The hen and the egg question in atopic dermatitis: allergy or eczema comes first

Departmentof Pharmacology, University of Bern, Bern, SwitzerlandKey words: atopic dermatitis; clinical features;constitutional dermatitis; epidemiology; extrinsictype; immunopathology; intrinsic type.Prof. Dr B. Wu¨thrichAllergy Unit, Department of DermatologyUniversity Hospital8091 ZurichSwitzerlandAccepted for publication 22 March 2001

Targeting the skin in atopic dermatitis

Common and distinct roles for TH2 and TFH cells in shaping the spectrum of allergic diseases

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report

Does atopic dermatitis cause food allergy? A systematic review

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011

The Editors' Choice

Background: Atopic dermatitis (AD) and food allergy (FA) are common allergic diseases in early childhood. AD may be concomitant with FA, particularly in young children. Although studies report the prevalence of FA in children with AD, there is insufficient data regarding different phenotypes of FA. Objective: The aim of our research was to determine the prevalence and clinical predictors of different phenotypes of concomitant FA in children with AD. Methods: This cross-sectional multicenter study included patients younger than 24 months old diagnosed with AD, recruited from 14 pediatric allergy centers. Patients were categorized into two groups using skin testing, allergen-specific IgE, and ultimately food challenge testing (FCT): those with FA and those without. Individuals with FA were classified into three distinct phenotypes: IgE-mediated, non-IgE-mediated, and concurrent IgE- and non-IgE-mediated. Results: The data of 530 children [59% male, median-age 7 months (IQR: 5–11)] were analyzed. IgE-mediated FA was found in 28.1% of participants, whereas 22.4% (n = 119/530) exhibited non-IgE-mediated FA. Concurrent IgE- and non-IgE-mediated FA was reported in 12.1% (n = 64/530) of patients. Cow’s milk (69.6%) and egg-white (68.9%) were identified as the most prevalent allergens. Cow’s milk was primarily responsible for non-IgE-mediated and egg-white for IgE-mediated FA. The most significant predictors of FA were severe AD and the presence of blood in stool with odds ratios of 8.25 (95% Cl: 3.04–22.39) and 10.04 (95% CI: 2.03–49.59), respectively (p < 0.01) (p < 0.005). Conclusions: The study’s findings indicate that children with early-onset and mild-to-moderate AD deserve to be comprehensively assessed for FA symptoms. The most significant indicators of concomitant FA in AD patients were the presence of blood in stool and severe AD. It is important to consider that those who exhibit IgE-mediated FA may also have concurrent non-IgE-mediated FA. We underline that it is important to consider that children with AD who exhibit IgE-mediated FA may also have concurrent non-IgE-mediated FA. Addressing these symptoms may assist healthcare practitioners in clinical practice to improve the quality of care for AD patients having FA.

The role of CD30 in atopic disease.

Atopic dermatitis (AD) is a common skin disease which has been known from antiquity. According to the Roman biographer Suetonius, the emperor Augustus suffered from this disease ( 1). The increasing incidence of allergic diseases in general, and especially AD, has recently focused public interest on these diseases. Numerous articles and books by nonmedical professionals, various self-help groups for all kinds of allergic diseases, and even dedicated news groups on the Internet are stressing this phenomenon. The direct cost to treat these disorders, as in the charges of medical professionals and the cost of medication, as well as the indirect socioeconomic cost, e.g., as a result of lost working days, has been calculated to be several hundred million dollars every year in the US and the UK ( 2, 3), and the annual cost to society was put at 7 billion Deutschmarks in Germany ( 4). Despite intensive research and significant progress in the field of immunodermatology, a unifying pathogenetic concept of AD has still not been established. The term "atopy" was coined by Arthur Fernandez Coca and Robert Cooke in a paper, published in 1923, "On the classification of the phenomena of hypersensitivity" ( 5). In general, the atopic diathesis describes a certain morbid susceptibility to hay fever, asthma, and AD but is not regarded as a disease entity in itself. Since atopic subjects develop their diseases at some particular point during their lifetime, it is widely accepted that latent atopy derives from a complex genetic background. Unfortunately, we have no exact marker of atopy. Since the term "atopy" is clinically meaningful and useful, it is widely used in clinical medicine throughout the world. However, there is no generally accepted precise definition of atopy ( 6). During the last 10 years, some excellent textbooks ( 7, 8) and review articles ( 9–12) on the clinical and pathogenetic aspects of this condition have been published. New approaches, which may become important for our understanding of the disease ( 13, 14), as well as novel therapeutic strategies ( 15–17), have evolved in the last decade of the 20th century. This review touches on clinical and therapeutic aspects, but focuses on the current knowledge of the genetic background and immunopathogenesis of AD. AD is a chronic inflammatory skin disease with a wide variety of clinical manifestations. Regardless of the patient's age, mild to severe erythema, scaling, and excoriations that reflect the severe itch are generally present. The distribution pattern of the skin lesions changes during the patient's lifetime from more generalized eruptions with oozing and crusted lesions to the adult distribution pattern of flexural eczema with lichenification and a scaly, xerotic, dry uninvolved skin. This so called "dryness of skin" actually describes the reduced softness, smoothness, and water and lipid content of the skin surface ( 7, 18). The stigmata of an atopic constitution are features known to be characteristic of atopy. Dry skin (xerosis), hyperlinearity of the palms and soles, an infraorbital fold (Dennie–Morgan's sign), white dermographism, facial pallor, orbital darkening, thinning of the lateral part of the eyebrows (Hertoghe's sign), and a low hairline may help the clinician identify atopic patients with a single glance. However, these stigmata are more related to the atopic state and – with the exception of dry skin – are not specific for AD ( 19). A high serum-IgE level can be considered an immunologic stigma of the atopic constitution ( 20). Bacterial superinfection, mostly with Staphylococcus aureus, is the most common complication of AD. An appropriate antibiotic treatment reduces the amount of topical glucocorticosteroids needed to control this exacerbation of disease. A generalized superinfection with the herpes simplex virus, known as eczema herpeticum, or Kaposi's varicelliform eruption, is the most severe and feared complication of AD. Immediate antiviral chemotherapy and hospitalization are needed in most such patients. Widespread infection of AD lesions with human papilloma virus or the molluscum contagiosum virus, known as eczema verrucatum, or eczema molluscatum, are seen less frequently, mostly in younger patients. The diagnosis of AD is easy if the patient presents with lichenified flexural eczema; however, this is not the rule. A thorough history, together with a skillful allergologic workup, should lead to the identification of the individual triggering factors for each patient ( 21). At present, therapeutic options are based on proper skin care, avoidance of individual triggering factors, and transient anti-inflammatory treatment, depending on the actual skin status of the patient. If all disease features are present, AD has a highly characteristic phenotype. Incomplete or minimal disease forms are encountered frequently in clinical practice and lead to a wide gray area of cases that some dermatologists would label as AD and others would not. This may cause a major problem if results are to be compared between different investigators or even different centers. However, the clinical diagnosis of AD is usually much more reliable than the application of diagnostic criteria to an individual patient. Diagnostic criteria for AD have been proposed by several dermatologists. All of these have some major drawbacks, since they are either 1) not widely accepted; 2) too complicated for daily use; 3) too insensitive, because they do not detect mild disease forms; or 4) too unspecific, because they would, for example, identify nickel contact dermatitis in a patient with hay fever as AD. While highly specific criteria provide a good basis for definition of clinical trial populations, their usually low sensitivity makes them unsuitable for epidemiologic use. Essentially, the classical criteria proposed by Hanifin & Rajka in 1980 are still the most widely used to define AD study populations ( 22). The diagnostic criteria developed by Diepgen et al. ( 23) in Erlangen (Germany) seem to have a higher sensitivity and specificity but are not as widely accepted in the medical community. The UK working party's diagnostic criteria, established in Nottingham in 1994 ( 24), have been validated by the proposing authors ( 25). The attempt to validate these criteria by an independent group from Tehran (Iran) in a population sample of 416 patients revealed the high specificity but low sensitivity of these criteria, making them useful for clinical trials, but not for epidemiologic studies ( 26). The usefulness of the newly designed "millennium criteria" ( 27) has still to be confirmed. These criteria raise the issue of the "extrinsic" form, i.e., IgE-associated dermatitis, and the "intrinsic" form, i.e., dermatitis without increased IgE serum level (see below). In conclusion, the choice of the diagnostic criteria used in clinical trails and epidemiologic studies may have a substantial influence on the results. Approximately 20% of patients suffer from a skin disease which clinically resembles the skin lesions and distribution pattern of AD, but is not associated with elevated total serum IgE levels and does not exhibit sensitization to environmental or food allergens. Therefore, the pathogenesis of this "intrinsic" AD (IAD) ( 28) seems to be different from that of the disease known as classical, or "extrinsic", AD (EAD). Diagnostic criteria for IAD have not formally been proposed, but, according to Wüthrich (personal communication) and our own understanding, these should run as follows: a clinical phenotype of AD, fulfilling the diagnostic criteria of Hanifin & Rajka ( 22) low or moderate total serum IgE levels (<200 kU/l) in combination with negative in vitro IgE screening for aeroallergens and food allergens (e.g., SX1-RAST and SX-5 RAST), as well as negative prick test results for standard aero- and food allergens absence of other atopic diseases such as allergic rhinoconjunctivitis or allergic bronchial asthma. Hence, patients may initially be suspected to have IAD, but during the allergologic work-up they may need to be reclassified as having EAD. Recent immunodermatologic investigations show differences in T-cell cytokine secretion, immunohisto-logy, and the immunophenotype of the epidermal dendritic cells between EAD and IAD ( 29, 30). This argues strongly against the hypothesis ( 14) that a mere replacement of aeroallergens by the recently characterized autoantigen Hom s 1 is the basis for IAD. Several epidemiologic studies by different groups have clearly shown the increasing incidence of AD ( 31–34). Furthermore, there is evidence of a higher incidence of AD in second than firstborn children ( 35). This may be causally linked either to the birth rank or to the age of the mother. There is much discussion of the beneficial effects of breast-feeding, but there is no conclusive evidence of this effect from the epidemiologic data available ( 36–39). More recent studies indicate that the most important risk factor for the development of AD is the "Western lifestyle", although we do not know exactly which factor of our sociocultural behavior is relevant to disease development ( 40). The immunohistology of AD is stage dependent and includes spongiosis, epidermal hyperplasia, thickening of the papillary dermis, and parakeratosis, as well as a superficial perivascular inflammatory infiltrate. An unequivocal diagnosis of AD by histologic means alone is difficult for the following reasons: there is already uncertainty about the clinical aspect of the primary lesion scratching and prolonged rubbing of the pruritic skin results in various secondary histologic changes the histopathology of AD shares certain similarities with contact, nummular, and dyshidrotic dermatitis ( 41). Therefore, many authors tend to regard the histologic findings of clinical lesions in AD as nonspecific ( 42, 43). However, epidermal dendritic cell phenotyping, a recently standardized technique based on the flow cytometric analysis of epidermal single-cell suspensions from inflammatory skin lesions, has the advantage of high sensitivity and specificity in combination with the potential to analyze individual skin lesions ( 44, 45). This method is based on the immunophenotype of the two CD1a-positive epidermal cell populations present in inflammatory human skin; namely, Langerhans cells and inflammatory dendritic epidermal cells (IDEC) ( 46). Pathophysiologic puzzle of atopic dermatitis. Circled letters refer to respective pathophysiologic aspects, corresponding to discussion under lettered headings in text. Most of the clinical aspects of AD involve components of the skin immune system. This system may be regarded as the interactive network of all cells and signals that are either resident in the cutaneous environment (static component) or are actively recruited into the skin during inflammatory processes (dynamic component) ( 47, 48). AD has been shown to occur in a previously nonatopic patient after allogenic bone-marrow transplantation ( 49). This key case indicated that a bone-marrow-derived cell plays a pathogenetic role in the formation of AD lesions. An overview of the different pieces from the pathophysiologic puzzle of AD is given in Fig. 1, and the single components will be discussed in the following subsections. There is no doubt of the genetic background in the pathogenesis of AD ( 50). The many genetic studies on AD published have been recently reviewed ( 51). These may be classified into two different approaches: linkage analysis studies and candidate gene studies. The former aim to detect an association of the AD phenotype with any of the chromosome regions. To detect associations with polymorphisms of previously unknown genes, such studies need high numbers of investigations. On the other hand, the candidate gene studies investigate the association of gene polymorphisms of a specific gene with the atopic phenotype ( Table 1) . They are restricted to the investigation of a single, already known gene locus but are easier to perform in limited numbers of patients. Most of these studies focus on components of the skin immune system, such as cytokines or cell-surface receptors. As is the case with many other diseases, HLA-type combinations have been identified with increased frequency in either elevated IgE levels or specific atopic disorders ( 52). However, in subsequent studies, a cosegregation of these markers could not be demonstrated ( 51). This may have been due to the heterogeneous causes of the atopic diseases. In 1968, Szentivanyi proposed his "beta adrenergic blockade theory of the atopic abnormality" ( 53), with reference to a pulmonary atopic disease phenotype with the respective gene located at 5q32–q33. Some reports agree with this hypothesis, but newer data suggest that alteration in the β-adrenergic system is a consequence rather than a cause of respiratory atopic disease ( 54). The association of a gene locus on 5q, encoding the IL-4 gene cluster, has been reported to be associated with the total serum IgE level ( 55), but this could not be confirmed by other investigators ( 56). The gene locus 11q13, a region encoding for the β chain of the high-affinity IgE receptor FcεRIβ, has been linked to the AD phenotype by the studies of Cookson et al. and other groups ( 57, 58). However, this association failed to be confirmed by studies in Japan and the UK ( 59, 60). A gene which has been thought to be specifically linked to AD, but not to other atopic diseases, is that of the mast-cell chymase, encoded at 14q11.2 ( 61, 62). However, this association could not be confirmed by another Japanese study ( 63). In 1998, linkage analysis showed a gene encoded at 16p11.2–12 to be linked to the total serum-IgE level ( 64). This gene region is the location of the IL-4-receptor gene alpha, which is located at 16p11.2–12.1 ( 65). Initially, it was suspected that a mutation putatively leading to increased IL-4 receptor activity (Q576R) could be responsible for elevated IgE secretion ( 66). However, subsequent analyses have shown that polymorphisms affecting at least four different amino acids in the cytoplasmic domain of IL-4Rα may significantly influence the outcome of IL-4 receptor signaling and consequently IgE secretion ( 67). In conclusion, there are numerous reports of associations between gene loci and atopic disease, but contradictory results have frequently been published by rival groups shortly after the first claim of a newly identified locus. In addition, these reports are mostly related to IgE levels, and less frequently to respiratory disease, and are rarely specific to the cutaneous manifestations of AD. Although it had long been postulated that atopic patients may have a defect in the metabolism of essential fatty acids, only in 1982 were reduced levels of prostaglandin (PG) precursors demonstrated in the blood of atopic patients, and a defective delta-6-desaturase function was proposed as the biochemical basis of atopy ( 68). Like other studies, a recently published controlled study could not confirm this impaired delta-6-desaturase activity in allergic schoolchildren ( 69). The phosphodiesterase activity of monocytes from AD patients is higher than that found in nonatopic patients, leading to a decreased level of cAMP and consequently a higher formation of the proinflammatory PGE2 in the affected patients ( 70, 71). PGE2 has been shown to inhibit Th1 responses and to increase the IL-4 production of Th2 cells ( 71). These studies, undertaken in peripheral blood monocytes, are in good accordance with the clinically relevant immune deviation of AD patients but do not explain the eczematous phenotype of cutaneous atopic disease. Furthermore, clinical trials using topical type-4 PDE inhibitors have shown significant, but not dramatic, improvement of skin lesions ( 72). The subdivision of human T cells, based on their cytokine secretion patterns, into the Th1 and Th2 subgroups is generally accepted. After activation, indeterminate T cells (Th0) may be primed to one of the following secretion patterns: Th1 cells produce IL-2 and IFN-γ, and Th2 cells secrete IL-4 and IL-5. On a clinical basis, Th1 secretion patterns are associated with delayed-type hypersensitivity (DTH) reactions such as the tuberculin reaction, whereas the Th2 secretion pattern is associated with IgE-mediated reactions such as exogenous allergic urticaria ( 73). AD is associated with an immune deviation favoring IgE-mediated immune responses in the presence of a certain susceptibility to skin infections, such as bacterial skin infections, common warts, or molluscum contagiosum. If these Th2-like immune responses were the only basis of AD, the phenotype of the cutaneous atopic disease would be urticarial lesions. However, the phenotype of AD resembles a DTH reaction, corresponding to contact dermatitis lesions; i.e., it rather resembles a Th1-mediated skin disease. Mitosis of mast cells has been observed in AD lesions ( 74), suggesting a pathophysiologic role for mast cells in this disease. Furthermore, it has been shown that mast cells may be an initial source of IL-4 in the lesions, a cytokine which may drive the lesional T cells in a Th2 direction ( 75). An increased number of tryptase-positive mast cells lacking anti-inflammatory chymase activity have been demonstrated in nonlesional skin of AD and nummular eczema ( 76), and may be linkable to the mast-cell tryptase proposed as a candidate gene for AD. During their period of maturation, keratinocytes form the stratum corneum of the epidermis. The function of this epidermal barrier is impaired even in the clinically uninvolved skin of AD patients, as may be seen in the increased transepidermal water loss. However, it is unclear whether this peculiar weakness of the epidermal barrier function is the cause or the result of the underlying atopic disease ( 18). Thus, it has remained unclear whether keratinocytes in AD patients have an intrinsic defect that explains these clinically most important features. In this regard, an enhanced production of GM-CSF by keratinocytes from AD patients has been shown in response to IL-1α, and both gene expression and protein release in both atopic and control keratinocytes could be reduced by hydrocortisone ( 77). Furthermore, conditioned medium from PMA-treated keratinocytes from AD, together with exogenous IL-4, could support phenotypic and functional maturation of peripheral blood precursors into dendritic cells ( 77). Enhanced production of GM-CSF by keratinocytes may thus contribute to the establishment and chronicity of AD lesions; in particular, to the increased number and enhanced antigen-presenting function of the dendritic cells. IgE-mediated antigen presentation of (aero-) allergens has been considered a key event in the pathogenesis of AD ( 13). By this mechanism of antigen uptake, antigen-presenting cells may, in the presence of antigen-specific IgE, increase their presenting capacity up to 100-fold. This mechanism, also known as "antigen focusing" or "facilitated antigen presentation", has been shown to be effective by different research groups in different cell systems ( 78–80). Thus, IgE receptors are the connecting link between the specificity-gaining IgE molecules and the antigen-presenting cells. Recent research on the identification and characterization of IgE receptors on the cell surface of the antigen-presenting cells has led to the identification of three different IgE receptors on the cell surface of human epidermal Langerhans cells; namely, the low-affinity IgE receptor CD23/FcεRII ( 81), the high-affinity IgE-receptor ( and the protein ( Therefore, seems to be the most and relevant ( the presentation of allergens to T cells, cells may be to produce high of This IgE may in to the on the antigen-presenting cells, a of antigen flow cytometric has demonstrated a significant of molecules on the epidermal dendritic cells from lesional skin in AD ( 46). the Langerhans cells, a second cell population lacking this Langerhans could be demonstrated the by and ( 46). The immunophenotype and of the cell the have been characterized ( but and function are still under Since a function of the in of Langerhans cells and could be demonstrated ( and both cell have been shown to molecules on their cell surface ( a proinflammatory function of may be is to that not only ( but also which are the relevant cell the the Th2-like immune response during their of the skin into a immune The or flow of aeroallergens or ( 14) into the of antigen presentation may define the pathophysiologic basis of the or of AD frequently seen in patients. The application of aeroallergens such as in the recently standardized atopy test ( that it is to eczematous skin lesions by application of aeroallergens to the skin. on the antigen presentation of AD, the need for an identification of the individual factors in each patient for diagnostic based on the IgE ( 21). of and various may be after a thorough prick test and in vitro IgE diagnostic AD patients frequently are by in the exacerbation of skin lesions, may be from most of these skin lesions, and many of these are of ( On one hand, these are as in the of the complex to the respective antigen-specific T On the other hand, the the complex and are of the complex to all T cells with the of their antigen By these antigen-specific as well as T-cell lead to proinflammatory signals the of the skin immune system, up the of antigen of from this clearly explains the effect seen in an antibiotic or topical treatment of AD. Since the oozing skin lesions of the AD patients provide for these this may be relevant to the of the AD lesions. clinical that factors, such as are important in exacerbation of AD. On the other hand, of the disease has been observed in patients shortly after from a such as a dermatologists are to the exact of between the system and the immune system. is a and found that are associated with Langerhans cells the human epidermis. have shown that may inhibit the antigen presentation by Langerhans cells ( Therefore, may have effects in Furthermore, it has been shown that under appropriate produce i.e., which in seem to the secretion of ( These may be in negative signals the inflammatory reactions in the skin. with a inflammatory and immunologic which have recently been reviewed ( are and However, the exact of the are still under There is no known of AD as However, individual skin lesions may be by a variety of topical treatment of the dry skin in AD with is for the patient but are frequently by and the patients is of the to patients not to this of the skin lesions have application is still the reference standard of anti-inflammatory This is due to the of topical glucocorticosteroids in AD the avoidance of a the wide variety in the therapeutic of the as well as of the which as therapeutic is frequently in AD, a and therapeutic to the topical The is effective as but should be restricted to the more severe forms in adult patients due to the potential of this therapeutic The therapeutic of is to that of but the is and the are still may be a for some patients, but due to the high and of treatment, this should be limited to severe cases ( of human have been in a of patients and not show any ( A highly topical treatment of AD are the recently developed topical of ( The key ( as well as the ( has been shown to be effective in the control of AD, and clinical trials with ( and ( as well as a study with ( have been in this disease. AD is the clinical basis for a number of research The results of epidemiologic investigations in both the intrinsic and the of AD will be of The role of keratinocytes in the and of the inflammatory skin lesions is under clinically research will be needed to increase our current knowledge of in this disease.

Biomarker discovery and food allergy profiling distinguishes DOCK8 deficiency from atopic dermatitis

Dietary prevention of allergy, atopy, and allergic diseases

Atopic dermatitis (AD) has been associated with atopic manifestations (AMs), such as food allergies, asthma, allergic rhinitis, and allergic conjunctivitis. To (1) compare the risk of developing AMs in patients with AD versus those without AD, (2) estimate the incremental costs attributable to AMs in patients with AD, and (3) examine the factors associated with incremental costs. In this retrospective cohort study, the authors used MarketScan research databases containing medical and pharmacy claims with dates of service from January 1, 1999, to December 31, 2004. Patients were considered to have AD if they had at least 1 medical claim with a primary or secondary diagnosis of AD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 691.8x) or contact dermatitis or other eczema of unspecified cause (ICD-9-CM codes 692.9x). To create comparable study cohorts, patients with AD were matched with non-AD patients using propensity scores that represented the likelihood of developing AD as predicted by logistic regression. After propensity score matching, the AD and non-AD cohorts did not statistically differ with respect to age, gender, geographic region, type of health insurance, Charlson Comorbidity Index, or baseline measures of medical and prescription drug utilization. The relative risks of developing AMs in the AD and non-AD cohorts were estimated using competing risk-survival analysis. AM was defined by ICD-9-CM codes for asthma (493.xx), allergic rhinitis (477.xx), allergic conjunctivitis (372.05 or 372.14), and food allergy (693.1x, 692.5x, 995.60). The annual incremental cost attributable to AMs in these AD patients was calculated from medical claims with AM and AD diagnosis codes and from pharmacy claims for prescription drugs used to treat asthma, allergic rhinitis, allergic conjunctivitis, or food allergy, and 95% confidence intervals (CIs) were calculated using the bootstrap method. Patients with AD were significantly more likely to develop AMs than patients without AD (21.8% versus 16.9%, adjusted relative risk [RR] = 1.33, 95% CI, 1.28-1.38). Among AD patients who developed AMs, allergic rhinitis was the most frequent manifestation (66.3%), followed by asthma (24.8%), allergic conjunctivitis (7.6%), and food allergy (1.8%). The incidence and adjusted RRs of developing AM for AD patients versus comparison patients were 5.3% versus 4.5% for asthma (RR = 1.20, 95% CI, 1.12-1.29), 14.6% versus 11.2% for allergic rhinitis (RR = 1.35, 95% CI, 1.29-1.41), 1.6% versus 1.1% for allergic conjunctivitis (RR = 1.50, 95% CI, 1.31-1.72), and 0.3% versus 0.1% for food allergy (RR = 2.35, 95% CI, 1.66-3.32). The annual AD + AM treatment costs for patients with AD increased substantially after they developed AMs. The additional financial burden attributable to AMs was estimated to be $482 per year, an almost 1.5-fold increase compared with AD cost alone (from $338 before AM development to $820 afterward, P < 0.001), with approximately equal distribution of costs between medical services ($243) and prescription drugs ($239). The largest incremental costs were observed in asthma ($973), followed by allergic rhinitis ($341). Patients with AD are significantly more likely to develop AM compared with patients without AD. The total treatment costs for AD patients who developed AMs were nearly 2.5 times the total treatment costs for patients with AD alone.

The Natural History of Atopic Dermatitis and Its Association with Atopic March

Objective To investigate the distribution characteristics in the positive ratio distribution of serum allergen specific immunoglobulin E(sIgE) in atopic dermatitis children with multiple sensitization factors, which could help to assess the atopic condition and offer recommendation for the avoidance of allergens. Methods A total of 90 children with atopic dermatitis were enrolled(male 66, female 24, aged 0.3-16.1 years). All the patients were divided into 3 groups according to the patients' age: 0-3 years old group (48 patients), 4-7 years old group (31 patients), 8-16 years old group (11 patients). The serum sIgE levels of 29 kinds of food and inhalation allergens in each patient were detected by the UniCAP 250 quantified IgE measurement system. Results The positive ratio of each food allergen in all the patients were as follows: 55.6%(50/90 cases) for egg white, 42.2%(38/90 cases) for milk, 32.2%(29/90 cases) for egg yolk, 12.2%(11/90 cases) for shrimp, 11.1%(10/90 cases) for crab, 7.8%(7/90 cases) for chicken, 4.4%(4/90 cases) for fish, 54.4%(49/90 cases) for wheat, 37.8%(34/90 cases) for peanut, 34.4% (31/90 cases) for soybean, 33.3%(30/90 cases) for tomato and 28.9%(26/90 cases) for peach. The positive ratio of each inhalation allergen in all the patients were as follows: 51.1% (46/90 cases) for house dust, 45.6% (41/90 cases) for alternaria alternata, 41.1% (37/90 cases) for dermatophagoides pteronyssinus, 40% (36/90 cases) for dermatophagoides farinae, 33.3% (30/90 cases) for dog dander, 28.9% (26/90 cases) for cockroach, 27.8% (25/90 cases) for cat dander, 21.9% (19/90 cases) for blomia tropicalis, 36.7% (33/90 cases) for ambrosia elatior, 34.4% (31/90 cases) for white ash, 32.2% (29/90 cases) for london plane, 32.2% (29/90 cases) for artemisia vulgaris, 31.1% (28/90 cases) for common silver birch, 27.8% (25/90 cases) for willow, 25.6% (23/90 cases) for mountain juniper, 25.6% (23/90 cases) for humulus scandens and 25.6% (23/90 cases) for chenopodium album. The positive ratios of sIgE for egg white, milk, egg yolk of patients in the 0-3 years old group were higher than those in the 4-7 years old group and 8-16 years old group (χ2=29.27, 15.98, 18.58, all P<0.05). The positive ratios of sIgE for dermatophagoides pteronyssinus, dermatophagoides farinae, blomia tropicalis, cat dander, mountain juniper, humulus scandens of patients in the 8-16 years old group were higher than those in the 0-3 years old group and 4-7 years old group (χ2=12.94, 14.31, 7.77, 7.65, 9.41, 6.93, all P<0.05). The positive ratios of sIgE for food allergens and animal dander in the patients of diagnosed as atopic dermatitis alone were higher than those of diagnosed as atopic dermatitis combined with asthma or allergic rhinitis. The positive ratios of sIgE for common inhalation allergens in the patients diagnosed as atopic dermatitis alone were lower than those diagnosed as atopic dermatitis combined with asthma or allergic rhinitis . Conclusions Allergens such as animal protein, house dust, mites and molds are the main sensitization allergens for atopic dermatitis children with multiple sensitization factors. Atopic dermatitis children in 0-3 years old group often presented sensitive to food allergens, while those in 8-16 years old group are more commonly sensitive to inhalation allergens. Patients diagnosed as atopic dermatitis alone are often presented sensitive to food allergens and animal dander, while those diagnosed with asthma or allergic rhinitis are more commonly sensitive to inhalant allergens. Key words: Atopic dermatitis; Specific immunoglobulin E; Allergen