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[Study on the genesis of atopic dermatitis--atopic dermatitis and IgE].

For the purpose of investigating how IgE is correlated in the genesis of Atopic dermatitis (abbreviated as AD) micronizing method of RIST (necessary serum 10 microliter) was utilized. Serum IgE obtained from 369 cases AD, age ranged from 1 month old to 52 years old were studied. In 78 cases, IgE of the objects' parents were also studied as well. Serum IgE of the healthy control, age ranging from 3 days old to 49 years old, were studied and made comparison with those of the objects. Analysis was made in accordance with the factors like age, complication, disease type and prognosis. RAST (house dust, mite, egg, milk) and SKIN TEST (Scratch test) were carried out in order to observe the correlation between serum IgE and Specific IgE or to see the possible induction of eczematous lesion by specific IgE. The following were obtained as conclusion. Serum IgE of AD will show high level in significant manner in comparison with the healthy control from the time of infantile period. Low IgE group will show high rate of improvement after 3 years period of time. High IgE of parents will more or less affect serum IgE of their child or children. Correlation between serum IgE and the severity of AD is not noted in the infantile period but significant in the adult period. In the Scratch test immediate type of reaction could not induce eczematous lesion of AD. Induction of eczematoid reaction in AD was noted with high incidence following the Scratch test of Candida antigen. From the above it is assumed that in AD, although serum IgE level is high, induction of eczematous lesion could not be made by skin invasion of specific IgE antigen to the skin, pruritus by immediate type of reaction following release of chemical mediator will bring the tearing off the skin by scratch and invasion to the epidermis of inflammation inducing materials like human dander, sweat, bacteria or mycological agents eczematous lesion will start to take place.

Adolescent↗

Identification of Malassezia species isolated from patients with seborrhoeic dermatitis, atopic dermatitis, pityriasis versicolor and normal subjects.

We identified Malassezia species isolated from 42 patients with seborrhoeic dermatitis, 17 patients with atopic dermatitis, 22 patients with pityriasis versicolor, 35 normal subjects and 73 healthy medical students. Regarding the prevalence of Malassezia species in the 35 normal subjects, the frequency of isolation of Malassezia globosa was 22%, M. sympodialis 10% and M. furfur 3%. M. slooffiae, M. pachydermatis, M. restricta and M. obtusa were infrequently isolated from normal skin. Two different species were isolated coincidentally from seven samples. In the patients with atopic dermatitis, M. furfur was isolated more frequently from lesional skin (21%) than non-lesional skin (11%). However, there was no statistical significance. Therefore, this result, by itself, is insufficient to prove that M. furfur should be considered to be an exacerbating factor of atopic dermatitis. In seborrhoeic dermatitis, M. furfur (35%) and M. globosa (22%) were isolated from lesional skin on the face at significantly high rates in comparison with the normal subjects. Therefore, M. furfur and/or M. globosa may be pathogens of seborrhoeic dermatitis. M. globosa was isolated at a frequency of 55% from lesional skin of pityriasis versicolor, while all other species were below 10%. These data suggest that the pathogenic species of pityriasis versicolor is M. globosa.

Adolescent↗

Sesquiterpene lactone mix patch testing supplemented with dandelion extract in patients with allergic contact dermatitis, atopic dermatitis and non-allergic chronic inflammatory skin diseases.

We investigated the value of patch testing with dandelion (Compositae) extract in addition to sesquiterpene lactone (SL) mix in selected patients. After we detected a case of contact erythema multiforme after patch testing with dandelion and common chickweed (Caryophyllaceae), additional testing with common chickweed extract was performed. A total of 235 adults with a mean age of 52.3 years were tested. There were 66 men and 169 women: 53 consecutive patients with allergic contact dermatitis (ACD); 43 with atopic dermatitis (AD); 90 non-atopics suffering from non-allergic chronic inflammatory skin diseases; 49 healthy volunteers. All were tested with SL mix 0.1% petrolatum (pet.) and diethyl ether extracts from Taraxacum officinale (dandelion) 0.1 and 3.0% pet. and from Stellaria media (common chickweed) 0.1 and 3% pet. A total of 14 individuals (5.9%) showed allergic reaction (AR) to at least 1 of the plant allergens, 4 (28.6%) to common chickweed extract, and 11 (78.6%) to Compositae allergens. These 11 persons made the overall prevalence of 4.7%: 8 (3.4%) were SL-positive and 3 (1.3%) reacted to dandelion extract. 5 persons (45.5%) had AD, 2 had ACD, 2 had psoriasis and 2 were healthy controls. The Compositae allergy was relevant in 8 cases (72.7%). The highest frequency of SL mix sensitivity (9.3%) was among those with AD. Half the SL mix-sensitive individuals had AD. ARs to dandelion extract were obtained only among patients with eczema. A total of 9 irritant reactions (IRs) in 9 individuals (3.8%) were recorded, 8 to SL mix and 1 to common chickweed extract 3.0% pet. No IR was recorded to dandelion extract (P = 0.007). Among those with relevant Compositae allergy, 50.0% had AR to fragrance mix and balsam of Peru (Myroxylon pereirae resin) and colophonium. SLs were detected in dandelion but not in common chickweed. Our study confirmed the importance of 1 positive reaction for emerging, not fully established, Compositae allergy. In conclusion, the overall prevalence of 4.7% in our study represents a basal SL mix detection rate of 3.4% reinforced and safely supplemented by testing with the dandelion extract.

Adolescent↗

Clinical, immunological and MRI features of myelitis with atopic dermatitis (atopic myelitis).

In order to clarify the characteristic features of myelitis with atopic dermatitis (AD), we compared the clinical, immunological and MRI findings between 14 myelitic patients with AD and 12 myelitic patients without AD. The myelitic patients with AD showed the following distinct features, compared with those without AD. (1) A preferential involvement of the cervical cord, as shown by neurologic as well as MRI examinations (14/14 vs. 5/12; P=0.0012), (2) paresthesia/dysesthesia as the predominant symptoms and a rare occurrence of definite muscle weakness (0/14 vs. 5/12; P=0.0120) and dysuria (1/14 vs. 8/12; P=0.0029), (3) a lower Expanded Disability Status Scale score (mean, 1.5 vs. 3.5; P=0.0018), (4) normal cerebrospinal fluid (CSF) findings including those for the IgG index and oligoclonal IgG bands and (5) a persistence of neurologic symptoms and MRI lesions during the follow-up periods (mean, 17 months). In addition, both the serum total IgE level and the frequency of specific IgE to Dermatophagoides farinae were significantly higher in the myelitic patients with AD (median IgE=1266 U/ml, specific IgE 14/14) than in those without AD (145 U/ml, P=0.0034 and 8/12, P=0.0331, respectively) and in 40 healthy controls (86 U/ml, P<0.0001 and 12/40, P<0.0001, respectively). Since myelitis with AD has distinct features and atopy to mite antigens appears to be the underlying cause of this condition, it may therefore be a distinct subtype of myelitis.

Acute Disease↗

Studies of HLA-ABC and DR antigens in pure atopic dermatitis and atopic dermatitis combined with allergic respiratory disease.

The HLA-ABC antigens were investigated in 29 patients with pure atopic dermatitis and 43 patients with atopic dermatitis combined with atopic respiratory disease (ARD). Furthermore, the DR antigens were studied in 10 patients with dermatitis alone and in 24 patients with combined atopic disease. The frequencies of antigens and the HLA phenotypes A1, B8 and A3, B7 in the entire group of patients and in two subgroups did not differ significantly from those in controls, when correction was made for the number of comparisons made. However, the frequency of HLA-DR7 was strikingly low, but this observation needs confirmation. IgE levels were measured in eight patients with pure dermatitis and in 24 patients with dermatitis combined with ARD and found equally increased in both groups compared to controls.

Adolescent↗

Atopic dermatitis, extrinsic atopic dermatitis and the hygiene hypothesis: results from a cross-sectional study.

BACKGROUND: Atopic Dermatitis (AD), hayfever and asthma are commonly summarized as atopic diseases. The spatial distribution of AD differs from that of asthma and hayfever, suggesting that AD might follow a different risk pattern than these diseases. AD can be differentiated into an allergic extrinsic form (EAD) and a non-allergic intrinsic form (IAD). Only EAD might follow the distribution and risk pattern that have been ascribed to asthma and hayfever. OBJECTIVE: To investigate the distribution and risk factor profile of AD and EAD focusing on environmental factors relating to the hygiene hypothesis. METHODS: Population-based cross-sectional study on 12,601 children aged 5-7 and 9-11 years from Dresden (Eastern Germany) and Munich (Western Germany). Information was obtained by International Study of Asthma and Allergic Childhood questionnaires, dermatological examinations and skin prick testing. AD-diagnosis ever, current AD-symptoms and visible eczema were investigated with their respective extrinsic forms. RESULTS: Maternal and paternal history of AD were equally strong determinants of the child's AD status. Factors related to the hygiene hypothesis like day-care attendance and number of older siblings were not associated with a decreased risk of AD. The proportion of EAD within AD was higher in Eastern than in Western Germany. The determinants of the diseases appeared to be similar for both EAD and IAD. CONCLUSIONS: There was no evidence of the hygiene hypothesis holding true for AD or EAD. AD might be a separate entity than respiratory atopic diseases. Little is known about the risk factors of AD and factors different from those of respiratory allergic diseases should be considered in future research.

Child↗

The economics of topical immunomodulators for the treatment of atopic dermatitis.

Atopic dermatitis is a common, chronic, relapsing inflammatory skin disease frequently affecting infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5--20% of the paediatric population. First-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of antihistamines and oral antibacterials. Topical corticosteroids improve the lesions of atopic dermatitis; however, concern on the part of physicians and patients regarding adverse effects has led to reluctance to utilise topical corticosteroids early and especially for prolonged periods. Topical immunomodulators (TIMs), including tacrolimus ointment and pimecrolimus cream, were recently introduced for the treatment of atopic dermatitis. Clinical data show that TIMs are effective in atopic dermatitis, yet do not cause the significant adverse effects associated with topical corticosteroids. Questions remain regarding the place of TIMs as a treatment for atopic dermatitis and how to use them most effectively, from both therapeutic and pharmacoeconomic standpoints. Specifically, two major issues remain unresolved: (i) how TIMs measure up to other therapies, especially topical corticosteroids; and (ii) how members of the TIM drug class compare against each other. Previous research has established that atopic dermatitis has a significant impact on quality of life (QOL) and carries a substantial economic burden. Some studies have also measured the utility of various atopic dermatitis disease states. While there is a need for further research, early economic studies provide evidence that TIMs positively affect the QOL of patients and families. In certain patients, TIMs may be cost effective and have an acceptable incremental cost utility compared with topical corticosteroids.Making cost-effectiveness comparisons between tacrolimus and pimecrolimus is challenging because there are limited head-to-head comparative data. Given currently available efficacy data, the results of one study suggest that tacrolimus may be more cost effective than pimecrolimus in paediatric patients with moderate atopic dermatitis. The full economic and QOL benefits of both agents are yet to be completely understood. The studies reviewed herein are the first to delineate the pharmacoeconomic benefits of TIMs in atopic dermatitis, and lay the foundation for future analyses. TIMs represent an exciting advance in the treatment of atopic dermatitis. Additional research will help determine the proper place of TIMs among the current array of therapeutic options for atopic dermatitis.

Administration, Topical↗

The Wiskott-Aldrich syndrome gene as a candidate gene for atopic dermatitis.

Atopic dermatitis is a multifactorial disorder probably caused by environmental factors in combination with susceptibility genes. The clinical similarity between atopic dermatitis and the eczema manifestation in patients with Wiskott-Aldrich syndrome made the previously identified WAS gene in chromosome sub-band Xpl 1.23 an interesting candidate gene for atopic dermatitis. We studied linkage and association to the WAS gene region using four polymorphic microsatellite markers in 406 Swedish families with at least two siblings affected with atopic dermatitis (in total 1514 individuals). In the analyses, we studied two qualitative traits: atopic dermatitis and elevated allergen-specific serum IgE antibodies, and one quantitative trait, a severity score of atopic dermatitis. We found that the marker MAOB gave positive linkage with a maximum lod score of 1.68 (p<0.05) to the severity score of atopic dermatitis. Association could not be seen to atopic dermatitis nor to elevated allergen-specific serum IgE antibodies in this region using the transmission disequilibrium test. Our results indicate that either the WAS gene or another gene in the area contributes to the severity of atopic dermatitis.

Age of Onset↗

Ceramide and cholesterol composition of the skin of patients with atopic dermatitis.

Atopic dermatitis skin tends to be easily irritated and appears dry. These clinical peculiarities correspond to impaired barrier function and to increased transepidermal water loss (TEWL) values. A few studies suggest that a reduced amount of total ceramides (especially of ceramide 1) is responsible for functional abnormalities of the skin of atopic dermatitis patients. The aim of this study was to analyze the relationship between epidermal lipids and barrier impairment in the skin of patients with atopic dermatitis. The quantity of ceramides, cholesterol sulphate and free cholesterol of 47 patients with atopic dermatitis and 20 age- and sex-matched healthy subjects was assessed by cyanoacrylate stripping and thin layer chromatography. Capacitance and TEWL were recorded at the same site of the lipid sample. In patients with atopic dermatitis, the levels of ceramide 1 and 3 were significantly lower and values of cholesterol significantly higher with respect to healthy subjects. Moreover, the CER/CH ratio was significantly lower with respect to normal skin. Patients with active signs of eczema also had higher TEWL values and lower capacitance values. By contrast, patients with no active signs of atopic dermatitis had a normal barrier function and intermediate values of ceramides and cholesterols, when compared to patients with atopic dermatitis with active lesions and normal subjects. The quantity of ceramide 3 was significantly correlated with TEWL impairment. These findings suggest that a decrease in ceramides in the stratum corneum is involved in barrier impairment in atopic dermatitis skin. Our data confirm those of other authors and support the view that impaired metabolism of ceramides may be the cause of dry skin and impaired barrier function in atopic dermatitis.

Adolescent↗

The potential role of allergen-specific sublingual immunotherapy in atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease associated with increasing prevalence, morbidity, and cost in developed Western countries. Frequently associated with respiratory allergy during adulthood, atopic dermatitis often represents the first phenotypic appearance of atopy in early childhood when the allergic 'march' starts and progressively moves toward food allergy, asthma, and rhinitis. At present, a consistent body of evidence supports the view that atopic dermatitis may represent the skin compartmentalization of a systemic allergic inflammation. Lymphocytes infiltrating early lesional skin express a T helper (Th) 2 pattern of cytokine secretion (increased levels of interleukin [IL]-4 and/or IL-13 and decreased levels of interferon-gamma) as well as the typical Th2-type chemokine receptor CCR4, specific to the thymus and activation-regulated chemokines. Keratinocytes from patients with atopic dermatitis produce thymic stromal lymphopoietin, a novel cytokine that supports the early lymphocyte development in mouse models, and activates dendritic cells involved in the pathogenesis of allergic diseases in humans. Increased levels of circulating hemopoietic precursor cells have been reported in atopic dermatitis, as in allergic asthma and rhinitis. Furthermore, the recognition of CD34+ hemopoietic precursor cells, and evidence for cellular differentiation/maturational events occurring within atopic dermatitis skin lesion infiltrates, are consistent with the recent reinterpretation of the Th2/Th1 paradigm, where Th2 cells appear to belong to the early stages and Th1 to the ultimate stages of a linear, rather than divergent, pattern of lymphoid differentiation. This more detailed understanding of the immunologic derangements contributing to the atopic dermatitis pathogenesis has led to growing interest in allergen-specific immunotherapy for the disease. Due to the complexity intrinsic to atopic dermatitis and the lack of consensus-based guidelines for standardized outcome measure, only eight studies are available in the literature for a qualitative evaluation of this treatment approach. Two of these studies were double blind and placebo controlled, and six were cohort studies. Immunotherapy was found to be effective in one controlled study and five observational reports. Uncertain results were provided by one low-powered, controlled study, and negative outcomes were raised by a unique study performed with oral immunotherapy, which is not an effective route of mucosal allergen administration. Thus, more efficacy studies are required before immunotherapy could be recommended for the routine treatment of atopic dermatitis. Allergen-specific sublingual immunotherapy, given its excellent safety profile and ability to interfere with the systemic aspects of allergic inflammation, appears a good potential candidate for the pathogenetic treatment of the disease.

Administration, Sublingual↗

The millennium criteria for the diagnosis of atopic dermatitis.

Atopic dermatitis forms an active area of basic and clinical research, where important new knowledge about genetics and immunopathogenesis has surfaced over the past years, and where simultaneous development of new and innovative therapies is under way. However, the inclusion of any patient in an atopic dermatitis study, whether it is on its genetics, pathogenesis or therapy, requires a diagnosis which is irrefutable. Since there is no simple and also no complicated laboratory procedure to reach a diagnosis of atopic dermatitis, different sets of clinical criteria have been developed for the purpose of making the diagnosis uniformly in different studies as well as in different study centers. The most commonly used are Hanifin and Rajka's set of diagnostic features, which have major and minor clinical criteria to be fulfilled in order to establish a diagnosis of atopic dermatitis. Recent developments in the immunology of atopy have clearly established the major abnormality in this syndrome, the preferential production of allergen-specific IgE. In this contribution, it is suggested that the presence of such antibodies in a given patient should be a mandatory criterium for the diagnosis of atopic dermatitis. Such a diagnostic test however establishes a diagnosis of atopic syndrome, not atopic dermatitis. Thus, for atopic dermatitis we have to rely, for the time being, on additional clinical criteria. The clinical features described in the literature are critically evaluated, and it is suggested that in addition to the mandatory presence of allergen-specific IgE, 2 of 3 principal criteria (pruritus, typical morphology and distribution, chronic or chronically relapsing) should be present for such a diagnosis. Finally, the minor features originally described by Hanifin and Rajka and later evaluated by others are revised and divided over 4 subcategories; a) related to subclinical eczema; b) related to dry skin; c) extra skin folds; and d) ophthalmological pathology. They are suggested to be used as additional criteria only, needed when clinical suspicion is high but the new mandatory and principal diagnostic criteria described here are inconclusive. For study purposes, we suggest that the mandatory and principal criteria are sufficient. They are now evaluated and validated in ongoing atopic dermatitis treatment studies.

Animals↗

Expression of T cell receptor V beta chain in lesional skin of atopic dermatitis.

Atopic dermatitis is a chronic, relapsing inflammatory skin disorder characterized by local infiltration of T cells. To date, numerous reports have shown that Staphylococcus aureus may exacerbate atopic dermatitis, and superantigens produced by this organism are thought to be one of the major causative factors in atopic dermatitis. The purpose of this study was to evaluate the role of staphylococcal superantigen in atopic dermatitis by observing expression of the variable region of beta chain of T cell receptor (TCR V beta) in the inflammatory cells infiltrating cutaneous lesions of atopic dermatitis. Fourteen patients with atopic dermatitis were enrolled. Punch biopsy specimens were obtained from lesional and normal-appearing skin of all patients. The expression of TCR V beta was studied by means of immunohistochemical technique using monoclonal antibodies. In 4 out of 14 patients, the tendencies of preferential expression of specific TCR V beta were found in lesional skin. This study suggested that staphylococcal superantigen and its corresponding T cell subsets may act as causative or pathogenic factors in a subgroup of atopic dermatitis.

Adolescent↗

Efficacy and economics of topical calcineurin inhibitors for the treatment of atopic dermatitis.

Atopic dermatitis is a chronic, relapsing inflammatory skin disease that frequently affects infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5-20% of the pediatric population. Studies have shown that atopic dermatitis is associated with considerable economic costs and decreased quality of life. There is no proven curative therapy at present for atopic dermatitis; first-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of histamine H1 receptor antagonists (antihistamines) and oral antibacterials as appropriate. Topical corticosteroids, while effective in many patients, carry the concern of local and systemic adverse effects. As a result, physicians and patients are reluctant to utilize stronger topical corticosteroids in certain areas of the body and for prolonged periods of time. The purpose of this article is to review the efficacy and economics of topical calcineurin inhibitors in the treatment of atopic dermatitis. This new class of agents (specifically tacrolimus ointment and pimecrolimus cream) represents an exciting advance in the treatment of atopic dermatitis. Clinical data show that topical calcineurin inhibitors are effective and do not cause the adverse effects associated with topical corticosteroids. Several studies have provided evidence that topical calcineurin inhibitors positively affect the quality of life of patients and their caregivers. Compared with branded topical corticosteroids and previous standards of care, topical calcineurin inhibitors appear to be a cost-effective treatment option. Drawing comparisons between tacrolimus and pimecrolimus is difficult because definitive head-to-head comparative studies involving these drugs have not been conducted.

Administration, Topical↗

Secular change in the occurrence of atopic dermatitis.

Atopic dermatitis is a common disease, and population-based studies indicate that the frequency of atopic dermatitis has increased substantially during recent decades. It has been generally accepted that disease onset occurs before 7 years of age in 80-90% of the cases, and consequently the epidemiology of atopic dermatitis has been studied mostly in children on admission of first grade school. Before 1960 about 2-3% of children suffered from atopic dermatitis. In the 1960s, some 4-8% was recorded in several studies, and for those born after 1970 most researchers found that 9-12% developed atopic dermatitis during childhood. The diagnostic criteria of Hanifin and Rajka are cumbersome for population studies not designed specifically for children. In order to compare epidemiologic data from varying times and locations, a framework for questionnaire studies in atopic dermatitis is proposed.

Child↗

Immunophenotyping of skin-infiltrating T-cell subsets in dogs with atopic dermatitis.

Atopic dermatitis in dogs has many clinical features that are identical to those of the same disorder in man. To investigate the pathogenesis of this disease in dogs and the possibility of similarities to the pathogenesis in humans we compared the presence and ratio of CD4+ and CD8+ T-cells in the cutaneous infiltrate of lesional and non-lesional skin of atopic dogs with that in the skin of healthy dogs. In ten dogs with atopic dermatitis and ten healthy dogs the skin was biopsied at the predilection sites for atopic dermatitis and histological sections were immunohistochemically stained for CD4 and CD8. The staining showed an increase in CD4+ and CD8+ T-cells in canine lesional atopic skin, with a predominance of CD4+ T-cells in the epidermis. In non-lesional atopic skin there was also an infiltration with CD4+ and CD8+ T-cells, but without predominance of CD4+ T-cells. The results in the separate predilection sites did not differ substantially from the mean results. These observations indicate further similarities in the immunopathogenesis of atopic dermatitis in dogs and humans, which may have consequences for the control of atopic dermatitis in dogs and contributes to a possible role of the dog as a model for human atopic dermatitis.

Animals↗

Peripheral blood mononuclear cell responses to major and minor Dermatophagoides allergens in canine atopic dermatitis.

Atopic dermatitis is a chronic inflammatory and pruritic skin disease commonly seen in dogs and humans. Most cases involve hypersensitivity to the house dust mites (HDM) Dermatophagoides farinae and Dermatophagoides pteronyssinus. Human atopic dermatitis is associated with the HDM derived allergens Der f 1 and 2, and Der p 1 and 2. Serological data, however, suggest that a 98/104kD protein is the most important allergen in dogs with atopic dermatitis. The aim of this study was to characterise the specificity of circulating T-cells in canine atopic dermatitis for HDM derived allergens. Peripheral blood mononuclear cells (PBMCs) from dogs with atopic dermatitis that were skin test positive for D. farinae and D. pteronyssinus were cultured with crude extracts of D. farinae, D. pteronyssinus and D. microceras, a 98/104kD allergen purified from D. farinae, Der f 1 and Der f 2. There was significantly greater responsiveness of PBMCs to the D. farinae and D. pteronyssinus extracts compared to the D. microceras extract, and similarly to the purified 98/104kD allergen compared to Der f 1 and Der f 2. The close association between serological findings and PBMC proliferation implies that the 98/104kD HDM protein is a major target of immune recognition and that T-cells also participate in the pathogenesis of canine atopic dermatitis by supporting IgE production.

Allergens↗