Phadiatop infant in the diagnosis of atopy in children with allergy-like symptoms.

Background and Objective. Allergy-like symptoms such as wheezing and eczema are common in young children and an early diagnosis is important to initiate correct management. The objective of this study was to evaluate the diagnostic performance of Phadiatop Infant, an in vitro test for determination of early sensitisation to food and inhalant allergens. Patients and Methods. The study was conducted, retrospectively, using frozen sera from 122 children (median age 2.7 years) admitted to the hospital with suspected allergic symptoms. The doctor's diagnosis atopic/nonatopic was based on routinely used procedures such as clinical evaluation, SPT, total and allergen-specific IgE antibodies. The performance of Phadiatop Infant was evaluated in a blinded manner against this diagnosis. Results. Eighty-four of the 86 children classified as atopic showed a positive Phadiatop Infant test. Thirty-six were classified as nonatopic, 32 of who had a negative test. With a prevalence of atopy of 70% in this population, this gives a sensitivity of 98%, a specificity of 89%, and a positive and negative predictive value of 95% and 94%, respectively. Conclusion. The results from the present study suggest that Phadiatop Infant could be recommended as a complement to the clinical information in the differential diagnosis on IgE-mediated disease in young children with allergy-like symptoms.

Is there an increased frequency of food allergy in children delivered by caesarean section compared to those delivered vaginally?

AIM: Allergic diseases are increasing. At the same time an increasing number of children are delivered by caesarean section. These children do not get the same contact with their mother's gut flora as babies delivered vaginally. Theoretically, lack of exposure to maternal vaginal and perineal bacteria might change the gut flora, with secondary changes in the immune system. The aim of this study was to investigate whether children delivered by caesarean section were more prone to develop food allergy. METHODS: Six hundred and nine children were included at birth. At 2-year follow-up, 512 children participated, 171 delivered by caesarean section, 341 born vaginally. The children reported to have symptoms consistent with possible food allergy, were examined at the outpatient clinic. The diagnosis was based on the history, skin prick test (SPT), specific IgE, elimination/challenge test and double blind placebo controlled challenge. RESULTS: Thirty-five (6.8%) children were diagnosed with adverse reactions to food, 27 with non-IgE-mediated and eight with IgE-mediated allergy. There was no over representation of children born by caesarean section. CONCLUSION: In this study there seems to be no increased risk for food allergy in the first 2 years of life in children delivered by caesarean section.

Adverse reactions to milk in infants.

AIM: To study the age when symptoms of adverse reactions to milk occur, in premature and term children, the debut of various symptoms, immunoglobulin E (IgE)- and non-IgE-mediated reactions and the frequency of tolerance at 1 year. METHODS: Six hundred and eight children, 193 premature and 416 term infants, were followed. Symptomatic children were invited to a clinical examination. The criteria for the diagnosis were: histories of suspected cow's milk allergy (CMA) and proven IgE-mediated reactions to cow's milk or positive elimination/challenge tests. RESULTS: Twenty-seven out of 555 (4.9%) were diagnosed with adverse reactions to cow's milk. All had symptoms before 6 months of age. The main symptoms were: pain behaviour (13), gastrointestinal symptoms (7), respiratory symptoms, (6) and atopic dermatitis (1). One child had proven IgE to cow's milk. Premature and term infants displayed the same symptoms and age of debut. Thirteen children were tolerant to cow's milk at 1 year. CONCLUSION: Adverse reactions to milk start early in life, with pain behaviour, gastrointestinal, and respiratory symptoms being the most common, and rarely atopic dermatitis. Non-IgE-mediated reactions were the most frequent. Symptoms and age of debut were the same in premature and term infants. Half of the children tolerated cow's milk at age 1.

Lupin sensitization and clinical allergy in food allergic children in Norway.

AIM: The aim of the present pilot study was to investigate to what extent children in Norway sensitized to lupin had clinical lupin allergy, and to compare sensitization to lupin with sensitization to other legumes. METHODS: Thirty-five children with food allergy referred to a national referral hospital were evaluated with skin prick test (SPT) and analysis of serum-specific IgE to lupin, peanut, pea and soy. The children with positive SPTs to lupin were offered oral food challenges with lupin flour. RESULTS: Fifteen children (43%) had positive SPT and 17 children (49%) had serum-specific IgE to lupin. Ten SPT-positive children underwent oral food challenges and one experienced an allergic reaction to lupin flour. This child was one of six challenged children with IgE antibodies to peanut >15 kU(A)/L. There was a strong relationship between positive SPT to lupin flour and positive SPT to soy and between positive SPT to lupin and specific IgE to soy, pea and peanut. CONCLUSIONS: Children with sensitization to lupin are not likely to have a clinical lupin allergy. Avoidance of lupin on the basis of lupin sensitization or peanut allergy would lead to unnecessarily strict diets. Food challenge is currently necessary to diagnose lupin allergy.

Casein-specific immunoglobulins in cow's milk allergic patient subgroups reveal a shift to IgA dominance in tolerant patients.

Differences in casein-specific immunoglobulin (Ig) G-subclass and IgA serum levels between reactive and tolerant patients may hint at the immunopathogenesis during tolerance development in cow's milk allergy (CMA). alpha-, beta- and kappa-casein-specific IgG(1), IgG(4), IgE and IgA serum levels were compared in clinically reactive and tolerized IgE-mediated (n = 15) and non-IgE-mediated (n = 14) CMA with delayed gastrointestinal symptoms, using enzyme-linked immunosorbent assay (ELISA) and immunoblot techniques. The median anti-casein IgE levels in clinically reactive IgE-mediated CMA patients (n = 9) were 140- to 180-fold higher than in tolerized patients (n = 6) and 160- to 200-fold higher than in controls (n = 10). Median alpha-, beta- and kappa-casein-specific IgG(1) and IgG(4) levels were nine- to 60-fold higher in reactive patients and five- to 60-fold in tolerized patients. Clinical tolerance in IgE-mediated CMA was thus associated with decreased casein-specific IgE, IgG(4) and IgG(1), whereas serum IgA anti-alpha -, beta- and kappa-casein remained practically unaltered. Tolerized cow's milk protein (CMP)-sensitive atopic dermatitis had, in particular, decreased kappa-casein-specific IgG(1) levels, compared with clinically reactive patients. The ELISA levels to immunoblot correlation profile for the alpha-, beta- and kappa-casein-specific IgE suggested that the IgE-mediated CMA patients predominantly reacted to tertiary alpha- and beta-casein epitopes whereas the IgE in non-IgE-mediated patients reacted to linearized alpha-, beta- and kappa-casein epitopes. Clinical tolerance in non-IgE-mediated CMA patients (n = 9) was associated with a four- to 10-fold decrease in casein-specific IgE levels, accompanied by a five- to eightfold decrease in IgG(1) and five- to 60-fold decrease in IgG(4) levels, whereas casein-specific IgA levels remained unaltered. Thus, tolerance in both patient groups was characterized by a generalized decreased humoral immune response to caseins, which induced a functional shift to IgA dominance.

Memory T cell proliferation in cow's milk allergy after CD25+ regulatory T cell removal suggests a role for casein-specific cellular immunity in IgE-mediated but not in non-IgE-mediated cow's milk allergy.

BACKGROUND: Previously reported increased lymphocyte proliferative responses in cow's milk allergy (CMA) may have been influenced by the lipopolysaccharides (LPS) which contaminate most commercial cow's milk protein (CMPs). Moreover, peripheral blood mononuclear cells (PBMC) contain both B cells, CD45RA+ naïve T cells, CD25+ regulatory T cells (Tregs) in addition to antigen-specific CD45RA- memory T cells. METHODS: PBMC from clinically reactive and tolerised patients with IgE- and non-IgE-mediated CMA were depleted of CD45RA+ T cells and putative CD25+ Tregs. The proliferative index to LPS-depleted alpha-, beta- and kappa-casein and beta-lactoglobulin was compared in the memory T-cell-enriched, Treg-depleted PBMC and in bulk PBMC. RESULTS: Clinically reactive IgE-mediated CMA patients had increased responses to caseins only. Tolerised patients, particularly those with atopic dermatitis, had decreased responses to kappa-casein which were restored after Treg depletion. Interleukin-4 and interferon-gamma were generally not detected in the culture supernatants. No differences were seen between reactive and tolerant delayed non-IgE-mediated CMA patients. CONCLUSIONS: Proliferative responses to alpha-, beta- and kappa-caseins (but not beta-lactoglobulin) were observed in clinically reactive IgE-mediated CMA patients only. A markedly decreased proliferative response to kappa-casein in tolerised IgE-mediated CMA patients with atopic dermatitis, which was abrogated by Treg depletion, suggested a role for kappa-casein in tolerance induction. Non-IgE-mediated CMA patients had no increased proliferative response to any milk proteins.

Changes in humoral responses to beta-lactoglobulin in tolerant patients suggest a particular role for IgG4 in delayed, non-IgE-mediated cow's milk allergy.

The major cow's milk allergen beta-lactoglobulin (beta-LG) is relatively resistant to enzymatic degradation and may therefore be involved in non-immunoglobulin (Ig)E-mediated cow's milk allergy (CMA) with delayed gastrointestinal symptoms. Serum levels of beta-LG-specific IgG(1), IgG(4), IgE, and IgA were compared in clinically reactive and tolerized IgE-mediated and non-IgE-mediated CMA with delayed gastrointestinal symptoms (n = 29) and controls (n = 10). Tolerance was associated with decreased beta-LG-specific IgE, IgG(1), and IgG(4) levels in both patient groups. However, the significantly increased beta-LG-specific IgG(4) levels in clinically reactive non-IgE-mediated CMA patients, and its median 36-fold reduction in tolerant patients, suggested a possible immunopathological role for IgG(4) in delayed CMA. Similarly, the significantly increased beta-LG-specific IgE levels in IgE-mediated CMA patients were decreased 44-fold in tolerant patients. The tolerant patients had apparently shifted the humoral immune response from a beta-LG-specific IgE- and/or IgG(4)-dominated immune response to an IgA-dominated immune response as the IgA/IgE or IgA/IgG(4) ratios increased 90- and 15-fold in tolerant IgE-mediated-, and non-IgE-mediated CMA patients, respectively. Thus, the marked difference in beta-LG-specific Ig ratios suggested a tolerance-induced inhibition of a Th(2)-type of immune response with significantly increased IgA dominance in both CMA patient groups.

[Diagnosing allergic reactions to ingested wheat in children]. / Diagnostikk av reaksjon på hvete i maten hos barn.

BACKGROUND: Sensitisation to wheat demonstrated by specific IgE without clinical reactions to ingested wheat is common. Clinical allergy towards wheat may cause anaphylactic or mild reactions. Until now, oral challenge tests have been necessary for diagnosing severe reactions to ingested wheat. We wanted to distinguish between severe and mild reactions by using three different IgE tests against wheat. MATERIAL AND METHODS: 29 children with elevated levels of specific IgE against wheat (f4 test) were referred to our hospital for further diagnostic procedures. We performed specific IgE tests against different wheat components (f4, f79 and f98) and oral provocation tests. RESULTS: 10 children with severe clinical reactions had high levels at all three specific IgE tests and comparable levels between the tests. The 4 children with mild reactions showed varying values of IgE but very similar levels between the three different tests. 15 children had negative provocation tests, varying levels of specific IgE, and less similar levels between the tests. INTERPRETATION: Available specific IgE tests are not useful in order to distinguish between severe, mild or no clinical reactions to ingested wheat. Oral challenge tests are still needed for correct diagnosis of severe wheat allergy.

[Growth and dietary intake among children with previous cow's milk allergy]. / Vekstutvikling og kosthold hos barn som har hatt kumelkallergi.

BACKGROUND: Approximately 2-3% of children develop allergy or intolerance to cow's milk and many of them go on a milk-free diet for a long time. Few studies have been done on growth and dietary intake among these children. MATERIAL AND METHODS: 28 children aged 6-10 who had recovered from cow's milk allergy, divided into groups "low-milk" and "ad lib milk", were compared with a control group of 32 children of same age. Growth rates from age one and dietary intake at present age based on four days weighed dietary assessment were used. RESULTS: Among the allergic children at ages 6-10, 50% had developed tolerance to cow's milk protein, while 35% used some dairy products. A totally milk-free diet was kept by 15%; these children were excluded from the study. The children with allergy had low body weight and height at ages one, two and four and at the present age compared with the controls. The energy intake was the same in both groups. The total sample had higher intake of sugar and lower intake of vitamin D than the recommended values. The 35% of children with restricted intake of cow's milk had lower intake of calcium, riboflavin and protein. The 50% of children with ad lib intake of milk products had a diet that differed little from that of the non-allergic children. INTERPRETATION: There is a need for further studies on growth, dietary intake and development of tolerance that could give health workers better knowledge for dealing with this group of children.

[Anaphylactic reactions after intake of products with wheat]. / Anafylaktiske reaksjoner etter inntak av produkter med hvetemel.

BACKGROUND: Food allergy is common in small children. Sensitisation to wheat is frequent, reactions to ingested wheat more seldom and mostly associated with atopic eczema and exercise-induced anaphylaxis. MATERIAL AND METHODS: Eleven children with severe reactions after ingestion of small amounts of wheat were referred to us for further diagnostic procedures. Skin prick tests, total and specific IgE as well as oral provocation test were performed. RESULTS: All but two children had strongly positive skin prick tests results to wheat. The same two children had specific IgE to Immunocap f4 (a-amylase) < 10 kUa/L while the nine other children had specific IgE to f4 > 29 kUa/L. All children had general reactions when provoked orally with small amounts of wheat with the need for administration of adrenalin and in most cases oral steroids. INTERPRETATION: It is important to identify children at risk for general reactions to wheat, as cereals are staple foods in our community. Identification of the proteins involved in serious reactions is essential.

The effects of long meditation on plasma melatonin and blood serotonin.

BACKGROUND: The benefits of meditation are well documented, but the biochemical mechanisms have not been fully identified. One effect mechanism may be via influence on neurotransmitters. MATERIAL/METHODS: Therefore, plasma melatonin and blood serotonin concentrations were measured before and after one hour of meditation in advanced male meditators (n=27, mean age 46 years). They were compared with a matched reference group (n=29, mean age 43 years) who rested for one hour. In the meditators, melatonin and serotonin from before and after three consecutive hours of meditation were also compared. RESULTS: Initially, the median melatonin level was 4.9 pg/ml-1 in the meditators and 3.1 pg/ml-1 in the reference group (p<0.01). After one hour of practice, melatonin had decreased to a median of 3.4 pg/ml-1 in the meditators (p<0.0001), but was unchanged in the reference group. After three hours of meditation, melatonin had declined further in the meditators. After one hour of practice, serotonin concentrations decreased in both the meditators and the reference group (p<0.01). CONCLUSIONS: The findings suggest that advanced meditators have higher melatonin levels than non-meditators. Melatonin decreases during long meditation, a finding the study does not explain. Serotonin declines after both one-hour meditation and rest, indicating that serotonin may be a marker of general rest and not meditation-specific relaxation.

[Oral provocation tests for adverse reactions to food]. / Kostprovokasjoner ved unormale reaksjoner på mat.

BACKGROUND: Diagnosis of adverse reactions to food is difficult, but important. The prevalence of perceived adverse reactions is high, especially in small children. MATERIAL AND METHODS: 72 children 0-17 years of age hospitalised in our clinic for investigation of adverse food reactions. Oral provocation tests were performed open, blind and double blind. RESULTS: 41 (20 %) positive provocation tests were registered, 31 by nurses and doctors only, ten solely by parents. Eggs and cow's milk were the most common causes of positive reactions, fish and wheat gave somewhat less reactions. Of the positive provocations, 19 had different outcomes from what was expected; 89 % of the children could have one or more foods added to their diet, wholly or in part. INTERPRETATION: Systematic use of oral provocation tests may be of use to eliminate unnecessary diets in children.