Atopic Dermatitis in Childhood and Adolescence

W. Kiess, T. Werfel, J. M. Spergel

• Verlag: S. Karger
• Jahr: 2011
• ISBN:
  9783805595711
• Thema: Medicina
• Thema: Medicina pediátrica

Atopic dermatitis is amongst the most common disorders of the skin in young people around the world. This timely book presents the newest insights and novel concepts in relation to all aspects of this skin disorder. Classification, clinical features and differential diagnosis are reviewed in the first chapter, while risk factors, susceptibility and an epidemiological overview are outlined in the next chapter, followed by a detailed discussion of the immunology of the skin and the pathophysiology of dermatitis. Further chapters present exciting new data delineating clinical aspects of current genetic findings and insights into concepts of neuroimmunology, as well as the very crucial and severe clinical aspect of itching. New data on the topic of inhalant allergy, specific immunologic treatments and the latest on food allergy are also included. A valuable reference for anyone interested in atopic dermatitis, this book is particularly useful for pediatricians and clinical practitioners seeing children and adolescents with atopic dermatitis on a daily basis.

Werfel T, Spergel JM, Kiess W (eds): Atopic Dermatitis in Childhood and Adolescence. Pediatr Adolesc Med. Basel, Karger, 2011, vol 15, pp 64-81

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Role of Food Allergy in Atopic Dermatitis

Jonathan M. Spergel

Children's Hospital of Philadelphia, Allergy Section, Division of Allergy and Immunology, Philadelphia, Pa., USA

Food Allergy Classification

Adverse food reaction is a broad term representing any abnormal clinical response associated with ingestion of a food and they are further classified as food intolerance or food allergy based on the pathophysiological mechanism of the reaction. Food intolerance refers to an adverse physiologic response to a food and may be due to inherent properties of the food (i.e. toxic contaminant, pharmacologic active component) or to characteristics of the host (i.e. metabolic disorders, idiosyncratic responses, psychological disorder), they may not be reproducible and are often dose dependent. It is believed that food intolerance represents the majority of the adverse reactions to food. Food allergy refers to an immunologic response to a food that occurs in a susceptible host. These reactions are reproducible each time the food is ingested and they are often not dose dependent. Based on the immunological mechanism involved, food allergies may be further classified in (a) IgE-mediated, which are mediated by antibodies belonging to IgE and are the best-characterized food allergy reactions, (b) cellmediated when the cell component of the immune system is responsible of the food allergy and mostly involve the gastrointestinal tract, and (c) mixed IgE mediated-cell mediated when both IgE and immune cells are involved in the reaction [1–4].

Pathogenesis

Food allergy is an immunological reaction against a food allergen and is typically IgE mediated, not-IgE mediated (i.e. cell mediated) or mixed IgE and not-IgE mediated.

IgE-mediated classic food allergic reactions are those that are immediate, reproducible, and readily diagnosed by detection of food-specific IgE. In food-allergic individuals, the majority of acute allergic reactions to foods are due to the engagement of allergen-specific IgE antibody with its high-affinity receptor (FcεRI) that is expressed on mast cells and basophils and low affinity receptor (FcεRII), which is present on macrophages, monocyte, lymphocytes and platelets. When a specific antigen binds the IgE linked to the FcεRI, it determines a receptor cross-linking and consequent release of mediators [2, 4]. Even if it was initially thought that mast cells were the principal effector cells in IgE-mediated acute reaction, further studies have shown that basophils play also a major role in acute food allergy symptoms. Indeed, patients with atopic dermatitis (AD) and food hypersensitivity have higher rates of spontaneous release of histamine from basophils that normalizes after the offending food has been removed from the diet. Normal serum tryptase levels (a specific marker of mast cell activation) in patients with food-induced anaphylaxis have been reported on occasions, suggesting an involvement of histamine release from tryptase-negative cells, such as basophils [5, 6] and a role for platelet-activating factor [7].

The intrinsic properties of the food allergens may contribute to whether the allergen favors allergic immune responses. Indeed, relatively few foods (egg, milk, peanut, tree nuts, fish, shellfish, wheat, and soy) account for most of the allergic reactions [8]. Characteristics common to 'major' food allergens are that they are water-soluble glycoproteins, 10-70 kD in size, and are relatively stable to heat, acid, and proteases. In addition, the presence of immunostimulatory factors in the food may also contribute to such a sensitization. For example, the major glycoprotein allergen from peanuts, Ara h 1, is not only very stable and resistant to heat/digestive enzyme degradation but also acts as a TH2 adjuvant due to the expression of a glycan adduct [9]. However, the biochemical characteristics of a food allergen cannot alone explain its allergenicity as only a minority of patients exposed to it develop an allergy. Indeed, the natural consequence of exposure to new foods is tolerance.

Oral tolerance depends on an intact and immunologically active gastrointestinal barrier. This barrier includes the epithelial cells joined by tight junctions and a thick mucus layer, as well as luminal and brush-border enzymes, bile salts, and extremes of pH, which contribute to make antigens less immunogenic. In addition, innate (natural killer cells, polymorphonuclear leukocytes, macrophages, epithelial cells, and Toll-like receptors) and adaptive immunity (intraepithelial and lamina propria lymphocytes, Peyer's patches, IgA, T regulatory cells and cytokines) provide an active barrier to foreign antigens [10–14].

As food allergy is more common in infants [10], higher permeability of the intestinal mucosa in infants and early exposure to allergenic antigens have been proposed as a possible cause of sensitization in infants [10]. However, it has been shown that the gastrointestinal mucosa reaches its maturity in terms of permeability at day 2-3 of life and the increased permeability observed in some children with food allergy is a consequence rather than a cause of the allergic inflammation [10, 11, 15, 16]. In contrast, early exposure to foods might prevent the development of food allergy under some conditions. This is suggested by a recent study that has shown that Israeli children, who frequently consume a popular peanut snack beginning before age 1 year, have a 10-fold lower prevalence of peanut allergy compared with children in the United States and United Kingdom, where peanuts are rarely consumed before the age of 12 months [17]. Additional factors have been proposed as necessary to breach the oral tolerance. A temporary increase of permeability due to an infectious inflammatory process may increase the absorption of allergenic antigens and favor sensitization [11]. Alternatively, sensitization is facilitated if the gastrointestinal barrier is bypassed by presentation of proteins via alternative routes, such as the respiratory tract or skin in AD. Data from murine models demonstrate that epicutaneous application of food proteins may result in very strong allergic sensitization and TH2 inflammation [18]. Indirect evidence in humans of possible skin sensitization to food allergens is a study [19] where an increased risk of peanut allergy in offspring was found to be related with the use of infant skin creams containing peanut and not to maternal peanut ingestion during pregnancy or lactation.

Oral tolerance may also be breached due a TH2-biasing dysregulation of the active immunological barrier that favors sensitization [10–14]. Recent epidemiological studies identify potential environmental influences that may promote such dysregulation, including reduced exposures to bacteria and infections (the 'hygiene hypothesis'), a rise in consumption of omega-6 and decreased consumption of omega-3 polyunsaturated fatty acids, reduced dietary antioxidants, and excess or deficiency of vitamin D [11, 20, 21]. It has been proposed that the TH2 dysregulation is due to an altered equilibrium in the finely regulated relationship between epithelial cells, antigen-presenting cells (dendritic cells) and regulatory T cells that ultimately determine the type of T cell response that a food allergen elicits. Intestinal epithelial cells may act as nonprofessional antigen-presenting cells for T lymphocytes as they express a class II major histocompatibility complex (MHC); however, they lack a 'second signal', essential for T cell expansion after antigen presentation, suggesting their potential role in induction of tolerance to food antigens [13]. Several regulatory T cells have been found to be important for oral tolerance: Th3 cells, a population of CD4+ cells that secrete transforming growth factor (TGF)-β; Tr1 cells, cells that secrete IL-10; CD4+CD25+ regulatory T cells that express the transcription factor FoxP3; CD8+ suppressor T cells; and gamma-delta T cells. The role for regulatory T cells in food allergy comes from a family with severe food allergy carrying with a FOXp3 mutation [22]. Furthermore, increased levels of T regulatory cells have been reported to be associated with acquired tolerance to cow's milk [23].

T cell homing to target organs may explain why some food-allergic diseases are localized and not systemic as in the case of food-associated AD or eosinophilic esophagitis. For example, casein (milk protein)-reactive T cells that can localized to the skin were found in higher concentrations in children with milk allergy and AD, when compared to milk-allergic patients without AD and normal controls [24, 25]. In eosinophilic esophagitis, a gene microarray analysis of esophageal tissue has shown that the mRNA for eotaxin-3 was the most highly upregulated transcript in eosinophilic esophagitis tissue compared to healthy control esophagus and was correlated with tissue eosinophilia [26].

The non-IgE-mediated food allergies represent the minority of immunologic reactions to food and occur in the absence of demonstrable food-specific IgE antibody in the skin or serum. They are less well characterized, but typically are due to an acute or chronic inflammation in the gastrointestinal tract, where eosinophils and T cells seem to play a major role [4, 27, 28]. For patients with food protein-induced enterocolitis, TNF-α appears to have an important role. TNF-α can be cultured in vitro from peripheral blood monocytes in infants with food protein-induced enterocolitis syndrome [29]. Chung et al. [30] also found increased staining for TNF-α in duodenal biopsies of infants with food protein-induced enterocolitis syndrome. For eosinophilic esophagitis, eosinophils and their growth and chemotactic factors play a key...