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PubMed2004

How atopic is atopic dermatitis?

BACKGROUND: The extent to which the phenotype of atopic dermatitis (AD) is truly atopic has been the subject of much debate. OBJECTIVE: We sought to systematically evaluate the evidence for the value of measurement of IgE antibodies in diagnosing AD and whether knowledge of IgE sensitization increases clinical diagnostic and predictive ability. METHODS: We searched Medline from its inception until September 2003. Only studies that measured atopy as either skin prick test positivity or IgE-antibody sensitization to environmental allergens were included within a descriptive analysis. Because the small number of studies of adequate quality did not allow a formal meta-analysis, we assigned strength of evidence according to predefined quality criteria and ranked studies accordingly. RESULTS: Inclusion of atopy as part of the diagnostic criteria for AD did not enhance the criteria's sensitivity and specificity in relation to the clinical phenotype of AD. The strength of association between atopy and AD varied significantly between hospital studies (47% to 75%; n=14 studies) and was stronger in hospital than in community populations (7.4% to 78%; n=13 studies). Whereas study quality did not have an effect on atopy prevalence in hospital populations, low atopy prevalences in community surveys were seen in less rigidly conducted studies. AD severity was positively associated with the number of positive skin prick test responses or IgE-antibody levels in 7 of 8 studies that measured both. Only one study suggested that IgE-specific sensitization to hen's egg is associated with subsequent development of AD, and 2 studies found that allergen-specific IgE sensitization in patients with AD is a prognostic marker for allergic airway disease in later life. Atopy-associated AD might also have a worse long-term prognosis than AD that is not associated with atopy. CONCLUSION: Although atopy is clearly associated with AD, the role of IgE sensitization in AD needs further study. Current evidence suggests that up to two thirds of persons with AD are not atopic, which implies that continued use of the term atopic dermatitis is problematic. Longitudinal studies are needed to compare the treatment response and prognosis of IgE-associated and non-IgE-associated AD.

Dermatitis, Atopic↗
PubMed1998

Purified Der p1 and p2 patch tests in patients with atopic dermatitis: evidence for both allergenicity and proteolytic irritancy.

Atopic dermatitis has many similarities with allergic contact dermatitis. Previous studies have revealed delayed-type allergic reactions indicating specific cell-mediated immune reactions in subgroups of patients. It has recently been recognized that purified house dust mite major allergens, Der p1 and Der p2 from Dermatophagoides pteronyssinus, exhibit a proteolytic enzyme activity similar to papain and maybe serine proteases (e.g. trypsin), respectively. This opens the possibility that house dust mites apart from an allergic epitope could elicit irritant reactions in atopic skin. We examined cutaneous reactivity to the purified proteins of house dust mite antigens, Der p1 and Der p2, in 36 consecutive patients with atopic dermatitis. We also patch-tested with trypsin and papain, in order to see if these proteolytic enzymes could induce irritant reactions. Twelve patients had type 1 allergy to Der p1 and two of these had type IV reactivity to D. pteronyssinus extract. Positive reactions were observed in another four patients, but they had also irritant reactions to papain and trypsin, indicating that the enzymatic activity may have elicited the reactions. The cutaneous reactivity was not linked to total serum IgE, but the patients with specific allergic patch tests had type I reactions to D. pteronyssinus extract. Our observations indicate that allergic patch tests towards Der p1 and p2 are rare and that irritant reactions from D. pteronyssinus proteolytic activity may be a more common phenomenon when patch-testing atopic dermatitis patients with house dust mite antigen extract.

Adolescent↗
PubMed1984

[Provocation of atopic dermatitis by intestinal candida mycosis].

We discuss atopic dermatitis in relation to candidamycosis of the intestine. In 11 out of 36 patients with atopic dermatitis, we found specific Candidin-IgE-antibodies. With all patients, candidamycosis of the stool samples was positive in culture. Increasing incidences of both diseases support the clinical relevance of these observations.

Adolescent↗
PubMed1997

[Atopic dermatitis and related factors observed at infant physical examination at health centers].

We investigated the incidence of atopic dermatitis and related factors at infant physical examination at health centers. Subjects were 900 infants (290 four-month-old infants, 298 one-year and six month-old infants, 312 three-year-old infants) who participated in infant physical examinations in Kanazawa-ku, Yokohama City. Overall, we analyzed 696 infants whose mothers had cooperated with the survey by completing questionnaires during physical examinations, and who submitted to examination by consulting dermatologists. The incidence of atopic dermatitis was 11.6% in 4-month-old infants, 12.2% in 1.5-year-old infants, and 12.1% in 3-year-old infants. The following were found to be related to the atopic dermatitis of infants. 1. Family history of atopic dermatitis in their mothers and older siblings. 2. Mothers' limited diet during pregnancy (avoiding some food which are suspected allergens). 3. Past history of molluscum contagiosum. 4. The frequency of taking bath. While epidemiological surveys of atopic dermatitis have previously been performed, the criteria at each survey was not identical and results could not be compared precisely. In this survey, 1. Dermatologists specializing in atopic dermatitis performed examinations. 2. All diagnoses were made according to standardized criteria which are applied nationwide. 3. All subjects were from a specific region. Because of this approach, this survey provides important information that can form the basis of comparison for future epidemiological surveys of atopic dermatitis.

Age Factors↗
PubMed2004

Correlation of serum total IgE, eosinophil granule cationic proteins, sensitized allergens and family aggregation in atopic dermatitis patients with or without rhinitis.

Atopic dermatitis (AD) is a complex disease with both a genetic background and environmental interactions. Although multiple linkage-analyses about AD have been studied, there have been only a few family aggregation tests of AD or perennial allergic rhinitis (AR) to date. The association of allergen-specific IgE in AD and atopic dermatitis with allergic perennial rhinitis (ADR) have also been seldom discussed. The purpose of this study was to evaluate family aggregation and assess allergen-specific IgE in patients with AD and ADR. We also planned to investigate the effect of family history of AD on the prevalence of allergen-specific antibodies. The serum levels of IgE, eosinophil cationic protein (ECP) and major basic protein (MBP) were measured and compared in patients with AD and those with ADR. Proportional analysis compared allergen-specific IgE between AD and ADR. The family aggregation was conducted to estimate the odds ratio for various atopic diseases in different family members. Total IgE and allergen-specific antibodies in serum were compared between those patients who had AD with AR and those without. The result revealed that allergic rhinitis is the most common concomitant atopic disease associated with AD. The ADR group was more likely to have serum mite-, cockroach-, and feather-specific IgE. The positive rates for wheat, peanut and soybean were higher in those AD without rhinitis. In the family aggregation of AD, the odds ratio for siblings was higher than for parents, the ratios for brother and sister were 9.91 and 8.75, respectively. However, the odds ratio for parents of ADR was higher than siblings; the ratios for father and mother of ADR were 8.22 and 2.94, respectively. AD patients with family histories of AD were more likely to have mite-, soybean-, and peanut-specific antibodies in their serum. We concluded that aeroallergens are the most important allergens aggravating atopic diseases in Taiwan. Food plays an important role in the pathogenesis of AD. Measurement of serum total IgE combined with the MAST-CLA test could be helpful in the diagnosis of atopic diseases. The differential aggregation tendency for AD and ADR implicated the complexity of the gene-environment interaction in these atopic diseases.

Adult↗
PubMed2006

Model-based clustering of binary longitudinal atopic dermatitis disease histories by latent class mixture models.

Atopic dermatitis is a skin disease which affects mainly children, has a very strong genetical component, and manifests itself clinically as flexural excema in connection with torturing itching. The course of disease is notoriously changeable and runs in phases, therefore it is difficult to predict the future course of disease. To improve prediction it would be interesting to identify clusters of children with different disease histories because this would shed light on common genetic and environmental risk factors. We use, relying on previous work of Nagin, a Latent class mixture model to estimate, in a data-dependent and model-based fashion, a clustering of typical binary atopic dermatitis disease histories in children. The data were collected from 1990 to 1997 in the so called MAS-study, a prospective cohort study of 1314 children in five German cities. The original method of Nagin is extended in two different aspects, first we use bootstrap confidence intervals to account for uncertainty in curve fitting, and second, we propose to model covariates for cluster membership by Anderson's Stereotype regression model. We feel that the Latent class mixture model is a valuable tool for assessing the course of atopic dermatitis, yielding a wealth of communicable and graphically displayable results.

Algorithms↗
PubMed2001

Urine eosinophil protein X (EPX) is an in vitro parameter of inflammation in atopic dermatitis of the adult age.

BACKGROUND: Eosinophils are important effector cells in several atopic diseases. The levels of eosinophil granule-derived mediators (ECP, EPX) in serum and body fluids have been proven to be correlated with disease activity in atopic respiratory diseases and atopic dermatitis. The study aimed to demonstrate an interrelationship between urine EPX and disease activity in adult patients with atopic dermatitis. METHODS: We determined urine EPX concentration, serum ECP concentration, and peripheral blood eosinophil count in 40 adult patients with mild to severe atopic dermatitis and compared it with the disease activity as assessed with the SCORAD index. RESULTS: Urine EPX and serum ECP concentrations were significantly higher in patients with severe atopic dermatitis than in patients with mild or moderate disease (median values 123.5 vs 78.3 microg/mmol creatinine, P<0.0001; 25.4 vs 14.9 microg/l, P<0.0001, respectively). We found a significant correlation between urine EPX levels, serum ECP levels, and the SCORAD (r=0.36, P<0.0001 and 0.34, P<0.0001, respectively). CONCLUSION: Urine EPX is a useful in vitro parameter of inflammation in atopic dermatitis of the adult age.

Adult↗
PubMed2004

Parents' reported preference scores for childhood atopic dermatitis disease states.

BACKGROUND: We sought to elicit preference weights from parents for health states corresponding to children with various levels of severity of atopic dermatitis. We also evaluated the hypothesis that parents with children who had been diagnosed with atopic dermatitis would assign different preferences to the health state scenarios compared with parents who did not have a child with atopic dermatitis. METHODS: Subjects were parents of children aged 3 months to 18 years. The sample was derived from the General Panel, Mommies Sub-Panel, and Chronic Illness Sub-Panel of Harris Interactive. Participants rated health scenarios for atopic dermatitis, asthma, and eyeglasses on a visual analog scale, imagining a child was experiencing the described state. RESULTS: A total of 3539 parents completed the survey. Twenty-nine percent had a child with a history of atopic dermatitis. Mean preference scores for atopic dermatitis were as follows: mild, 91 (95% confidence interval [CI], 90.7 to 91.5); mild/moderate, 84 (95%CI, 83.5 to 84.4); moderate, 73 (95%CI, 72.5 to 73.6); moderate/severe, 61 (95%CI, 60.6 to 61.8); severe, 49 (95% CI, 48.7 to 50.1); asthma, 58 (95%CI, 57.4 to 58.8); and eyeglasses, 87(95%CI, 86.3 to 87.4). CONCLUSIONS: Parents perceive that atopic dermatitis has a negative effect on quality of life that increases with disease severity. Estimates of parents' preferences can provide physicians with insight into the value that parents place on their children's treatment and can be used to evaluate new medical therapies for atopic dermatitis.

Adolescent↗
PubMed1998

Circulating CLA+ lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal-related T-cell receptor variable segments.

BACKGROUND: Atopic dermatitis is an allergic T-cell mediated skin inflammation. Staphylococcus aureus colonization is very common in cutaneous atopic dermatitis lesions. The cutaneous lymphocyte-associated antigen (CLA) is a T cell skin homing receptor that defines T lymphocytes associated with the cutaneous immune response. OBJECTIVE: To study whether CLA+ T cells from atopic dermatitis children present a selective expression for Staphylococcus aureus-related TCR Vbeta segments. METHODS: Peripheral blood T cells were stained with HECA-452 (anti-CLA) and a panel of TCR Vbeta specific monoclonal antibodies and analysed by flow cytometry. RESULTS: Atopic dermatitis patients have a higher percentage of circulating CLA+ CD3+ lymphocytes compared with healthy controls. Patients with active atopic dermatitis during the study expressed a higher percentage of cells positive for the TCR Vbeta2 and Vbeta5.1 segments in the CLA+ but not in the CLA- subset. These TCR Vbetas are recognized by staphylococcal superantigens. Moreover, there was an increased percentage of HLA-DR+ expression by CLA+ Vbeta5.1+ T cells in patients with active atopic dermatitis, but those patients whose eczema was inactive had very similar values to healthy controls regarding TCR Vbeta and HLA-DR phenotype in circulating CLA+ T lymphocytes. CONCLUSION: Our data indicate that circulating skin-homing T cells of patients with active atopic dermatitis contain an increased percentage of cells bearing TCR Vbeta segments related with Staphylococcus aureus. Staphylococcus superantigens may therefore trigger expansion or at least circulation of appropriate CLA+ T cells.

Antibodies, Monoclonal↗
PubMed1997

Bronchial and skin reactivity in asthmatic patients with and without atopic dermatitis.

It is unclear whether the presence and severity of atopic dermatitis (AD) is predictive for the occurrence and severity of early and late asthmatic responses to inhaled allergens. The aim of this study was to compare the bronchial effects of allergen inhalation challenge in allergic asthma (AA) and atopic dermatitis. We therefore studied these responses in: nine patients with mild-to-moderate AA without AD; eight patients with mild-to-moderate AA and mild AD; eight patients with severe AD and mild AA; and eight patients with severe AD without AA. Allergen challenge was performed by inhaling doubling doses until the dose provoking a 20% fall in forced expiratory volume in one second (PC20) was reached. The late asthmatic reaction (LAR) was defined as a fall of >20% in peak expiratory flow (PEF) between 3 and 8 h after the challenge. All but four of the patients with severe AD without AA developed an early asthmatic response (EAR). A LAR was seen in all patients with severe AD and mild AA, in four patients with mild AD and mild-to-moderate AA, and in three patients with mild-to-moderate AA without AD. The LAR was most pronounced in patients with a combination of mild AA and severe AD. This could be explained, in part, by a decreased skin sensitivity in these patients, which made the Cockcroft formula for prediction of PC20 allergen less accurate in such patients. We conclude that patients with severe atopic dermatitis and mild asthma are at risk for developing pronounced late asthmatic responses after allergen exposure. This suggests that eosinophils activated in atopic dermatitis also predispose to airway inflammation.

Adolescent↗
PubMed1986

Skin levels of arachidonic acid-derived inflammatory mediators and histamine in atopic dermatitis and psoriasis.

Since the biochemical events leading to cutaneous inflammation in atopic dermatitis and psoriasis are unknown, we studied the levels of arachidonic acid-derived mediators of inflammation as well as histamine in the suction blister fluid obtained from lesional and nonlesional skin of patients with these dermatoses. Mediator levels were determined radioimmunologically. Skin from healthy controls and uninvolved skin from patients contained very low or unmeasurable levels of the 5-lipoxygenase metabolite of arachidonic acid, leukotriene (LT) B4. In contrast, higher levels of LTB4-like immunoreactivity were detected in suction blister fluid from lesional atopic dermatitis skin, and even higher concentrations occurred in psoriasis lesions. LTB4-like immunoreactivity from atopic dermatitis suction blister fluid cochromatographed on reverse-phase high-pressure liquid chromatography with authentic LTB4, thus excluding cross-reaction of the LTB4-antibody with arachidonic acid or monohydroxyeicosatetraenoic acids. In contrast, suction blister concentrations of the cyclooxygenase metabolite of arachidonic acid prostaglandin (PG) E2 showed no significant differences between lesional and nonlesional patient skin and healthy control skin. PGD2 determined as a stable metabolite could not be detected in these samples. Histamine concentrations in lesional skin were within normal range. The elevated levels of the potent proinflammatory and immunomodulating mediator LTB4 could be involved in the pathogenesis of cutaneous inflammation in atopic dermatitis and psoriasis. In addition, they might explain the therapeutic efficiency of glucocorticosteroids, which among other actions inhibit the release of arachidonic acid from phospholipid stores by blocking the enzyme phospholipase A2. However, the specificity of disease expression in atopic dermatitis and psoriasis must be due to factors other than cutaneous LTB4 elevation.

Adolescent↗
PubMed1997

[Cataracts occur in patients with atopic dermatitis when the serum IgE increases].

The serum-IgE (sIgE) levels of eight patients with cataract complicated by atopic dermatitis (atopic cataract) who had undergone cataract surgery were reported. Five of them were diagnosed as having cataract the first visit to our eye clinic. The other three cases did not show cataract at the first visit but developed it later. The average sIgE of the five cases with cataract was 25,478 +/- 15,936 (mean +/- standard deviation) iu/ml whereas that of the latter three cases without cataract, at the first visit was 4,638 +/- 1,810 iu/ml. The average sIgE of these three cases when their cataracts were diagnosed first went up to 13,210 +/- 5,574 iu/ml. These results suggested that a high level of sIgE may be a warning of the appearance of atopic cataract.

Adolescent↗
PubMed1999

Enhanced expression of eotaxin and CCR3 in atopic dermatitis.

Chemokines are thought to play an important part in the development of inflammation in atopic dermatitis. Eotaxin, a CC chemokine, is a potent chemoattractant and activator of human eosinophils, basophils and Th2 lymphocytes which acts via the chemokine receptor CCR3. We studied the expression of eotaxin and CCR3, as well as MCP-3, MIP-1alpha and interleukin-8, in atopic dermatitis and normal skin by immunohistochemistry and nested reverse transcriptase-polymerase chain reaction. Skin biopsy specimens were obtained from nonlesional and lesional skin of patients with atopic dermatitis and of nonatopic controls. Immunoreactivity and transcripts of eotaxin and CCR3 were significantly increased in lesional skin from atopic dermatitis, but not in nonatopic controls. In nonlesional atopic dermatitis samples CCR3 expression was also significantly increased at the mRNA and protein level, whereas eotaxin was increased at the mRNA level only. No significant difference in the expression of MCP-3, MIP-1alpha, and interleukin-8 was observed between skin samples from atopic dermatitis and nonatopic controls. The enhanced local production of eotaxin may lead to the recruitment of eosinophils and T lymphocytes, which both express CCR3 and contribute to the initiation and maintenance of inflammation.

Adolescent↗