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Cell-mediated immunity in untreated and PUVA treated atopic dermatitis.

In 22 adult patients with atopic dermatitis, lymphocyte subpopulation counts, mitogenic responses to several PHA and Con A concentrations, nonspecific mitogen induced, and indomethacin sensitive suppressor cell functions and leukocyte migration inhibitory factor production were investigated. Patients with severe atopic dermatitis had normal PHA and Con A responses, although somewhat lower than matched controls, while mild AD patients equalled controls in this respect. No significant differences between AD patients and controls were detected with respect to lymphocyte subpopulations, suppressor cell function or leukocyte migration inhibitory factor production. Methoxalen plus ultraviolet light (PUVA) therapy induced significant clinical improvement in 9 out of 10 treated patients. A concomitant decrease of the mitogenic responses and increase of the Con A induced nonspecific suppressor cell activity was recorded, while other immunological parameters remained unaffected by the therapy. Thus PUVA therapy induces both local clinical and systemic immunological manifestations. The possibility that the observed immunological changes would be operative in the PUVA induced healing process, however, seems unlikely, as the present study did not disclose any obvious relationship between immune parameters and severity of atopic dermatitis.

Adult↗

HLA and atopic dermatitis with high serum IgE levels.

Patients with atopic dermatitis usually exhibit allergen-specific IgE antibodies against several environmental antigens. HLA restriction is presumed to be involved in the recognition of such antigens, but several previous reports have so far failed to find a significant association between atopic dermatitis and HLA antigens. In this study we examined 38 unrelated Japanese patients with severe atopic dermatitis and high serum IgE levels (greater than 800 U/ml). We investigated the serological HLA types and HLA class II alleles in this group of patients with atopic dermatitis. Frequencies of HLA-A24, A33, Cwblank, B44, DR13 and HLA-DRB1*1302, DQB1*0604, DPB1*0301 alleles were increased in the patients. In contrast, frequencies of HLA-Cw1, Bw6, DR4, DR53, and HLA-DQB1*0302 allele were decreased. However, none of these remained significant after p values were corrected. Further study on HLA association with atopic dermatitis through characterization of specific antigens or antigen epitopes is needed.

Adolescent↗

An efficient new formulation of fusidic acid and betamethasone 17-valerate (fucicort lipid cream) for treatment of clinically infected atopic dermatitis.

To relieve the dryness of atopic dermatitis skin, a lipid formulation of fusidic acid and betamethasone 17-valerate (Fucicort Lipid cream) was developed as an additional treatment option to the established Fucicort cream. The two formulations were compared in patients with clinically infected atopic dermatitis. A total of 629 patients were randomized to twice daily double-blind treatment for 2 weeks with either Fucicort Lipid cream, Fucicort cream, or the new lipid cream vehicle. Clinical assessment was based on a Total Severity Score of the eczematous lesions. Bacteriological samples were taken at inclusion and at subsequent visit(s) if clinically infected lesions persisted. At the end of treatment, the mean reduction in Total Severity score was 82.9% in the lipid cream group, 82.7% in the cream group, and 33.0% in the vehicle group. The percentage of patients with a successful bacteriological response was 89.7%, 89.6% and 25.0%, respectively. Thus, the clinical and anti-bacterial effect of the lipid cream was found to be similar to that of the established cream formulation, and significantly better than that of the vehicle. The new lipid formulation, therefore, offers an efficient, safe and well-tolerated alternative for the short-term treatment of clinically infected atopic dermatitis.

Administration, Topical↗

Atopic dermatitis: review 2000 to January 2001.

A review on atopic dermatitis is given, considering as basic information articles published over the period of February 1, 2000 to January 31, 2001. Atopic dermatitis is a chronic, inflammatory, primarily genetic-determined skin disease of which the cause is unknown. Its prevalence is rising in the industrialized countries, and no one knows why. The hygienic theory is most promising. Although most cases of atopic dermatitis are mild, the disease may be severe and widespread, with much impact on morbidity and social life. Mild cases usually clear and compromise 60% of the cases. Atopic dermatitis may always turn back. The clinical features are age related. Recently, a new subgroup was noted by several dermatologists in different parts of the world, consisting of people who suffer from atopic dermatitis for the first time at adult age. Food allergy, intolerance, and diet are still controversial and play a role especially in children until the age of 5 years. Diagnostic tests, such as the Atopy Patch Test, using food allergens, adds 10% or more positives and imitates the late-phase clinical manifestations. The Atopy Patch Test is still experimental as a diagnostic tool and has shortcomings, like difficulty in reading. Financial costs of treating and caring for atopic dermatitis may be high, stressing the importance of health care.

Age Factors↗

Severity distribution of atopic dermatitis in the community and its relationship to secondary referral.

Although atopic dermatitis is the most common inflammatory dermatosis affecting children, no previous studies have evaluated the relationship between disease severity and the referral pattern to secondary health care services. We carried out a cross-sectional survey of 1760 children aged 1-5 years selected from the age-sex registers of four urban and semiurban general practices in Nottingham. Atopic dermatitis was diagnosed by a dermatologist on the basis of symptoms and signs of a flexural itchy rash that had been present in the previous 12 months. The severity of atopic dermatitis was assessed clinically by the same dermatologist on the basis of reported symptoms over the previous 12 months and clinical signs, and was graded on a three-point scale as mild, moderate or severe. Information on the use of primary and secondary health care services was recorded at the time of the interview. The 1-year period prevalence of atopic dermatitis was 16.5% (95% confidence interval 14.7-18.2%). The severity distribution of atopic dermatitis was: mild 84% (n = 242), moderate 14% (n = 41) and severe 2% (n = 7). Of those children with atopic dermatitis, 96% (n = 278) had consulted their general practitioner in the previous 12 months and 6% (n = 17) had been seen in secondary care. Overall, 4% (n = 11) of those children with atopic dermatitis had a consultation with a dermatologist. Other sources of secondary care referral included the paediatric department (n = 2) and accident and emergency department (n = 6). Referral to secondary care was found to be positively related to disease severity, with referral occurring in 3% of mild cases, 15% of moderate cases and 43% of severe cases. Although the relative referral rate of mild and moderately severe disease was low, these cases were found to represent a significant proportion (82%) of the total numbers of children seen in secondary care. This study has shown that: (i) most cases of atopic dermatitis in the community are mild in severity; (ii) referral to secondary health care services by general practitioners is infrequent; (iii) disease severity is an important determinant of referral to secondary care; and (iv) any potential change in the referral pattern of mild/moderate cases of atopic dermatitis to secondary care is likely to produce a significant increase in workload for dermatology departments.

Child, Preschool↗

Penetrating keratoplasty in patients with atopic dermatitis with and without systemic cyclosporin A.

PURPOSE: Clinical experience suggests that atopic dermatitis is a considerable risk factor in penetrating keratoplasty. The scientific evidence, however, has been equivocal. Systemic cyclosporin A reduces the threat of immune reactions and simultaneously improves atopic dermatitis. The purpose of this study was to evaluate to what extent and for how long systemic cyclosporin A improves graft prognosis in patients with atopic dermatitis. PATIENTS AND METHODS: Between November 1986 and July 1994, 173 penetrating keratoplasties were performed on keratoconus patients without skin disease (I). Fifteen penetrating keratoplasties were performed on patients with keratoconus associated with slight atopic dermatitis (II), 24 on patients with keratoconus associated with severe atopic dermatitis (III), and 13 on patients with keratitis in atopic dermatitis but without keratoconus (IV). Systemic cyclosporin A was administered for at least 6 months in groups III and IV. Clear graft survival was estimated according to Kaplan and Meier, and statistical significance was evaluated via log-rank test. RESULTS: Six months/6 years postoperatively 99.5 and 96.5% (I), 80 and 80% (II), 96 and 83.2% (III), and 100 and 65.8% (IV) of the grafts were clear. Only the differences between the survival curve of group I and the curves of each of groups II-IV were statistically significant (p < 0.001). CONCLUSIONS: To our knowledge, this is the first study proving that atopic dermatitis with and without keratoconus deteriorates graft prognosis statistically significantly. The application of systemic cyclosporin A improves graft prognosis in atopic dermatitis as long as the drug is applied, and this effect slowly fades thereafter.

Adolescent↗

Immediate reactions following challenge-tests in children with atopic dermatitis.

It has been shown that atopic dermatitis improves in children when certain foods are eliminated from the diet. Because of the unreliability of the history and the low sensibility of the total and specific IgE and skin tests, at present the elimination-provocation test is the most definitive means to establish which are the offending food(s). Although many authors claim that reactions following the challenge test in atopic dermatitis are only of the delayed type, others assert that immediate reactions are frequent and can sometimes threaten life. The pathogenesis of such reactions is not yet completely understood. However, it has been suggested that a direct IgE-mediated mechanism, inducing a release of anaphylactic mediators, could play some role. The aim of our study is to investigate the incidence of immediate reactions which can follow the food challenge in children with atopic dermatitis who have never experienced such reactions and, in addition, to investigate the reliability of total and specific IgE and skin tests in predicting immediate reactions after the challenge test. Our preliminary data indicate that immediate reactions following food challenge are frequent. Moreover they can be severe and cannot be predicted by the history, by the total and specific IgE levels and by the skin tests' results.

Animals↗

Expression of T-lineage early developmental markers by cells establishing atopic dermatitis skin infiltrates.

The association between the atopic dermatitis, eczema and T-cell immunodeficiency disorders are well known, thus suggesting that bone marrow T-precursors could use the micro-environment of the skin as an extrathymic site for compensatory ontogenesis. In keeping with this hypothesis, we analyzed the atopic dermatitis skin lymphocytic infiltrate phenotypes to establish their ontogenetic stage of development. Cryostatic sections (4 microns) obtained from acute lesional skin biopsies of six patients with extrinsic atopic dermatitis were processed with indirect immunoperoxidase, using a panel of first-step monoclonal antibodies (mAb) specific to CD104 (integrin beta 4 chain), CD90w (Thy 1 antigen), CD44 (phagocytic glycoprotein-1; Pgp-1), CD1a and the DNA polymerase terminal deoxynucleotidyl transferase (TdT). Within the lymphocytic dermal infiltrate different levels of immunoreactivity were observed with respect to CD104, CD90w and CD1a. A strong, spread staining was also detected for mAb specific to Pgp-1 and TdT. Together, the reported features indicate that the atopic dermatitis skin-homing lymphocytes express immunophenotypes which are distinctive of the early T-ontogeny.

Adult↗

In vitro histamine and serotonin release studies in atopic dermatitis.

6 patients suffering from severe atopic dermatitis with high serum IgE were investigated. 3 of the patients had elevated plasma histamine levels (1.5-2.0 ng/ml). Compared to 9 nonatopic normal volunteers, the patient showed increased in vitro histamine release from peripheral leukocytes after stimulation with iothalamate and methacholine: while there was no significant histamine release at a methacholine concentration of 10(-4) M in normals, 4 of the patients with atopic dermatitis showed measurable histamine release under these conditions in vitro. The uptake of radiolabeled serotonin by platelets in vitro was decreased in 2 of the patients. There was no significant difference in serotonin release induced in vitro by different concentrations of thrombin, epinephrine and methacholine; 2 patients showed an increased platelet release reaction after iodipamide stimulation. It is concluded that a general tendency to release vasoactive mediators, even after 'nonimmunologic' stimulation, might play a role in the pathogenesis of atopic dermatitis.

Adult↗

Optimal management of atopic dermatitis.

Optimal treatment of patients with atopic dermatitis requires the knowledge of its pathogenetic factors and the often time-consuming attention to the course of the disease in each individual patient. In the therapeutic attempt, altered skin barrier function, possible provocation factors and psychological matters have to be taken into account. Basic therapy should comprise optimal skin care and the strict avoidance of triggering factors if possible. During periods of acute exacerbation, topical glucocorticosteroids in combination with classic antihistamines with sedative effects are still the drugs of first choice and will result in the rapid relief of symptoms in most patients. UVA1 phototherapy has proven to be a glucocorticoid-equivalent alternative therapy for exacerbated atopic dermatitis. If superinfection with Staphylococcus aureus is evident, topical antiseptics are useful in treating localized lesions, while a general superinfected eczema should be treated with systemic staphylococcal-effective antibacterials. Cyclosporin or extracorporeal photochemotherapy are reserved for patients with very severe atopic dermatitis that is unresponsive to conventional treatment protocols. Promising future therapeutic approaches consist of an improvement in the antipruritic treatment options, the topical application of immunomodifying treatment modalities or phosphodiesterase inhibitors, and possibly Chinese herbal therapies and psychological intervention strategies.

Dermatitis, Atopic↗

Role of the skin patch test in diagnosing food allergy in children with atopic dermatitis.

UNLABELLED: The aim of the study was to determine peculiarities of food allergy in children with atopic dermatitis and to evaluate the significance of skin patch test in determining the main food allergens. METHODS: One hundred and eight children (57 boys and 51 girls) with atopic dermatitis were examined. Atopic dermatitis was diagnosed by standard diagnostic criteria, severity of the progress of the disease was determined using SCORAD index and the amount of total IgE in blood, skin prick and patch tests with the main food allergens were performed. RESULTS: The age of the patients varied from 6 months to 16 years, however, almost half (41%) of them were toddlers (1-3 years old). Mild form of atopic dermatitis was dominating (52%). Analysis of the total IgE amount in blood showed different degree of sensitivity of the children tested. Normal amount of the total IgE in blood was found in 73.1% of children with atopic dermatitis, and the increased total IgE amount was found only in 26.9% of children. Positive skin prick test with the standard and the most common food allergens was found only in 4.63% of children with atopic dermatitis, while the positive skin patch test with 25 food allergens was found in 68.5% of children. Depending on the type of the allergic reaction, immediate type reaction dominated only in 10.3% of children with atopic dermatitis, while the delayed type allergic reactions were characteristic to food allergies in 48.3% of children with atopic dermatitis. Food allergy was not found in one fifth of children with atopic dermatitis. CONCLUSIONS: Skin patch test is an informative and reliable diagnostic test in evaluating the delayed type allergic reactions. In about half of the tested persons with atopic dermatitis, food allergy appeared in delayed type allergic reactions. Therefore it is very important to do the skin patch test for toddlers and pre-school age children. The most common allergens found with the help of skin patch test are soy, milk, peanuts, carrot, egg whites, wheat, and corn.

Adolescent↗

An assessment of the role of Candida albicans antigen in atopic dermatitis.

An immediate hypersensitivity reaction to Candida albicans (C. albicans) antigen has been observed in patients with atopic dermatitis. Recent data from a comparative study of the immune response to C. albicans antigen in patients with atopic dermatitis and non-atopics suggest a shift form type 1 helper T cells to type 2 helper T cells in the immune response to C. albicans antigen in atopic dermatitis. To delineate the role of C. albicans in the pathogenesis in atopic dermatitis, we evaluated skin reaction of C. albicans antigen, as well as the serum IgE antibody level against C. albicans in patients with atopic dermatitis, patients with nasal allergy, and non-atopics. In addition, the clinical effect of antifungal drugs was evaluated in the patients with atopic dermatitis. As a result, we found that immediate hypersensitivity to C. albicans antigen is strongly correlated with the patients with atopic dermatitis. On the other hand, the delayed-type hypersensitivity to this antigen, which is highly prevalent in atopics without dermatitis as well as non-atopics, was reduced in most of these patients. Antifungal drugs markedly improved the skin manifestations in patients with atopic dermatitis that have IgE antibodies against C. albicans, and the serum IgE levels also decreased. These results suggest that C. albicans antigen is a potent intrinsic factor in inducing skin lesions in atopic dermatitis because of IgE-mediated hypersensitivity of C. albicans antigen.

Adolescent↗

Prevalence and some clinical aspects of atopic dermatitis in the community of Sør-Varanger.

A study of the prevalence of atopic dermatitis among 7-12-year-old children was carried out in a rural community in Northern Norway close to the Russian border. Of the 424 children investigated, 37% had a past and/or present history of atopic dermatitis (cumulative incidence), whereas 23% were classified as having atopic dermatitis by clinical examination (point prevalence). A history of atopic dermatitis during the past year was reported by 26% of the children. Flexural lichenified dermatitis was present in 88%, and 12% of the children had facial and extensor involvement with or without hand dermatitis. Two thirds of the children showed mild and one third moderate symptoms; only 3 children had severe symptoms confirmed by clinical examination. The ratio of girls with atopic dermatitis to boys with atopic dermatitis was about 1.3:1. Onset of atopic dermatitis within the first 2 years of life occurred in 64% of cases, with no sex differences. Remission of atopic dermatitis occurred in 1 of 8 before the age of 5, with earlier cessation in boys. Mucous membrane atopy alone was reported by 13% of them and in combination with atopic dermatitis also in 13%. Parental history of atopic diseases was reported by 37% of all children, more frequently in mothers than in fathers. In families with no parental history of atopic diseases, 41% of the children appeared to develop some kind of atopic disease; this increased to 63% with a single and to 75% with a double parental history.(ABSTRACT TRUNCATED AT 250 WORDS)

Age of Onset↗

Production of interleukin-2 by mononuclear cells in vitro in patients with atopic dermatitis and psoriasis. Comparison with serum interleukin-2 receptor levels.

Atopic dermatitis is associated with profound immunological alterations, in particular decreased lymphoproliferative responses upon stimulation with T-cell mitogens. T-cell blastogenesis involves the production of the soluble cytokine interleukin-2 (IL-2), which in turn upregulates the expression of its own receptor. To investigate the potential role of this cytokine for the pathomechanisms present in atopic dermatitis, 24-h supernatants of PHA-stimulated peripheral blood mononuclear cells from patients with atopic dermatitis (n = 30) of a moderate to severe disease activity were tested for IL-2 activity. In addition, serum concentrations of soluble interleukin-2 receptor (IL-2R) were measured. Non-atopic healthy controls (n = 19) and patients with psoriasis (n = 20), an inflammatory skin disorder with distinct pathogenesis, served as controls. In comparison with psoriasis patients and normal controls, PHA-stimulated mononuclear cells of atopic dermatitis patients released significantly less IL-2 into supernatants. Moreover, there was an inverse correlation between IL-2 concentrations and body surface involvement or serum IgE levels. In contrast, serum IL-2R levels were significantly elevated in both atopic dermatitis and psoriasis, as compared with healthy controls. Furthermore, IL-2R levels in atopic dermatitis patients showed a significant correlation with IgE levels and body surface involvement. The data indicate that T cell activation may occur in both skin diseases. Atopic dermatitis, however, is further characterized by the decreased capacity of mononuclear cells to release IL-2 upon stimulation in vitro.

Adolescent↗

Soluble CD30 plasma concentrations correlate with disease activity in patients with atopic dermatitis.

The levels of soluble CD30 in 79 patients with atopic dermatitis were compared with those found in 54 patients with psoriasis and 36 control individuals (no psoriasis, no atopic dermatitis). In relation to the control group, patients with atopic dermatitis were found to exhibit an increased concentration of sCD30 of at least 1.5-fold (p < 0.001). In addition, sCD30 concentrations were shown to correlate with the severity of the disease as measured by the score index for atopic dermatitis and different stages of disease activity, such as acute, subacute, or chronic forms, and localized or generalized distribution of atopic dermatitis. The application of topical glucocorticoid therapy for a period of 2 weeks resulted in a decrease in the level of sCD30 by 46% in 8 patients, especially in the acute, generalized form of atopic dermatitis. Psoriasis patients showed no significant differences in sCD30 levels in relation to the control group. This study demonstrates a correlation between sCD30 concentration and the activity of the disease and therefore suggests sCD30 as a prognostic marker, being superior to predictions from measurements of IgE or eosinophil cationic protein.

Administration, Topical↗

Common burden of chronic skin diseases? Contributors to psychological distress in adults with psoriasis and atopic dermatitis.

BACKGROUND: Chronic skin diseases, such as atopic dermatitis and psoriasis, are known to affect quality of life by heightening psychological distress. Knowledge about factors contributing to psychological distress is essential for supporting physicians in diagnostic and multidisciplinary treatment options for patients psychologically at risk. OBJECTIVES: To examine whether generic physical, psychological and social factors relevant to patients with chronic diseases might contribute to psychological distress in adults with psoriasis and atopic dermatitis. METHODS: Self-report data on clinical skin status, physical symptoms of itching and fatigue, impact of the disease on daily life, illness cognitions and social support were collected from 128 patients with psoriasis and 120 patients with atopic dermatitis (aged over 16 years). RESULTS: For patients with either skin disease, clinical status and physical symptoms of itching scarcely affected psychological distress. Instead, higher levels of fatigue, perceived helplessness and less social support best predicted psychological distress in patients with both skin diseases in multiple regression analyses. CONCLUSIONS: Results demonstrate that generic physical, psychological and social aspects play a role in chronic skin diseases and suggest that multidisciplinary care for patients with psoriasis and atopic dermatitis can be greatly improved by integrating common screening and treatment components for chronic diseases.

Adolescent↗

High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis.

Recently, it was shown that lesional skin of atopic dermatitis patients expresses low levels of some antimicrobial peptides, compared with psoriasis patients. Here we performed microarray analysis on mRNA from purified lesional epidermal cells of patients with chronic plaque psoriasis and chronic atopic dermatitis, to investigate whether this is a general phenomenon for host defense proteins, and how specific it is for this class of molecules. Microarray data were confirmed on a selected set of genes by quantitative PCR and at the protein level by immunohistochemistry. We found overexpression of many antimicrobial proteins in keratinocytes from psoriatic skin compared with atopic dermatitis skin. Interestingly, we observed that markers of normal differentiation and the activated/hyperproliferative epidermal phenotype were expressed at equal levels. Chronic lesions of psoriasis and atopic dermatitis patients are remarkably similar with respect to cellular proliferation. We conclude that psoriatic epidermis expresses high levels of host defense proteins compared with atopic dermatitis epidermis, and this phenomenon appears to be specific for these proteins. It remains to be investigated whether this is caused by genetic polymorphisms in pathways leading to an epidermal antimicrobial response, or by differences in the cellular infiltrate in psoriasis compared with atopic dermatitis.

Anti-Infective Agents↗

An open study of a lotion formulation to improve tolerance of tacrolimus in facial atopic dermatitis.

BACKGROUND: We identified 19 patients with facial atopic eczema who failed to respond to tacrolimus (FK506) ointment, although tacrolimus ointment has shown excellent benefit for the treatment of recalcitrant facial erythema in most patients with atopic dermatitis. OBJECTIVES: We attempted to determine the efficacy of an original lotion formulation of tacrolimus for facial atopic dermatitis resistant to tacrolimus ointment. PATIENTS/METHODS: Recalcitrant facial erythema of these 19 patients was treated with an original tacrolimus lotion preparation for 6 months. Patch testing with white petrolatum was performed in both the 19 patients and in 30 other atopic dermatitis patients who had experienced excellent results with tacrolimus ointment. RESULTS: Of the 19 resistant patients, those whose symptoms were greatly or moderately improved by the lotion were 95%, 89% and 89% after 2 weeks, 3 months and 6 months of treatment, respectively. Further, patch testing to petrolatum showed positive reactions in several (six of 19) patients, compared with none of 30 controls with atopic eczema that had responded to topical tacrolimus ointment. CONCLUSIONS: The tacrolimus lotion had a significant effect on the recalcitrant facial erythema in adult patients with atopic dermatitis who were resistant to tacrolimus ointment. We suggest that one reason for the unresponsiveness to tacrolimus ointment may be because of contact sensitivity to white petrolatum.

Adolescent↗