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The immune system has vital functions for homeostasis and host defense. Thus, imbalances of the immune system whether associated with allergy, hypersensitivity, or autoimmunity are of great importance, as is manifest from common diseases such as atopic diseases, urticaria, and angioedema, and drug hypersensitivity reactions. These can affect patients' quality of life and can generate high costs for health care. Epidemiological studies have provided evidence for changing patterns of allergic diseases caused by lifestyle and climate changes which have consequences for medical care. Deeper insights into the pathogenesis of allergic/immunologic diseases, combined with novel technologies, provide improved diagnostic options and treatment measures. This review will summarize novel aspects of the epidemiology, pathogenic mechanisms, as well as disease management in the fields of allergy and clinical immunology. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease presenting with recurrent eczematous lesions and intense pruritus. It is common and affects both children and adults, often beginning in infancy. Due to the unpredictable disease course, its visible skin lesions, itching and scratching followed by sleeplessness, other associated atopic diseases, and behavioral and psychiatric disorders, AD is an immense burden for patients and caregivers. AD is determined by a genetic predisposition characterized by an impaired skin barrier and a T-helper-2-predominant inflammation. Restoration of the skin barrier is the main approach for treating and preventing AD. In order to cope with acute flares, usually topical corticosteroids (TCS) are applied, while topical calcineurin inhibitors (TCI) are used mainly for maintenance therapy. There is a small group of patients who are refractory to TCS and TCI and require systemic immunosuppressive drugs such as ciclosporin. Novel, targeted therapies are under clinical investigation, among which an anti-IL-4/IL-13 receptor antibody has recently been approved in several countries. As we learn to understand the pathomechanisms of AD, the characteristics of the different patient subgroups, and the effectiveness of various targeted therapies, a personalized treatment ensuring the best efficacy and safety and, probably, a disease-modifying effect will result. [ABSTRACT FROM AUTHOR]

Allergic diseases are of great concern because of their high prevalence, which is still rising in several regions, their impact on patients' physical and psychological health, the huge burden they place on patients' quality of life, as well as the socioeconomic consequences that they cause. Recent research has provided new data on both genetic and environmental risk factors of atopic/allergic diseases. The application of new technologies such as "omics" has allowed a better understanding of the pathogenesis and has helped with the identification of therapeutic targets. Immense progress has been made in developing and applying novel, targeted therapies, for example for asthma and urticaria. Intensive efforts are being made to find biomarkers that help to classify patients, to identify their potential responsiveness to specific therapies, and to monitor the disease severity. Based on recent insights in the pathogenesis of food allergy and drug hypersensitivity, novel strategies for diagnostics, allergen avoidance, and induction of tolerance have been developed. Here, we summarize important findings in the field of clinical allergy and immunology with a special focus on asthma, allergic rhinitis, atopic dermatitis, food allergy, urticaria, angioedema, and drug hypersensitivity. [ABSTRACT FROM AUTHOR]

Background: Although allergic mechanisms appear to be important, the pathogenesis of both extrinsic and intrinsic forms of atopic dermatitis (AD) is unknown. Methods: We compared the cytokine production of peripheral blood mononuclear cells of extrinsic AD (EAD) and intrinsic AD (IAD) patients and normal control individuals after stimulation with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAbs) in the presence or absence of anti-CD2-blocking mAb. The cytokine production was measured by immunoassays in supernatants of 24-hour cultures. Results: EAD patients showed a decreased capacity to synthesize interferon gamma and granulocyte-macrophage colony-stimulating factor upon anti-CD3 mAb stimulation as compared with IAD patients. Both EAD and IAD patients demonstrated an increased production of interleukin (IL)-5 and IL-13. As expected, interferon gamma, granulocyte-macrophage colony-stimulating factor, and IL-5 levels were reduced in the presence of anti-CD2-blocking mAbs. CD28 costimulation restored the release in cultures with anti-CD2 mAbs added, suggesting that CD2 and CD28 have redundant functions in T cell activation and subsequent cytokine production. Strikingly, the IL-13 production was not blocked by anti-CD2 mAbs and also not increased by agonistic anti-CD28 mAb, in particular within the EAD patient group. Conclusion: The signalling pathway initiated by the T cell receptor complex leading to increased IL-13 production in AD patients appears to be highly sensitive and is largely independent on CD2 costimulatory signals.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. Methods: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. Results: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. Conclusion: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype. [ABSTRACT FROM AUTHOR]

Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5. In this study, we examined 60 patients with idiopathic eosinophilia. Sixteen patients had circulating T cells with an aberrant immunophenotype that, in most cases, were associated with different forms of skin inflammation. The abnormal T cells produced large amounts of interleukin-5, which may have increased eosinophil differentiation in the bone marrow of these patients.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: An increased expression of interleukin (IL)-15, a cytokine with a key role in stimulating innate and adaptive immune cells, such as dendritic cells (DC), natural killer cells, and T cells, has been observed in infectious and inflammatory diseases, including autoimmune diseases as well as cancer. Atopic dermatitis (AD) is a common inflammatory skin disease characterized by a type 2 immune response. Objective: To explore the expression of IL-15 and its pattern in AD skin. Method: Immunofluorescence staining was performed on skin specimens of AD skin, nonlesional AD skin (AD NL), and normal skin (NS) using antibodies directed against IL-15 and CD3, mast cell tryptase, eosinophil cationic protein, CD68, CD11b, CD1a, and vimentin. Results: A significantly higher IL-15 expression in AD and AD NL was observed in both the epidermis (p = 0.0003) and the dermis (p = 0.0154) as compared to NS. Cells expressing IL-15 were mainly keratinocytes, CD1a+ DC, CD11b+ DC, CD68+ macrophages, and vimentin+ fibroblasts. In AD, an increase in the relative numbers of IL-15 expressing CD1a+ DC, macrophages, and fibroblasts was noted. Conclusion: Our results demonstrate an expression of IL-15 in AD similar to that of eosinophilic esophagitis which is also a type 2 disease. IL-15 may serve as a therapeutic target for AD. [ABSTRACT FROM AUTHOR]

This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU. [ABSTRACT FROM AUTHOR]

Eosinophils and their secretory mediators play an important role in the pathogenesis of infectious and inflammatory disorders. Although eosinophils are largely evolutionally conserved, their physiologic functions are not well understood. Given the availability of new eosinophil-targeted depletion therapies, there has been a renewed interest in understanding eosinophil biology as these strategies may result in secondary disorders when applied over long periods of time. Recent data suggest that eosinophils are not only involved in immunological effector functions but also carry out tissue protective and immunoregulatory functions that actively contribute to the maintenance of homeostasis. Prolonged eosinophil depletion may therefore result in the development of secondary disorders. Here, we review recent literature pointing to important roles for eosinophils in promoting immune defense, antibody production, activation of adipose tissue, and tissue remodeling and fibrosis. We also reflect on patient data from clinical trials that feature anti-eosinophil therapeutics. [ABSTRACT FROM AUTHOR]

Limited evidence is available regarding the effect of partially hydrolyzed whey-based formula (pHF-W) on growth and atopic dermatitis (AD) risk reduction in infants within the general infant population, and without a familial history of allergy as an inclusion or exclusion criterion. We reviewed the current evidence available from studies using pHF-W in the general population and summarized the data on safety (growth) and efficacy outcomes (reduction of AD), comparing the studies side by side. A total of 8 clinical trials were identified from the literature search, 7 of which used the same pHF-W. Six out of 8 studies indicated a reduction of atopic manifestations using a specific pHF-W versus cow's milk formula (CMF) in the first years of life. Data were summarized and compared side by side for growth (3 studies) and efficacy (5 studies). In these diverse general populations, the results on growth and AD were consistent with the previous findings reported on infants with a family history of allergy, but numerous limitations to these studies were identified. This literature review confirms that pHF-W supports normal growth in infants, and suggests that the risk of AD may be reduced in not-fully breastfed infants from the general population when supplemented with a specific pHF-W when compared to CMF during the first 4–6 months of life. Further studies are warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Focuses on a study which explained the existence and activation of CD8+ T cells in eczema lesions contributing to immunoglobulin E production and eosinophil survival and development, chronicity and exacerbation of atopic dermatitis (AD). Classification of AD as a skin disease; Role played by T cells in both AD and contact dermatitis; Way in which additional evidence for in vivo activation of CLA+ T cells appears.