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Background: Peanut and tree nut allergies are common in childhood and often severe in nature. The clinical picture shows a wide variety of symptoms., Objective: To analyze the distribution of clinical symptoms and severity during oral food challenges (OFC) in children., Methods: Analysis of 1.013 prospectively recorded, positive OFCs with peanut (n = 607), hazelnut (n = 266), walnut (n = 97), and cashew (n = 43). Symptoms were categorized as immediate-type skin, gastrointestinal, upper and lower respiratory, cardiovascular symptoms, and eczema exacerbation. Symptom severity and treatment were recorded., Results: Skin symptoms presented in 78%, followed by gastrointestinal (47%), upper (42%), and lower respiratory symptoms (32%). Cardiovascular symptoms presented in 6%. In three-quarter of the reactions, more than one organ was involved. Importantly, severe reactions occurred at every dose level. Peanut- and cashew-allergic patients had a higher relative risk of gastrointestinal symptoms compared with hazelnut- and walnut-allergic patients. Patients without vomiting had a 1.7 times higher risk developing immediate-type skin and/or lower respiratory symptoms. Three-quarter of the patients ever had eczema but worsening presented in only 10.5% of the OFCs. In patients with multiple food allergies, organs involved, eliciting dose and severity differed between allergens., Conclusion: Although comparisons between allergen groups with different clinical history, severity, comorbidities and laboratory data are difficult and might contain bias, our data confirm the high allergenic potential of peanut and tree nuts. The rare occurrence of eczema worsening emphasizes that avoidance diets of peanuts and tree nuts to cure eczema seem to be unnecessary and may hamper tolerance maintenance., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: It has previously been shown in an uncontrolled study that the IgE response to vaccine antigens is downregulated by co-vaccination with cellular Bordetella pertussis vaccine., Methods: In the present study, we compared in a controlled trial the humoral immune response to diphtheria toxoid (D) and tetanus toxoid (T) in relation to co-vaccinated cellular or acellular B pertussis vaccine. IgE, IgG4, and IgG to D and T were analyzed at 2, 7, and 12 months of age in sera of children vaccinated with D and T (DT, N = 68), cellular (DTPw, N = 68), 2- or 5-component acellular B pertussis vaccine (DTPa2, N = 64; DTPa5, N = 65)., Results: One month after vaccination, D-IgE was detected in 10% sera of DTPw-vaccinated children, whereas vaccination in the absence of whole-cell pertussis resulted in 50%-60% IgE positivity. Six months after vaccination, the IgE antibody levels were found to be more persistent than the IgG antibodies. These diphtheria findings were mirrored by those for tetanus. Only minor differences between vaccine groups were found with regard to D-IgG and T-IgG. No immediate-type allergic reactions were observed., Conclusion: Cellular (but not acellular) B pertussis vaccine downregulates IgE to co-vaccinated antigens in infants. We assume that the absence of immediate-type allergic reactions is due to the high levels of IgG antibodies competing with IgE antibodies., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Blinded food challenges are considered the current gold standard for the diagnosis of food allergies. We used data from a pan-European multicenter project to assess differences between study centers, aiming to identify the impact of subjective aspects for the interpretation of oral food challenges., Methods: Nine study centers of the EuroPrevall birth cohort study about food allergy recruited 12 049 newborns and followed them for up to 30 months in regular intervals. Intensive training was conducted and every center visited to ensure similar handling of the protocols. Suspected food allergy was clinically evaluated by double-blind, placebo-controlled food challenges using a nine dose escalation protocol. The primary challenge outcomes based on physician's appraisal were compared to documented signs and symptoms., Results: Of 839 challenges conducted, study centers confirmed food allergy in 15.6% to 53.6% of locally conducted challenges. Centers reported 0 to 16 positive placebo challenges. Worsening of eczema was the most common sign when challenged with placebo. Agreement between documented objective signs and the challenge outcome assigned by the physician was heterogeneous, with Cohen's kappa spanning from 0.42 to 0.84., Conclusions: These differences suggest that the comparison of food challenge outcomes between centers is difficult despite common protocols and training. We recommend detailed symptom assessment and documentation as well as objective sign-based challenge outcome algorithms to assure accuracy and comparability of blinded food challenges. Training and supervision of staff conducting food challenges is a mandatory component of reliable outcome data., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Wheat is one of the most common food allergens in early childhood. In contrast to other food allergies, wheat-specific IgE correlates badly with clinical symptoms and relevant components have been identified mostly for wheat-depended exercise-induced anaphylaxis. Moreover, a high percentage of patients present with immediate type symptoms but wheat-specific IgE cannot be detected with commercial available systems., Objective: We addressed the question whether the IgE recognition pattern between wheat allergic (WA) and clinically tolerant (WT) children differs in order to identify individual proteins useful for component-resolved diagnostics., Methods: Sera of 106 children with suspected wheat allergy, of whom 44 children had clinical relevant wheat allergy and 62 were tolerant upon oral food challenge, were analyzed for wheat-specific IgE using the ImmunoCap system as well as immunoblots against water and salt soluble, and water-insoluble protein fractions. 40 randomly selected sera were analyzed for specific IgE to ω5-gliadin., Results: Sixty-three percent of the WT and 86% of the WA children were sensitized to wheat with >0.35 kUA /l in ImmunoCAP analysis. We could confirm the role of α-, ß-, γ-, and ω-gliadins, and LMW glutenin subunits as major allergens and found also IgE binding to a broad spectrum of water- and salt-soluble protein bands. It is of great importance that wheat allergic and tolerant patients showed IgE binding to the same protein bands. WT and WA did not significantly differ in levels of ω5-gliadin-specific IgE., Conclusions & Clinical Relevance: Children with challenge proven clinical relevant food allergy and tolerant ones had a similar spectrum of IgE binding to the same protein bands. These findings imply that component-resolved diagnostics might not be helpful in the diagnostic work-up of wheat allergy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Many infants with atopic dermatitis (AD) are sensitized against food or airborne allergens. The severity of AD, using the SCORAD, seems to correlate with elevated serum levels of TARC/CCL17. Other chemokines, such as CCL20 or CCL25, have been described in the context of allergic inflammation. The aim of this study was to analyze whether chemokine serum levels differ within a cohort of infants suffering from varying severities of AD with or without allergic sensitization., Methods: Chemokine serum levels (CCL8, CCL17, CCL20, CCL25) as well as food and airborne allergen-specific IgE were analyzed in infants with AD., Results: About 60.9% (78/128) infants with AD (median age 8.8 months, 49 (38%) girls and 79 (62%) boys) showed a positive screening test to common food allergens and 26.6% to common airborne allergens. There was a strong correlation between serum levels of CCL17 and SCORAD in food-sensitized infants (r(s) = 0.646, p = <1e-04) and airborne-sensitized infants (r(s) = 0.587, p = 0.00065) in contrast to non-sensitized ones. Moreover, food-sensitized infants showed significantly higher levels of CCL25 compared to non-food-sensitized ones (p = 0.007)., Conclusion: The strong correlation between TARC/CCL17 and SCORAD in infants with specific sensitizations may be accounted for by the impaired skin barrier. As TARC/CCL17 has been found mainly in the (inflamed) skin but not in the gut, the detection of significantly higher levels of CCL25, ligand of CCR9, localized primarily in the gastrointestinal tract, suggests its impact on food allergen-induced inflammation processes in food-sensitized infants., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This article is the result of consensus reached by a working group of clinical experts in paediatric allergology as well as representatives from an ethical committee and the European Medicine Agency (EMA). The manuscript covers clinical, scientific, regulatory and ethical perspectives on allergen-specific immunotherapy in childhood. Unmet needs are identified. To fill the gaps and to bridge the different points of view, recommendations are made to researchers, to scientific and patient organizations and to regulators and ethical committees. Working together for the benefit of the community is essential. The European Academy of Allergy and Clinical Immunology (EAACI) serves as the platform of such cooperation., (© 2012 John Wiley & Sons A/S.)

Anaphylaxis is the most severe reaction of an IgE-mediated hypersensitivity. Data about affected patients may help to improve our knowledge of anaphylaxis and its medical care. We analysed data from the anaphylaxis registry of German speaking countries with regard to the provoking allergens and treatment modalities of anaphylaxis in children and adolescents. Inclusion criteria were severe systemic allergic reactions with concomitant pulmonary and/or cardiovascular symptoms. The data are collected by a password-controlled online-questionnaire. For this analysis, data of 197 reported anaphylactic reactions from children and adolescents registered between 2006 and 2009 were included. The data show that within the registered cases the most frequently affected organ systems for children and adolescents were the skin (89%) and the respiratory tract (87%) followed by symptoms of the cardiovascular system (47%) and the gastrointestinal tract (43%). The most frequent elicitors were food allergens accounting for 58% of cases, followed by insect venom (24%) and drugs (8%). The most frequent food allergens were peanuts followed by tree nuts and animal related food products. In 18% aggravating factors such as physical exercise were noted by the clinicians. 26% of the analysed patients had experienced more than one reaction. The data regarding the emergency treatment show that antihistamines (87%) and corticosteroids (85%) were often used but that adrenaline was rarely used (22% of the registered cases). Taken together these data show that the analysis of anaphylaxis by registration of affected individuals can provide data about provoking allergens and treatment measures but also suggest the impact of aggravating factors on anaphylactic reactions. The under-represented usage of adrenaline indicates the need of educational measures for patients and their physicians., (© 2011 John Wiley & Sons A/S.)

The recommendation to use sublingual-swallow immunotherapy (SLIT) in children and adults with allergic rhinitis has been established over the past decade. Recently, ultra-rush titration of SLIT has become more and more common, raising concerns about its safety in children with asthma. Fifty-four children with asthma and adolescents aged 6–14 with documented allergic disease because of tree pollen (birch and possibly alder and/or hazel) from 14 study centers in Germany participated in a randomized, double-blind, and placebo-controlled study. Twenty-seven were randomized to receive SLIT with standardized birch pollen allergen extract and the other 27 to receive placebo. An ultra-rush high-dose SLIT titration regimen reaching the maintenance dose of 300 index of reactivity (IR) within 90 min (30–90–150–300 IR) was used. The difference in mean PFR changes during ultra-rush titration between SLIT and placebo was not significant (p = 0.056). A 95% probability that SLIT does not decrease PFR during ultra-rush titration was demonstrated. Neither anaphylactic shock nor else serious systemic reactions to the study drug occurred. No serious adverse event assessed by the investigator as related to study drug treatment was reported.

Natural rubber latex represents a potent allergen, which for many years had an important impact on occupational health problems but especially on certain risk groups such as spina bifida. Luckily, these problems decreased when powder-free, latex-poor gloves were introduced. Latest data show that in children with spina bifida, who grew up completely latex-free from birth on, sensitization to NRL as well as clinical relevant allergy significantly decreased. Furthermore, sensitization to aeroallergens also went down and even the prevalence of allergic diseases decreased significantly to rates of the general population. This new data clearly indicates that potent allergens (such as latex) in high-risk groups (such as spina bifida) can induce sensitization spreading, and corresponding avoidance can reverse this development. In conclusion, it can be stated that 'new' allergies can suddenly arise, there are allergen-specific risk groups, local IgE-production is also possible in the CNS, allergen avoidance can be very effective in terms of primary prevention, sensitization spreading can be made reversible by effective prevention, and finally, certain allergies can luckily become history within a relatively short period of time. Furthermore, these new findings clearly end the debate about whether patients with spina bifida have a disease-inherited risk for allergy to NRL and show that the cause is the meningi and the multiple surgical interventions - and therefore sequelae can be reversed by implementing preventive measures., (© 2010 John Wiley & Sons A/S.)

Psychogenic and functional breathing disorders are common and affect mostly children and adolescents, resulting in considerable morbidity and contributing significantly to patient and physician cost and frustration. The most common non-organic clinical entities are psychogenic cough, throat clearing tic, sighing dyspnoea, hyperventilation syndrome, and vocal cord dysfunction. Combinations of organic respiratory diseases and psychogenic aspects can coincide. The mainstay of the diagnosis of psychogenic and functional breathing disorders is full and meticulously taken history. A list of possible questions is presented. Furthermore, the value of a thorough physical examination is often underestimated. If a diagnosis cannot be made clear enough by history taking and examination alone, some baseline instrumental diagnostics are meaningful. An interview with an experienced clinical psychologist and a visit at the physiotherapist may add further information in some cases. Criteria, which differentiate psychogenic or functional breathing symptoms from organic ones, include no nocturnal symptoms, mostly no typical trigger factors, symptoms may occur suddenly and even at rest, speaking is possible without problems and there are normal diagnostic results during episodes of symptoms. Intensive efforts should be made to diagnose psychogenic and functional symptoms, because this will reduce or eliminate harm, prevent stigmatization and fixation of symptoms and disease, allow an untroubled life (including sports), and prevent patients from undergoing unnecessary and potentially harmful therapies., ((c) 2010 John Wiley & Sons A/S.)

Cow's milk protein allergy (CMPA) is best treated by complete elimination of cow's milk from the diet. For infants with CMPA who cannot be breast-fed, formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow's milk-based formulas. In this study, we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose (eHF) with those who were fed an amino acid formula (AAF). This was a prospective, multi-center, randomized, reference-controlled study. Seventy-seven infants <12 months old with suspected CMPA were enrolled. In 66 of these, CMPA was confirmed by oral challenge in a double-blind, placebo-controlled food challenge (DBPCFC) or by a medical history of severe allergic reaction to cow's milk and a positive skin prick test. These infants were then tested for their reaction to eHF and AAF in a DBPCFC. All infants tolerated both formulas and were randomized to receive either eHF (n = 34) or AAF (n = 32) for 180 days. Growth (weight, length, and head circumference) and tolerance [skin, gastro-intestinal, and respiratory tract symptoms of allergy] were evaluated after 30, 60, 90, and 180 days. There were no significant differences between the two groups in any of the growth measurements. Length and head circumference were similar to Euro-growth standards, but weight was slightly lower. Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups. However, whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF, there was a slight decrease in those fed AAF. Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools. The new eHF is safe and well tolerated in infants diagnosed with CMPA.

Allergy testing is an important pre-requisite for both early identification of infants at increased risk for later development of allergic diseases and for specific allergy treatment including specific allergen avoidance measures, pharmacotherapy and specific immunotherapy. The aim of this study was to investigate the influence of in vitro allergen-specific immunoglobulin E (IgE) testing on the primary care physician's diagnosis and clinical management of children with symptoms of eczema, wheezing/asthma and rhinitis. The trial was a prospective study performed at 14 paediatric primary care practices in Germany, covering 380 children below 6 yr of age. For one group of children the physician received the IgE test results as soon as possible and used them as an additional tool when diagnosing and giving clinical management advice. For the other group of children the IgE test results were not made available to the physician until the children were brought to a second visit, about 7 wk later. When diagnosis was made without access to allergen-specific IgE results, 8% of the children were diagnosed as allergic, 6% as non-allergic and in 86% of the cases the physician was uncertain. With access to allergen-specific IgE results the figures were 13%, 65% and 22%, respectively. Concerning clinical management advice no statistically significant differences between the two study groups were observed. When comparing the first and second visits of the patients coming for a second visit advice to reduce aeroallergen exposure was given to 27% of the patients at visit 1 and to 36% of the patients at visit 2 (p = 0.002). The difference between the first and second visits of the other clinical management advice studied did not reach statistical significance. In this study the availability of IgE test results to the primary care physician had an impact on the decision-making process of the diagnosis but not on the pharmaceutical or avoidance advice given. The reason why IgE test results were not fully exploited needs to be further scrutinized.

Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.

The symptoms of patients presenting with non-allergic food-related reactions may partly mimic allergic responses. Therefore, correct delineation of food allergies is often difficult and various differential diagnoses have to be considered. We describe three cases of differential diagnoses to food-induced symptoms: A 14-month-old with lactose intolerance, an 8-month-old with severe diet-induced malnutrition and subsequent development of kwashiorkor and a 12-yr-old with chronic urticaria due to colouring agents. These cases represent common symptom constellations involving food-induced reactions. A proper and correct diagnosis of food-related symptoms is particularly important for children - not only in order to find the appropriate diet but also to avoid unnecessary exclusion diets, which may lead to severe impairments in growth and development.

The interpretation of the atopy patch test (APT) to foods is not standardized. This study aimed to validate the reading of the APT in terms of the diagnostic accuracy of individual skin signs. Eighty-seven children (mean age 2.4 +/- 2.5 yr, range 0.5-13.5; 57 male) with atopic dermatitis (AD) and suspected food allergies underwent APT to cow's milk, hen's egg, wheat and soy. Twelve-millimetre Finn chambers were applied for 48 h, and results were read after 48 and 72 h. Skin changes were graded for erythema, induration, papule formation and 'crescendo' phenomenon (increase of skin sign severity from 48 to 72 h). Food allergy was assessed by double blind, placebo-controlled food challenges (DBPCFC). Sensitivity, specificity and predictive values were calculated for each skin signs in relation to challenge outcome. Of 165 DBPCFC children, 75 (45%) were positive. The combination of any skin induration plus papules (seven or more), or of moderate erythema plus any induration plus seven or more papules had a positive predictive value (PPV) and specificity for the challenge outcome of 100%; however, the sensitivity was low (8% and 15%). The best diagnostic accuracy for single signs was found for induration beyond the Finn chamber margin (PPV 88%, specificity 99%, sensitivity 9%) and presence of at least seven papules (PPV 80%, specificity 96% sensitivity 21%). Presence of both induration and of at least seven papules at 72 h were the APT skin signs with the greatest diagnostic accuracy for food allergy in children with AD.

Glutathione S-Transferase P1 (GSTP1) is an important enzyme in the detoxification of products of oxidative stress. Several studies have shown an association of the amino acid variant Ile105Val with bronchial asthma and the reaction of the lung to inhalant pollutants. The aim of this study was to test the two known amino acid variants in GSTP1 for association with bronchial asthma and airway hyper-responsiveness in two German pediatric populations. We genotyped Ile105Val and Ala114Val in the Multicenter Allergy Study cohort (85 children with asthma, 123 controls) and asthmatic children from Freiburg (n = 178). We did not find association of either polymorphisms with bronchial asthma or airway hyper-responsiveness. We conclude from our data that polymorphisms within GSTP1 do not play a major role in the development of bronchial asthma in German children.

Histamine plays an important role in the allergic inflammation. Histamin N-Methyltransferase (HNMT) catalyses the major pathway of histamine metabolism in the human lung. A common functional single nucleotide polymorphism (SNP) within the HNMT gene (C314T) was recently related to asthma. We tested this SNP for associations with asthma and asthma associated traits in two German pediatric populations (1. MAS-cohort, n=888, 85 children with asthma; 2. asthmatic children from Freiburg, n=176). Non-asthmatic (n=515) and non-atopic (n=211) children from the MAS-cohort were used as controls. For genotyping melting curve analyses (Light Cycler System) were applied. In contrast to a previous study, no association of the HNMT 314T allele with asthma, bronchial hyperresponsiveness (BHR) or other asthma related phenotypes could be observed in either study population. We conclude that this SNP might not play a major role in the pathogenesis of asthma or BHR in German children.

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.

The role of primary prevention of allergic disease has been a matter of debate for the last 40 years. In order to shed some light into this issue a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. The design of observational and interventional studies was evaluated with relevance to the important factors influencing outcome of studies on allergy development/prevention. in this analysis the statements of evidence as defined by WHO were applied. Best evidence of recommendations are those fulfilling the criteria for statements category 1 and 2 and grade of recommendations A and B as proposed by WHO. This survey include target group for dietary prevention and methods and diagnostic criteria of atopic dermatitis, asthma and food allergy for prevention studies., (Copyright 2004 Blackwell Munksgaard)

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.

Recent studies suggest an association between atopic phenotypes and serum IgE levels. In contrast to asthma, this association has not been proven for atopic dermatitis. For 345 children (mean age 2.9 years), we investigated a correlation of the severity of eczema (defined by SCORAD score) and serum IgE levels. Additionally, the data was analyzed for differences between children with high and low SCORAD quartile. Parameters such as genetic background, the prevalence of other atopic phenotypes such as bronchial asthma, allergic rhinoconjunctivitis, and allergic sensitization were recorded. Our results indicate a significant correlation between SCORAD and serum IgE levels (R = 0.31, p < 0.001), but the standard deviation was large. Children with atopic dermatitis showed a high prevalence of sensitization to foods independent of the IgE levels; children with high SCORAD levels showed a sensitization to aeroallergens significantly more often (p < 0.02). No differences were found in prevalences of atopic family background, or a number of additional atopic symptoms such as asthma and allergic rhinoconjunctivitis. These results suggest that serum IgE levels seem to correlate with the degree of eczema. Children with severe atopic dermatitis and high IgE levels are at risk for sensitization to food allergens and aeroallergens.

Unconventional methods are increasingly used to treat allergic diseases. This article identifies various factors influencing physicians and patients in their choice of treatment and therapist. It is often difficult for patients and physicians to distinguish between the natural course of disease and the effects of medical intervention. The 'placebo-effect' as well as other mechanisms may contribute to the therapeutic success. Chances and risks of unconventional methods are discussed. However, only by considering controlled studies can conventional and unconventional diagnostic and therapeutic methods be advocated on the basis of evidence rather than ideology.

We report on a 13-year-old-boy who had been admitted to our hospital for dyspnea, hypoxia, and pulmonary infiltrates. The diagnosis of allergic alveolitis was based on history (provocation by exposure), lung function tests, bronchoalveolar lavage, and transbronchial lung biopsy. No specific allergen could be identified. Five courses of methylprednisolone pulse therapy (15 mg/kg on three consecutive days) stabilized the patient with normalization of lung function and blood gas analysis. Between pulses the boy returned to his home on a farm without relapse. It is estimated that the effect of a single pulse lasted for at least 2-4 weeks. We conclude that pulse therapy can be used instead of continuous therapy in this rare disease in childhood.

The diagnosis of a functional respiratory disorder is sometimes difficult and time-consuming, because the symptoms often resemble those of organic diseases. The most common entities are hyperventilation syndrome, psychogenic cough, sighing dyspnea, and vocal cord dysfunction. Typical signs are heavy breathing or dyspnea, cough or sneezing, various breathing sounds, tightness of the throat or chest, pain, and fear. Criteria for differentiation include the lack of nocturnal symptoms, the sudden occurrence, no typical trigger factors, the variable duration, a quick regression, and that symptoms do not respond to adequate pharmacotherapy and finally normal results of diagnostic work-up. Therapeutic options comprise psychological intervention (by reassurance, relaxation techniques, and behaviour therapy) and physiotherapy (e.g. breathing therapy, voice training). Intensive efforts should be made to diagnose functional symptoms at an early stage because this will prevent stigmatization and fixation of symptoms and disease, and also prevent children from undergoing unnecessary and potentially harmful therapies.

There are very few case reports on allergic reactions to lychee in the literature - so far only in adults. We report on a 12-year-old girl who developed swelling of lips, pruritus, generalized urticaria and dyspnea 30 min after eating a raw lychee. A second event occurred after eating a piece of cake covered with a fruit cocktail. All other foods were well tolerated. In infancy the girl had suffered from atopic dermatitis, which disappeared in childhood; for the previous 2 yr she had presented with seasonal allergic rhinoconjunctivitis. Upon oral provocation, she developed restlessness, flush, generalized urticaria and inspiratory stridor 50 min after eating half a lychee. The diagnostic work up showed a clear positive skin prick test to raw lychee and specific immunoglobulin E (IgE) in serum to latex but not to lychee. In the cellular antigen stimulation test (CAST) carried out with lychee extracts in several concentrations, the same positive results could be found confirming an allergic reaction. Cross-reactivity of lychee to latex was shown by inhibition experiments using the UniCAP 100-system. In conclusion, it seems worthwhile considering the rare allergy to lychee in the case of unclear food-allergic reactions and lychee should be added to the list of foods cross-reacting with latex.

Several birth cohort studies have been initiated during the past two decades to study environmental and genetic risk factors for atopic dermatitis, asthma and allergic rhinitis. This article summarizes results from the German Multicentre Allergy Study (MAS), which has followed children (initially 1,314) from birth (in 1990) to the present time. The effects of immunizations, allergen exposure, early sensitization patterns as well as upper airway infections on the subsequent development of asthma and atopy at school age are described. Furthermore, candidate gene studies of atopic dermatitis and increased total serum IgE levels on chromosomes 5q, 12q and 17q in MAS-children and their parents are outlined.

Cow's milk allergy/intolerance is treated by complete avoidance of cow's milk proteins. Because cow's milk is an important food for infants, its avoidance may lead to an increased risk of growth impairment. Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow's milk formulate (eHF) in infants with cow's milk allergy/intolerance, little is known about the effects of amino-acid-based formulae (AA) in such infants. We therefore performed a prospective, controlled, multi-center trial to study the efficacy of AA in comparison with eHF, on the growth and clinical symptoms of 73 infants (median age 5.7 months) with cow's milk allergy/intolerance and atopic dermatitis. Cow's milk allergy/intolerance was proven in all infants by double-blind, placebo-controlled food-challenge. We observed a significant improvement in the SCORAD index in both groups, from a mean of 24.6, at entry, to a mean of 10.7 (p < 0.0001) after 6 months. In the AA group there was a significant increase in the length standard deviation score (p < 0.04), whilst there was no difference in the eHF group. The weight-for-length values were stable in both groups. The energy intake during the study was similar in both groups. Both an AA and eHF resulted in a significant clinical improvement in infants with an early onset of symptoms of cow's milk allergy/intolerance. Feeding an AA resulted in improved growth compared with feeding eHF, despite similar dietary intakes, and may therefore be considered as a beneficial alternative in infants with severe cow's milk allergy intolerance.

Patients with spina bifida represent the highest-risk group for developing hypersensitivity to latex. Recognized risk factors for these patients are repeated surgery and an atopic disposition. Our aim was to study the influence of a ventricular shunt as an independent risk factor. One hundred and sixty-one patients with spina bifida (median age 10 years) were investigated for the presence of a shunting device and the number, type and date of previous surgical interventions. Additionally, skin-prick tests and provocation tests were performed in order to classify sensitized and symptomatic latex-allergic individuals. Eighty-eight patients (54.7%) were sensitized; 55 (34.2%) were provocation-positive. Patients with a shunt system had undergone a significantly higher number of surgical procedures (p < 0.0001) and showed significantly higher levels of immunoglobulin E (IgE)-antibodies to latex (p < 0.0001) than patients without a shunting device. The total number of operations correlated significantly with the level of IgE-antibodies to latex in serum (p < 0.0001), whereas the number of shunt operations in patients with a ventricular shunt did not significantly correlate with the degree of sensitization. In conclusion, patients with spina bifida who have a ventricular shunt are at particularly high risk because they undergo a significantly higher number of operations than patients without a ventricular shunt. However, the ventricular shunt does not seem to be an independent risk factor. Furthermore, this study emphasizes that individuals at high risk, such as patients with spina bifida, should be handled latex-free from the very beginning of life.

While there is established data on the value of various assays for determining specific immunoglobulin E (IgE) in serum, little has been reported about semi-quantitative dipstick methods. Therefore, in a pilot study we compared a new dipstick assay (Allergodip) with a well-evaluated commercial assay (Pharmacia CAP-system), in terms of sensitivity and specificity, in sensitized and nonsensitized, symptomatic and non-symptomatic patients with spina bifida. One-hundred and thirty-five patients with spina bifida (median age 10.8 years) were included in this study. Sixty-nine patients (51.1%) were positive in the CAP-system, 61 patients (45.2%) were positive in the Allergodip assay, and 67 patients (49.6%) were positive in a skin prick test with natural rubber latex milk. The concordance between the CAP-system and Allergodip was good. Forty-seven patients (34.8%) showed a positive response to the provocation test. The sensitivity of Allergodip was 85.1% compared with 91.5% for the CAP-system. Specificity was 75.0% for the Allergodip assay and 70.5% for the CAP-system. We conclude that the new dipstick test is a useful screening test for diagnosing sensitization to latex, e.g. when planning surgical interventions. However, in instances of doubtful reactions, discrepancies with clinical features or for scientific work it does not replace quantitative determination of specific IgE.

Diagnostic sting challenges have been shown to provide information on the risk of further anaphylactic reactions to bee stings. We present a follow-up study in wasp venom-hypersensitive children after diagnostic venom extract challenges to analyze their risk of further anaphylactic reactions. Responses were obtained from 104 patients with wasp venom hypersensitivity out of 115 former patients. Only one of the 104 patients showed more than a severe local reaction to the sting challenge irrespective of the performance of a single or sequential challenge; therefore, only one patient received venom immunotherapy. The performance of a diagnostic sting challenge with wasp venom extract in children had a high negative predictive value of 94.6% for the risk of further systemic reactions. This was shown by analysis of later field stings, since 37 children experienced further field stings and only two of these children(5.4%) developed a mild systemic reaction (urticaria) equal to or less severe than the index sting. The value of the venom extract challenge can be interpreted in two ways: either it is less sensitive than a native sting challenge since the rate of systemic reactions to the challenge was very low, or the prognosis of wasp venom hypersensitivity in children is extremely favorable. Since the latter hypothesis is supported by the low incidence of systemic field sting reactions, we postulate that venom immunotherapy is necessary only in a minority of children with wasp venom hypersensitivity with an index sting reaction of Mueller grade I or II. However, the value of venom extract challenges as a general diagnostic instrument in children with Mueller I and II reactions due to wasp venom hypersensitivity may be questioned. It may have a place as a safe procedure in demonstrating to parents and physicians the often self-limiting natural course in most of these children.

Vocal cord dysfunction (VCD) is a paradoxical function of the vocal cords, leading to intermittent predominantly inspiratory dyspnea, but with no response to bronchodilator and anti-inflammatory drug therapy. We report on three children with VCD: 1) A 12-year old boy, who was treated for many years for bronchial asthma and who presented with inspiratory dyspnea and a functional reduction of the inspiratory and expiratory flow-volume curve, 2) a 13-year old girl who was also treated for bronchial asthma on a long-term basis and in whom the paradoxical vocal cord movement could be demonstrated by laryngoscopy, and 3) a 17-year old girl who, besides clinical symptoms of bronchial asthma in her anamnesis, suffered from an intermittent severe inspiratory dyspnea, refractory to bronchodilator treatment. Laryngoscopy proved the diagnosis of VCD. No patient showed a deterioration on discontinuation of their antiasthmatic therapy. VCD is best diagnosed by assessment of the vocal cords during laryngoscopy. The following therapeutic measures are helpful: 1) Demonstration of diagnosis (e.g. videodocumentation of laryngoscopy) and reassurance of patients and parents, 2) speech therapy, and 3) psychological intervention and/or psychotherapy. Our three cases point to a differential diagnosis of recurrent dyspnea in children and adolescents which may be overlooked. It is important to question earlier diagnoses, and to objectively evaluate the type of dyspnea.

The aim of the study was to investigate possible associations between the time course of early sensitization to latex and various life style factors. Of the 398 children from a prospective birth cohort study, 20 (5%) showed specific serum IgE to latex at the age of 5 years. Sensitization started beyond the first year of life and 19 out of 20 sensitized children showed increasing specific IgE-values over time. All 20 sensitized children were atopic (p < 0.00000). Total IgE was significantly higher in the sensitized group (median 394.5 kU/I) than in the non-sensitized group (median 39.2 kU/l) (p < 0.00001). Comparing the latex-sensitized group with the non-sensitized children, there were significantly more operations in the latex group (p < 0.05) during the first 5 years of life. Medical history, certain foods, the use of pacifiers, mattress composition and socio-economic data proved not to be significant risk factors. From our study we conclude that besides the number of operations and an atopic predisposition--no other definite risk factor for developing sensitization or allergy to latex (such as everyday household objects) can be identified in children up to 5 years of age.

Clinical manifestations of cow's milk allergy rarely occur in the first days after birth. We report on a newborn presenting with hemorrhagic meconium in the first hour of life followed by bloody diarrhea in the next few days. At day 14, an elevated total IgE, specific IgE to cow's milk and an eosinophilia in peripheral blood were found. Symptoms disappeared when the milk feed was changed to an extensively hydrolyzed casein-formula. Two challenges with cow's milk formula (on day 30 and at 7 months of age) were followed by recurrence of vomiting, watery diarrhea and failure to thrive. At the age of 17 months cow's milk was tolerated well. Although other pathogenetic mechanisms cannot completely be ruled out, there is strong evidence that cow's milk allergy--induced by intra-uterine sensitization--explains the symptoms in our patient. In conclusion, cow's milk allergy can occur even in the first days of life, and our clinical observation supports the concept of intra-uterine sensitization to allergens.

As natural rubber latex (latex) has become more widespread in our environment, physicians have become increasingly aware of the problem of possible allergic reactions. Many fatal and near-fatal incidents have been reported (mainly during surgery) (1-3) and data has been published on groups frequently exposed to latex, such as patients with spina bifida (4-9), healthcare professionals (10-12) and occupationally exposed persons (13). The incidence of latex allergy in children seems to be increasing (14). Tests are therefore needed which can reliably detect sensitization to latex. Our aim was to compare the diagnostic accuracy of three commercial immunoassays for measuring specific IgE in serum to latex.

In order to study the possible relationship between domestic fungal exposure and sensitization to fungi, the homes of 20 children with allergic diseases (mainly bronchial asthma) were inspected for visible fungal growth and airborne viable fungal propagules were sampled. Inclusion criterion was sensitization to at least one of the tested fungi as shown by proof of specific IgE in serum. Twelve of 19 homes (63%) revealed a considerable amount of viable fungal propagules and/or visible fungal growth. Penicillium, Cladosporium, Aspergillus, Mycelia sterilia and yeasts were most prevalent. There was no clear-cut relationship to serologically proven sensitization.

To study the sensitivity and allergy to latex in children, we investigated sera of 306 atopic and 303 non-atopic children (median age 4.5 years) for specific IgE to latex. In patients with specific IgE to latex, a questionnaire was sent to families and provocation tests were carried out. 60/306 atopic children (20.8%) and 1/303 non-atopic children (0.3%) showed specific IgE to latex in serum. The proportion of atopic, latex-sensitized and provocation positive children was 12/48 (25%). Specific IgE to latex was significantly higher (p < 0.03) in symptomatic compared to non-symptomatic patients. Specificity of a positive history was 92%, sensitivity 50%. Atopic dermatitis tended to be more prevalent among the 12 provocation positive atopic children (75%) compared to 36 provocation negative children (58%). There was a tendency that children of the symptomatic group underwent surgical interventions more frequently compared to non-symptomatic children. In conclusion, latex sensitization and latex allergy seem to have occurred more often in atopic children than previously known. Risk factors for the development of a sensitization to latex are atopy and the clinical diagnosis of atopic dermatitis; risk factors for a clinically manifest allergy to latex are an elevated specific IgE to latex, a positive history upon contact to material containing latex and probably frequent operations. Provocation tests should be performed to plan avoidance measures in latex-allergic children especially before surgical interventions.

To study the time-course of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) during bronchial allergen provocation, we investigated 32 asthmatic children sensitive to house-dust mites as well as 6 non-atopic young adult controls. In all subjects, allergen challenges were performed with house dust mite extracts of Dermatophagoides pteronys-sinus or Dermatophagoides farinae. Blood samples were taken at regular intervals during the 24-h observation period. The individual time-courses of ECP and EPX revealed different characteristic groups of patterns: (1) an isolated early serum peak of both mediators during or within the first 60 min after provocation (2) an early plus a late peak (3) an isolated late peak 12 h after provocation (4) an isolated late peak 24 h after provocation, and (5) no significant variation during the 24-h observation period. The early peak could be due to short-term changes in eosinophil activation, while late peaks may reflect eosinophil proliferation, recruitment, subsequent priming and enhancing of the propensity to release their proteins. ECP and EPX showed a corresponding parallel time-course in nearly all challenges, with EPX-concentration exceeding that of ECP. There was no correlation between ECP/EPX serum concentrations and clinical parameters such as lung function data. From our results we conclude that the striking groups of time-courses of ECP/EPX serum concentration indicate different uniform patterns of eosinophil activation during allergen challenge-but do not predict clinical outcome of provocation. The role of the eosinophil in early asthmatic reactions remains to be established in further studies.

In order to study cell activation in peripheral blood on bronchial allergen provocation up to 24 h, we investigated 32 asthmatic children, sensitive to house-dust mites. Six healthy young adult volunteers served as controls. Lymphocyte subsets (CD3, CD19, CD4, CD8) and activation markers (CD25-T, HLADR-T, CD23) in peripheral blood as well as soluble IL2-R and soluble ICAM-1 in serum were evaluated. In terms of clinical reaction, 23 children exhibited a DAR, 6 an EAR, 6 a LAR and 3 children did not show a bronchoconstrictor response to allergen challenge with house-dust mite extract (NAR). In comparison to controls, asthmatic children showed a significantly higher expression of CD23 on B-lymphocytes (p < 0.05). Other subsets were in the same range in both groups. After provocation there was a significant increase of CD4/CD8-ratio only in asthmatic children. Serum levels of sIL2-R were significantly higher in asthmatic children compared to controls at baseline as well as at 12 and 24 h after provocation, without variation during observation period. No differences were noted for sICAM-1. Our results confirm the hypothesis that lymphocytes, as important cells in regulation of allergic immune response, are recruited into peripheral blood under allergen challenge conditions in sensitized asthmatic children.