A hydrolysed rice-based formula is tolerated by children with cow''s milk allergy: a multi-centre study

BACKGROUND: Children allergic to cow's milk are fed a soy- or a hydrolysed cow's milk-based substitute. Neither can rule out a sensitization risk. Previous studies have shown that hydrolysed rice is tolerated by animals and children with multiple food hypersensitivities. OBJECTIVE: A prospective clinical assessment of tolerance to a rice-based hydrolysed formula was carried out in children allergic to cow's milk. Patients and methods One hundred children (42 girls and 58 boys, mean age 3.17+/-2.93 years, median 2.20, range 0.18-14.6 years) with a history of immediate reactions to cow's milk and confirmed at double-blind, placebo-controlled food challenge (DBPCFC) when not contraindicated were assessed for clinical tolerance to cow's milk proteins. Their allergy work-up included skin prick tests with whole milk, alpha-lactalbumin (ALA), beta-lactoglobulin (BLG) and total caseins, and specific IgE determinations using CAP technology were performed against whole milk, ALA, BLG and casein. Sensitization to rice and rice-based hydrolysed formula was similarly investigated. Patients' sera were evaluated at immunoblotting for specific IgE to cow's milk proteins, rice and rice-based hydrolysed formula. DBPCFC was carried out with increasing doses of a rice-based hydrolysed formula. RESULTS: All patients were sensitized to cow's milk and/or at least one cow's milk protein fraction. Eighty-seven out of 99 were positive to cow's milk and/or a cow's milk protein fraction at skin prick test. Positive (>0.35 kUA/L) specific IgE determinations were found for cow's milk and/or milk fractions (92/95), rice (21/91) and hydrolysed rice infant formula (4/91). At immunoblotting, sera from 96 children were positive to alpha-casein (n=54), beta-casein (n=38), ALA (n=57), BLG (n=37) and bovine serum albumin (n=61). Similarly, although patients' sera often contained specific IgE against rice proteins at CAP (21/91) and immunoblotting (70/96), only six very weakly positive responses were observed against rice-based hydrolysed formula. All DBPCFC with rice-based hydrolysed formula were negative. CONCLUSIONS: Rice-based hydrolysed formula is a possible alternative not only for children with multiple allergies, but also for children with cow's milk allergy.     

The recognition pattern of sequential B cell epitopes of beta-lactoglobulin does not vary with the clinical manifestations of cow's milk allergy

BACKGROUND: beta-Lactoglobulin (BLG) represents one of the major allergens causing cow's milk allergy (CMA) - a disease with a wide spectrum of clinical symptoms. The aim of this study was to evaluate sequential B cell epitopes of BLG by the Pin-ELISA method. Furthermore, we wanted to investigate a possible association of the IgE recognition patterns in sera of patients with BLG sensitization and the type of clinical reactions following contact with cow's milk. METHODS: Overlapping sequential decapeptides corresponding to the amino acid sequence of BLG were used in Pin-ELISAs specific for human IgE. Tested sera were from 14 individuals with CMA, 8 of them with a history of immediate systemic reactions and 6 with delayed skin reactions following contact with cow's milk. All of them showed specific IgE antibodies to BLG in the CAP-RAST. Control sera were from 5 healthy nonallergic individuals. RESULTS: All sera from BLG-sensitized individuals showed IgE binding with one region of BLG corresponding to amino acids 95-113. Furthermore, individual sera showed reactions with two further regions, 12-27 and 124-135. Inhibition of IgE binding to BLG with one soluble synthetic peptide confirmed the major epitope. No differences were found in the B cell epitope recognition pattern to BLG in the two groups of patients with CMA, characterized by acute systemic or delayed skin reactions. CONCLUSIONS: Using IgE Pin-ELISAs we were able to confirm previously described sequential B cell epitopes of BLG. However, the recognition pattern of one of the major cow's milk allergens is not predictive of the clinical type of reaction.     

B-cell epitopes as a screening instrument for persistent cow's milk allergy

BACKGROUND: Cow's milk is one of the most common causes of food allergy in the first years of life. We recently defined IgE-binding epitopes of all 6 major cow's milk proteins (alpha(s1)-, alpha(s2)-, beta-, and kappa-casein; alpha-lactalbumin; and beta-lactoglobulin) and had some evidence suggesting that IgE antibodies from patients with persistent cow's milk allergy (CMA) recognize different epitopes on cow's milk proteins than do those from patients who were likely to outgrow their allergy. OBJECTIVE: In this study we sought to assess whether recognition of IgE antibodies of certain epitopes of cow's milk proteins would clearly separate the patients with life-long CMA from those who will become clinically tolerant to cow's milk. METHODS: According to the known IgE-binding regions of cow's milk proteins, 25 decapeptides of alpha(s1)-casein, alpha(s2)-casein, kappa-casein, alpha-lactalbumin, and beta-lactoglobulin, comprising the core epitopes, were synthesized on a cellulose-derivatized membrane. Sera from 10 patients with persistent CMA and 10 patients who subsequently outgrew their milk allergy were used to investigate the differences in epitope recognition. RESULTS: Five IgE-binding epitopes (2 on alpha(s1)-casein, 1 on alpha(s2)-casein, and 2 on kappa-casein) were not recognized by any of the patients with transient CMA but showed binding by the majority of the patients with persistent allergy. The presence of IgE antibodies against at least 1 of 3 epitopes (amino acid [AA] 123-132 on alpha(s1)-casein, AA 171-180 on alpha(s2)-casein, and AA 155-164 on kappa-casein) identified all patients with persistent CMA. CONCLUSIONS: The presence of IgE antibodies to distinct allergenic epitopes of cow's milk proteins can be used as a marker of persistent CMA. Prospective studies are needed to investigate the usefulness of these informative epitopes in predicting life-long CMA in young children.     

Maintenance of tolerance to cow''s milk in atopic individuals is characterized by high levels of specific immunoglobulin G4

BACKGROUND: The central role of specific IgE in cow's milk allergy (CMA) is well documented. However, less is known about the function of other immunoglobulin isotypes in allergy and tolerance to cow's milk proteins (CMPs). OBJECTIVE: To determine differences in the antibody responses that are associated with allergy and tolerance to cow's milk in allergic, atopic and non-atopic individuals of different age groups. METHODS: Nineteen infants (<1 year), 18 children (6-14 years) and 41 adults (21-68 years) were included. Each age group was comprised of subjects with CMA, atopic individuals without a history of CMA and non-atopic subjects. Levels of specific IgE, IgG4, IgG1 and IgA to whole cow's milk and the six most abundant individual CMPs were determined in plasma by ELISA. For comparison, specific IgE and IgG4 were measured to ovomucoid and house dust mite (HDM) in individuals allergic for the respective allergens, and in atopic and non-atopic subjects without allergy. RESULTS: In infants and children with CMA, alphas1-casein and beta-lactoglobulin induced the highest specific IgE response, whereas alphas1-casein was the most allergenic CMP in adult patients. Specific IgG4 and IgG1 responses were the highest to alphas1-casein and beta-lactoglobulin in all age groups, while kappa-casein and alpha-lactalbumin induced the highest levels of IgA. CMP-specific IgG4 was higher in atopic children and adults without CMA, as compared with non-atopic individuals. A similar difference between tolerant atopic and non-atopic subjects was observed for IgG4 specific to ovomucoid, whereas HDM-specific IgG4 was not detectable in these subjects. CONCLUSION: Maintenance of tolerance to cow's milk in atopic children and adults without CMA is associated with elevated levels of specific IgG4, in combination with low specific IgE. The up-regulation of specific IgG4 in tolerant atopic individuals may be related to the type of allergen and its regular dose of exposure.     

Role of conformational and linear epitopes in the achievement of tolerance in cow''s milk allergy

BACKGROUND: Cow's milk (CM) is one of the leading causes of food allergy in children. However, approximately 85% of milk-allergic children become clinically tolerant to CM within the first 3 years of life. The mechanisms involved in the achievement of tolerance remain unknown. OBJECTIVE: To study whether IgE antibodies from children with persistent cow's milk allergy (CMA) differ from children who become clinically tolerant in their ability to recognize linear and conformational epitopes of alpha(s1)- and beta-casein. METHODS: Thirty-six milk-allergic children were included in the study: 11 of the children became clinically tolerant, and 25 had persistent CMA. Blood was obtained from all patients during the time they showed clinical reactions to milk challenge. Six non-milk-allergic children served as controls. Specific IgE antibodies against linear (denatured) as well as conformational (native) milk proteins were determined by probing dot-blots with patients' sera. In addition, selected decapeptides from alpha(s1)- and beta-casein, previously found to be suggestive of persistent CMA, were synthesized on a cellulose-derivatized membrane and probed with individual sera from 10 patients who outgrew CMA and from 10 patients with persistent CMA. RESULTS: Analysis of immunodot-blots showed that, in comparison to tolerant patients, milk-allergic children with persistent symptoms had a significantly higher ratio of specific IgE antibodies to linearized than to native alpha- and beta-casein (P < 0.005 and P < 0.02, respectively). Comparing the selected decapeptides, six of the 10 patients with persistent allergy recognized the peptide corresponding to amino acids 69-78 from alpha(s1)-casein while none of the patients who outgrew CMA had IgE binding to this epitope. CONCLUSION: Patients with persistent milk allergy possess higher detectable levels of IgE antibodies to linear epitopes from alpha(s1)- and beta-casein than children who have achieved tolerance. Specific IgE binding to particular linear epitopes in alpha(s1)-casein may be a predictive factor for persistence of CMA.     

Infant feeding patterns affect the subsequent immunological features in cow''s milk allergy

BACKGROUND: The first exposure to food antigens provokes an immune reaction in an infant, its type depending on the quantity and frequency of doses and the age at introduction, and also being influenced by genetic factors. Most infants develop tolerance to food antigens, but in a small minority they provoke adverse symptoms. OBJECTIVE: To study the effects of breast and formula feeding and other environmental and genetic factors on the subsequent type of cow's milk allergy classified by the presence or absence of immunoglobulin (Ig) E antibodies to cow's milk. METHODS: A cohort of 6209 infants was followed prospectively from birth for symptoms of cow's milk allergy. The infant-feeding regimen was recorded at the maternity hospital and at home. At a mean age of 6.7 months, a total of 118 infants (1.9%) reacted adversely to a challenge with cow's milk. Before the challenge, the response to a skin-prick test with cow's milk and serum IgE cow's milk antibodies was measured. RESULTS: At challenge, 75 (64%) infants showed IgE-positive reactions to cow's milk, their most common symptom being acute-onset urticaria. Significant risk factors for the presence of IgE cow's milk antibodies in allergic infants were long breast-feeding (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.6-9.8), exposure to cow's milk at the maternity hospital (OR 3.5, 95% CI 1.2-10.1) and breast-feeding during the first 2 months at home either exclusively (OR 5.1, 95% CI 1.6-16.4) or combined with infrequent exposure to small amounts of cow's milk (OR 5.7, 95% CI 1.5-21.6). Fifty infants had their first adverse symptoms during exclusive breast-feeding, and 32 infants were sensitized during exclusive breast-feeding. Most of the infants in both cases were IgE-positive: 37 and 23, respectively. CONCLUSIONS: In infants who are prone to developing cow's milk allergy, prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of cow's milk during the first 2 months of life induces development of IgE-mediated response to cow's milk.     

Prevalence of soy protein hypersensitivity in cow's milk protein-sensitive children in Korea

This study was aimed to evaluate the prevalence of soy protein hypersensitivity in cow's milk protein-sensitive children in Korea. A total of 1,363 patients with atopic dermatitis, urticaria, enterocolitis syndrome, bronchial asthma or allergic rhinitis were recruited. First, we estimated the prevalence of sensitization to soy in children sensitized to cow's milk. Specific IgE levels > 0.7 kU/L by CAP assay were considered positive. Next, the prevalence of soy allergy in cow's milk allergy (CMA) patients was investigated. Those children whose parents agreed to participate the open challenge test with soy had a convincing history of allergic reactions elicited by cow's milk and these symptoms were relieved by elimination. All of them had negative soy-specific IgE. Patients with positive soy-specific IgE accounted for 18.3% of 224 children sensitized to cow's milk protein. The prevalence of sensitization to soy decreased with age (36.8% in the first year of life, 16.4% in the second year, and 13.7% in the third year). Of 21 CMA patients, 42.9% (n=9) were determined to have soy allergy (mean age 10.3 months). Our results suggest that soy protein formula should be carefully used as a substitute for cow's milk in CMA patients, especially during infancy.     

Evaluation of the utility of atopy patch testing, skin prick testing, and total and specific IgE assays in the diagnosis of cow's milk allergy.

BACKGROUND: Information on the utility of atopy patch testing (APT) in the diagnosis of food allergy is derived from studies of children with atopic dermatitis. OBJECTIVE: To evaluate the usefulness of APT in the diagnosis of cow's milk allergy (CMA) and to determine interleukin 4 and interferon-gamma production by peripheral blood mononuclear cells. METHODS: Thirty-seven children (median age, 11 months) with suspected CMA who had a variety of symptoms that involved many organ systems were evaluated using double-blind placebo-controlled food challenges (DBPCFCs), and the performances of milk specific IgE, skin prick testing (SPT), and APT were determined. To search for a possible relationship between the diagnostic tests and the TH1/TH2 immune response, we measured interferon-gamma and interleukin 4 levels in the supernatants of peripheral blood mononuclear cell cultures. RESULTS: Seventeen children with positive DBPCFC results and 6 with a history of anaphylaxis were diagnosed as having CMA. The combined use of APT and SPT had a sensitivity of 100% and a negative predictive value of 100% but a specificity of 50% and a positive predictive value of 76%. The addition of milk specific IgE assays to APT and SPT did not improve these values. Pattern of cytokine secretion was not associated with APT positivity or a specific response to DBPCFC. CONCLUSIONS: Atopy patch testing may be a useful adjunct to SPT in excluding CMA in children who have allergic manifestations other than atopic dermatitis. However, DBPCFCs are still necessary in the presence of positive test results.     

Cow's milk allergy in adults is rare but severe: both casein and whey proteins are involved

Background Studies on cow's milk allergy (CMA) in adults are scarce. Little is known about the clinical symptoms, eliciting doses (ED), and allergens involved.
Objective The aim of this study was to analyse the clinical symptoms, ED and allergen recognition in adult CMA patients, compared with cow's milk (CM)-sensitized, but tolerant controls.
Methods Adult CMA patients were evaluated by standardized questionnaires ( n =30), skin prick tests (SPTs) and specific IgE for CM allergens ( n =18), and a double-blind placebo-controlled food challenge (DBPCFC, n =10). A control group ( n =25) of CM-sensitized, but tolerant adults was included.
Results The majority of CMA patients (20/30, 67%) reported severe symptoms. In all patients participating in DBPCFC, CMA was confirmed. ED for subjective symptoms (0.3–300 mg CM protein) were significantly lower than that for objective symptoms (300–9000 mg CM protein). The severity of CMA by history and ED was not correlated with SPT or IgE. Patients had higher SPT reactivity than controls for CM, α-lactalbumin and β-lactoglobulin ( P =0.002, P =0.014 and P =0.004) but not for casein. Specific IgE to CM tended to be higher ( P =0.068) and IgE to casein was higher in patients than that in controls ( P =0.016). No difference was observed for IgE to α-lactalbumin and β-lactoglobulin.
Conclusion Adult CMA is severe in nature. ED are low, starting from 0.3 mg CM protein. Patients with CMA recognize the same major allergens (casein and whey proteins) as controls, but display a stronger SPT and IgE reactivity.     

A dual long-term effect of breastfeeding on atopy in relation to heredity in children at 4 years of age

BACKGROUND: The long-term effect of early feeding on atopic sensitization is still unsolved. The aim of this study was to evaluate the long-term effect of breastfeeding on atopy in groups of 4-year-old children stratified by atopic heredity. METHODS: We collected four groups of 4-year-old children from a birth cohort: two groups with differing backgrounds of atopic heredity, all exclusively breast-fed for at least 3 months; and two groups with differing atopic heredity, but all fed with cow's milk-based formula during their first weeks. The data were collected with a questionnaire, skin prick testing, and measurement of serum total and allergen-specific IgE levels. RESULTS: Breastfeeding significantly decreased the risk of allergic rhino-conjunctivitis [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.18-0.95] and sensitization to furred pets, as measured by skin prick results, in children with atopic heredity, whereas in children without atopic heredity, breastfeeding was related to an increased risk of symptomatic atopy (OR 2.57, 95% CI 1.16-5.70), and high serum IgE values. A significant interaction was found between heredity and breastfeeding. CONCLUSIONS: The long-term effect of breastfeeding was dual: in children with atopic heredity, breastfeeding protected against atopy, whereas in children without atopic heredity, it increased the risk of atopy.     

Determination of allergenicity to three cow''s milk hydrolysates and an amino acid‐derived formula in children with cow''s milk allergy

BACKGROUND: Products based on hydrolysed cow milk proteins or amino acid mixtures are recommended in children with cow's milk hypersensitivity. However, some children who are allergic to cow's milk and who clinically react to substitute milk formulas have been observed. OBJECTIVE: To determine the tolerance and allergenicity of protein hydrolysate or amino acid-derived formulas in children with IgE-mediated cow's milk allergy. METHODS: Twenty children with positive cow's milk challenges, positive skin prick tests and/or serum-specific IgE antibodies to cow's milk were selected. Oral challenges, skin prick tests and serum-specific IgE antibodies to extensively hydrolysed whey formula, partially hydrolysed whey formula, extensively hydrolysed casein formula and amino acid-derived formula were performed. RESULTS: Five out of 17 (5/17) children reacted to partially hydrolysed whey formula, (3/16) to extensively hydrolysed whey formula, (2/10) to amino acid-derived formula, (1/16) to extensively hydrolysed casein formula. Only extensively hydrolysed casein formula was tolerated by at least 90% (with 95% confidence intervals) of children. Hydrolysates provoked early and delayed clinical reactions, amino acid mixtures only delayed reactions. Partially hydrolysed whey formula elicited a significantly higher number of positive skin prick test reactions than other formulas. Two children had specific IgE antibodies to extensively hydrolysed whey formula, one to partially hydrolysed whey formula, one to extensively hydrolysed casein formula and none to amino acid-derived formula. CONCLUSION: In this study, none of the cow's milk substitutes has been found to be non-allergenic. Our results suggest that in children with IgE-mediated cow's milk allergy, the first ingestions of extensively hydrolysed cow's milk protein formulas require strict medical supervision because of immediate reactions. This is not the case for amino acid-derived formula. Moreover, our data suggest that treatment of children allergic to cow's milk with cow's milk substitutes should be monitored for several days to document tolerance.     

Natural course of sensitization to cow''s milk and hen''s egg in childhood atopic dermatitis: ETACTM Study Group

BACKGROUND: Sensitization to food allergens has been implicated in the pathogenesis of atopic diseases, in particular atopic dermatitis (AD). The aim of the present paper is to investigate the natural course of sensitization to egg and to cow's milk and its relationship with the severity of AD. METHODS: The placebo intention-to-treat population of the ETACTM (Early Treatment of the Atopic Child) study consisted of 397 children with AD aged 12-24 months (mean+ SD: 17.2 + 4.1 months) who were followed for 18 months. All children were examined for objective SCORing Atopic Dermatitis (SCORAD) and specific IgE amongst other, to egg and to cow's milk at inclusion and after 3, 12 and 18 months. Fifteen patients were excluded from this analysis due to major protocol violations thus leaving 382 patients in the analysed population. RESULTS: Sensitization to egg and to cow's milk was more common in atopic children with severe AD at all time-points. At inclusion, children sensitized to both egg and to cow's milk had the most severe AD (Kruskall-Wallis test P= 0.007). The degree of sensitization expressed in RAST classes was significantly related to the severity of AD. Furthermore, children sensitized to egg or to cow's milk at inclusion had a higher risk of persistence of AD (84% and 67%, respectively, vs. 57% in those not sensitized) and a higher objective SCORAD after 18 months follow-up. CONCLUSION: We found an association between severity of AD and sensitization to egg or to cow's milk. Moreover, sensitization to egg, and to a lesser extent cow's milk, indicates a worse outcome of AD in terms of persistence and severity of the disease.     

Risk factors of adverse reactions to food in German adults

Background Allergic diseases have been increasing during the last decades. Previous studies suggest an impact of a variety of risk factors on the prevalence of food hypersensitivity. Objective Data of a cross‐sectional population‐based survey were analysed to study the prevalence of food hypersensitivity in females and males adjusted for age and education. Methods A population aged 18–79 years from a representative, randomly sampled survey studying 13 300 inhabitants from Germany (Berlin) was analysed. The Berlin study data were weighted with regard to age, sex, education and allergic diseases such as atopic dermatitis, rhinoconjunctivitis and asthma. Instruments for evaluation included mailed questionnaires, structured telephone interviews, physical examinations, detection of total IgE, skin prick tests and double‐blind, placebo‐controlled food challenge tests (DBPCFC). Results Three thousand two hundred and twenty‐seven questionnaires were evaluated. The data show a significantly higher risk of self‐reported symptoms in the female group, among persons with higher education and in the age group of 18–39 years. Among individuals with clinical symptoms, females were at lower risk of having positive skin prick tests [aOR=0.32; 95% CI (0.21–0.50); P<0.01] and having a raised total IgE [aOR=0.37; 95% CI (0.24–0.56); P<0.01], but showed a higher risk of non‐IgE and IgE‐mediated food hypersensitivity [aOR=2.27; 95% CI (1.31–3.93); P<0.01] than males. Based on weighted data, the point prevalence of adverse reactions to food resulted in 3.3% [95% CI (2.4–4.5%)] for women and 1.8% [95% CI (1.2–2.7%)] for men after DBPCFC. Conclusion From a general population survey conducted in Germany, we determined that women are at greater risk of having symptoms of food allergy and also at greater risk of having DBPCFC‐confirmed symptomatic food allergy. However, among individuals with symptoms of food allergy, men have a higher prevalence of food‐specific IgE‐sensitization and of raised total IgE than women.     

The natural history of cow's milk allergy in north-eastern Poland

PurposeThe rate of cow's milk allergy diminishes with age. There is not enough information concerning geographical trends in persistent cow's milk allergy in children. The objective of the study was to evaluate the prevalence of persistent cow's milk allergy in children previously diagnosed with IgE-mediated cow's milk allergy (CMA).Material/MethodsDiagnosis of cow's milk allergy was established by a medical history of symptoms associated with exposure to cow's milk, positive skin prick tests with cow's milk, the presence of milk-specific IgE, and by a positive double- or single-blind placebo-controlled food challenge with milk confirmed by a positive open-controlled milk challenge. A second oral challenge was performed after at least one year of a milk-free diet and children with a positive oral milk re-challenge were diagnosed as having a persistent CMA.ResultsTwo hundred ninety-one children, 2–14 years of age (mean 5.30±3.16 years, 95% CI, 5.02-5.62 years) completed the study. Persistent CMA was diagnosed in 79 patients (27.1%). Two hundred twelve children (72.9%) outgrew their allergy to cow's milk at a mean age of 5 years after an average time of 16.4±0.8 months on an elimination diet. Eighty percent of children below 3 years of age became milk tolerant. Milk-specific IgE (p=0.018) and history of paternal bronchial asthma and/or rhinitis (p=0.020) were associated with persistence of cow's milk allergy in regression analysis.ConclusionsAn age above 3 years, as well as features of atopy, individual and familial, may be associated with a risk of delayed tolerance to milk in children.     

Tolerance to a rice hydrolysate formula in children allergic to cow''s milk and soy

BACKGROUND: Even hydrolysed cow's milk formulae may retain residual allergens and there are few nutritional options for children with cow's milk allergy (CMA) who also react to soy. OBJECTIVE: To assess clinical tolerance to a rice-based hydrolysate in children with such a clinical presentation. PATIENTS AND METHODS: Eighteen children (six girls and 12 boys; median age 5 years; range 1-9 years) with CMA, who developed clinical reactions to a soy-based formula after 2-18 months' treatment, were recruited between January 1998 and June 1999. Clinical evaluation was by skin prick test (SPT) with cow's milk, casein, lactalbumin, soy and rice allergen extracts, fresh cow's milk, soy and hydrolysated rice formula (HRF). Serology was investigated by CAP system technology and immunoblotting. Assessment of the rice formula was carried out by double-blind, placebo-controlled food challenge with rice hydrolysate. RESULTS: Thirteen children had positive SPT to casein, 10 to lactalbumin, eight to rice and two to rice hydrolysate. Positive serology was found in all patients' sera tested with cow's milk, with soy in 13 sera and with rice in seven. Double-blinded, placebo-controlled challenge with an HRF was negative in all cases. CONCLUSIONS: Children allergic to cow's milk and soy tolerate an HRF clinically. This suggests that rice hydrolysate may be used as a protein source for children with multiple food-induced reactions.     

Distinct patterns of cow's milk allergy in infancy defined by prolonged, two-stage double-blind, placebo-controlled food challenges

Background The clinical manifestations of cow's milk allergy (CMA) are highly variable, and challenges usually identify only immediate. IgE mediated reactions. Objective To clearly identify CMA of immediate and delayed types using a two-stage. double-blind, placebo-controlled food challenge (DBPCFC), and to prospectively compare the clinical history and analyses of specific IgE antibodies to milk in predicting outcome of DBPCFC. Methods A total of 69 patients (33 girls, 36 boys) were recruited for sludy based on a history highly suggestive of CMA and resolution of symptoms on a bovine protein-free diet. After skin-prick tests (SPTs) and search for allergen-specific serum IgE antibodies by enzyme allergosorbent test (EAST), a two-stage DBPCFC was performed over several days. Results Of 16 patients (mean age 36.9 months) classified as probable immediate reactors based on the history, 10 (62.5%) had a positive DBPCFC with similar patterns to historical adverse reactions (≥ 2 h after milk exposure). The other 53 (77%) patients (17.3 months) had a history of probable delayed type CMA presenting with predominantly gastrointestimal symptoms from 2h and up to 6 days after milk exposure. Of these. 15 (28.8%) had a positive DBPCFC. again with a symptom pattern similar to the history. Sensitivity/specificity of SPT was similar to that of EAST for both immediate (70/83% and 62/83% respectively. NS) or delayed (0/97% and 0/97%) CMA confirmed by DBPCFC. Conclusions Using our two-stage, prolonged DBPCFC, we clearly identified two groups of children with CMA, reflecting different pathogenesis of either immediatetype IgE-dependent, or delayed-type IgE-independent allergy. Although useful in immediate reactors. IgE antibody determination cannot predict the outcome of DBPCFC in delayed reactors. A thorough clinical history was the mo.st helpful tool to predict the type of response in challenge positive patients.     

Risk factors for asthma in urban Ghana.

BACKGROUND: Asthma is increasing in prevalence and severity in Africa. Previous studies have suggested that the prevalence of atopy in West Africa was low. OBJECTIVE: We sought to investigate the risk factors for asthma in Ghanaian school children. METHODS: Fifty children (age range, 9-16 years) with a physician diagnosis of asthma and asthma symptoms within the previous 12 months and 50 age- and sex-matched healthy control subjects were randomly selected and evaluated by means of questionnaire, skin testing, total and specific IgE measurements, and allergen level measurements from bed dust samples (mite, cat, dog, and cockroach). RESULTS: Asthmatic children were exposed to higher levels of mite allergens than were control children (geometric mean, 19 microg/g [95% CI, 13.6-26.5] vs. 11.2 microg/g [7.4-15.7]; P <.05). Cat and dog allergen levels were low. There was a marked dissociation between skin test responses and the presence of specific IgE to cat and dog (CAP method). However, 84% of subjects with positive cat dander-specific IgE levels in cat CAP tests and negative skin test responses did not have Fel d 1-specific IgE (chimeric ELISA). In the univariate analysis significant associations with the patient group were found for sensitization to mite (odds ratio [OR], 9.3; 95% CI, 3.7-23.4) and cockroach (OR, 3.9; 95% CI, 1.3-11.6), inner-city residence (OR, 3.5; 95% CI, 1.4-8.9), asthma in family member (OR, 3.5; 95% CI, 1.4-9.0), low (<5) position in sibship (OR, 3.6; 95% CI, 1.2-11), presence of smoker in home (OR, 3.7; 95% CI, 1.2-11.9), small household size (OR, 0.57; 95% CI, 0.35-0.93), and use of electricity as domestic fuel (OR, 0.34; 95% CI, 0.12-0.97). In the multivariate analysis sensitization to mites remained the strongest risk factor associated with the asthmatic group (OR, 10.4; 95% CI, 3.5-30.9). The other significant associations were inner-city residence (OR, 4.8; 95% CI, 1.5-5.2), sensitization to cockroach (OR, 4.9; 95% CI, 1.3-18.6), and position in sibship of less than 5 (OR, 6.3; 95% CI, 1.3-29.4). CONCLUSION: Sensitization to dust mite and cockroach allergens, inner-city residence, and low position in sibship were independent risk factors for asthma in Ghanaian children.     

Reducing the need for food allergen challenges in young children: a comparison of in vitro with in vivo tests

BACKGROUND: Double-blind placebo-controlled food challenges (DBPCFC), the gold standard for the diagnosis of food hypersensitivity, are time-consuming and not without risk. We have recently reported skin prick test (SPT) weal diameters to cow's milk, egg and peanut above which infants and young children referred for investigation of suspected food allergy showed an adverse reaction on food challenge. We have termed these the "100% diagnostic SPT levels". In this study, we compare in vivo with in vitro measurement of IgE antibody levels to three common food allergens--cow's milk, egg and peanut--in infants and young children with suspected food allergy, in order to reduce the need for food challenges. METHODS: SPT and Enzyme Allergo-sorbent Test (EAST) (from 1992 to 1998) and CAP values (from 1999 to 2000) were performed in 820 children < 2 years of age with suspected allergy to cow's milk and/or egg and/or peanut. SPT levels previously shown to be diagnostic of challenge-proven allergy to cow's milk, egg and peanut were used as the "100% diagnostic SPT levels" and compared with EAST and CAP values associated with IgE food allergy according to the manufacturer's definition. RESULTS: McNemar's test showed a significant difference between the "100% diagnostic SPT levels" and positive EAST in identifying patients who did not require food challenge for cow's milk (P = 0.01), egg (P < 10-6) and peanut (P < 10-6), and a significant difference between the "100% diagnostic SPT levels" and positive CAP (P < 10-6) for egg and peanut but not cow's milk. Twenty-three per cent of food challenges which, based on the results of EAST and CAP, would have been necessary to confirm the diagnosis of food allergy were avoided by the use of the "100% diagnostic SPT levels" . CONCLUSION: The use of the "100% diagnostic SPT levels" compared with in vitro measurement of IgE antibody to cow's milk, egg and peanut reduces the need for food challenge in young children with suspected food allergy.     

IgE and IgG binding epitopes on alpha-lactalbumin and beta-lactoglobulin in cow's milk allergy.

BACKGROUND: Cow's milk is one of the most common causes of food allergy in the first years of life. We recently defined IgE and IgG binding epitopes for alpha(s1)-casein, a major cow's milk allergen, and found an association between recognition of certain epitopes and clinical symptoms of cow's milk allergy (CMA). Since alpha-lactalbumin (ALA) and beta-lactoglobulin (BLG) are suspected to be significant allergens in cow's milk, we sought to determine the structure of sequential epitopes recognized by IgE antibodies to these proteins. We further sought to assess the pattern of epitope recognition in association with the clinical outcome of CMA. METHODS: According to the known amino acid sequence of ALA and BLG, 57 and 77 overlapping decapeptides (offset by two amino acids), respectively, were synthesized on a cellulose derivatized membrane. Sera from 11 patients 4-18 years of age with persistent CMA (IgE to cow's milk >100 kU(A)/l) were used to identify IgE binding epitopes. In addition, 8 patients < 3 years of age and likely to outgrow their milk allergy (IgE to cow's milk < 30 kU(A)/l) were used to investigate the differences in epitope recognition between patients with 'persistent' and those with 'transient' CMA. Seven patients 4-18 years of age were used for assessing the IgG binding regions. RESULTS: In patients with persistent allergy, four IgE binding and three IgG binding regions were identified on ALA, and seven IgE and six IgG binding epitopes were detected on BLG. The younger patients that are likely to outgrow their allergy recognized only three of these IgE binding epitopes on BLG and none on ALA. CONCLUSIONS: The presence of IgE antibodies to multiple linear allergenic epitopes may be a marker of persistent CMA. The usefulness of IgE binding to distinct epitopes on whey proteins in defining the patients that would have a lifelong CMA needs to be investigated in further studies.     

Concurrent cereal allergy in children with cow''s milk allergy manifested with atopic dermatitis

BACKGROUND: There is increasing consensus about the significance of food allergens in the pathogenesis of atopic dermatitis (AD) in infancy and childhood, with cow's milk and egg accounting for most of the reactions. Previous studies have indicated that multiple food sensitization, such as cereals, is very common in patients with cow's milk allergy (CMA). Evidence is lacking, however, as to its clinical relevance. OBJECTIVE: The purpose of this study was to determine the concurrent occurrence of cereal allergy among children with challenge-proven CMA who have residual symptoms, such as AD and/or gastrointestinal symptoms, during cow's milk elimination diet. Further, we sought to evaluate the utility of patch testing in prescreening foods other than cow's milk behind allergic symptoms in children. METHODS: The study population comprised 90 children, aged from 2.5 to 36 months (mean 1.1 years), with challenge-proven CMA. As a result of residual symptoms during meticulous cow's milk elimination diet (AD: n=80, and gastrointestinal: n=10), the children were put on a cereal elimination diet (oats, wheat, rye, and barley) and skin prick tests (SPT) and patch testing with cereals were performed. Open cereal challenge was performed to confirm cereal allergy. RESULTS: Cereal challenge was positive in 66 (73%) of the children with CMA. Of them, 17% reacted with immediate reactions and delayed-onset reactions were seen in 83% of the children. SPT was positive in 23%, patch test in 67%, and either SPT or patch test was positive in 73% of the children with cereal allergy. SPT gave the best positive predictive value, whereas SPT together with patch test gave the best negative predictive value. CONCLUSIONS: Residual symptoms, such as eczema or gastrointestinal symptoms in CMA children may be a sign of undetected allergy to other food antigens. SPT with cereals aids in diagnosing cereal allergy in small children, especially when used together with patch testing.