General paediatricians and the case of resolving peanut allergy

Children with peanut allergy are almost always advised to avoid nuts for life. There have been recent reports from academic centres that in some cases the allergy might resolve and thus these dietary restrictions can be lifted. To evaluate resolution of peanut allergy in a selected group of children in a general paediatric setting. Children 4-16 yr old with a clear history of an allergic reaction to peanuts who had not had any reaction in the previous 2 yr were eligible. Specific immunoglobulin E (IgE) or skin prick test (SPT) at the time of diagnosis was sought. A SPT and specific IgE was then done and if this was 相似文献   

A new model for low-dose food challenge in children with allergy to milk or egg

Background: Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. Aim: To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg. Methods: In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests. Results: Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems.
Conclusion: We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.     

Monitoring of IgE-mediated food allergy in childhood

Background: The prevalence of IgE-mediated food allergy (FA) in childhood varies from 6% to 8% in the first year of life compared to 1% to 2% in adults. In contrast to adults, FA in childhood, often part of the “allergic march”, resolves in more than 85% of children, especially those with hypersensitivity to cow's milk and egg. Aim: This paper explains the rationale for continuing care for childhood FA and describes how children should be monitored for resolution/persistence of FA. Methods: A clinical, multidisciplinary approach and management algorithm based on relevant, peer-reviewed original research articles and reviews using the keywords anaphylaxis, atopic eczema, children, milk allergy, double-blind placebo-controlled food challenge, egg allergy, epinephrine, failure to thrive, food allergy, food challenge, food hypersensitivity, immunoglobulin E, nutrition, natural history, paediatrics, peanut allergy, prevalence, psychosocial factors, quality of life, radioallergosorbent test, and tolerance from years 1966 to 2003 in MEDLINE. Additional studies were identified from article reference lists. Results: A combination of outcome measures, a multidisciplinary approach involving a dietitian and allergy nurse specialist, and a management algorithm are useful tools in clinical management.

Conclusions: Prospective studies of non-selected children, optimally from birth cohorts, are needed to evaluate the effects of such management programmes regarding FA in childhood.     

Parental satisfaction with oral peanut food challenges; perception of outcomes and impact on management of peanut allergy

Nguyen M, Wainstein BK, Hu W, Ziegler JB. Parental satisfaction with oral peanut food challenges; perception of outcomes and impact on management of peanut allergy.
Pediatr Allergy Immunol 2010: 21: 1119–1126.
© 2010 John Wiley & Sons A/S Oral peanut food challenges (OPFC) are the ‘gold standard’ for diagnosing peanut allergy in children. However, there are few data on parental perception of such challenges. We aimed to investigate the parental experience of and satisfaction with OPFC and reported dietary management of children with a history of peanut allergy following OPFC. Telephone interviews were conducted with parents of children who had undergone an open‐label OPFC at a specialist paediatric allergy centre. Forty‐six of 76 eligible parents participated. Of those parents, 54% were very satisfied with the OPFC. The highest levels of satisfaction were reported in relation to (i) clarification of the severity of the child’s peanut allergy (ii) the support provided by staff and (iii) determining the child was tolerant of peanut or assessed to be at low risk of anaphylaxis from accidental peanut exposure. When the outcome of the challenge was perceived to be equivocal, levels of parental satisfaction were lower. Other areas of dissatisfaction included difficulties inducing peanut ingestion, parental distress at seeing their child unwell and perception of inadequate follow‐up. Ninety‐four per cent of parents could not remember the amount of peanut ingested, and 24% could not remember whether management advice was given after the OPFC or reported that none was given. Reported compliance with recalled advice to avoid peanut was found in all cases but one, whilst recalled advice to reintroduce peanuts following a negative challenge was followed in 5/9 cases. Although 12 parents reported that their child had an allergic reaction caused by accidental exposure to peanut since the OPFC, only four were certain peanut was the cause. Comprehensive education, counselling and follow‐up subsequent to an OPFC are required. Parents of children whose challenge outcome is inconclusive should be targeted for support.     

Increasing specific immunoglobulin E levels correlate with the risk of anaphylaxis during an oral food challenge

Background

Oral food challenges (OFCs) are necessary to diagnose food allergies; however, these tests can cause anaphylaxis. Higher specific immunoglobulin E (sIgE) levels to causative food have been associated with a positive OFC. To date, no data have been found to indicate the factors associated with severe symptoms or anaphylaxis among challenge‐positive patients. This study aimed to clarify the association of sIgE with causative foods and anaphylaxis during OFC among the whole study population and challenge‐positive patients.

Methods

This cross‐sectional study collected symptom and severity data between June 2012 and December 2016 during an open OFC to diagnose food allergy or confirm tolerance acquisition. We analyzed the risk factors for anaphylaxis during OFC.

Results

A total of 2272 cases were analyzed (median age: 3.5 years; egg: 1166 cases; milk: 589 cases; wheat: 388 cases; and peanut: 129 cases). Among 979 challenge‐positive patients, anaphylactic reactions were observed in 334 cases. A statistically significant association was observed between anaphylaxis during OFC and higher sIgE levels to causative foods (odds ratio: 2.71, 95% confidence interval: 1.94‐3.78, for the third compared to the first tertile, P‐value for trend <.001). Only gastrointestinal, respiratory, cardiovascular, and neurological symptoms were also statistically significantly associated with higher sIgE levels to causative foods.

Conclusions

The risk of all symptoms, except skin symptoms, during OFCs increased with increasing sIgE levels, and this consequently increased anaphylaxis during OFCs. The mechanism of how sIgE affects the prevalence of gastrointestinal, respiratory, cardiovascular, and neurological symptoms or anaphylaxis is unknown; thus, further study is required.     

Continuing food-avoidance diets after negative food challenges

Negative food challenges for follow-up in patients previously diagnosed with food allergy should logically be followed by a normal diet. However, all patients do not reintroduce the food. The aims of the study were to define the proportion of negative food challenge not followed by a normal diet, and to identify possible reasons for not reintroducing the food. Patients with a negative food challenge were sent a questionnaire by mail. Items in the questionnaire included the symptoms at diagnosis, the duration of the diet, the fear of an accidental reaction during the avoidance diet and how it influenced the social life. Patients were also asked if the food was reintroduced after the negative food challenge, and if not, for which reasons. In 25.4% of the questionnaires (18/71) respondents reported that the food was not reintroduced. Patients with a previous diagnosis of peanut allergy tended to reintroduce the food less frequently than patients allergic to other foods. Girls were found to significantly less frequently reintroduce the food than boys. However, neither the severity of the initial reaction, the anxiety of an accidental reaction during the avoidance diet, nor a prolonged avoidance diet did influence the decision to reintroduce the food. Among other reasons listed, fears of persistence of allergies, with recurrent pruritus or non-specific skin rashes after eating the food, were reported in 12.7% of the total number of questionnaires. Patients who reintroduced the food reported that their social life generally improved. One quarter of previously allergic patients continue a food avoidance diet despite a negative challenge. We suggest reassessing food consumption in all patients after a negative food challenge, and in those still avoiding the specific food to consider a repeated challenge test.     

Prevalence of intolerance to food additives among Danish school children

The prevalence of intolerance to food additives was assessed in a group of unselected school children aged 5–16 years. A study group of 271 children was selected on the basis of the results of a questionnaire on atopic disease answered by 4, 274 (86%) school children in the municipality of Vihorg. Denmark. The children in the study group followed an elimination diet for two weeks before they were challenged with a mixture of food preservatives, colourings and flavours. The challenge was open and the additives were prepared as a fizzy lemonade. If the open challenge was positive, a double-blind placebo controlled challenge with gelatine capsules was perfomed. The study included 281 children. 10 were excluded, and the remaining 271 children were given the open challenge (98 healthy controls and 173 with atopic symptoms). The open challenge was negative in all 98 healthy control children who had not reported any atopic symptoms. of the 173 children reporting present or previous atopic disease 17 had a positive open challenge. Of these 17 children 1 experienced gastrointestinal symptoms, 13 reacted with aggravation of atopic eczema, and 3 with urticaria. Twelve of these 17 children went through the double-blind challenge which was positive in 6 cases. Five of these 6 children had positive reactions to synthetic colourings and l to citric acid. No serious reactions were seen. Based upon calculations of the results from this study and an earlier multi-center study in children referred to hospital clinics, the prevalence of intolerance to food additives in school children is estimated to be 1-2%.     

Safe immunization of allergic children against measles, mumps, and rubella

A series of 135 subjects (134 children and one adult) with documented or suspected systemic allergy were prick-tested before a measles, mumps, and rubella (MMR) vaccination. Atopic eczema was documented in 68, asthma in 47, and cow's-milk allergy in 11 examinees; eight children were evaluated because of severe systemic reactions following diphtheria-pertussis-tetanus, measles, or inactivated polio (Salk) vaccinations. In one child, there was only a suspicion of general allergy. The undiluted MMR prick test gave negative reactions in 126 cases (93%). The highest rate of nonreactivity was observed in those with atopic eczema (96%) and in children with asthma (91%) or cow's-milk allergy (82%). All examinees with systemic reactions after other vaccinations also had negative prick-test reactions. A total of 122 (95%) of the 129 examinees were eventually vaccinated with MMR. No untoward reactions developed, except mild generalized urticaria or fever in two vaccinees. We conclude that at least 95% of children with common forms of systemic allergy can be vaccinated safely with MMR and, in general, that allergic diseases should not interfere with execution of the vaccination programs.     

Follow‐up of patients with uncertain symptoms during an oral food challenge is useful for diagnosis

Background

Uncertain symptoms often emerge during an oral food challenge (OFC), and Open‐OFCs with those uncertain mild symptoms are ordinarily regarded as positive. Double‐blind placebo‐controlled food challenges should be conducted to determine these associations. Nevertheless, studies regarding the diagnosis of uncertain food allergy symptoms are lacking. We examined the diagnostic decision for a food allergy based on uncertain symptoms during an Open‐OFC.

Methods

We conducted an Open‐OFC between August 2005 and April 2012 with 2271 cases who suspected as allergic to hen's eggs, cow's milk, or wheat. For the primary diagnosis, Open‐OFCs with obvious symptoms were classified as “positive,” no symptoms as “negative,” and uncertain, indeterminate symptoms as “uncertain.” We encouraged the children in the uncertain group to consume the causative foods at home more than twice; if any definitive symptoms were induced, children were classified as “intolerant,” and children without any symptoms were classified as “tolerant,” for the final diagnosis.

Results

We analyzed 454 uncertain cases excluding 781 positive cases and 1036 negative cases. The symptoms that occurred for the uncertain cases included slight abdominal pain, localized skin rash, and an isolated cough. Of these cases, 362 (79.7%) were considered tolerant at the final diagnosis. Of the intolerant children at the final diagnosis, the induced symptoms at home were not serious.

Conclusions

Monitoring of recurring symptoms following consumption of causative foods at home by patients with uncertain symptoms improves the diagnostic accuracy of an Open‐OFC.     

The Prevalence of food hypersensitivity in young adults

A rising prevalence of food hypersensitivity (FHS) and severe allergic reactions to foods have been reported in the last decade. However, little is known on the prevalence in young adults. This study estimated the prevalence of FHS to the most common allergenic foods in an unselected population of young adults. We investigated a cohort of 1272 young adults 22 years of age by questionnaire, skin prick test (SPT) and histamin release (HR) followed by oral challenge to the most common allergenic foods. FHS was divided into primary and secondary FHS. Primary FHS was defined as being independent of pollen sensitization, whereas secondary FHS was defined as reactions to pollen related fruits and vegetables in pollen allergic patients. The questionnaire was returned by 77.1%. Primary FHS was reported by 19.6% and secondary FHS by 16.7% of the participants. Confirmed primary FHS by oral challenge was 1.7% [1.1% - 2.95%]. In primary FHS, the most common allergenic food was peanut (0.6%) followed by additives (0.5%), shrimp (0.2%), codfish (0.1%), cow's milk (0.1%), octopus (0.1%) and soy (0.1%). In secondary FHS, kiwi allergy was reported by 7.8% of the participants followed by hazelnut (6.6%), pineapple (4.4%), apple (4.3%), orange (4.2%), tomato (3.8%), peach (3.0%) and brazil nut (2.7%). This study found a 1.7% [1.1% - 2.95%] prevalence of primary FHS confirmed by oral challenge to the most common allergenic foods in an unselected population of young adults.     

Patterns of food hypersensitivity during sixteen years of double-blind, placebo-controlled food challenges

For 16 years the double-blind, placebo-controlled food challenge (DBPCFC) has been used at the National Jewish Center for Immunology and Respiratory Medicine to determine whether adverse reactions to foods do occur in children. The objective of these studies was to explore these reproducible adverse reactions and to characterize them. Although skin testing was performed on all subjects, a history of an adverse reaction to food and to subsequent DBPCFC were the only criteria for entry into this study. Of 480 children studied, 185 (39%) have had positive DBPCFC results. In these 480 children, 245 (24%) of 1014 DBPCFCs showed positive results. Egg, peanut, and cow milk accounted for 73% of the positive DBPCFC reactions, but many foods produced reactions. Skin test results were positive in most children with a positive DBPCFC reaction, but the large number of patients with asymptomatic hypersensitivity limited the accuracy of a positive skin test result alone as a predictor of clinical symptoms during food ingestion. Evaluation of results in this large number of children for a prolonged period revealed reproducible patterns of symptoms, timing, and incriminated foods. Placebo reactions were rare. The procedure was safe. Twelve youngsters with a negative DBPCFC result subsequently had positive reactions to open challenges when large amounts of the challenge food were used. In each of these cases the reactions were limited to areas of direct contact with the food or could be explained by the larger amount of food ingested during the open challenge. Multiple food hypersensitivity has been a rare finding. The DBPCFC should be the "gold standard" for both research and clinical diagnostic evaluations until it is superseded by methods that have yet to be developed.     

Combining skin prick, immediate skin application and specific-IgE testing in the diagnosis of peanut allergy in children

Previous studies have suggested various diagnostic cut-offs of allergy tests for the diagnosis of clinical peanut allergy in children. There are few data relating to the use of combinations of these tests in children. We aimed to determine the validity of previously reported diagnostic cut-off levels of peanut allergen skin tests and peanut specific-immunoglobulin (Ig) E, as well as the usefulness of combinations of these, for predicting clinical peanut allergy in our Allergy Clinic. Children attending the Allergy Clinic with a positive peanut skin prick test (SPT; n = 84) were included in the study. Immediate skin application food tests (I-SAFT) using 1 g of peanut butter (positive if any wheals were detected at 15 min), peanut specific-IgE levels and open-label peanut food challenges were performed. Fifty-two of 85 peanut challenges were positive. Skin prick test specificity was 67% at >or=8 mm and 100% at >or=15 mm. The I-SAFT was 82% specific. A peanut specific-IgE level of 0.37 kU/l was 98% sensitive but 33% specific. A level of 10 kU/l was 100% specific. Combinations of a SPT of >or=8 mm with a positive I-SAFT and a peanut specific-IgE >or=0.37 kU/l were 88% specific with a sensitivity of 38%. Using challenge outcomes as the standard, available in vitro and in vivo diagnostic tests for peanut allergy have poor sensitivity and specificity and combining them does not significantly improve their clinical usefulness. Previously described diagnostic cut-off levels do not have general applicability. Allergy practitioners may need to interpret results of allergy tests in the context of their own practices.     

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??Abstract??Objective To investigate the diagnostic value of mean diameter of SPT in food allergic infants. Methods Totally 91 infants suspected with food allergy ??median age 7.35±2.94 months?? were selected??and all patients received family history inquiry??skin prick test and open food challenge.The mean diameter of SPT was measured??and OFC was performed to confirm food allergy.Diagnostic value of skin prick test, including the sensitivity and specificity, was calculated.In addition??receiver operating characteristic curve??ROC?? was plotted and area under the curve??AUC??was calculated to quantify the accuracy of the parameter.The SPSS software package version 13.0 for windows was used for all statistical analysis. Results A total of 128 babies received food challenge test?? in which there were 109 times of OFC positive and 19 times negative??totally 79 infants were diagnosed with FA.The induced symptoms of food challenge test included skin symptoms??70.6%??, gastrointestinal symptoms??20.2%??, rest with crying?? coughing?? rubbing eyes??etc.??9.2%??.When the rash MD was ≥3 mm??the sensitivity of SPT diagnosis milk??egg white and protein allergy was 19%??60.6% and 60.5% respectively??the area under ROC curve of rash MD in the milk??egg white??protein was 0.718??0.604 and 0.716 respectively?? the rates of three food SPT test results complying with the OFC were 44.4%??53.7% and 65.9%??the rates being 62.5%?? 58.3% and 31.3% in positive family history??when family history was negative??the area under the ROC curve of rash MD was 0.793. In the cases with positive family history??the area of ROC curve was 0.533.When rash MD of milk??egg white and protein was ≥2.2??5.0??4.7 mm or the rash MD was ≥3.25mm in children with a negative family history??SPT FA diagnostic specificity could be up to 100%. Conclusion SPT has some value in the diagnosis of FA. By finding the critical value of SPT FA and comprehensive analysis of family history??doctors can improve the diagnostic rate of FA. SPT can prevent some suspicious FA infants from food challenge test. It is very important to obtain rapid clinical diagnosis and to reduce the risk and burden to their families.     

Atopy patch test for the diagnosis of food protein-induced enterocolitis syndrome

Food protein-induced enterocolitis syndrome (FPIES) is thought to be a non-IgE mediated food allergy syndrome. Affected infants typically demonstrate gastrointestinal symptoms after hours after ingestion of the offending food. Traditional allergy testing is not useful for this disorder because tests for food specific IgE are routinely negative. A diagnostic oral food challenge (OFC) is the only method to confirm the diagnosis of FPIES. This prospective study was undertaken to determine whether the atopy patch test (APT) is able to predict the results of the OFC. Nineteen infants with suspected FPIES by clinical history underwent APT to the suspected foods. After APT was performed, subjects underwent OFC to determine whether FPIES was present. The results of APT and OFC were compared and used to calculate sensitivity and specificity of the APT. APT predicted the results of oral food challenges in 28/33 instances. There were 16 cases of FPIES confirmed by oral food challenges. In all 16 cases of FPIES, the APT was positive to the suspected food. However, the APT was positive in five instances where the oral food challenge was negative. All 12 patients with a negative APT had a negative oral food challenge to the suspected food. APT appears to be a promising diagnostic tool for the diagnosis of FPIES.     

Reported symptoms of food hypersensitivity and sensitization to common foods in 4-year-old children

AIM: To characterize reported food hypersensitivity (FHS) among young children in a birth cohort. METHODS: At 4 years of age a parental questionnaire on FHS and allergic symptoms was evaluated. Blood was collected for analyses of IgE-antibodies to egg, milk, fish, wheat, peanut and soy. Complete questionnaire data was available for 3694 children (90%), and blood samples were obtained from 2563 children (63%). RESULTS: FHS was reported in 11% of the children (n=397). Eczema was the most commonly reported symptom and the only symptom in half of these children. Food-related reactions from the airways, facial oedema or urticaria were reported in 198 children, and the majority of these children (75%) reported multiple symptoms. Furthermore, a combination of airway symptoms, facial oedema or urticaria together with sensitization to food suggested a more severe form of FHS. This was found in 1.6% of all children. Symptoms caused by peanut were closely associated with sensitization to peanut (p<0.001). CONCLUSIONS: FHS in 4-year-old children with any of asthma, rhino-conjunctivitis, facial oedema or urticaria in combination is in most cases associated to sensitization to food. This phenotype of FHS is likely to represent a more severe form of FHS.     

The diagnosis of IgE-mediated food allergy in childhood

IgE-mediated food allergy is a common condition in childhood and a recognized public health concern. An accurate diagnosis of food allergy facilitates the avoidance of the allergen – and cross-reactive allergens – and allows for safe dietary expansion. The diagnosis of food allergy relies on a combination of rigorous history, physical examination, allergy tests [skin prick tests (SPT) and/or serum-specific IgE] and oral food challenges. Diagnostic cut-off values for SPT and specific IgE results have improved the diagnosis of food allergy and thereby reduced the need to perform oral food challenges. This clinical case series seeks to highlight a contemporary approach to the diagnosis of food allergy in children strategies.     

Correlation between skin prick test using commercial extract of cow''s milk protein and fresh milk and food challenges

The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of cow's milk protein allergy. It is not known whether commercial extracts have any advantage over fresh milk. The aims of the study were to (i) compare the diagnostic capacity of SPTs for the three main cow's milk proteins (alpha-lactalbumin, casein and beta-lactoglobulin) with fresh milk and (ii) determine a cut-off that discriminates between allergic and tolerant children in a controlled food challenge. A study was carried out on 104 children consecutively attending two paediatric allergy clinics for suspected cow's milk allergy. A clinical history, SPTs with fresh cow's milk and commercial extracts of its three main proteins and a challenge test were performed on all the children. A study of the validity of the prick test was also performed by taking different cut-off points for fresh milk and its proteins. Twenty-eight of 104 challenge tests (26.9%) were positive. At a cut-off point of 3 mm, fresh milk showed the greatest negative predictive value (98%), whereas casein showed the greatest positive predictive value (PPV, 85%). Calculation of 95% predicted probabilities using logistic regression revealed predictive decision points of 12 mm for lactalbumin, 9 mm for casein, 10 mm for beta-lactoglobulin and 15 mm for fresh cow's milk. We found that the greater the number of positive SPTs for milk proteins, the more likely the positive response to challenge. Having a positive SPT for all three milk proteins had PPV of 92.3% and would seem more clinically useful than any cut-off. Both fresh milk and cow's milk extract of the three main proteins could be useful in the diagnostic work-up of cow's milk allergy. Finding positivity to all three cow's milk proteins seems to be a simpler and more useful way of avoiding oral food challenges.     

Do we still need oral food challenges for the diagnosis of food allergy?

Food challenges are standard in the diagnosis in patients suspected of being allergic to food. However, their role is regularly questioned due to the time required to perform them, and to their cost and the inherent risk of severe reactions. Food challenges have been challenged by recent advances defining threshold values for food‐specific IgE helping to predict the probability of having symptoms to the suspected food. Also, identification of major allergens to various highly allergenic foods such as peanuts or tree nuts has contributed to an increased accuracy of IgE testing. Altogether, these new data have contributed to a better definition of the role of oral food challenges in the diagnosis of food allergy. Oral food challenges are not outdated and remain the gold standard in the diagnosis of food allergy.     

Is there an association between microbial exposure and food allergy? A systematic review

The environmental factors driving the recent increase in the prevalence of food allergy (FA) are unclear. Since associations have been demonstrated between microbial exposure and the likelihood of eczema and respiratory allergies, we reviewed the evidence for FA. Medline was systematically searched from inception to the end of July 2012 for studies investigating links between FA and environmental exposures, likely to influence microbial exposure, such as Caesarean delivery, family size, day‐care attendance, childhood infections, immunizations and antibiotic use. We selected studies reporting food challenge data, reported doctor‐diagnosed (RDD) FA and food sensitization. Methodological differences and study heterogeneity precluded meta‐analysis. A total of 46 studies were identified, of which 28 (60.9%) were prospective and 13 (28.3%) used food challenges to diagnose FA. Caesarean delivery was investigated in 13 studies, of which three infant cohorts demonstrated an increase in challenge‐proven FA (one cohort) and food sensitization (two cohorts), and one cross‐sectional study reported increased RDDFA. Four studies investigated the effect of having siblings, with one infant cohort demonstrating less challenge‐proven FA and a cross‐sectional study showing a decrease in RDDFA. Attending childcare before 6 months was associated with less challenge‐proven FA in one cohort. A cross‐sectional survey identified an inverse relationship between hepatitis A serology and peanut sensitization. One of eleven trials investigating probiotics demonstrated a quicker acquisition of milk tolerance amongst allergic infants. Factors influencing microbial exposure may be partly responsible for rising FA burden, but further prospective studies using double‐blind placebo controlled food challenges as an outcome are required.