Development of natural tolerance and induced desensitization in cow’s milk allergy

Cow’s milk allergy (CMA) affects 2–3% of infants. It resolves in the great majority spontaneously during childhood. CMA encompasses a spectrum of clinical and immunologic characteristics. Non‐IgE‐mediated allergy typically resolves earlier than IgE‐mediated allergy. The most documented prognostic characteristic is that intense‐specific IgE response predicts persistence of CMA. Low serum levels of cow’s milk (CM)‐specific IgG4 are also associated with persistent CMA. Natural development of tolerance involves an immunologic shift where Th2 responses diminish, and Th1 as well as T regulatory cell responses strengthen. Accordingly, specific IgE levels decrease and specific IgG4, possibly also IgA, levels increase in serum. Specific oral immunotherapy (OIT) with CM induces desensitization in most cases where spontaneous recovery has not yet occurred. Data on long‐term tolerance induction are still scarce. According to current research data, the immunologic changes induced by OIT resemble those seen during natural development of tolerance.     

Oral desensitization in children with immunoglobulin E-mediated cow's milk allergy – follow-up at 4 yr and 8 months

Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow‐up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)‐mediated cow’s milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long‐term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4–5 yr were recorded. Children underwent SPT, and end‐point SPT, with casein and α‐lactoalbumin. Specific CM IgE was also measured. At follow‐up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or α‐lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and α‐lactoalbumin (end‐point SPT) significantly decreased after the 6‐month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow‐up. A significant reduction of serum‐specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time‐consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff.     

Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies

Scott‐Taylor TH, Hourihane J, Strobel S. Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies.
Pediatr Allergy Immunol 2010: 21: 935–944.
© 2010 John Wiley & Sons A/S Cytokines can affect the quantity and class of allergen‐specific immunoglobulins through the T cell polarization that accompanies atopy. Antigen‐specific IgG subclasses and IgE antibodies were compared with intracellular T cell cytokine changes to sensitizing antigens in 23 children with multiple food allergies and 20 healthy controls. Allergic children showed higher levels of total and food‐specific IgE, IgG1 and IgG4 to peanut, milk and egg than non‐atopic children or adults, coinciding with a TH2 cytokine response to sensitizing antigens. IgG1 and IgG4 antibodies specific to milk and egg and peanut protein were elevated relative to age‐matched healthy children (p ≤ 0.05) and, in milk‐ and egg‐sensitized children, correlated with cytokine responses (p < 0.05). Peanut‐sensitized children additionally had elevated levels of IgG2 and IgG3 also which correlated inversely (p < 0.003 and p < 0.04, respectively) with IFNγ production. Elevated allergen‐specific IgG subclass antibodies in sensitized children correlated with total IgE levels (p ≤ 0.05) in all three food allergen groups. The ratio of specific IgG1 to IgG4 was highest in those with high IgE, inverted with resolution of allergy, and correlated with total IgE levels (p ≤ 0.01) in milk‐ and egg‐sensitized children. The correlation of TH2 responses with allergen‐specific antibodies would implicate polarized T cells in food allergic children in IgE hypersensitivity and overproduction of particular IgG subclasses alike. IgG1:IgG4 ratio declines with allergy sensitization and may denote emerging tolerance.     

Delayed- and immediate-type reactions in the atopy patch test with food allergens in young children with atopic dermatitis

In recent years, the atopy patch test (APT) has been suggested as an addition in the allergological work‐up of children with atopic dermatitis (AD) and suspected food allergy. We initiated a prospective clinical study in children with AD younger than 3 yr, to evaluate the additional clinical value of the APT next to our own standardized allergological work‐up in case of a suspected food allergy. One hundred and thirty‐five children were included in the study. They were tested using the skin application food test (SAFT), the APT and measurement of specific IgE. The allergens used in the skin tests were freshly prepared food stuffs and included commercially available cow’s milk (CM), the egg white of a hard boiled hen’s egg and mashed peanuts in a saline solution. Allergy was defined using a flowchart incorporating the results from the SAFT, oral challenges (OCs) and elimination and (re)introduction periods. To determine the additional value of the APT next to the SAFT, we analyzed the SAFT negative patients per allergen and used an exact binary logistic analysis to evaluate the simultaneous effects of the APT and measurement of specific IgE, calculating mutually adjusted odds ratios (ORs) for positive APTs and specific IgE levels above 0.70 U/l. We found clinically relevant food allergies in 23% (egg white) to 28% (CM and peanut) of our study population. Positive SAFT reactions were observed in 14% (peanut), 16% (egg white) and 21% (CM) of our patient population. Next to the SAFT, we did not observe a significant additional value of the APT for the diagnosis of CM or egg white allergy, but we did find a significant additional value for the diagnosis of peanut allergy (OR = 11.56; p < 0.005, 2‐sided). In clinical practice this statistically significant value does not exclude the need for OC and controlled elimination and (re)introduction periods due to the presence of false‐negative as well as false‐positive results in the APT. In conclusion, we could not find enough support for the current addition of the APT to our standardized allergological work‐up in young children below the age of 3 yr with AD and suspected food allergy. At the moment the additional value of the classical delayed‐type APT next to the SAFT seems to be very limited at best in this study population and does not justify the time‐consuming nature of the skin test.     

Incidence,clinical features,and outcomes of food allergy in children who underwent liver transplant: 16‐year experience

Food allergies often develop after liver transplant, especially in young children. However, data are scarce on clinical characteristics and patient outcomes. When we evaluated our pediatric liver transplant patients over a 16‐year period, food allergy incidence was 8% (19/236 patients). All patients with food allergies were <18 months old, with incidence in this age group of 19.2% (19/99). Two patients had a single food and 17 had multiple food allergies. Five patients showed only non‐IgE‐mediated food allergies. Eggs, milk, nuts, and wheat were the most common allergens. Presenting symptoms included diarrhea, flushing, angioedema attacks, wheezing/chronic cough, and vomiting. Seven patients had EBV, and two patients had CMV infections at time of food allergy diagnosis. Twelve patients had eosinophilia. Seven patients (36.8%) were able to regain tolerance to all food allergens. However, one patient with single nut allergy and three with multiple food allergies were still on allergen‐eliminated diets. Eight patients with multiple food allergies gained tolerance to some of the food allergens. In conclusion, food allergies in our patients were mainly against multiple foods and IgE mediated. Infections like EBV and CMV may play a role in food allergies after liver transplant, especially in pretransplant‐naive patients.     

Survey of family history on allergy in 1-year-old and 6-year-old children

A retrospective survey of a family history of allergy employing a special questionnaire for children was performed. The survey included 1-year-old (n = 267) and 6-year-old children (n = 410) with allergies as well as 1-year-old (n = 313) and 6-year-old children (n = 329) without allergies. An ‘Allergy Risk Score’ (ARS) for each subject was calculated according to the history of allergy in three family members: father, mother and a sibling. Each family member was scored as 2.0 (overt history of allergies), 1.0 (provable), 0.5 (possible) or 0 (absent), and the ARS of the subjects was calculated as the total of the family members' scores. The ARS of children in the allergy groups was statistically higher than that of the control groups in both age groups. The ARS increased with an increase in the odds ratio (an approximate value of the risk), especially in 6-year-old children. An ARS calculated on the basis of family history could be a useful and practical index for estimating the risk of allergy development in children, and may be helpful in predicting and preventing allergies in infants and children.     

Managing a child with possible allergy to vaccine

Similarly to other medications, vaccines may be responsible for allergic reactions. Although IgE‐mediated allergies to vaccine are extremely rare, they are clearly overdiagnosed. Indeed, accurate diagnosis of vaccine allergy is important not only to prevent serious or even life‐threatening reactions, but also to avoid unnecessary vaccine restriction. Systematic approaches have been proposed and, if implemented, will likely reduce the number of children being inappropriately labeled as allergic to vaccine. In diagnosis of vaccine allergy, the patient's history is central although not sufficient. In case of suspicion of an allergy, the child should be referred to an allergist in order to perform a complete allergy workup, based primarily on skin tests and/or specific IgE. Highlighting the most recent literature, this article will address the management of children with a possible allergy to vaccine.     

Oral immunotherapy and tolerance induction in childhood

Prevalence rates of food allergy have increased rapidly in recent decades. Of concern, rates of increase are greatest among children under 5 yrs of age and for those food allergies that persist into adulthood such as peanut or tree nut allergy and shellfish allergy. Given these trends, the overall prevalence of food allergy will compound over time as the number of children affected by food allergy soars and a greater proportion of food‐allergic children are left with persistent disease into adulthood. It is therefore vital to identify novel curative treatment approaches for food allergy. Acquisition of oral tolerance to the diverse array of ingested food antigens and intestinal microbiota is an active immunologic process that is successfully established in the majority of individuals. In subjects who develop food allergy, there is a failure or loss of oral tolerance acquisition to a limited number of food allergens. Oral immunotherapy (OIT) offers a promising approach to induce specific oral tolerance to selected food allergens and represents a potential strategy for long‐term curative treatment of food allergy. This review will summarize the current understanding of oral tolerance and clinical trials of OIT for the treatment of food allergy.     

Allergy,total serum immunoglobulin E,and airflow in children and adolescents in TENOR

Haselkorn T, Szefler SJ, Simons FER, Zeiger RS, Mink DR, Chipps BE, Borish L, Wong DA, for the TENOR Study Group. Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR.
Pediatr Allergy Immunol 2010: 21: 1157–1165.
© 2010 John Wiley & Sons A/S In children and adolescents with difficult‐to‐treat asthma, few data exist characterizing the relationships between basic patient characteristics (e.g., age, sex) and atopic indicators in asthma. These associations were examined in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR), an observational study of a large cohort of patients with severe or difficult‐to‐treat asthma. To characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and airflow in young patients with severe or difficult‐to‐treat asthma. A total of 1261 patients from the TENOR study were stratified into four age groups at baseline (6–8, 9–11, 12–14, and 15–17 yr). The objective was to characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and ratio of pre‐bronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) in young patients with severe or difficult‐to‐treat asthma. The chi‐square test for categorical variables and analysis of variance for continuous variables were used to identify significant differences among age groups. Multivariable linear regression was used to evaluate the association between IgE and FEV₁/FVC. Allergic rhinitis was reported in approximately two‐thirds of patients. Up to 25% of patients had atopic dermatitis, which differed across age groups in boys (p < 0.05). Positive allergen skin test rate differed across age groups in boys (p < 0.05). Rates of asthma triggers were higher and differed across age groups in girls (p < 0.05), particularly around menarche (12–14 yr). IgE levels were higher in boys and differed across age groups in boys (p < 0.01) and girls (p < 0.05). IgE was associated with a lower FEV₁/FVC after adjusting for age and sex (p < 0.01). Severe or difficult‐to‐treat asthma in children and adolescents is characterized by high frequencies of comorbid allergic diseases, allergen sensitization, and high IgE levels. This burden is amplified by the association of more airflow limitation with higher IgE levels, suggesting the need for allergy evaluations.     

Food allergy after liver transplantation in children: a prospective study

Food allergy has been increasingly reported in children who had orthotopic liver transplantation (OLT). We aimed to conduct a prospective study to investigate the prevalence of sensitizations and food allergy in pediatric OLT recipients. We also aimed to identify potential risk factors. The study group consisted of 28 children (14 male, 14 female, mean age 4.96 ± 0.76 yrs) who had OLT. Total eosinophil count (TEC), total IgE, and specific IgEs were studied before and 3, 6, 12 months after OLT. Six patients (21%) developed multiple food allergies. Mean age of six patients at OLT who developed food allergy was younger compared to the non‐food allergy group (10.2 months vs. 68.9 months, p < 0.05). Food allergy has been developed within 1 yr in 5, and in 20 months in one patient after OLT. All six patients had cow’s milk and egg allergy after OLT. Five children developed wheat, one children developed lentil and another one developed peach allergy in addition to cow’s milk and egg allergy. Out of six food‐allergic patients after OLT, four children developed Epstein–Barr virus (EBV) infection prior to food allergy. Before OLT, TECs and total IgE levels were not differed among food allergic and non‐food allergic patients (p > 0.05). Mean of TECs were significantly higher in food allergic group compared to non‐food allergic group at each time point after OLT (p < 0.05). Though statistically insignificant, mean of total IgE levels were also higher in the food allergic group (p > 0.05). These findings suggest that food allergy should be considered after OLT in patients who are younger than 1 yr of age, who developed hypereosinophilia, high total IgE levels or EBV viremia.     

A Prospective 12-Year Follow-up Study of Children with Wheezy Bronchitis

Eighty children with wheezy bronchitis were followed prospectively for 12 years. At the end of the follow-up period only 22 (28 %) still had symptoms of asthma. Forty-three children (54 %) had ceased to wheeze before the age of 3 years, four children between 3 and 7 years of age and 11 children between 7 and 11 years of age. Of the 22 children who still had asthma, all but one were much improved, although 70 % of them noticed asthmatic symptoms during exercise. Heredity for asthma/wheezing, allergy, the occurrence of eczema, and onset of wheezing after 18 months of age were associated with an increased risk of persistent asthma. Allergy had developed in 59 % of the children with persistent asthma and in 10 % of those who had stopped wheezing. Serum IgE was above the mean +1 SD in 45 % and above the mean +2 SD in 24 % of the children at the end of the 12-year follow-up. A serum IgE above the mean +2 SD was found in 8 of 13 children with asthma combined with proven allergy, but only in 1 of 9 children with asthma without allergy. Surprisingly, 8 of 48 children who had stopped wheezing and had no clinical allergy had as high IgE levels as the children with asthma and allergy, which reduced the allergy predictive value of a high serum IgE to 36 %. Some of these high IgE levels seemed to be a family trait.     

Milk oral immunotherapy is effective in school‐aged children

Aims: To study the efficacy of oral immunotherapy (OIT) in schoolchildren with cow’s milk (CM) allergy (CMA). Methods: Twenty‐eight children aged 6–14 years with CMA documented by oral challenge were enrolled into a randomized, double‐blind, placebo‐controlled OIT study. In the active treatment, CM protein amount was increased during 23 weeks from 0.06 mg to a maximum of 6400 mg (200 mL of milk). Results: Twenty‐four (86%) patients completed the protocol: 16/18 in active and 8/10 in placebo groups. All children in the active and 2/3 in the placebo group suffered from symptoms considered by the parents as induced by milk. The children were contacted by phone 12 months later, and 13 (81%) used daily CM or milk products corresponding 6400 mg of CM protein. After double‐blind OIT, all 10 children in the placebo group completed successfully an open‐label OIT by an identical protocol, and all used daily CM or milk products 6 months later. Three to 3.5 years later, one child more had discontinued daily milk use. Thus, the long‐term success rate was 22/28 (79%). Conclusions: This placebo‐controlled, double‐blind study confirmed that OIT was effective in desensitizing schoolchildren with CMA. With occasional exceptions, the reached desensitization sustained for more than 3 years.     

Status of children with cow's milk allergy in infancy by 10 years of age

To assess the development of milk protein tolerance and atopic diseases in children diagnosed for cow's milk allergy (CMA) in infancy, we conducted re-examinations of 56 CMA subjects at the age of 10 y using 204 age-matched controls. The children underwent clinical examinations and skin prick tests (SPT), and their IgE-specific antibodies to milk and five other food allergens were determined. By the age of 10 y, all but four subjects had become tolerant to at least small amounts of milk protein. However, gastrointestinal symptoms relating to more abundant milk consumption were reported by 45% of the study subjects and 15% of the controls (p < 0.001). The incidence figures for asthma, allergic rhinitis and dermatitis, as well as the occurrence of recurrent otitis, were three to four times higher than in the controls. Positive SPTs were seen in two-thirds of the subjects, the figure being highest (83%) in those with dermatitis onset CMA. Seven subjects showed positive titres of IgE-class milk-specific antibodies, and five showed a clinical response. CONCLUSION: This re-examination study showed that CMA in infancy, even when properly treated, has significant clinical consequences by posing special risks for respiratory atopy and persistence of atopic dermatitis as well as positive SPT and recurrent ear infections. However, each of these clinical manifestations seems to have an independent curriculum unrelated to the persistence of CMA itself.     

Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy

To cite this article: Savilahti EM, Viljanen M, Kuitunen M, Savilahti E. Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy. Pediatric Allergy Immunology 2012: 23: 590-596. ABSTRACT: Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to β-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to β-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to β-lactoglobulin than infants with negative DBPC CM challenge (p?=?0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p?=?0.04). The relation of CM IgE to β-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p?相似文献   

CLINICAL AND IMMUNOLOGICAL ASPECTS OF FOOD ALLERGY IN CHILDHOOD I. Estimation of IgG, IgA and IgE Antibodies to Food Antigens in Children with Food Allergy and Atopic Dermatitis

Abstract Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

Serum immunoglobulin E,IgA, and IgG antibodies to different cow's milk proteins in children with cow's milk allergy: Association with prognosis and clinical manifestations

Diverse pathogenic mechanisms elicit different clinical manifestations in cow's milk allergy (CMA). Our aim was to determine the concentration of serum immunoglobulin levels to different cow's milk proteins in patients with CMA and to determine how these values were related to clinical symptoms and prognosis. Fifty children (mean age 10.9 months, range: 1–34 months) with previously confirmed CMA were enrolled in this study. All had various clinical manifestations of CMA, including gastrointestinal, skin, and respiratory symptoms. At the diagnosis of CMA the serum total and the milk‐specific immunoglobulin (Ig)E values were measured by enzyme immunoassay and fluoroimmunoassay, respectively, while the relative levels of serum IgA and IgG antibodies against different cow's milk proteins were determined by a sensitive enzyme‐linked immunosorbent assay (ELISA). The results were compared to those of 30 non‐atopic age‐matched control children. On average, after 9.2 months (range 2–31 months) on a milk‐free diet, a repeated challenge was performed in 38 children. At the re‐challenge, 12 patients had clinical symptoms while the remaining 26 children were symptom‐free. The IgG antibody level to bovine serum albumin (BSA) was significantly lower in the patients than in the controls (median: 0.36 vs. 2.94, p < 0.01). There was a close correlation among all individual IgA and IgG antibodies to different cow's milk proteins. The anti‐α‐casein IgG level (of 2.10) in children with a positive reaction at the re‐challenge was significantly higher than in those with a negative reaction (0.89) (p < 0.05). The total IgE serum concentration was also significantly higher in those who had symptoms at the re‐challenge compared to those who did not have any reaction at this time (22.9 vs. 6.8 kU/l, geometric mean, p < 0.02). There was no association between the clinical manifestations and the IgG and IgA antibody levels to the cow's milk proteins studied, except for the anti‐BSA IgA level, which was higher in patients with gastrointestinal symptoms. The serum total IgE and anti‐α‐casein IgG levels could have prognostic values; their increase at the beginning of the disease may indicate the development of tolerance to cow's milk only at a later age and after a longer duration of CMA. However, as there is considerable overlap among the values observed in different groups of patients, there is a limitation of these tests for predicting the prognosis.     

Fish allergy in childhood

Fish and its derived products play an important role in human nutrition, but they may also be a potent food allergen. Fish can be an ingested, contact, and inhalant allergen. Gad c I, a Parvalbumin, the major allergen in codfish, is considered as fish and amphibian pan‐allergen. Prevalence of fish allergy appears to depend on the amount of fish eaten in the local diet. In Europe, the highest consumption occurs in Scandinavian countries, Spain and Portugal. In Spain, fish is the third most frequent allergen in children under 2 yr of age after egg and cow’s milk. An adverse reaction to fish may be of non‐allergic origin, due to food contamination or newly formed toxic products, but the most frequent type of adverse reactions to fish are immunologic‐mediated reactions (allergic reactions). Such allergic reactions may be both IgE‐mediated and non‐IgE‐mediated. Most cases are IgE‐mediated, due to ingestion or contact with fish or as a result of inhalation of cooking vapors. Some children develop non‐IgE‐mediated type allergies such as food protein induced enterocolitis syndrome. The clinical symptoms related to IgE‐mediated fish allergy are most frequently acute urticaria and angioedema as well as mild oral symptoms, worsening of atopic dermatitis, respiratory symptoms such as rhinitis or asthma, and gastrointestinal symptoms such as nausea and vomiting. Anaphylaxis may also occur. Among all the species studied, those from the Tunidae and Xiphiidae families appear to be the least allergenic.     

Non‐IgE‐mediated gastrointestinal allergies—Do they have a place in a new model of the Allergic March

The rise in food allergy has been described as the “second wave” of the allergy epidemic, with some developed countries reporting a prevalence of 10% of challenge‐proven food allergies. Recognition of the Allergic March has played a crucial role in identifying causality in allergic conditions, linking atopic dermatitis to food allergy and food allergy to other atopic disorders, thereby highlighting opportunities in prevention and the importance of early intervention. This publication will establish the value of weaving the less well‐understood, non‐IgE‐mediated food allergy into the Allergic March and mapping its progression through childhood and its associated co‐morbidities. The proposed non‐IgE‐mediated Allergic March highlights the concomitant presentation of gastrointestinal symptoms and atopic dermatitis as early presenting symptoms in confirmed non‐IgE‐mediated allergies and the later development of atopic co‐morbidities, including asthma and allergic rhinitis, similar to the IgE‐mediated Allergic March. This publication highlights recent observations of a link between non‐IgE‐mediated food allergy in early childhood and functional gastrointestinal disorders in later life and also the reported occurrence of extra‐intestinal manifestations at later ages. Although significant limitations exist in regard to the proposed evolution of the Allergic March model, the authors hope that this publication will influence the management of non‐IgE‐mediated gastrointestinal allergies and inform future research and interventions.     

Identification of the etiologies of chronic urticaria in children: A prospective study of 94 patients

Jirapongsananuruk O, Pongpreuksa S, Sangacharoenkit P, Visitsunthorn N, Vichyanond P. Identification of the etiologies of chronic urticaria in children: A prospective study of 94 patients.
Pediatr Allergy Immunol 2010: 21: 508–514.
© 2009 John Wiley & Sons A/S The etiologies of chronic urticaria (CU) in childhood remains incompletely understood because of limited data in children. The objective of this study was to examine some of the possible etiologies of CU in children by focusing on the functional autoantibody to FcεRIα and IgE, thyroid autoimmunity, urticarial vasculitis, parasitic infestation and food allergy. Children 4–15 yr of age with CU were investigated for complete blood count, erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), CH₅₀, free‐T4 (FT₄), thyroid stimulating hormone (TSH), anti‐thyroglobulin and anti‐microsomal antibody, autologous serum skin test (ASST), skin prick tests (SPT) for foods, food challenges, and stool examination for parasites. Ninety‐four children who met the criteria for CU were recruited. Patients with physical urticaria were excluded. Eosinophilia and elevated ESR were found in 23% and 13%, respectively. High ANA titers were found in 2%. None of these patients had clinical features of urticarial vasculitis, abnormal CH₅₀ level, abnormal TSH and FT₄. Anti‐thyroglobulin and anti‐microsomal antibodies were not detected. Positive ASST was found in 38%. There were no differences in medication requirement and CU remission between patients with positive and negative ASST. Parasites were found in 5% without clinical correlation. SPT to foods was positive in 35%. Positive food challenges were found in six/nine patients with positive history of food allergy and two/seven patients with negative history. Food avoidance was beneficial to the subgroup of patients with positive history of food allergy only.