A study on 300 asthmatic children, 300 controls and their parents confirms the genetic transmission of allergy and asthma.

BACKGROUND: Several studies have shown the role of genetic factors in allergies, and ascertained that atopic diseases are transmitted by parents, especially by mothers. MATERIALS AND METHODS: In order to explore the genetic risk of a child with a family history (FH) of allergy, we have enrolled into this prospective study 300 children, 173 males and 127 females, aged 3.5 to 7.5 years (median age 4.4 years), that included: family (FH) and personal history skin prick tests (SPTs) and specific IgE (RAST), who attended the Pediatric Allergy and Immunology Division of Rome University because affected with respiratory allergy We have studied the FH of these children asking whether their parents and brothers/sisters had atopic diseases, and detailing whether such diseases were respiratory or food allergies (FA). The parents of all children gave their informed consent. We analyzed data using the X2 method. RESULTS: One hundred and twentyseven parents were atopic (42.3%), in addition to 20 brothers/sisters. In detail 90.2% of fathers, 84% of mothers and 65% of brothers/sisters had asthma or allergic rhinitis (AR). Very less parents had urticaria, especially the mothers and brothers/sisters suffered with atopic dermatitis (AD), and some mothers with FA. In 23 children from these parents most had AD and respiratory allergy. In 300 children comparable for age and sex with no respiratory illness recruited from our out-patient clinic 40 parents, 14 mothers and 26 fathers and 9 brothers/sisters had asthma or AR (p = 0.0001), some fathers had also urticaria and two brothers AD. CONCLUSION: A relevant part of respiratory allergy is not transmitted by mothers. Our prospective study stresses that 42.3% of parents are atopic, and FH of their children was positive for respiratory allergy in 82-92% of cases. Thus respiratory allergy can have an autosomal dominant mode of inheritance, but considering the other atopic diseases, the transmission can be polygenic. The impact of genetic factors in these children is emphasized by the high part of asthmatic brothers/sisters.

Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by qualitycontrol failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen ex-pressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians.

The prick by prick test is safe and reliable in 58 children with atopic dermatitis and food allergy.

The initial diagnostic approach of food allergy (FA) is to take a detailed history and to perform a careful physical examination in the gastrointestinal, cutaneous and respiratory systems. Subsequently, verification of the relationship between the symptom(s) and the ingestion of the offending food(s) is mandatory, and finally determination of the immunologic mechanisms involved with in vivo and in vitro tests should be performed. The diagnosis of FA in infancy and in childhood is a challenge both for the pediatrician and allergist because it can be easily accomplished only when there is a correlation between the ingestion of the offending food(s) and the onset of the symptoms, and when it can be demonstrated that these symptoms are the consequence of an immunological reaction. However the underlying immunologic mechanisms may be difficult to document, and the only immunologic mechanism easily to prove in current practice is the IgE-mediated one. In this paper on 58 food-allergic children and 60 nonatopic controls we demonstrate that the prick + prick (P+P) tests are very effective and easy to perform. In addition we stress that FA cannot be excluded only because skin prick tests (SPTs) are negative, as recently suggested.

Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by quality-control failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen expressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians.

A home-made meat-based formula for feeding atopic babies: a study in 51 children.

BACKGROUND: Several elimination diets have been suggested based on results of skin prick tests (SPTs) or IgE antibodies to foods, thus allowing the identification of the most common offending food(s), including CM (cow's milk), egg, peanut and wheat. But unbalanced, inappropriate dietary manipulation in infants with food allergy (FA) can have critically deleterious consequences. We have investigated the effectiveness of a home-made meat-based formula (HMMBF) (Rezza's diet) in babies with food-induced atopic dermatitis (AD), a common, disabling, chronic disease of infancy. PATIENTS AND METHODS: Rezza's diet was given for two months to 25 infants (median age 6.9 months) affected with AD and FA and the differences of body weight and AD severity score were recorded before and after the diet period. Data were analysed using the T and c2 tests. RESULTS: There was a significant improvement in both the evaluated parameters, whereas in 26 control atopic babies they remained unchanged. CONCLUSION: The results of our study indicate that the HMMBF, also based on the experience of several authors, is a useful oligoantigenic diet for the treatment of food-induced AD, and the prevention of the atopic march.

Neonatal cow milk sensitization in 143 case-reports: role of early exposure to cow's milk formula.

OBJECTIVE: Cow's milk (CM) allergy (CMA) is a disease of infancy, usually appearing in the first months of life. Symptoms triggered by CM at first introduction are not completely defined. The evaluation of infants for possible CMA is one of the more common problems encountered by pediatricians. Purpose of this study was to investigate the prevalence of severe reaction to CM and clinical manifestation triggered by CM administration in the nurseries. MATERIALS AND METHODS: The series includes 143 prospectively studied CM-allergic babies. RESULTS: At the first introduction of CM, at the age of 1-8 months (median 4 months) all infants had immediate symptoms The babies were probably sensitized during the first days of life. Particularly sensitizing appears to be the exposure to CM formulas in the neonatal nursery. DISCUSSION: Little doses of allergens are more sensitizing than larger ones. We provide clear evidence of the immunological effects of oral antigen administration during the neonatal period, and discuss the possible critical allergen transmission to the nursing baby via breast milk (BM).

Allergenicity of a whey hypoallergenic formula in genetically at risk babies: four case reports.

BACKGROUND: Hydrolysate formulas (HF) have been developed with the goal of reducing the allergenicity of cow's milk (CM) proteins, thus providing a suitable formula for feeding babies with CM allergy (CMA). OBJECTIVE: More recently, whey HFs have provoked 208 reactions in babies at high risk of atopy when given for CMA prevention. MATERIAL AND METHODS: We report the clinical and immunologic findings of four babies apparentlly sensitized by a partially whey hydrolysate formula (PWHF) in the nursery. They were exclusively BM (breast milk)-fed by their mothers avoiding highly allergenic foods, but experienced anaphylaxis after a re-feeding with the PWHF. RESULTS: Sensitization to PWHF seems to have occurred in the first days of life. No baby suffered from allergic symptoms during BM-feeding. DISCUSSION: These case reports suggest that a PWHF may be allergenic not only in an already sensitized subject, but also sensitizing in a genetically predisposed baby being immunogenic in the IgE system. These data strongly indicate that maternal diets during BM-feeding, in two instances suggested by family doctors, are effective as a BM complement.

Significant decrease of IgE antibodies after a three-year controlled study of specific immunotherapy to pollen allergens in children with allergic asthma.

BACKGROUND: Specific immunotherapy (SIT) in children being not an optional treatment should be administered as soon as possible, also in children aged 2-3 years, due to the very early asthma and rhinitis onset, contrarily to opponents continuing to stress the danger of anaphylactic reactions without displaying reliable data. MATERIALS AND METHODS: We report 56 children who underwent SIT and 56 controls seen consecutevely at the Allergy and Immunology Division, Department of Pediatrics, University of Rome "La Sapienza". The control group was treated with all appropriate medications. RESULTS: They were highly in favor of SIT with statistically significant differences. We stress that IgE antibodies significantly decreased after treatment only in the study group, and IgG antibodies very significantly increased after treatment only in the study group. DISCUSSION: We demonstrate that SIT is the only treatment which can alter the natural course of respiratory diseases, whereas drugs represent only a symptomatic treatment.

Epidemiology of passive smoke: a prospective study in 589 children.

BACKGROUND: Several studies have found that in children of smoking parents there is an increased incidence of respiratory illnesses and diminished pulmonary function. In infants of smoking atopic parents IgE levels are higher, atopic symptoms start earlier, and children are more likely to wheeze if the mother smokes than if she does not. Maternal smoking of 0.5 packs or more/day was identified as a risk for asthma developing in the 1st year of life. Among the environmental measures of our prevention program there is an absolute prohibition of smoking in the house of a "at risk" baby. MATERIALS AND METHODS: We have studied 289 atopic children, 169 males and 120 females, aged 3.5 to 7.5 years, attending our Division because affected by respiratory allergy. We have asked their parents if they smoked and if there were smoking relatives in their homes, independently of the number or the packs of cigarette smoked. The parents of 300 children comparable for age and sex visiting our outpatient clinic for non respiratory disease served as controls. RESULTS: Smokers were 175 fathers and 109 mothers of the asthmatic children and 153 fathers and 89 mothers of the controls. DISCUSSION: Analysis of data shows that passive smoking is significantly associated with the development of asthma in atopic children, and that males are more at risk than females. We stress that a high number of asthmatic children have atopic, and asthmatic parents. Cigarette smoke is not only a triggering factor of respiratory allergy in babies at risk of atopy, but especially an additional genetic factor, since asthma can be more easily provoked if an atopic parent smokes (more if both parents smoke), and even in children of not atopic, smoking parents.

A prospective study of asthma desensitization in 1182 children, 592 asthmatic children and 590 nonatopic controls.

BACKGROUND: The aim of this prospective study was to evaluate the prevalence of allergic asthma and or rhinitis (AR) in 1182 children. Systemic reactions (SRs) to asthma desensitization, previously, specific immunotherapy (SIT) in children with allergic asthma and or AR are scarcely known. MATERIALS AND METHODS: Since 1999, we have consecutively enrolled all children ranging in age from 3 to 11 years attending our Division because affected with severe asthma (592). Controls were 590 nonatopic children matched for age and sex recruited from our outpatient clinic. The study children were treated with a personalized asthma desensitization, the controls were treated with all usual medications. The parents of all children gave their informed consent. Data were analyzed using the X2 method. RESULTS: The 592 atopic children with severe asthma, 370 males and 222 females, aged 3.5 to 10.5 years, tested positive for Der p and Der f (47.1%) or for pollen allergens (52.9%). We have demonstrated a high increase of ashma incidence, since at the start there were 135 asthmatic children and 215 during 2000, with a 62.5% increase. During 2001 there were 242 children, with a 88.8% increase compared to 1999. All of these children were subjected to asthma desensitization, previously SIT (SARM, Roma). At the third yearly control, the study children had a significantly greater reduction as regards days (p = 0.0001) and nights (p = 0.0005) without asthma and drug usage (p = 0.0003) compared with drug-treated children. The number of SPTs and/or sigE to inhalants also decreased, spirometry data were also notably improved The clinically adverse events only were mild or transient. DISCUSSION: The positive results obtained in this large study add to its safety in our opinion because the children were followed by their doctors also on the basis of "as frequently as needed". Accordingly, the early onset of childhood asthma emphasizes that an early treatment is the only means to significantly abate the march of atopic asthma. We have documented an unexpected prevalence of pediatric asthma that should by evaluated in light of the very early asthma development in children which is present even before asthma would be diagnosed based on clinical symptoms The causes of this dramatic increment (10.4%/month in the last six months) may be identified chiefly in the worldwide increase in air pollution and secondhand tobacco smoke.

Epidemiology of alternaria alternata allergy: a prospective study in 6840 Italian asthmatic children.

BACKGROUND: The prevalence of Alternaria Alternata (AA), a mold causing in children severe asthma is scarcely known, also due to the underdiagnosis of AA allergy, frequently due to multiple sensitizations to molds. OBJECTIVE: To analyze this issue we prospectively studied all children attending our Division between January 4, 1990 and December 31, 1997. METHODS: A total of 6840 children with asthma or allergic rhinitis were evaluated. Diagnosis was established by family and personal history, physical examination, skin prick tests (SPTs) and RAST (Radio Allergo-Sorbent Test) for inhalants including AA. We further evaluated: (1) sensitization only to AA allergens without positivity for additional inhalants; (2) prevalence of AA positivity among children with asthma or allergic rhinitis; (3) concordance between SPTs and RAST for allergy to molds, (4) proportion of children treated with specific immunotherapy (SIT). RESULTS: Among the 6840 children 213 were positive to AA (3.3%), only 89/6840 children (1.3%) had AA monosensitization (p = 0.0001), a concordance between SPTs and RAST was present in 21/89 (23.6%) children (p = 0.0009), and only 9 children out of 89 were SIT treated. Concerning the clinical manifestations, 83 had asthma or allergic rhinitis, and 6 had asthma associated with atopic dermatitis. Family history was positive in 82.9% of children. The mean onset of AA sensitivity was at age 4 for males, and at age 5 for females. CONCLUSIONS: In childhood, AA allergy is a genetic affection. The SPT concordance with history and clinical examination appears to be operative. Due to life-threatening reactions in children with AA allergy, we suggest that those with suspected inhalant allergy be tested with AA allergens, and treated with SIT if positive.

Natural history of cow's milk allergy. An eight-year follow-up study in 115 atopic children.

BACKGROUND: Cow's milk allergy (CMA) is a disease of infancy and usually appears in the first few months of life. The evaluation of infants for possible CMA is one of the more common problems shared by pediatricians. The role of foods in determining and/or aggravating the clinical features of atopic dermatitis (AD) has been stressed in the last decades. OBJECTIVE: The aim of the present study was to investigate, in children with food related AD, the development of tolerance to the offending food(s), clinical or laboratory data to predict the development of food tolerance, and whether there are clinical or laboratory data to predict the onset of respiratory allergy. MATERIALS AND METHODS: In this prospective study we report on 115 babies, first examined at a median age of 6 months, and followed-up for 8 years. We have investigated several factors as predictive of the outcome, as follows: early onset; widespread or not-typical (reverse pattern) skin lesions, family history positive for atopy; persisting FA, high levels of total and specific IgE antibodies, association with CMA and asthma. RESULTS: All these parameters were significantly predictive of a long-term morbidity of AD children with CMA. The median age for tolerance to cow's milk was 7 years + 11 months, to egg 6 years + 6 months, and to wheat 7 years + 2 months. However a great number of both tolerant and intolerant children developed multiple sensitizations. Only 66 children (57%) acquired food tolerance, but there was the onset of asthma in 54% of cases. CONCLUSION: The natural history of CMA is not well-known, since not many related studies have been done in children. The several predictive factors, all in a negative sense, may be the norm in atopic children. We suggest possible areas of intervention in children at risk due to parental atopy. Preventive measures may induce a dramatic improvement in children with food allergy, but we stress that the long-term prognosis is challenging, since asthma prevalence may increase up to 54% during a long follow-up. Therefore, the natural history of IgE-mediated AD in atopic children sensitized to several allergens may be less optimistic than generally reported.

Epidemiology of atopy in 220 children. Diagnostic reliability of skin prick tests and total and specific IgE levels.

BACKGROUND: We have prospectively studied 220 children attending our Division because they suffered from atopic dermatitis (AD), asthma, and allergic rhinitis (AR), to assess the epidemiology of atopic diseases, and effectiveness of the diagnostic tests commonly used in allergic children. METHODS: Among the 220 children there were 142 males (64.5%) and 78 females (35.5%) aged as follows: 57 (25.9%) 0-2 year-old, 48 (21.8%) 2-4 year-old, 49 (22.3%) 4-6 year-old, 66 (30%) >6 year-old. The diagnosis included family and personal history, physical examination, skin prick tests (SPT) and total and specific IgE (sIgE) levels. We tested inhalant and food allergens. RESULTS: There were 101 asthmatic, 88 with AD, and 31 children with AR. The analysis of variance confirmed the age influence of PRIST with a high significance (p=0.0001). SPTs were prevalent in all groups for Der p, but casein only in 1 group, and Lolium perenne only in 2 groups. RAST showed a higher uniformity, that is CM (cow's milk) and egg for one group, Der p and Lolium perenne for the remaining groups Several correlations among diagnostic tests and the age of children were evaluated with the analysis of variance. CONCLUSIONS: We emphasize that atopic diseases are genetically transmitted, that AD develops at a younger age than asthma (p=0.0052), and that SPTs have a greater effectiveness for inhalant allergens, positive at all age levels; in food allergy (FA) SPTs are less adequate and feasible.

Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients.

McKusick-Kaufman syndrome comprises hydrometrocolpos, polydactyly, and congenital heart defects and overlaps with Bardet-Biedl syndrome, comprising retinitis pigmentosa, polydactyly, obesity, mental retardation, and renal and genital anomalies. Bardet-Biedl syndrome is genetically heterogeneous with three cloned genes ( BBS2, BBS4, and MKKS) and at least three other known loci ( BBS1, BBS3, and BBS5). Both McKusick-Kaufman syndrome and Bardet-Biedl syndrome are inherited in an autosomal recessive pattern, and both syndromes are caused by mutations in the MKKS gene. However, mutations in MKKS are found in only 4%-11% of unselected Bardet-Biedl syndrome patients. We hypothesized that an analysis of patients with atypical Bardet-Biedl syndrome and McKusick-Kaufman syndrome (Group I; 15 probands) and patients with Bardet-Biedl syndrome who had linkage results inconsistent with linkage to the other loci (Group II; 12 probands) could increase the MKKS mutation yield. Both mutant alleles were identified in only two families in Group II. Single (heterozygous) sequence variations were found in three Group I families and in two Group II families. Combining these results with previously published data showed that only one mutant allele was detected in nearly half of all patients screened to date, suggesting that unusual mutational mechanisms or patterns of inheritance may be involved. However, sequencing of the BBS2 gene in these patients did not provide any evidence of digenic or "triallelic" inheritance. The frequency of detected mutations in MKKS in Group II patients was 24%, i.e., six times higher than the published rate for unselected BBS patients, suggesting that small-scale linkage analyses may be useful in suitable families.

Immunogenicity of hydrolysate formulas in children (Part 2): 41 case reports.

Hydrolysate formulas (HF) have been developed with the purpose of reducing the allergenicity of cow's milk proteins, thus providing a suitable formula for feeding babies with cow's milk (CM) allergy (CMA). More recently, used for the treatment of CMA HFs have provoked 211 reactions in babies at high risk of atopy . In this paper we report 81 babies, who attended the Allergy and Clinical Immunology Division of the Pediatric Department of Rome University "La Sapienza" (study children) between June 1997 and October 1998, 41 of whom were tested with Nidina HA (a whey partial HF) and 40 with whole CM. Ninety-seven healthy children with no history of atopy of comparable age and sex formed the control group. All study children reacted to Nidina HA and to CM with similar symptoms. All the control babies tested negative. With these 41 case reports the number of reactions to HFs totals 252. These data strongly indicate that partial HFs may be allergenic not only in an already sensitized individual, but also immunogenic in a predisposed baby.

Transgenic foods, pesticides, dioxin, passive smoke. Consequences on breast milk.

In recent years the efforts of companies manufacturing cow milk (CM) formulas have led to the development and availability of special formulas, which have dramatically reduced the morbidity of infants with food allergy (FA). However, the safety of several infants and children with food allergy is put to a severe test by transgenic foods, pesticides, and dioxin entering the scenario, also provoking breast milk contamination. Regarding transgenic foods, it is significant the attitude taken against people attempting to call them Frankenstein food, whereas pesticides and dioxin present in dietary foods for infants and young children, after a first arising of alarmed and inflamed controversies, have almost fallen into oblivion. Several of these substances are able to trigger immune alterations. Recent reports have shown that pears can contain pesticides in 54% of cases, a finding which obliges us to review elimination diets devised for allergic babies. However, these foods are far from being ideal both from the nutritional adequacy and hypoallergenicity; moreover, passive smoke is now a genetic factor. We would like to stress, according to the Latin wisdom that stands on the portal of our Clinic in puero homo, which means. In infant is the seed of the future man, that our goal is not only to reduce morbidity and mortality, but mainly to insure the best quality of life both to infants and adults.

Antihistamines and the torsade de point in children with allergic rhinitis.

Allergic rhinitis (AR) is a very common disease, occurring in approximately 10% of children and up to 20% of adolescents. It is often underdiagnosed and its importance as a cause of morbidity is also underestimated, especially in asthmatic children. It has been estimated that 75% of asthmatic children suffer from AR, and its prevalence has increased during the last years, due to changes in environmental factors. AR may be a cause of serious discomfort for the child as well as for the family. AR may cause several complication, including serous otitis media, abnormal facial development with orthodontic problems, eustachian tube dysfunction and sinusitis. The frequent association of paranasal sinusitis in children with asthma has been observed and sinusitis has been considered a contributing factor in bronchial asthma Second-generation antihistamines are the golden therapy for AR. However, reports of potentially life-threatening dysrhythmias, specifically torsades de pointes, were described. In conclusion, we comment the in vitro inhibition of several ion channels, in particular predisposing the heart to dysrhythmias by terfenadine and astemizole. In this paper we examine recent reports on safety of both cetirizine and loratadine.

Genetically modified foods and children potential health risks.

AIM: Professor Pusztai was publicly humiliated over claims that genetically modified (GM) Frankenstein food may be harmful. He was stripped of his post and described as 'muddled' by his superiors after he referred to experiments in which rats had been damaged when fed genetically-altered potatoes. Who is in an unsound scenario, supported by verbal expressions ("substantially"), should even more expend further effort in conducting scientific investigation into the safety of GM varieties of plants. OBSERVATIONS: Of particular concern is the exposure of infants and children to GM foods (GMFs) because of their possible increased susceptibility for untoward effects. Several examples stress that the ascertainment of human disease emerged after certain materials were widely used. Studies show that some compounds were not adequately tested for toxicity before their commercial introduction, whereas proper premarked testing would have prevented a prolonged exposure. CONCLUSIONS: Too often the toxicity of these substances is untested and the potential hazards that they may pose to children have not been examined. Nobody has evaluated whether intrauterine and infant exposure to GMFs may have profound permanent and irreversible consequences even in adult life. In this paper we analyse issues pertaining to children's health that have been largely ignored.

Pathogenesis of atopic dermatitis (AD) and the role of allergic factors.

OBJECTIVE: In this paper we will demonstrate that the exact pathogenesis of atopic dermatitis (AD) remains enigmatic, however the central defect is genetically determined, and the several dysfunctions we will highlight all point to a vicious cycle of allergen exposure, allergen-specific IgE production, and chronic Th2 cell stimulation. An important role is played by the late phase of IgE-mediated hypersensitivity, and evidence is accumulating that eosinophils actively participate in late phase-allergic reactions also in the skin. OBSERVATIONS: AD is the first atopic disease to appear in the absolute sense: dendritic cells (DC) develop firstly in the skin and then in lung, in addition to homing receptors for T lymphocytes that are selective for skin localizations and not for lung. Among the DC, a primary role is reserved to Langerhans cells (LC) that express E-cadherin, a homophilic adhesion molecule that is prominently represented in epithelia. In addition keratinocytes and the interleukins (IL) they express are capable of activating a host of IgE-bearing cells. CONCLUSION: Although much new information regarding the pathogenesis of AD has evolved over the past several years, the basic underlying etiology of this disorder remains elusive. Preventive measures are the only treatment for AD. We hope that the coming years will witness the development of new strategies for the treatment of AD, aimed at specific targets based on a thorough understanding of its pathogenesis.

Immunogenicity of hydrolysate formulas in children (part 1). Analysis of 202 reactions.

Cow's milk protein hydrolyzed formulas appeared in the 1940s with the aim of decreasing or eliminating the allergenicity of cow's milk proteins, in addition to reducing the risk of sensitization. In recent years, the so-called "hypoallergenic" formulas have been developed. The use of such hydrolyzed formulas is based on the premise that predigested proteins, when fed as amino acids and peptides, provide nutrients in a nonantigenic form. Thus, protein hydrolyzed formulas have been classified as hypoallergenic. These formulas are processed by heat and enzymatic hydrolysis, and the conformational and sequential structures are more or less changed. The formulas contain peptides of lower molecular weight than the native protein source, which are thought to be less immunogenic. Hydrolyzed formulas appear to be nutritionally adequate and infants generally gain weight until they refuse the formula because of its bad taste. However, caution should be taken when such formulas are given for prolonged periods since no data are available on nutritional assessment of infants exclusively fed hydrolyzed formulas for several months. In this paper we report and discuss more than 202 reactions to different hydrolyzed formulas, including cases of anaphylactic shock and apparent life-threatening events. The cross-reactivity between different hydrolyzed formulas and cow's milk proteins, and the potential immunogenicity of such formulas are discussed. We conclude that none of the hydrolyzed formulas are nonallergenic, both for allergic children and for high-risk babies. Moreover, we suggest that double-blind placebo-controlled food challenge studies in larger cohorts of babies evaluated with well-defined and well-validated diagnostic methods may establish a more reliable prevalence of allergy to hydrolyzed formulas.