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Background: The association between pet exposure in infancy, early childhood eczema, and FLG mutations remains unclear., Methods: This was a birth cohort study performed in Tokyo, Japan. The primary outcome was current eczema based on questionnaire responses collected repeatedly from birth to 5 years of age. Generalized estimating equations and generalized linear modeling were used to evaluate the association., Results: Data from 1448 participants were used for analyses. Household dog ownership during gestation, early infancy, and 18 months of age significantly reduced the risk of current eczema. Household cat ownership also reduced the risk of current eczema, albeit without statistical significance. The combined evaluation of children from households with pets, be it cats, dogs or both, the risk of current eczema at 1-5 years of age was lower in those with household pet exposure ownership during gestation (RR = 0.59, 95 % CI 0.45-0.77) and at 6 months (RR = 0.49, 95 % CI 0.36-0.68). , Reduced risks of eczema were also observed at 2-5 (RR = 0.52, 95 % CI 0.37-0.73) and 3-5 years of age (RR = 0.50 95 % CI 0.35-0.74) when the respective household pet ownership were evaluated at 18 months and 3 years of age. These protective associations of reduced risk of eczema were only observed in children without FLG mutations., Conclusions: Household dog and pet (dog, cat, or both) ownership was protective against early childhood eczema in a birth cohort dataset. This protective association was observed only in children without FLG mutations, which should be confirmed in studies with larger cohorts., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Biologic therapies for psoriasis can cause paradoxical eczema. The role of genetic factors in its pathogenesis is unknown. To identify risk variants, we conducted a GWAS of 3,212 patients with psoriasis, of whom 88 developed paradoxical eczema. Two lead SNPs reached genome-wide significance (P ≤ 5 × 10 -8 ) for association with paradoxical eczema: rs192705221 (near UNC5B, P = 9.52 × 10 -10 ) and rs72925168 (within SLC1A2, P = 1.66 × 10 -9 ). Genome-wide significant SNPs from published GWAS were used to generate polygenic risk scores (PRSs) for atopic eczema, general atopic disease, or a combination, which were tested for association with paradoxical eczema. Improvement over a clinical risk model was assessed by the area under the curve. All three atopy polygenic risk scores were associated with paradoxical eczema (P < 0.05); polygenic risk score for a combination of atopic eczema and general atopic disease had the strongest association (OR = 1.83, 95% CI = 1.17-2.84, P = 0.0078). Including atopic polygenic risk scores in the multivariable model, which included age, sex, atopic background, and psoriatic arthritis history, increased the area under the curve from 0.671 to 0.681-0.686. Atopic genetic burden is associated with paradoxical eczema occurring in biologic-treated patients with psoriasis, indicating shared underlying mechanisms. Incorporating genetic risk may improve treatment outcome prediction models for psoriasis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Highly effective targeted therapies are available to treat noncommunicable chronic inflammatory skin diseases. In contrast, the exact diagnosis of noncommunicable chronic inflammatory skin diseases is complicated by its complex pathogenesis and clinical and histological overlap. Particularly, the differential diagnosis of psoriasis and eczema can be challenging in some cases, and molecular diagnostic tools need to be developed to support a gold standard diagnosis. The aim of this work was to develop a real-time PCR-based molecular classifier to distinguish psoriasis from eczema in formalin-fixed and paraffin-embedded-fixed skin samples and to evaluate the use of minimally invasive microbiopsies and tape strips for molecular diagnosis. In this study, we present a formalin-fixed and paraffin-embedded-based molecular classifier that determines the probability for psoriasis with a sensitivity/specificity of 92%/100%, respectively, and an area under the curve of 0.97, delivering comparable results to our previous published RNAprotect-based molecular classifier. The psoriasis probability, as well as levels of NOS2 expression, positively correlated with the disease hallmarks of psoriasis and negatively with eczema hallmarks. Furthermore, minimally invasive tape strips and microbiopsies were effectively used to differentiate psoriasis from eczema. In summary, the molecular classifier offers broad usage in pathology laboratories as well as outpatient settings and can support the differential diagnosis of noncommunicable chronic inflammatory skin diseases on a molecular level using formalin-fixed and paraffin-embedded tissue, microbiopsies, and tape strips., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Eczema is also known as atopic dermatitis is well-known for the skin disease globally. In Saudi Arabia, exome sequencing studies have not been documented. The purpose of this study was to scrutinize the disease causing mutations in children affected with eczema with exome sequencing in the Saudi population., Methods: We recruited randomly three sporadic cases of children diagnosed with eczema and simultaneously, three more cases were adopted for control samples. Exome sequencing was carried out by applying a pipeline that captures all the variants of concern related to the samples by using the Ion torrent., Results: In this study, we have documented 49 variants, among which 37 variants were confirmed through eczema children and remaining 30 variants through control children. However, from the analysis of the 6 samples, we have identified rs10192157 (1646C>T; Thr549Ile), rs2899642 (27C>G; Asn9Lys), chr1:152127950 (1625G>A; Gly542Asp) and chr1:152128041 (1534C>G; Gly512Arg) variants which are rarely linked to the disease eczema. In the rs10192157, we have documented these mutations in all three eczema children and one in the control; the rs2899642 mutation appeared in only a couple of eczema children, whereas the mutation in the chr1:152127950 regions appeared in only one eczema patient. However, the chr1:152128041 mutations appeared in only one case of eczema and also in two control children., Conclusion: Our study revealed four mutations which had not previously been connected with eczema within the database. However, the rs10192157 and rs2899642 mutations were documented with asthma disease. The remaining mutations such as chr1:152127950 and chr1:152128041 have not been reported anywhere else. This study recommends screening these 4 mutations in eczema cases and their relevant controls to confirm the prevalence in the Saudi population. It is recommended that future studies examine the 4 mutations in detail., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Previous studies on the putative role of allergy in the aetiology of childhood leukaemia have reported contradictory results. The present study aimed to analyse the relation between a medical history of asthma or eczema and childhood acute lymphoid leukaemia (ALL) in light of potential candidate gene-environment interactions., Methods: Analyses were based on a subset of 434 cases of ALL and 442 controls successfully genotyped and of European ancestry children enrolled in a French population-based case-control study conducted in 2003-2004. Information about medical history was obtained during a standardized interview with the mothers. Candidate polymorphisms in genes of the Th2 cytokines IL4, IL10, IL13 and IL4-receptor, were genotyped or imputed., Results: None of the variant alleles were directly associated with childhood acute lymphoid leukaemia. A medical history of asthma or eczema was reported more often in the control group (OR = 0.7 [0.5-1.0]). This association was mostly seen in the group of children not carrying the IL13-rs20541 variant allele (Interaction Odds Ratio IOR 1.9, p-interaction = 0.07) and in those carrying the IL10 triple variant haplotype (IOR 0.5, p-interaction = 0.04). No interaction was observed with the candidate polymorphisms in IL4 and IL4R., Conclusion: This study provides a new insight into the relationship between allergic symptoms and childhood acute lymphoid leukaemia, by suggesting this inverse association could be limited to children carrying certain genetic polymorphisms. If confirmed, these results could help better understand the biological mechanisms involved in the development of childhood acute lymphoid leukaemia., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Essentials FLG mutations cause atopic dermatitis, previously found to be associated with ischemic stroke. Association between FLG mutations and ischemic stroke was examined in 97 174 Danish individuals. FLG mutations were associated with increased ischemic stroke risk in the general population. The association was most pronounced in younger individuals, and in current and former smokers., Summary: Background Heritability studies have shown a considerable genetic component to ischemic stroke risk; however, much is unknown as to which genes are responsible. Also, previous studies have found an association between atopic dermatitis and increased ischemic stroke risk. Objective To test the hypothesis that FLG loss-of-function mutations, known to be associated with atopic dermatitis, were also associated with ischemic stroke. Methods A total of 97 174 individuals, with 3597 cases of ischemic stroke, from the Copenhagen General Population Study, the Copenhagen City Heart Study and the Copenhagen Carotid Stroke Study were genotyped for the two most common filaggrin mutations, FLG R501X and FLG 2282del4. Results FLG mutation carriers had an odds ratio for ischemic stroke of 1.15 (95% confidence interval [CI], 1.02-1.30) compared with non-carriers. Risk of ischemic stroke for FLG mutation carriers was higher among individuals aged < 50 years, with an odds ratio of 1.72 (1.11-2.67), compared with non-carriers. When stratified for smoking, ischemic stroke risk was primarily seen in current and former smokers, with an odds ratio of 1.25 (1.08-1.44). FLG mutations were not associated with conventional cardiovascular risk factors except for slightly more pack-years smoked among mutation carriers, but were associated with increased risk of self-reported eczema, with an odds ratio of 1.42 (1.32-1.52). Finally, self-reported eczema was associated with increased ischemic stroke risk, with an age and sex adjusted hazard ratio of 1.24 (1.01-1.52); however, the association was not statistically significant after multifactorial adjustment. Conclusion In this study of 97 174 individuals from the Danish general population, FLG loss-of-function mutations were associated with increased ischemic stroke risk; however, residual confounding is a possibility., (© 2017 International Society on Thrombosis and Haemostasis.)

Adult hematopoiesis requires tightly regulated cell-cell interactions between hematopoietic cells and the bone marrow stromal microenvironment. We addressed the question if the ectodomain sheddase ADAM10 is essential to regulate adult hematopoiesis. Induced ADAM10 deletion in hematopoietic cells resulted in morphological and histological abnormalities that resemble an unclassified myeloproliferative disorder (MPD). The MPD was characterized by an expansion of granulocytic subpopulations and their infiltration of peripheral hematopoietic tissues, the development of hepatosplenomegaly with extramedullary erythropoiesis, lymphnodepathy and death of the mice around 20weeks after induction. ADAM10 expression analysis during the different stages of the MPD revealed that non-targeted hematopoietic cells repopulated the immune system of the ADAM10-deficient mice. Examination of mice with a myeloid- or epidermis-specific deletion of ADAM10 and bone marrow transplantation (BMT) experiments indicated that the development of the MPD can be triggered by non-cell autonomous effects. We found that plasma levels of clinical markers for MPD such as G-CSF, TIMP-1 and IL-16 were significantly elevated in ADAM10-deficient mice. Our findings indicate that a tightly controlled ADAM10 expression is needed to balance hematopoietic cell-fate decisions in adult mice., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The genetically determined impairment of the skin barrier is a primary cause of eczema. As numerous genes essential for an intact epidermis reside within the epidermal differentiation complex (EDC), we screened the National Center for Biotechnology Information (NCBI) database for putatively functional polymorphisms in the EDC genes and tested them for association with eczema. We identified 20 polymorphisms with predicted major impact on protein function. Of these, 4 were validated in 94 eczema patients: a nonsense mutation in FLG2 (rs12568784), a stop codon mutation in LCE1D (rs41268500), a 24-bp deletion in SPRR3 (rs28989168), and a frameshift mutation in S100A3 (rs11390146). The minor allele frequencies were 15.1, 6.1, 47.2, and 0.4%, respectively. Association testing of the validated polymorphisms in 555 eczema patients and 375 controls identified a significant effect of rs28989168 (SPRR3) on eczema. The association was replicated in another 1,314 cases and 1,322 controls, yielding an overall odds ratio of 1.30 (95% confidence interval 1.12-1.51; P=0.00067) for a dominant mode of inheritance. Small proline-rich proteins (SPRRs) are crossbridging proteins in the cornified cell envelope (CE), which provides the main barrier function of stratified squamous epithelia. The SPRR3 variant associated with eczema carried an extra 24-bp repeat in the central domain, which may alter the physical properties of the CE.

Eczema is very common and increasing in prevalence. Prospective studies investigating environmental and genetic risk factors for eczema in a birth cohort are lacking. We evaluated risk factors that may promote development of childhood eczema in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort (n=762) of infants with at least one atopic parent. Objective environmental exposure data were available for each participant. At annual physical examinations, children underwent skin prick tests (SPTs), eczema was diagnosed by a clinician, and DNA was collected. Among Caucasian children, 39% developed eczema by age 3. Children with a pet dog were significantly less likely to have eczema at age one (odds ratio (OR)=0.62, 95% confidence interval (CI): 0.40-0.97) or at both ages 2 and 3 (OR=0.54, 95% CI: 0.30-0.97). This finding was most significant among children carrying the CD14-159C/T CC genotype. Carriers of the CD14-159C/T and IL4Ralpha I75V single-nucleotide polymorphisms (SNPs) had an increased risk of eczema at both ages 2 and 3 (OR=3.44, 95% CI: 1.56-7.57), especially among children who were SPT+. These results provide new insights into the pathogenesis of eczema in high-risk children and support a protective role for early exposure to dog, especially among those carrying the CD14-159C/T SNP. The results also demonstrate a susceptibility effect of the combination of CD14 and IL4Ralpha SNPs with eczema.

Wiskott-Aldrich syndrome (WAS) is a severe X-linked immunodeficiency caused by mutations in the gene encoding for WASP, a key regulator of signaling and cytoskeletal reorganization in hematopoietic cells. Mutations in WASP result in a wide spectrum of clinical manifestations ranging from the relatively mild X-linked thrombocytopenia to the classic full-blown WAS phenotype characterized by thrombocytopenia, immunodeficiency, eczema, and high susceptibility to developing tumors and autoimmune manifestations. The life expectancy of patients affected by severe WAS is reduced, unless they are successfully cured by bone marrow transplantation from related identical or matched unrelated donors. Because many patients lack a compatible bone marrow donor, the administration of WAS gene-corrected autologous hematopoietic stem cells could represent an alternative therapeutic approach. In the present review, we focus on recent progress in understanding the molecular and cellular mechanisms contributing to the pathophysiology of WAS. Although molecular and cellular studies have extensively analyzed the mechanisms leading to defects in T, B, and dendritic cells, the basis of autoimmunity and thrombocytopenia still remains poorly understood. A full understanding of these mechanisms is still needed to further implement new therapeutic strategies for this peculiar immunodeficiency.

Multiple genetic as well as environmental factors interact in the pathogenesis of eczema. Increased understanding of genetic predisposition in atopy and eczema has directed interest toward key pathogenic mechanisms including skin barrier dysfunction. This review provides a succinct update on the current state of knowledge regarding eczema genetics. We discuss the relevance of loss-of-function mutations in the filaggrin gene within the context of other candidate gene studies and suggest possible applications for future research. Knowledge of genetic factors in eczema may translate into a clearer understanding of pathogenic mechanisms and hence more focused therapeutic strategies, but this remains at present a distant possibility.

Clinicians agree that hand eczema is multifactorial, although there are many uncertainties regarding causative factors. Atopic dermatitis is assumed to be a major risk factor, whereas the role of allergies is overestimated. Twin studies may shed light on the contribution of other endogenous, possibly genetic factors versus the role of exposure to environmental agents, with the latter being amenable to prevention and intervention.

Genetic factors have been shown to influence the risk of hand eczema, and may theoretically influence the frequency of eruptions as well as age at onset of the disease. However, the result may be confounded by atopic dermatitis, which is a major risk factor for development of hand eczema and is known to be influenced by genetic factors. In this study, the importance of genetic and environmental risk factors in the etiology of hand eczema, independent of atopic dermatitis, was investigated in a population-based twin cohort. In addition, any possible genetic influence on frequency of hand eczema eruptions and age at onset was explored. In all, 4,128 twin individuals (response rate 82%) answered a questionnaire on self-reported hand eczema. Similarity within twin pairs was estimated and quantitative genetic modelling performed. Controlling for age and atopic dermatitis, the effect of genetic risk factors was moderate and explained 41% of the variance in liability to develop hand eczema, leaving 59% of the variance to be caused by environmental factors. Genetic factors accounted for 31% of the variance in liability regarding frequency of eruptions. Environmental factors explained the variance in liability concerning age at onset.

Background: Childhood interstitial lung disease (ILD) is a spectrum of diseases including many different rare lung conditions. We present a family with an unusual presentation of ILD in association with rheumatologic and immunologic abnormalities., Methods: Eight children with a common father were evaluated for evidence of lung disease in association with rheumatologic findings. All underwent routine history and physical examination, hematologic evaluation, and chest radiography and/or CT scan of the chest. Seven children underwent a more extensive immunologic evaluation. Those who were able underwent pulmonary function testing, and four children underwent lung biopsy., Results: Six of eight children with a common father were found to have radiographic findings consistent with ILD. These children also had evidence of autoimmune disease with joint symptoms, alopecia, rheumatoid factor production, and hypergammaglobulinemia. Open-lung biopsy in four children revealed a spectrum of pulmonary lymphoid proliferations ranging from reactive lymphoid hyperplasia to lymphoid interstitial pneumonia., Conclusion: The findings of ILD and autoimmunity in a kindred of children suggest a novel genetic disorder of autosomal dominant pattern and variable penetrance. Although the precise pathogenesis remains unclear, these cases provide valuable insight into childhood ILD.

Atopic dermatitis (AD) is a common disease with a complex etiology in childhood and adult life. A significant proportion of childhood AD is transient, but in many cases it persists into adulthood. We have recently shown that null mutations in the filaggrin gene (FLG) are an important predisposing factor for childhood eczema and eczema-associated asthma, but persistence to adulthood has not been analyzed. Here we studied a cohort of adult patients with persistent AD, which had been present since early childhood. In this cohort, the combined allele frequency of the two common FLG null variants was 0.270 (cf. population frequency 0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3-10.9 and a chi2 P-value of 1.7 x 10(-53). Our data conclusively demonstrate that identification of FLG null alleles is an indicator of a poor prognosis in AD, predisposing to a form of eczema that starts in early infancy and persists into adulthood. This study helps to further define the nature of the AD phenotype associated with FLG null alleles.

The association of filaggrin null alleles with eczema has been replicated in several European populations. Three large, well-conducted studies confirm this association and offer insights into the phenotypic nature of eczema associated with these alleles. Early data suggest that FLG-associated eczema may be more persistent, more likely to have palmar hyperlinearity, and more likely to be associated with asthma. These initial hints will require further confirmation in cohort studies.

Fas ligand (FasL) causes apoptosis of epidermal keratinocytes and triggers the appearance of spongiosis in eczematous dermatitis. We demonstrate here that FasL also aggravates inflammation by triggering the expression of proinflammatory cytokines, chemokines, and adhesion molecules in keratinocytes. In HaCaT cells and in reconstructed human epidermis (RHE), FasL triggered a NF-kappaB-dependent mRNA accumulation of inflammatory cytokines (tumor necrosis factor-alpha, IL-6, and IL-1beta), chemokines (CCL2/MCP-1, CXCL1/GROalpha, CXCL3/GROgamma, and CXCL8/IL-8), and the adhesion molecule ICAM-1. Oligomerization of Fas was required both for apoptosis and for gene expression. Inhibition of caspase activity abolished FasL-dependent apoptosis; however, it failed to suppress the expression of FasL-induced genes. Additionally, in the presence of caspase inhibitors, but not in their absence, FasL triggered the accumulation of CCL5/RANTES (regulated on activation normal T cell expressed and secreted) mRNA. Our findings identify a novel proinflammatory role of FasL in keratinocytes that is independent of caspase activity and is separable from apoptosis. Thus, in addition to causing spongiosis, FasL may play a direct role in triggering and/or sustaining inflammation in eczemas.

As a first step in an intervention study of asthma and allergic diseases among school children, a cross-sectional study was performed during Winter 1996 in three towns (Kiruna, Luleå and Piteå) in the northernmost province of Sweden, Norrbotten. The cross-sectional study aimed to measure the prevalence of asthma, type-1 allergy and allergic diseases in order to make it possible to measure the incidence of the diseases, conditions and symptoms related to the diseases. Another aim was to perform a screening for possible risk factors. All children enrolled in the first and second classes at school, 7 and 8 years old, were invited to take part in this study. The ISAAC questionnaire with added questions about symptoms, morbidity, heredity and environment was distributed by the schools to the parents. The response rate was 97%, and 3431 completed questionnaires were returned. The children in two of the municipalities were also invited to skin test, and 2149 (88%) were tested with 10 common airborne allergens. The results showed that 7% of the children were currently using or had used asthma medicines during the last 12 months. Six percent had asthma diagnosed by a physician, and 4% were using inhaled corticosteroids. The prevalence of wheezing during the last 12 months was 12%, rhinitis without colds 14%, and eczema 27%, while 21% had a positive skin test. The respiratory symptoms and conditions were significantly greater in boys and, further, they were most prevalent in Kiruna in the very north, though not significantly. Type-1 allergy and asthma had different risk factor patterns. The main risk factors for asthma were a family history of asthma (OR = 3.2) followed by past or present house dampness (OR = 1.9), male sex (OR = 1.7) and a smoking mother (OR = 1.6). In Kiruna, when none of these three risk factors were present, none of the children had asthma, but when all three were present, 38% of these children were using asthma medicines.

The literature in relation to the development of atopic and allergic disorders has been reviewed, in order to assess the claim that prolonged and exclusive breast feeding protects against the development of such disorders. The data in the literature show little consistent evidence to identify any protective association between breast feeding and either eczema, wheezing/asthma or other types of atopy or allergic response.

Background: Atopy is a common syndrome underlying asthma, rhinitis, and eczema, and is characterised by high immunoglobulin E (IgE) responses to common antigens. IgE and mast-cell chymase (MCC-a serine protease secreted by skin mast cells) have a key role in atopic or allergic inflammation of the skin. The gene for MCC is located within a cluster of genes for cellular proteases on chromosome 14q11.2. We aimed to identify variants of MCC and another gene within this complex, and assess whether there is a genetic association between variants of MCC and atopic disorders-particularly eczema., Methods: We randomly selected 100 controls and recruited patients-100 in each group-with atopic asthma, non-atopic asthma, atopic rhinitis, and atopic eczema. PCR amplification was used to test genomic DNA for an association between allelic polymorphisms in MCC and a flanking gene (CGL1, for the cathepsin-G-like protein) on chromosome 14q11 and asthma, rhinitis, and eczema., Findings: We found a significant association between a BstXI polymorphism in MCC and eczema (odds ratio 2.17 [95% CI 1.21-3.88], p = 0.009), but no association with atopic asthma, rhinitis, or non-atopic asthma. There was no association between an Mboll polymorphism in CGL1 and any of the atopic disorders., Interpretation: These findings suggest that variants of MCC may be one source of genetic risk for eczema.

Eighteen cases of early mycosis fungoides were compared with 18 cases of eczematous dermatitis by multiparametric image cytometry. A minimum of 100 lymphocytes was measured in each case. A large number of measurements was acquired for each lymphocyte, characterizing nuclear DNA content, area, shape, and texture. There were significant differences between the two groups, especially in nuclear DNA content and texture. These differences allowed the two groups of nuclei to be distinguished with 78% accuracy. The two groups of lesions were distinguished with 94% accuracy, using neural network analysis.

Rates of reported eczema during early childhood were studied in 3 national cohorts of children born in 1946, 1958, and 1970. Overall rates rose from 5.1% in children born in 1946, to 7.3% in those born in 1958, to 12.2% in the 1970 cohort. In the 1958 and 1970 cohorts there was a positive association between eczema and breastfeeding. This relationship remained significant after allowing for parental history of allergy and socioeconomic status. Social classes I and II children born in 1946 were less likely to be reported as having eczema, compared with children from lower social classes, whereas children born into higher social classes in 1958 and 1970 had higher rates. These findings may reflect secular changes in the diagnosis of eczema or may represent a real increase in the disorder. The positive association with breastfeeding in the more recent cohorts suggests a new environmental agent may be crossing in breast-milk. The agent(s) may well be in other infant foods, since the rate of reported eczema in non-breastfed children rose from 5.7% in the 1946 and 1958 cohorts to 11.1% of children born in 1970.

A new familial immunodeficiency disease characterised by recurrent and persistent pyoderma, folliculitis, and atopic dermatitis is described in a father and son. It is accompanied by abnormalities of lymphocyte function (including defective proliferative responses to phytomitogens, and subnormal response in immunoglobulin production after stimulation of the lymphocytes by pokeweed mitogen) and defective leucocyte chemiluminescence responses, which were associated with defective ability for intracellular killing of microbial organisms. The abnormalities of lymphocyte and leucocyte function, as well as the clinical manifestations, responded dramatically to treatment with the histamine-1 antagonist, chlorpheniramine, suggesting that the underlying defect in this disease may relate to defective histamine metabolism or abnormal expression of histamine receptors on lymphocytes and leucocytes.

198 infants were followed up from birth until 4 1/2-5 years to observe the development of eczema and asthma and its relation to infant feeding. Findings here refer only to eczema. Comparison between those initially breastfed, regardless of duration, and those fed on cows milk preparations showed little difference in the incidence of eczema, but there was a higher incidence of eczema in those with an immediate family history of atopy than in those with no such history. Comparison of infants breastfed for less than and more than 12 weeks showed: the incidence of eczema fell in infants with an immediate family history of atopy when exclusive breastfeeding was continued beyond 12 weeks, whereas the incidence of eczema rose in all breastfed infants, regardless of their atopic family history, when breastfeeding, combined with other foods, was continued beyond 12 weeks.

In a prospective study of the development of reaginic allergy, infants of allergic parents were either subjected to an allergen-avoidance regimen from birth for six months or managed conventionally. The group on the allergen-avoidance regimen had less eczema at six months and one year than did the control group at six months. They also had a lower mean serum-total-IgE level at six weeks.