Family History Of Atopic Dermatitis Research Articles

Lack of association of CCR4 single nucleotide polymorphism with atopic dermatitis in Japanese patients.

CCR4, a member of the CC chemokine receptor family, is believed to play an important role in the pathogenesis of atopic dermatitis. To examine whether CCR4 single nucleotide polymorphism (SNP) is associated with susceptibility to atopic dermatitis, we investigated the allele and genotype frequencies of C1014T SNP of CCR4 in 198 Japanese patients with atopic dermatitis and controls by a PCR-restriction fragment length polymorphism method. There was no significant difference in allele or genotype frequencies between patients with atopic dermatitis and controls. Serum IgE levels and peripheral blood eosinophil counts were not significantly different among genotypes. There was also no significant difference in allele or genotype frequencies between the patient subgroup with and without asthma, with mild or moderate disease, with and without family history of atopic dermatitis, or with and without family history of atopic disorders. C1014T SNP of CCR4 does not appear to be associated with susceptibility to atopic dermatitis in Japanese patients.

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

The aetiology of atopic dermatitis (AD) is presumably multi-factorial, with interactions between genetic and environmental factors. To investigate the relation between atopic family history and development of AD up to 4 years. Using annual questionnaires, we studied the cumulative incidence of AD in 0-4-year-olds in a prospective birth cohort of 4089. Atopic diseases in parents and siblings were recorded at birth. The occurrence of serum immunoglobulin E (IgE) antibodies to inhalant and food allergens was analysed in 2614 4-year-olds, and AD was divided into non-IgE-associated and IgE-associated. Of the children without atopic parents, 27.1% developed AD; of those with single or double parental atopic history, 37.9% and 50.0%, respectively, did so. The effects of parental history of eczema and of atopic respiratory disease (ARD) did not differ significantly, nor did those of maternal and paternal history. Parental history of ARD increased the risk significantly more for IgE-associated AD than for non-IgE-associated AD (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.5-2.8 vs. OR 1.3; 95% CI 1.0-1.8), whereas the two forms lacked major differences in the effect of parental eczema. A history of eczema in older siblings was a risk indicator for both forms of AD (OR 2.1; 95% CI 1.4-3.3 vs. OR 1.8; 95% CI 1.2-2.6). We found no difference between the effects of maternal and paternal atopic history. Parental eczema was a risk factor for AD irrespective of its association with IgE, but parental history of ARD mainly increased the risk of IgE-associated AD.

EARLY SENSITIZATION TO HOUSE DUST MITE IS A MAJOR RISK FACTOR FOR SUBSEQUENT DEVELOPMENT OF BRONCHIAL ASTHMA IN JAPANESE INFANTS WITH ATOPIC DERMATITIS: RESULTS OF A 4-YEAR FOLLOW-UP STUDY

Ohshima Y, Yamada A, Hiraoka M, et al. Ann Allergy Asthma Immunol. 2002;89:265–270To clarify factors involved in the development of bronchial asthma (BA) in children with atopic dermatitis (AD).One hundred sixty-nine infants (age <12 months) with AD who had been seen in the pediatric outpatient clinics of Kyoto, Gunma, and Gifu University Hospitals and affiliated hospitals between August 1994 and July 1995. The infants had neither BA nor episodes of recurrent wheezing at time of registration.Patients were followed for 4 years. The outcome of AD, development of BA, and changes in immunologic and other parameters were examined. Total immunoglobulin (IgE) levels and specific IgE against house dust mite (HDM), egg white, cow’s milk, wheat, rice, and soybean were examined using the CAP-RAST (radioallergosorbent test). Family history of AD and BA among relatives was obtained from interviews with the parents. Risk factors for the development of BA were analyzed for each follow-up year.One hundred three children remained in the study at the 4-year follow-up. Thirty-five percent had been diagnosed with asthma by pediatric allergists and 10.7% had episodes of wheezing, but were not diagnosed with asthma. Eighty-five percent of patients had specific IgE levels against at least 1 of the following 5 food allergens (egg white, milk, wheat, soybean, and rice). HDM-specific IgE increased from 11% at registration to 59% at the 1-year follow-up and 87% at the 4-year follow-up. Patients who developed BA showed early appearance of HDM-specific IgE and persistently high levels of food-specific IgE. Male sex, a positive family history of BA, and the appearance of HDM-specific IgE were identified as significant risk factors for the early development of BA, but the significance of these parameters decreased afterward. A positive family history of AD, the outcome of AD, and the keeping of furred pets were also identified as risk factors during part of the follow-up years. During the 4-year follow-up period, AD cleared in 33.8%, improved in 51.4%, was unchanged in 11.7% and worsened in 2.9% of the patients.The early appearance of HDM-specific IgE antibodies in early childhood is a major risk factor for the subsequent development of BA in children with AD. However, the influence decreases after longer follow-up.This study supports the idea that early atopic sensitization to food is a risk factor for subsequent inhalant sensitization and, therefore, a risk factor for the development of asthma. Risk factors appeared to shift during the 4-year follow-up, but this may have been influenced by the loss of 39% if the original study population. Furred animals also appeared to be a risk factor in the development of asthma, contrary to some recent studies claiming that a pet in the home might have some protective effect. Unfortunately, the authors did not obtain animal-specific IgE levels. Studies in infants with AD where occlusive bedding is used as an intervention to reduce HDM sensitization and possibly, by extension, asthma, would prove interesting.

The treatment of atopic dermatitis with systemic immunosuppressive agents

Atopic dermatitis (AD) is a chronic, relapsing skin disease that typically occurs in individuals with a personal or family history of atopy ie, hay fever, asthma, or AD itself. Typically beginning in early childhood, the disease affects approximately 7 to 17% of the pediatric population. Although in many cases there is moderation of the disease with increasing age, it may persist into adulthood in up to 60% of patients. AD can be managed in many patients with topical therapies, sometimes supplemented by systemic antibiotics, but some individuals, typically those with widespread disease or recalcitrant local disease that interferes with the quality of life, require more aggressive treatment. Management should embrace measures to control environmental “flare factors” such as house dust mites or in young children, certain foods. In addition, coincident skin infection, emotional distress, xerosis from dry ambient air or excessive bathing, and high temperatures causing sweating-induced exacerbations should be addressed with allergen avoidance, antibiotic therapy, relaxation techniques, bathing and skin hydration, humidification, and air conditioning, respectively. If control of flare factors combined with aggressive topical therapy or phototherapy fail to control symptoms of AD, a number of systemic immunomodulatory agents may play a role in treatment (Table 1). Because these agents have significant side effects, utmost care should be exercised in their use. It is also crucial to realize, particularly when contemplating the use of these agents in children, that none of them is approved for the treatment of AD in the United States. Informed consent, preferably in writing, for off-label use in the treatment of AD, should be obtained. Patients should be given written documentation of possible adverse effects and the treatment regimen should be tailored to each patient to limit overall exposure to the systemic agent. Although an extensive discussion of immunopathogenesis (see Kang et al, this issue) is beyond the scope of this paper, a basic understanding of the role of various immune cells and mechanisms in the causation of AD helps to clarify the rationale for using these agents.

The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: The German Infant Nutritional Intervention Study, a randomized double-blind trial

Background: The potential of extensively or partially hydrolyzed formulas to reduce the risks for allergies is controversial. Objective: We sought to assess the preventive effect of differently hydrolyzed formulas compared with cow's milk formula (CMF) in high-risk infants. Methods: Between 1995 and 1998, 2252 infants with a hereditary risk for atopy were enrolled in the German Infant Nutritional Intervention Study and randomly assigned at birth to one of 4 blinded formulas: CMF, partially hydrolyzed whey formula, extensively hydrolyzed whey formula, and extensively hydrolyzed casein formula (eHF-C). The primary end point at 1 year of age was the presence of allergic manifestation, which was defined as atopic dermatitis (AD), gastrointestinal manifestation of food allergy, allergic urticaria, or a combination of these factors. Results: At 12 months per protocol, analysis was performed on 945 infants exposed to study formula: 304 (13.5%) infants had left the study, 138 (6.1%) infants were excluded because of noncompliance, and 865 infants were exclusively breast-fed the first 4 months of life. The incidence of allergic manifestation was significantly reduced by using eHF-C compared with CMF (9% vs 16%; adjusted OR, 0.51; 95% CI, 0.28-0.92), and the incidence of AD was significantly reduced by using eHF-C (OR, 0.42; 95% CI, 0.22-0.79) and partially hydrolyzed whey formula (OR, 0.56; 95% CI, 0.32-0.99). Family history of AD was a significant risk factor and modified the preventive effect of the hydrolysates. Conclusions: Prevention of allergic diseases in the first year of life is feasible by means of dietary intervention but influenced by family history of AD. The preventive effect of each hydrolyzed formula needs to be clinically evaluated. (J Allergy Clin Immunol 2003;111:533-40.)

Early sensitization to house dust mite is a major risk factor for subsequent development of bronchial asthma in Japanese infants with atopic dermatitis: results of a 4-year followup study

Bronchial asthma (BA) often develops in children with atopic dermatitis (AD). Identification of factors that could predict the development of asthma in children with AD is useful for early intervention. We undertook a 4-year followup study to clarify the factors involved in the development of BA in infants with AD. We registered 169 infants with AD who were free of BA at registration and examined the prevalence and characteristics of the subsequent development of BA among these patients. Among the patients followed for 4 years, approximately 45% experienced asthma-like respiratory symptoms, and 35% were diagnosed as asthmatic patients by pediatric allergologists. Patients who developed BA showed early appearance of house dust mite (HDM)-specific immunoglobulin E (IgE) and persistently high levels of food-specific IgE. Male sex, a positive family history of BA, and the appearance of HDM-specific IgE were identified as significant risk factors for the early development of BA, but the significance of these parameters decreased thereafter. A positive family history of AD, the outcome of skin lesions, and keeping furred pets were also identified as risk factors in a part of the followup period. Among the parameters examined, the early appearance of HDM-specific IgE was the most significant risk factor. Appearance of HDM-specific IgE antibodies in early childhood, which seems to be mainly influenced by genetic factors, is a major risk factor for the subsequent development of BA in children with AD, but the influence decreases after longer followup.

Interleukin-13 gene polymorphism G4257A is associated with atopic dermatitis in Japanese patients

Interleukin (IL)-13 plays an important role in the induction of immunoglobulin E (IgE) and in the pathogenesis of atopic dermatitis (AD). We investigated the allele and genotype frequencies of three IL-13 single nucleotide polymorphisms (SNPs) (A704C and C1103T in the promoter region and G4257A in exon 4) in Japanese patients with AD. For A704C and C1103T SNPs, there were no significant differences in allele or genotype frequencies between AD patients and controls. For G4257A SNP, A allele was significantly increased in AD patients (39.5%) compared with controls (29.4%) ( P=0.016). The same proportion of each genotype and allele was observed in the patient subgroup with and without asthma. Serum IgE levels and peripheral eosinophil counts were not significantly different among genotypes in G4257A SNP. There was also no significant difference in allele or genotype frequencies between AD patients with mild disease and those with severe disease, between those with family history of AD and those without it, or between those with family history of atopic disorders and those without it. This result suggests that 4257A allele is associated with susceptibility to AD and that it may function in the pathogenesis of AD itself, presumably by other mechanisms than inducing IgE production.

Prevalence of atopic dermatitis in Korea.

This study was designed to estimate the prevalence and personal or family history of atopic dermatitis in school children in 3 areas of Korea: urban (Seoul), industrial (Ulsan) and rural (Chunchon). On the basis of dermatologists' physical examinations and the questionnaires completed by parents or guardians, the prevalence of atopic dermatitis was estimated to be 3.3% in the industrial area, 6.6% in the rural area and 7.8% in the urban area. The frequency of atopic dermatitis decreased with age and was significantly lower in the industrial area than in the rural and urban areas.

Atopic Dermatitis and Food Hypersensitivity Reactions

Wesley Burks A, James J, Heigel A, et alJ Pediatr.1321998132136The authors set out to determine the role and appropriate evaluation of food hypersensitivity in atopic dermatitis, using prick tests with a limited number of foods.One hundred sixty-five children, ages 4 months to 21.9 years, who met the criteria for a diagnosis of atopic dermatitis (AD), were enrolled in the study conducted in the pediatric allergy clinic of a teaching hospital.Precise histories were obtained as well as complete physical examinations. All patients underwent allergy prick tests with at least 12 common food antigens plus other foods that the parents thought caused symptoms. Food challenges were carried out on the basis of a positive skin test after the suspected food was eliminated for 2 to 3 weeks. A double-blind, placebo-controlled, food challenge (DBPCFC) was the method used. No child with a convincing history of a major anaphylactic reaction to a specific food was challenged with that food.A staggering 92% of these children had a family history of allergic rhinitis, asthma or AD! There were 2061 prick tests to foods performed with 323 (15.6%) read as positive. Ninety-eight patients had at least 1 positive test while 67 were completely negative. A total of 266 DBPCFC were performed and 88 were positive, plus an additional 22 were not performed because of a history of anaphylaxis. The results showed that a positive skin test had 100% sensitivity, 66% specificity, 65% positive predictive value, and 100% negative predictive value. The seven foods that accounted for 89% of the positive challenges were milk, egg, peanut, soy, wheat, cod/catfish, and cashew.Any child with significant AD who has been treated with the standard topical protocols plus systemic antihistamines and who fails to adequately respond should be considered for limited food prick skin testing, eg, the seven above. Elimination and challenge should be tried and if positive, an elimination diet should be instituted.We all encounter those children with tough to treat AD. The authors most convincingly present their case for a limited food skin test screening program. Your local friendly allergist may therefore be the best person to consult regarding your next troublesome AD patient. Rubbing “stuff” on and gulping pills does have it's limits, especially with the dramatic benefits that can be observed when food allergies are identified and appropriate diets are instituted.

Epidemiology and Clinical Pattern of Atopic Dermatitis in a North Indian Pediatric Population

Abstract: Various epidemiologic factors and clinical patterns of atopic dermatitis (AD) were evaluated in 672 children. Of these, 210 were infants (up to 1 year) and 462 were children. Mean age at onset and mean duration of the disease were 4.2 months and 3.3 months, respectively, in the “infantile AD” group. In the “childhood AD” group the corresponding figures were 4.1 years and 1.9 years. In both groups, patients from urban areas significantly outnumbered those from rural backgrounds. In the infantile AD group, the disease was aggravated in winter in 67.14%, in summer in 23.36% and in spring in 9.51% of patients. The corresponding figures in the childhood AD group were 58% in winter, 32.92% in summer, 7.43% in spring, and 1.74% in the rainy season. In the infantile AD group, personal and family history of atopy were seen in 0.91% and 36.19% of patients, respectively. No patient had a history of drug allergy. In the childhood AD group, 15.35% had a personal history of atopy, 36.44% had a family history of atopy, and 7.36% had both a personal and family history of atopy. A history of drug allergy was reported in 3.16% of children. In the infantile AD group, 79% had facial involvement, 42% had flexors affected, and 5.70% had both flexors and extensors affected. The types of eczema seen were acute in 52.72%, subacute in 23.35%, chronic in 23.35%, and follicular in 0.46%. In the childhood AD group, 74.50% had facial involvement, 35.53% had flexural involvement, 56.32% had extensor involvement, and 8.24% had both flexors and extensors involved. Acute eczema was seen in 28.79%, subacute in 23.38%, chronic in 47.40%, and follicular in 0.43% of the children.

Epidemiology and clinical pattern of atopic dermatitis in a North Indian pediatric population.

Various epidemiologic factors and clinical patterns of atopic dermatitis (AD) were evaluated in 672 children. Of these, 210 were infants (up to 1 year) and 462 were children. Mean age at onset and mean duration of the disease were 4.2 months and 3.3 months, respectively, in the "infantile AD" group. In the "childhood AD" group the corresponding figures were 4.1 years and 1.9 years. In both groups, patients from urban areas significantly outnumbered those from rural backgrounds. In the infantile AD group, the disease was aggravated in winter in 67.14%, in summer in 23.36% and in spring in 9.51% of patients. The corresponding figures in the childhood AD group were 58% in winter, 32.92% in summer, 7.43% in spring, and 1.74% in the rainy season. In the infantile AD group, personal and family history of atopy were seen in 0.91% and 36.19% of patients, respectively. No patient had a history of drug allergy. In the childhood AD group, 15.35% had a personal history of atopy, 36.44% had a family history of atopy, and 7.36% had both a personal and family history of atopy. A history of drug allergy was reported in 3.16% of children. In the infantile AD group, 79% had facial involvement, 42% had flexors affected, and 5.70% had both flexors and extensors affected. The types of eczema seen were acute in 52.72%, subacute in 23.35%, chronic in 23.35%, and follicular in 0.46%. In the childhood AD group, 74.50% had facial involvement, 35.53% had flexural involvement, 56.32% had extensor involvement, and 8.24% had both flexors and extensors involved. Acute eczema was seen in 28.79%, subacute in 23.38%, chronic in 47.40%, and follicular in 0.43% of the children.

A case-control study of possible causative factors in mycosis fungoides

A detailed case control study was carried out on 53 patients (33 males and 20 females) with histologically proven mycosis fungoides and on an age- and sex-matched control population. Possible causative factors investigated included occupation, recreation, and exposure to petrochemicals, pesticides, insecticides, and potential carcinogens. Exposure to plants of the Compositae family, tanning history, and chronic sun exposure were also investigated, as were smoking history, drug ingestion history, and other skin disease. Personal and family histories of other malignancies were also investigated. The only statistically significant difference to emerge was that the patients with mycosis fungoides had significantly more family history of atopic dermatitis. In view of the absence of any significant difference between patients and controls with regard to personal history of atopic dermatitis, this difference may be the result of multiple statistical testing rather than a phenomenon of true biological significance.

A Case-Control Study of Possible Causative Factors in Mycosis Fungoides

A detailed case control study was carried out on 53 patients (33 males and 20 females) with histologically proven mycosis fungoides and on an age- and sex-matched control population. Possible causative factors investigated included occupation, recreation, and exposure to petrochemicals, pesticides, insecticides, and potential carcinogens. Exposure to plants of the Compositae family, tanning history, and chronic sun exposure were also investigated, as were smoking history, drug ingestion history, and other skin disease. Personal and family histories of other malignancies were also investigated. The only statistically significant difference to emerge was that the patients with mycosis fungoides had significantly more family history of atopic dermatitis. In view of the absence of any significant difference between patients and controls with regard to personal history of atopic dermatitis, this difference may be the result of multiple statistical testing rather than a phenomenon of true biological significance.

Prognostic factors in atopic dermatitis

A long-term follow-up study (24 years minimum) was made of 955 individuals aged 24-44 years, who had atopic dermatitis (AD) in childhood. The material was divided into two groups; patients who in 1952-56 had been hospitalized on at least one occasion at the Department of Dermatology, Karolinska Hospital, Stockholm (Group 1), and patients who in 1955-56 had been out-patients in the same department (Group 2). At the time of investigation 62% and 40% of the patients in Groups 1 and 2 respectively had ongoing dermatitis, the majority with mild skin lesions. The frequency of healing of AD and severity of persistent or recurring dermatitis were influenced by several factors. In order of relative importance, disregarding sampling errors, persistent dry/itchy skin in adult life, widespread dermatitis in childhood, associated allergic rhinitis, family history of AD, associated bronchial asthma, early age at onset, and female sex were associated with low frequency of healing and increased severity of persistent or recurring dermatitis.

Factors influencing the occurrence of hand eczema in adults with a history of atopic dermatitis in childhood.

A series of 955 persons aged 24-44 years, with atopic dermatitis in childhood, were interviewed in order to identify factors which increase the risk of developing hand eczema in adult life, or aggravate already existing hand eczema. Endogenous (constitutional) factors were in general of greater importance than exogenous factors, viz. chemicals, water, soil and wear (friction). Eczematous involvement of the hands in childhood was of predominant importance. In individuals without such involvement, severe (widespread) dermatitis in childhood was a dominant factor. Other factors, each of them significantly more important than the exogenous ones, were persistent eczema on other parts of the body and dry/itchy skin. The factors female sex, family history of atopic dermatitis and simultaneous bronchial asthma/allergic rhinitis were associated with increased risk of developing hand eczema in adult life, but were of limited importance compared with the other endogenous and the exogenous factors.

Long term follow-up in atopic dermatitis.

A long-term follow-up study (minimum 24 years) has been carried out on 955 individuals with a history of atopic dermatitis (AD), who in childhood had been in- or out-patients at the Department of Dermatology, Karolinska Hospital, Stockholm. 62% of the in-patients and 40% of the out-patients still had dermatitis at investigation. The most common site was the hands. Eczematous hand involvement in childhood had been of predominant importance for the occurrence of hand eczema in adult life. Both tabular and stepwise logistic regression analyses revealed that the prognostically unfavorable factors as regards healing were, in order of importance, severe (widespread) dermatitis in childhood, family history of AD, associated allergic rhinitis, and/or bronchial asthma (with allergic rhinitis as the dominant of these two factors), female sex and early age at onset. Fewer than 20% of the individuals with all these prognostic factors were healed at the time of investigation, whereas 85% of those with none of the factors were healed. Persistent dry/itchy skin in adulthood was also found to be associated with persistent or recurring AD to a significantly (p less than 0.001) higher degree than normal skin. As this factor cannot be used as a predictor in childhood, it was not included in the regression analyses.