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Occurrence and clinical features of sensitization to Pityrosporum orbiculare and other allergens in children with atopic dermatitis.

One hundred and nineteen consecutive cases of children with atopic dermatitis aged 4-16 years (73 girls) from a pediatric dermatology outpatient clinic were included in a study of atopic sensitization. Structured interviews and clinical investigations were performed. IgE antibodies to common inhalant allergens, Pityrosporum orbiculare, Candida albicans, Tricophyton rubrum and Staphylococcus aureus were detected. Specific IgE antibodies frequently occurred to pollens, animal epithelia, C. albicans, house dust mites and moulds, whereas specific IgE antibodies to potential skin allergens were less prevalent. Twenty-six children (21.8%) had IgE antibodies to P. orbiculare, 14 (11.8%) to T. rubrum and 3 (2.5%) to S. aureus. Atopic dermatitis in children with one or several RAST positivities was worse, with a more chronic course, higher total eczema score, more frequent distribution in the head-neck-face regions and more itch compared to the children without serum detectable IgE antibodies. Severe itch disturbing nightly sleep was the only clinical feature that characterised P. orbiculare-positive cases. Allergy to P. orbiculare appears to be of little importance in early childhood atopic dermatitis but is likely to carry a poor prognosis.

Adolescent↗

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.

Adolescent↗

Lactose malabsorption in young Lithuanian children with atopic dermatitis.

AIM: To determine the prevalence of lactose malabsorption in young Lithuanian atopic dermatitis children; to evaluate the relationship between lactose malabsorption and the duration of exclusive breastfeeding, and the relationship between lactose malabsorption and cow's milk intolerance in parents and grandparents. METHODS: 144 children with atopic dermatitis aged 1.5-24 mo (study group) and 32 children without symptoms of allergic diseases aged 1.5-23 mo (control group) were investigated. Lactose and glucose-galactose absorption tests based on serial blood glucose determination, culture of stool, latex agglutination test for rotavirus and microscopic examination of stool for parasites were performed. RESULTS: Lactose malabsorption was determined in 59 (40.9%) and glucose-galactose malabsorption in 17 (11.8%) children with atopic dermatitis. The risk of developing lactose malabsorption was higher in children fed exclusively on breast milk up to 1 mo of age than in children fed exclusively on breast milk for 4 to 6 mo (OR: 2.62; 95% CI: 1.02-6.75). Lactose malabsorption was significantly more frequent in patients whose mothers did not tolerate cow's milk (20/30; 66.7%) than in patients whose mothers were tolerant to it (39/95; 41.1%) (p = 0.02). CONCLUSION: Lactose malabsorption was determined in 40.9% of Lithuanian atopic dermatitis children aged under 2 y. Lactose malabsorption appeared to be associated with the duration of exclusive breastfeeding up to only 1 mo and mothers' milk intolerance.

Child, Preschool↗

[The investigation of asthmatic children by multiple factor analysis. II. The influence of 17 allergic factors on atopic dermatitis and allergic rhinitis in asthmatic children].

We investigated possible influence of 17 allergy-associated factors on atopic dermatitis and allergic rhinitis using Multiple factor analysis in 150 asthmatic children. Atopic dermatitis was complicated in ninety-seven cases and allergic rhinitis in ninety-seven cases. 17 allergy-associated factors were as follows: 1) sex, 2) age, 3) onset age of asthma, 4) family history of allergy, 5) peripheral eosinophil counts, 6) IgE RIST, 7) IgE RAST score to egg white, 8) IgE RAST score to milk, 9) IgE RAST score to soybean, 10) IgG4 antibody titers to egg white, 11) IgG4 antibody titers to milk, 12) IgG4 antibody titers to soybean, 13) IgE RAST score to house dust, 14) IgE RAST score to Dermatophagoides farinae, 15) severity of asthma, 16) exercise-induced asthma, 17) atopic dermatitis or allergic rhinitis. We concluded as follows: 1) Factors which more strongly influenced both atopic dermatitis and allergic rhinitis were IgE RAST score to D.f., positive family history of allergy, IgE RIST and eosinophil counts. 2) Combination with high levels of IgG4 antibody to 3 food allergens such as egg-white, milk and soybean and IgE RAST to egg-white has a strong influence on atopic dermatitis, but high levels of IgG4 antibody to 3 food allergens except high level of IgG4 antibody to soybean have a weak influence on allergic rhinitis.

Adolescent↗

Increased concentration of beta-endorphin in the sera of patients with severe atopic dermatitis.

Serum beta-endorphin was measured by radioimmunoassay in 25 patients with atopic dermatitis and 100 healthy subjects. The neuropeptide was found to be markedly (p < 0.001) increased in patients with atopic dermatitis (9.2 +/- 3.4 pg/ml) as compared to normal controls (6.1 +/- 1.5 pg/ml). A correlation between increased serum beta-endorphin concentration and some clinical parameters of the disease has been found. The statistically significant elevation of beta-endorphin was found in patients with widespread atopic dermatitis lesions involving more than 20% of the skin surface (11.1 +/- 3.6 pg/ml), a high disease severity score (10.7 +/- 3.7 pg/ml), and previous bronchial asthma symptoms (11.6 +/- 3.1 pg/ml). A possible explanation of increased beta-endorphin is either its generation in atopic dermatitis lesions by inflammatory cells or activation of pituitary-adrenal axis by psychoneural factors in the mechanism of chronic stress.

Adolescent↗

Chronic pruritic dermatitis in asthmatic monkeys: a subhuman primate analogue of atopic dermatitis?

In a group of adult normal rhesus monkeys and monkeys with IgE-mediated asthma observed over a period of 15 years, 2 of the latter group were found to have chronic, generalized pruritus and dermatitis. The skin lesions were recurrent and located on the flexural surfaces of the forearms leading to the thickened, scaling, lichenified dermatitis in that area in the skin of 1 monkey. The pruritus and skin lesions subsided following therapy with depot methylprednisolone but recurred after this therapy was discontinued. Both animals had recurrent severe cutaneous infections in excoriated lesions following scratching without infections in other organs. The cutaneous infections responded to penicillin therapy but recurred with scratching. No deficiencies in immunoglobulin levels, or lymphocyte responses to phytohemagglutinin were found in these 2 monkeys. The 2 animals differed from normal animals by their high titers of immediate skin reactivity to ascaris antigen, persistent and severe asthmatic responses to ascaris antigen, high IgG antibody levels to ascaris antigen but all of the latter findings were also present in asthmatic monkeys without dermatitis. Cutaneous biopsies of lesions were nonspecific but provided no evidence for other explanations for the dermatitis which appears to be an analogue of human atopic dermatitis.

Adrenal Cortex Hormones↗

Local but not systemic administration of IFN-gamma during the sensitization phase of protein antigen immunization suppress Th2 development in a murine model of atopic dermatitis.

Biphasic Th1/Th2 development plays a central role in the pathogenesis of atopic dermatitis. In the sensitization phase after protein antigen exposure, an immune response polarized toward Th2 differentiation, which is due to the hosts' genetic proneness to the disease, initiates the skin lesions. Th1/Th2 antagonism is a potential mechanism that could be manipulated to suppress the initial Th2 deviation. IL-12 is the key cytokine for Th1 differentiation. Interferon gamma (IFN-gamma) can assist Th1 development through several mechanisms and suppress Th2 differentiation. We took advantage of a recently developed murine model of atopic dermatitis elicited by epicutaneous sensitization with protein antigen through patch application to examine the effects of different routes of IFN-gamma administration on Th1/Th2 differentiation during the sensitization phase of antigen exposure. Our data showed that systemic administration of IFN-gamma during the sensitization phase could not promote serum levels of specific IgG(2a). However, local administration (intradermal injection or patch application) of IFN-gamma during the sensitization phase could promote serum levels of specific IgG(2a) and suppress serum levels of specific IgE. Moreover, pretreatment of local IFN-gamma with protein antigen has a long-term modulatory effect on serum levels of specific IgG(2a) and IgE after repeated antigen immunization. Our results demonstrate that local but not systemic administration of IFN-gamma during the sensitization phase of protein antigen immunization could suppress the Th2 deviation in this murine model of atopic dermatitis. Thus, this may represent a novel strategy for the treatment and prevention of atopic dermatitis.

Allergens↗

Impaired monocyte cyclic AMP responses and monocyte cytotoxicity in atopic dermatitis.

Purified monocytes from 21 patients with mild and severe atopic dermatitis (AD) were compared with 22 healthy controls with respect to antibody-dependent cell-mediated cytotoxicity (ADCC) and cyclic adenosine 3',5'-monophosphate (cAMP) responses to stimulatory agents. ADCC was depressed in both severe and mild atopic dermatitis. The patients showed decreased cAMP responses to isoproterenol and histamine, the decrement being more distinct in severe atopic dermatitis. Formation of cAMP was diminished with PGE1 only in patients with severe AD. ADCC is inhibited by the agents that increase cAMP. In the severe dermatitis group reduced inhibition induced by isoproterenol, histamine, but not PGE1, was obtained. It is suggested that a general suppression of membrane activation may explain the reduced cAMP responses to various stimulatory agents and the impaired monocyte cytotoxicity.

Adolescent↗

Heterogeneity of interleukin 5 genetic background in atopic dermatitis patients: significant difference between those with blood eosinophilia and normal eosinophil levels.

BACKGROUND: Blood eosinophil levels in patients with atopic dermatitis vary widely during exacerbation of the disease. We considered that in addition to environmental factors, the genetic background involved with elevating blood eosinophil levels might be heterogeneous among atopic dermatitis patients. OBJECTIVE: We attempted to determine whether a polymorphism of the interleukin (IL)5 gene plays a role in atopic dermatitis, particularly in those patients with blood eosinophilia. Due to the close relation of blood eosinophilia to high IgE productivity, we also assessed these polymorphisms in patients with high IgE concentrations. METHODS: We determined the genotype of the IL5 polymorphism -703C/T in 451 atopic dermatitis patients and 116 normal subjects. The patients were classified into three groups by blood eosinophil levels; less than 7%, from 7 to 15%, and more than 15%, as well as by serum IgE concentrations; less than 500 IU/ml, from 500 to 2000 IU/ml, and more than 2000 IU/ml. RESULTS: IL5 -703C/T was not significantly associated with either total atopic dermatitis patients or individual patients who had both blood eosinophilia and high IgE productivity. However, the distribution of the IL5 -703C/T genotype was significantly different between patients with either blood eosinophilia or high IgE productivity and those without either condition (P=0.0476, P=0.0088, respectively). CONCLUSION: These results suggest that the IL5 gene may play a role in blood eosinophilia associated with atopic dermatitis. We also considered that the IL5 -703C/T gene polymorphism does not have a direct relationship to disease specificity.

Adolescent↗

Pharmacological abnormalities in atopic dermatitis.

Numerous investigations have described cutaneous and systemic physiological and pharmacological aberrations in atopic dermatitis and the atopic diathesis. Some of these studies set the stage for a focus upon cyclic nucleotide abnormalities. Elevated leukocyte cyclic AMP-phosphodiesterase accounts for low intracellular cyclic AMP levels in atopic dermatitis. The resultant permissive effect correlates with abnormal functional parameters such as increased basophil histamine release and in vitro IgE synthesis. In vitro and clinical use of phosphodiesterase inhibitors corrects abnormal parameters and may indicate future therapeutic directions.

B-Lymphocytes↗

Atopy patch test reaction to airborne allergens in the diagnosis of atopic dermatitis.

The aim of the study was to evaluate the possible use of atopy patch test in the diagnosis of atopic dermatitis and to characterize an optimal standardized system for atopy patch test in terms of allergen concentrations and time of allergen exposure. The study included 36 patients with atopic dermatitis and IgE-mediated airborne allergy. Patients presented positive results of skin prick tests and serum antigen specific IgE against house dust mite allergens and/or selected grass pollen allergens. Control groups consisted either of patients with allergic rhinitis (control group 1) or healthy volunteers with no signs or symptoms of atopy (control group 2). Allergologic diagnostic workup consisted of skin prick test, serum antigen specific IgE and total IgE evaluation, atopy patch test with selected airborne allergens of different concentrations (0.1xSPT, 1xSPT and 10xSPT), time of allergen exposure (8, 24 and 48 h), and readings of the results (8, 24, 48 and 72 h). Positive results of atopy patch test with airborne allergens were obtained in 47.2% of atopic dermatitis patients and none of control subjects. Contact reaction itself and the intensity of reaction were demonstrated to correlate with allergen concentration and time of allergen exposure on atopy patch test. The dose and time response analysis showed the optimal concentration of allergens for atopy patch test to be 10xSPT, 500000 SBE/ml, and optimal evaluation time 24 and 48 h of allergen application. There was no correlation between atopy patch test results and mean serum concentrations of total or antigen specific IgE. Atopy patch test results did not correlate with localization of skin lesions, severity and extensiveness of skin inflammation. A significantly higher contact reactivity to airborne allergens was recorded in the group of atopic dermatitis patients with polyvalent allergy in comparison with atopic dermatitis patients allergic to only one aeroallergen. It is concluded that atopy patch test is the only provocation test currently available with clinical relevance for contact IgE-mediated sensitization in atopic dermatitis patients. Using petrolatum as a vehicle, allergen concentration of 500000 SBE/ml and evaluation time of 24 and 48 h of allergen application may lead to improved atopy patch test results.

Adolescent↗

A body-weight-independent dosing regimen of cyclosporine microemulsion is effective in severe atopic dermatitis and improves the quality of life.

BACKGROUND: Cyclosporine has shown to be effective in severe atopic dermatitis. Little has been reported on the new microemulsion form (Sandimmune, Neoral) in the treatment of this disease. Also, it has not been investigated whether a body-weight-independent dosing regimen of cyclosporine is appropriate for the treatment of atopic dermatitis. OBJECTIVE: The goal of this study was to investigate a body-weight-independent dosing regimen of cyclosporine microemulsion in severe atopic dermatitis by comparing high and low starting doses of treatment. METHODS: A total of 106 adults with severe atopic dermatitis were enrolled in this double-blind study and randomized to receive a starting dose of either 150 mg (low) or 300 mg (high) of cyclosporine microemulsion daily. After 2 weeks the dose could be reduced by 50% if the clinical symptom score was reduced by 50% or more. After 8 weeks the responders entered a 4-week follow-up phase and were randomized to either stop treatment or to continue on their last effective dose every second day. RESULTS: After 2 weeks of treatment the total symptom score decreased from 59.0 to 39.3 with 150 mg and from 60.7 to 33.2 with 300 mg cyclosporine (P <.05). Until week 8 there was a further decrease in the clinical symptom score to 30.8 with low-dose therapy and 25.5 with high-dose therapy. Similar positive effects could be observed in assessments of affected body surface area, itching, sleep loss, and quality of life. At week 2, there was an increase of 0.6% in serum creatinine in patients receiving 150 mg, and 5.8% in the 300 mg group (P <.01). At week 8, the effect on serum creatinine was similar, with a 1.1% rise in the low dose group and a 6.0% increase in the high dose group. Body weight had no influence on efficacy or tolerability in this study. CONCLUSION: Body-weight-independent dosing with cyclosporine seems to be feasible in the short-term treatment of severe atopic dermatitis. Although the starting dose of 300 mg/day is more effective than 150 mg/day, the 150 mg dose would be preferable for the initiation of therapy because of its excellent renal tolerability.

Adult↗

Risk factors for atopic dermatitis in infants at high risk of allergy: the PIAMA study.

BACKGROUND: It has been suggested that the period immediately after birth is a sensitive period for the development of atopic disease. OBJECTIVE: We investigated whether birth characteristics and environmental factors are associated with the development of atopic dermatitis in the first year of life. METHODS: Seventy-six children with and 228 without atopic dermatitis, all children of mothers with respiratory allergy or asthma (PIAMA birth cohort study) were included in the study. Atopic dermatitis was defined as a positive history of an itchy skin condition with at least two of the following characteristics: visible dermatitis, history of outer arms/leg involvement, or general dry skin. Multiple logistic regression analysis was performed to study the independent effects of various risk factors. RESULTS: A birth weight >/=4000 g compared to 3000-4000 g was a significant risk factor for atopic dermatitis (odds ratio (OR)=2.4; 95% CI: 1.1-5.1) as was day care attendance (OR=2.9; 95% CI: 1.5-5.9). Exclusive breastfeeding in the first 3 months was negatively associated with atopic dermatitis (OR=0.6; 95% CI: 0.3-1.2), especially with visible dermatitis (OR=0.4; 95% CI: 0.2-1.0). Gender, gestational age, the presence of siblings or pets, and parental smoking were not significantly associated with atopic dermatitis. CONCLUSION: This study shows that a high birth weight and day care attendance increase the risk of atopic dermatitis in the first year of life, while exclusive breastfeeding is a protective factor when dermatitis is found on inspection.

Birth Weight↗

Correlation between clinical and immunological findings in atopic dermatitis.

Many immunological alterations have been reported in atopic dermatitis, and it is likely that in some cases they are capable of worsening the clinical course of atopic dermatitis (AD). More frequently these alterations are responsible for conditions associated with AD such as asthma, food allergy and infections. It seems probable that in some cases they are evidence of a preclinical allergic manifestation. However, in most cases, it is likely that the immunological alterations do not affect significantly the clinical course of the disease.

Allergens↗

The association of atopic dermatitis in infancy with immunoglobulin E food sensitization.

OBJECTIVE: To prospectively investigate the association of high levels of immunoglobulin E (IgE) sensitization to foods and the presence of atopic dermatitis (judged by reported topical steroid use during the first 16 months of life) in a birth cohort of 620 Australian children "at risk" of allergic disease because of family history. RESULTS: A total of 559 of the children in the cohort were fully evaluated, and the cumulative prevalence of atopic dermatitis was 24%. More children in the cohort who had atopic dermatitis had strongly positive skin test results (> or = 4+, histamine equivalent units, > or = approximately 6-mm wheal), consistent with IgE food sensitization to either cow's milk, egg, or peanut at 6 months (22% vs 5%, chi(2) = 35; P < 10(-6)) and at 12 months (36% vs 11%, chi(2) = 41; P < 10(-6)) than those without atopic dermatitis. The calculated attributable risk percent for IgE food sensitization as a cause of atopic dermatitis was 65% and 64% at these times. In a separate group of infants with severe atopic dermatitis, the equivalent rates of IgE food sensitization at 6 months was 83% and at 12 months, 65%. CONCLUSION: IgE food sensitization is a major risk factor for the presence of atopic dermatitis in infancy.

Dermatitis, Atopic↗

Is the prevalence of atopic dermatitis increasing?

Several studies have suggested that the prevalence of atopic dermatitis has increased over the last three decades, and similar trends have been reported with asthma and hay fever. However, in common with other 'allergic' disease, the definition and measurement of atopic dermatitis in populations has been fraught with problems and has led to difficulties in separating any real changes in disease prevalence from secular changes in diagnosis. In this article, the evidence surrounding the claims of an increased prevalence of atopic dermatitis is examined, and possible reasons for such a change are suggested.

Data Collection↗

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.

Adolescent↗

Skin barrier function in patients with completely healed atopic dermatitis.

Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.

Adult↗