic associations in 406 multiplex eczema families. RESULTS: Der p 2 patched mice developed a localized eczema and a Th 2 skewed systemic response. Real time PCR analysis confirmed a down regulation of CRNN mRNA in eczema-like skin in the mouse model and in human eczema. The CRNN polymorphism rs941934 was significantly associated with atopic eczema in the genetic analysis (P = 0.006), though only as part of an extended haplotype including a known associated variant (2282del4) in the filaggrin gene. CONCLUSIONS: CRNN mRNA expression is decreased in eczematous skin. Further studies are needed to verify whether the associated cornulin polymorphism contribute to the genetic susceptibility in eczema.

Elevated expression and genetic association links the SOCS3 gene to atopic dermatitis.

In a systematic analysis of global gene-expression patterns, we found that SOCS3 messenger RNA was significantly more highly expressed in skin from patients with atopic dermatitis than in skin from healthy controls, and immunohistochemical analysis confirmed a similar elevation of SOCS3 protein. Furthermore, we found a genetic association between atopic dermatitis and a haplotype in the SOCS3 gene in two independent groups of patients (P<.02 and P<.03). These results strongly suggest that SOCS3, located in a chromosomal region previously linked to the disease (17q25), is a susceptibility gene for atopic dermatitis.

Susceptibility loci for atopic dermatitis on chromosome 21 in a Swedish population.

BACKGROUND: Atopic dermatitis (AD) is a hereditary, pruritic, chronic, relapsing, inflammatory skin disease resulting from multiplex interactions between genes and environmental factors. We have previously found several loci showing suggestive linkage on chromosomes 3q14, 13q14, 15q14-15 and 17q21, and weaker linkage to chromosomes 1p32, 4q24-26 and 21q21 in 109 Swedish families. METHODS: In order to confirm the linkage to chromosome 21, we carried out a replication linkage analysis with additional microsatellite markers on chromosome 21 in another set of 295 families. RESULTS: In the extended material, the Z-score was 2.40 (P < 7.4 x 10(-4)) in the region 21q21 for a semi-quantitative variable measurement; the severity of AD. When combining the two data sets into 404 families and stratifying according to asthma status, suggestive linkage was found only in the group of AD patients who also had asthma (Z-score 2.45, P < 7.4 x 10(-4) and 2.69, P < 7.4 x 10(-4)) in two different regions. CONCLUSIONS: Our results suggest that 21q21 could contain a susceptibility gene modulating the severity of AD especially in combination with asthma.