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Serum eosinophil cationic protein in patients with atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin, frequently associated with a family history of atopy, raised serum IgE levels and other immunological abnormalities. Both eosinophils and their basic proteins have been detected in the skin lesions of AD patients. We measured the levels of eosinophil cationic protein (ECP) in sera of 24 children with AD and found them to be increased, compared to nonatopic controls, both children and adults. High ECP values were also obtained in 3 patients with the hyper-IgE syndrome. However, no direct relationship between IgE and ECP serum levels could be established. We found no correlation between serum ECP and the number of circulating eosinophils, suggesting that part of ECP was produced by cells infiltrating the tissues. Measurement of ECP might represent a noninvasive tool to assess the activity of AD in relation to eosinophil involvement in this disease.

Adolescent↗

CD4+ memory T cells in peripheral blood are not decreased in patients with atopic dermatitis.

Atopic dermatitis (AD) is a severe and chronic eczematous skin disease, to which increased IgE levels and imbalances of CD4+ T cells are related. CD4+ T cells, however, are heterogeneous and include at least two subpopulations being designated as CD4+ naive and memory T cells. They represent sequential maturational stages (naive into memory) in CD4+ T cell development differing in function and phenotype. Of these two subpopulations the CD4+ memory T cell compartment is a potent producer of gamma-interferon which suppresses IgE synthesis in B cells. Therefore, we speculated whether an inborn maturation defect of CD4+ memory T cells causes the increased IgE production in AD. In patients with AD and age- and sex-matched controls (both n = 10) we analyzed the distribution of both subpopulations in peripheral blood by two-color flow cytometry using monoclonal antibodies against the CD4, CD45RA and CD29 antigen. We provide evidence that the numerical values of CD4+ memory T cells and CD4+ naive T cells are equivalent in both groups. This supports the view that functional disturbances of lymphocytes or lymphocyte subsets are responsible for IgE excess and the pathogenesis of AD.

Adolescent↗

Injection of allergen-antibody complexes is an effective treatment of atopic dermatitis.

Atopic dermatitis (AD) can be exacerbated by contact with airborne allergens, amongst which Dermatophagoides pteronyssinus (Dpt) appears to be potentially important. Specific IgE antibodies towards Dpt are often found in AD, and it can therefore be speculated that suppression of the production of anti-Dpt IgE might result in a significant clinical improvement. Complexes of antigen and specific antibodies have been shown to suppress the production of antibody in other systems; we report here the evaluation in an open trial of the capacity of such complexes to improve symptoms of AD. Ten adult patients were enrolled in this study. In addition to satisfying the criteria of AD, they all suffered from a severe disease (more than 20% of the body surface involved) that had been stable for at least the last 2 years. The patients had high titers of total IgE antibodies and specific anti-Dpt antibodies. Allergen-antibody complexes were prepared from Dpt allergens and an excess of autologous specific anti-Dpt antibodies obtained by immunoadsorption. The patients received regular injections of these complexes throughout 1 year, during which clinical parameters of disease intensity, percentage of body surface affected and intensity of pruritus were regularly monitored. A significant clinical improvement was obtained after 3-4 months of therapy and was maintained through the 9th month. After 1 year of treatment, 2 patients were completely free of disease, 4 had residual lesions which continued to improve and 4 patients had a partial recurrence of dermatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

P1D6 inhibits FnBP-induced extracellular proteome remodeling: proteomic evidence for a novel intervention strategy in atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin disorder characterized by skin barrier impairment, chronic inflammation, and intense pruritus. Staphylococcus aureus (S. aureus) critically contributes to its pathogenesis; however, the mechanistic role of its virulence factor fibronectin-binding protein (FnBP) in keratinocytes remains poorly understood. This study used bibliometric analysis and quantitative proteomics to examine the relationship. We first performed a bibliometric analysis, revealing a sustained increase in publications on S. aureus and AD, peaking at 99 articles in 2023, with hotspots focused on skin barrier function, immune inflammation, and pediatrics. Quantitative proteomics was employed to investigate how FnBP reshapes the extracellular proteome and whether the anti-α5 integrin antibody P1D6 exerts interventional effects. HaCaT cells were stimulated with recombinant FnBP alone or in combination with P1D6, followed by data-independent acquisition (DIA)-based proteomic analysis of secretome changes. Proteomic analysis identified FnBP-induced differentially expressed proteins enriched in immune- and barrier-related pathways, including cell adhesion, cell junctions, and VEGFA-VEGFR2 signaling. P1D6 intervention significantly inhibited the secretome profile and identified 241 core responsive proteins, of which approximately 52% returned to baseline levels after intervention (P > 0.05). These proteins were primarily enriched in pathways governing protein homeostasis, folding, proteasomal degradation, and interleukin-7 signaling. Notably, P1D6 modulated the downregulation of ATP5F1B and P4HB, key effectors within the interleukin-7 pathway. This study demonstrates that FnBP remodels the keratinocyte secretome by disrupting protein homeostasis, consequently inducing barrier injury and chronic inflammation related to AD, which can be effectively blocked by P1D6. Combined with bibliometric trends and proteomic evidence, this study focuses on FnBP, an underexplored virulence factor, and provides novel insights into AD pathogenesis and therapeutic interventions.

Humans↗

[Pharmacological profile and clinical effect of tacrolimus ointment (Protopic ointment) for atopic dermatitis].

Atopic dermatitis (AD) is thought to be induced by a complex of various allergic reactions and T cells are implicated in its etiology. Since tacrolimus strongly inhibits T cell activation, tacrolimus ointment has been developed as a novel drug for AD throughout the world. Tacrolimus inhibits mast cell and eosinophil activation and antigen presenting activity of Langerhans cells in vitro. In the in vivo experimental animal models of AD, such as contact and spontaneous dermatitis in mice and repeated hapten treated skin inflammation in rats, tacrolimus ointment showed inhibitory activity. In clinical studies with AD patients in Japan, USA and Europe, tacrolimus ointment showed a marked effect. In comparative studies in Japan, it showed the same efficacy as a strong class steroid ointment on eczema at the trunk and extremities and superior efficacy at the face and neck compared to a medium class steroid. The most prominent adverse event is experienced at the local application site with reactions such as a burning sensation and erythema. Systemic side effects were rarely observed. While there is a possibility of skin infections when using tacrolimus, skin atrophy, even after long term treatment, was not observed. Thus tacrolimus ointment could be an efficient alternative to steroid ointment for AD.

Animals↗

The epidemiology of atopic dermatitis.

Atopic dermatitis is the most common chronic inflammatory skin disease and is a major cause of morbidity and suffering. This review examines its differing prevalence worldwide, its aetiology, and genetics.

Adolescent↗

Long-term safety of tacrolimus ointment in children treated for atopic dermatitis.

Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic inflammatory skin disease that is particularly prevalent in the paediatric population. Emollients and topical corticosteroids have represented the standard of treatment for patients with AD, despite their numerous adverse effects and patients' tendency towards steroid resistance. Topical tacrolimus marks the introduction of an entirely new class of medications, the non-corticosteroid topical immunomodulators. Numerous short- and long-term and ongoing paediatric and adult studies have demonstrated the excellent efficacy and superb safety profile of this anti-inflammatory agent. The authors review many of these landmark studies and discuss the mechanism of action and safety profile of tacrolimus, in the context of the pathophysiology of AD.

Administration, Cutaneous↗

Altered production of immuno-modulating cytokines in patients with atopic dermatitis.

Atopic dermatitis (AD) represents an inflammatory skin disorder which is characterized by many signs of immunodeficiency. Particularly, decreased lymphoproliferative responses upon stimulation with mitogens as well as bacterial antigens were reported repeatedly. Since there is increasing evidence for a network of immuno-modulating cytokines playing a crucial role in the regulation of immunity and inflammation, in the present study we investigated whether an altered production of these mediators is one of the pathomechanisms responsible for the altered immune response in AD. For this purpose the 24-h supernatants of LPS- and PHA-stimulated or unstimulated mononuclear cells (MNC) from patients with AD of a moderate to severe disease activity and from nonatopic healthy controls were tested for Interleukin-1 (IL-1) and Interleukin-2 (IL-2) activity. Whereas supernatants of unstimulated MNC of AD patients and controls did not contain significantly different levels of these cytokines, LPS-stimulated MNC of AD patients released significantly less IL-1 in the supernatants. Similarly, the production of IL-2 by PHA-stimulated MNC of AD patients was significantly decreased in comparison to the controls. Moreover, there was a strong correlation between IL-1 and IL-2 levels. These findings indicate that diminished lymphoproliferative responses in AD may partly be caused by a decreased capacity of MNC to release immuno-modulating cytokines, even upon appropriate stimulation.

Dermatitis, Atopic↗

Food sensitization in infants and young children with atopic dermatitis.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease. Children with AD tend to have a higher prevalence of food allergies. This study investigated the clinical significance of food sensitization in AD patients. A total of 266 AD patients participated in this study. The prevalence of food sensitization and clinically relevant sensitization were compared in the subjects according to their age and AD severity. Sera from all patients were analyzed for food-specific IgE levels using the Pharmacia CAP System FEIA. The serum specific IgE levels for egg, milk, peanut and soybean were measured. Patients were regarded as sensitized to the food if their food-specific IgE levels were above 0.35 kUA/L. Also the food-specific IgE levels, the so-called diagnostic decision point, which is recommended as the clinically relevant level, for clinical food allergy, as suggested by Sampson et al, was used as an alternative method. From the measurement of food-specific IgE antibodies of the four foods, egg was the most highly sensitized and the main causative allergenic food in children with AD. The positive rates of specific IgE to the four major food allergens, and the prevalences of clinically relevant food sensitization, were higher for all foods tested in the group less than 1 year of age, and were significantly higher in moderate to severe AD compared to mild AD in infants and young children. In summary, presence of food specific IgE is prevalent in infants and young children with AD, and clinically relevant food sensitization is important in Korean infants and children with moderate to severe AD.

Child, Preschool↗

Suppression of skin lesions by transdermal application of CpG-oligodeoxynucleotides in NC/Nga mice, a model of human atopic dermatitis.

Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by an elevation of the total IgE level in plasma, the infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 cells. NC/Nga mice kept in conventional conditions are known to develop skin lesions resembling human AD. We examined in this study the alterations of immune response in NC/Nga mice kept in conventional conditions, following transdermal application of CpG-oligodeoxynucleotides (ODN), which plays a critical role in immunity via the augmentation of Th1-type and suppression of Th2-type responses. CpG-ODN remarkably changed the immune response from type Th2 to Th1 as determined from cytokine mRNA and Ab levels. The serum IgE level was decreased and the expression of IgG2a was up-regulated. The application of CpG-ODN to the skin also decreased inflammatory infiltration of mast cells, and suppression in the skin lesions was observed. Furthermore, the generation of regulatory T cells, which are considered immune suppressive T cells, was observed in the skin on treatment with CpG-ODN. These results suggested CpG-ODN is effective for immunotherapy in patients with AD, which is characterized by Th2-dominated inflammation.

Administration, Cutaneous↗

The relationship between allergy, clinical symptoms and bronchial responsiveness in atopic dermatitis.

Atopic Dermatitis (AD) and asthma are closely associated with respect to epidemiology, hereditary factors and occurrence in the same individuals. Bronchial Hyperresponsiveness (BH), the hallmark of asthma, can also be a physiopathological feature of AD, even in the absence of clinical asthma. We studied 78 subjects with AD. A follow-up study was performed in 27 of these. Data on respiratory and dermatologic symptoms were collected by means of a standardized questionnaire. Skin reactivity was evaluated by prick testing, and in 57 subjects BH was assessed with a methacholine test (Mch). Twenty-one subjects had asthma and 36 showed a positive skin reaction. A PC20 FEV1 was measurable in 38 subjects. Males were found more likely to be Mch responders than females (p < 0.05). Mch responders also showed an earlier age at onset of AD than nonresponders (2.1 yrs vs. 6.2, p = 0.03). Determinants of the degree of BH were evaluated by a stepwise multiple regression analysis, taking the log of the slope of the concentration response curve as dependent variable. In the final model we found that the degree of BH was directly related to wheezing (p = 0.0017) and coughing (p = 0.04) and inversely related to lung function (p = 0.0082) and age (p = 0.0008). Neither skin reactivity nor grading of AD were statistically significant. The longitudinal study demonstrated that the courses of AD and BH seem to run parallel only in skin-negative subjects, whereas an increase in BH was observed in skin-positive subjects.

Adolescent↗

Understanding and treating atopic dermatitis.

Atopic dermatitis is a chronic, relapsing inflammatory pruritic skin disease commonly associated with respiratory allergy. The keys to successful management of this disease continue to include accurate diagnosis, hydration of the skin, control of pruritus and infections, appropriate use of topical corticosteroids and emollients, and identification and elimination of exacerbating factors. Treatment can be complicated and educating the patient regarding disease and therapy is critical for success.

Administration, Cutaneous↗

[A relationship between a psychosomatic and a skin condition in patients with atopic dermatitis].

Atopic dermatitis (AD) has been clinically well-known to be frequently exacerbated by some psychosomatic stress. In this study, we examined a relationship between a psychosomatic and a skin condition in patients with AD. Visual analogue scale (VAS) for the grade of general physical condition, mental stress and others were reported daily for themselves, while skin physiological parameters, resident skin bacteria and a psychological questionnaire (POMS) were measured every 2 weeks. It was observed that tense-anxious and depressive scores of POMS tended to correlate with skin conductance, a skin clinical score and a number of total skin bacteria and others. These results suggest that changes of psychosomatic condition reciprocally correlate with the exacerbation and improvement of skin symptom in patients with AD.

Adolescent↗

Pathogenetic mechanisms of atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory disease which results from complex interactions between genetic and environmental mechanisms. An altered lipid composition of the stratum corneum is responsible for the xerotic aspect of the skin and determines a higher permeability to allergens and irritants. Keratinocytes of AD patients exhibit a propensity to an exaggerated production of cytokines and chemokines, a phenomenon that can have a major role in promoting and maintaining inflammation. Specific immune responses against a variety of environmental allergens are also implicated in AD pathogenesis, with a bias towards Th2 immune responses. In particular, dendritic cells expressing membrane IgE receptors play a critical role in the amplification of allergen-specific T cell responses. Cross-linkage of specific IgE receptors on dermal mast cells provokes the release and synthesis of a vast series of mediators. Following their recruitment and activation into the skin, eosinophils are also thought to contribute relevantly to tissue damage. Thus, a complex network of cytokines and chemokines contributes to establishing a local milieu that favors the permanence of inflammation in AD skin.

Allergens↗

[Pathogenesis and guidelines for therapy of atopic dermatitis].

Atopic dermatitis (AD) is regarded as one of type 2 helper T cell (Th2)-mediated diseases. However, our data by in situ hybridization elucidated mRNA expressions of both Th1 and Th2 cyotokine in the lesions of AD. Some work revealed a decrease of Th1 mRNA without a change of Th2 mRNA after remission by therapy. Th1 may closely relate to skin lesions of AD. Our work showed a IL-4 and IL-5 production and a elevated expression of high affinity IgE receptor by eosinophils in the lesions of AD. Uptake of allergens may be mediated by the receptor and may lead to a release of cytokines. A guideline for therapy for AD, supported by a Ministry of Health and Welfare in Japan, is published in 1999. In this paper, the guideline was outlined.

Animals↗

Combination therapy and new directions for managing atopic dermatitis.

Atopic dermatitis is a common skin disease with a complex immunopathology that has a significant impact on the quality of life of patients and their families. Although topical corticosteroids have been the cornerstone of therapy, safety concerns, especially in children, with potent preparations or with chronic use have prompted treatment with various adjunctive therapies. Recently, topical calcineurin inhibitors, including tacrolimus and pimecrolimus, have been shown effective as monotherapy for this chronic relapsing disease.

Adrenal Cortex Hormones↗

[Cyclosporin A in atopic dermatitis].

Atopic dermatitis is a chronic inflammatory skin disease, with inherited predisposition. It has typical morphology and distribution. Patients generally can be controlled with the use of moisturizers and topical steroids. In severe cases, it is recommended the use of alternative management. Cyclosporine is an immunosuppressor drug which inhibit the expression of T activated cells. Many open and placebo-controlled trials have been made evaluating its use, efficacy and security, in adults and children. The results suggest an initial dose of 5-6 mg/kg per day and reducing the amount according to response (load dose and maintenance dose) at long term in order to reach complete remission after withdrawal of treatment and limit adverse effects, like renal toxicity and hypertension. The immunological changes in AD patients treated with cyclosporine include eosinophil count reduction, besides lower levels of E-selectin, and soluble CD30 (known as disease markers), but overall, it corrects the imbalance between Th1 and Th2 response present in these kinds of diseases.

Adult↗