Assessing eczema and food allergy in young children

Background: Atopic disease is an increasing problem. Eczema affects 10-20% of young children, and 33-37% of children with eczema are food allergic. Among other factors, nitric oxide (NO) is thought to play a role in eczema and food allergy. Following the atopic march, pproximately 80% of children with atopic eczema will become sensitized to aeroallergens and develop asthma and/or allergic rhinitis. Skin prick test is used for investigating sensitization and is considered a safe method. However, systemic allergic reactions may appear when the test is performed. In diagnosing food allergy and for evaluating achievement of tolerance, the oral food challenge is the method of choice, and the double-blind placebocontrolled fashion is 'the gold standard'. Skin prick test: We examined six cases of generalized allergic reactions in connection with skin prick testing in order to identify risk factors, and thereby increase safety, and we investigated the necessity of performing skin prick tests in duplicate. We found that all six children with generalized reactions were <6 months of age. When analyzing skin prick tests in duplicate, we found only 1.3% that showed diverging results, and in infants <6 months even fewer, 0.9%. Food challenge: We developed recipes and a protocol for low-dose oral food challenge to milk and egg to be used in young children outgrowing their food allergy so as to facilitate early re-/introduction of small amounts of milk and egg. We performed 52 challenges, both open and double-blind placebo controlled. The recipes were validated for blinding. The lowdose challenge was tolerated well by the children and was easy to perform. Four children had a positive challenge outcome, all reacting to very small amounts of milk. All but two of the non-reacting children were able to introduce milk and egg into their diet. Nitric oxide and eczema: We investigated the effect of eczema treatment on the NO levels in urine. The sum of nitrite and nitrate was measured in urinary samples from 94 infants at two visits, with an interval of 6 weeks, and the results were compared with clinical data. The levels of NO products increased significantly when the eczema improved. The atopic march: The aim was to evaluate the atopic march in children with eczema, from referral at <2 years until 4½ years of age. We followed 123 children with eczema, 78 sensitized and 45 not sensitized to milk and/or egg, with respect to eczema severity, other allergic manifestations, development of airway sensitization, and achievement of food tolerance. The difference in severity of eczema at referral was significant when comparing food-sensitized with non-sensitized children. At follow-up, 62% were still affected by eczema, although 56% only mildly so. Tolerance was achieved in 81% of the children allergic to milk and 68% of those allergic to egg. Fifty-eight percent of the food-sensitized children and 26% of the non-sensitized children had become sensitized to aeroallergens, a significant difference. The difference in airway symptoms was not significant. Very few children were exposed to tobacco smoke in their homes. Conclusions: Increased precautions should be considered when performing skin prick tests in infants <6 months of age. The use of a single prick, to avoid the risk of summation of reactions, is justified when performing skin prick tests. We report recipes and a protocol 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. NO products in urine increases when eczema improves. This might be due to a Th2/Th1 shift induced by the eczema treatment and skin healing, and the variation in NO response may be due to individual variations in NO-induced feedback downregulation of Th1 and Th2 proliferation. The prognosis for achieving clinical tolerance is very good in children early sensitized and allergic to milk and egg, but they will become significantly more often sensitized to aeroallergens

Linköping University Post Print Urinary nitric oxide excretion in infants with eczema

N.B.: When citing this work, cite the original article. This is the authors ’ version of the following article: which has been published in final form at

Running title: IgG4 and elimination diet Corresponding Author:

High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in lif

Urinary nitric oxide excretion in infants with eczema

Eczema is characterized by inflammation of the skin and is commonly associated with food allergy. It has been suggested that nitric oxide (NO) is an important player in eczema, food allergy and intestinal inflammation. The aim of this study was to assess the levels of urinary NO breakdown products in infants with eczema and the effect of eczema treatment on NO levels. Ninety-four infants with eczema, 58 boys and 36 girls, with a mean age of 7.5 ± 5.2 months (mean ± s.d.) at inclusion were examined twice with an interval of 6 wk. The sum of nitrite and nitrate was measured colorimetrically in urinary samples from both visits and compared with clinical data concerning eczema severity, nutrition, gastrointestinal symptoms, asthma and skin prick positivity. The levels of NO products increased significantly from the first to the second visit: 289; 374 μm (median; IQR) vs. 457; 678 μm (median; IQR) (p &lt; 0.001) in parallel with a significant improvement of the eczema. After eczema treatment consisting of skin care and elimination diet during the 6-wk interval between evaluations, the NO levels approached the values previously found in healthy children. The results support previous studies indicating that the homeostasis of nitrogen radicals is disturbed in childhood eczema.Tidigare titel: Nitric oxide urinary products in infants with eczema This is the authors’ version of the following article: which has been published in final form at:Irene Devenney, Gunilla Norrman, Tony Forslund, Karin Fälth-Magnusson and Tommy Sundqvist, Urinary nitric oxide excretion in infants with eczema., 2010, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, (21), 1, E229-E234which has been published in final form at: http://dx.doi.org/10.1111/j.1399-3038.2009.00892.xCopyright: Wiley-Blackwell</p

High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in life

Children with eczema and sensitization to foods are recommended skin care and, if food allergy is proven by challenge, an elimination diet. For most children the diet period is transient, but the process behind tolerance development and the influence of decreased allergen exposure is not fully known. The aim of the study was to investigate the effect of elimination diet on serum and salivary antibodies and to identify immunological parameters related to the ability to tolerate foods. Eighty-nine children, below 2 yr of age, with eczema and suspected food allergy were included. Recommended treatment was skin care to all children, and 60 children had a period of elimination diet. At 4½ yr of age, the children were divided into two groups, based on if they had been able to introduce the eliminated foods, or not. Serum and salivary antibodies were analyzed with enzyme-linked immunosorbent assay and UniCAP® before and after a 6-wk treatment period and at 4½ yr of age. Children sensitized to egg and/or milk that could eat and drink the offending foods at 4½ yr of age, had higher levels of Immunoglobulin G4 antibodies to ovalbumin and β-lactoglobulin and also higher IgG4/Immunoglobulin E ratios on inclusion in the study, than those who had to eliminate egg and/or milk from their diet, beyond 4½ yr of age. The highest IgG4/IgE ratios were found in children with circulating IgE antibodies to egg and/or milk but negative skin prick test on inclusion. The 6-wk treatment period did not significantly affect the levels of serum and salivary antibodies. In conclusion, eczematous, food sensitized infants with high levels of IgG4 and high ratios of IgG4/IgE antibodies to food allergens are more likely to consume these foods at 4½ yr than infants with low levels and ratios.The fulltext of this work is available at Blackwell-Syergy:Sara Tomičić, Gunilla Norrman, Karin Fälth-Magnusson, Maria C. Jenmalm, Irene Devenney and Malin Fagerås Böttcher, High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in life, 2008, Pediatric Allergy and Immunology, (5), 1, 35-41.http://dx.doi.org/10.1111/j.1399-3038.2008.00738.xCopyright: Blackwell-Synergyhttp://www.blackwellpublishing.com

Percentage of children who had had at least one episode of wheezing before inclusion in the groups who had no airway symptoms, allergic rhinoconjunctivitis and asthma at 10 years.

<p>Percentage of children who had had at least one episode of wheezing before inclusion in the groups who had no airway symptoms, allergic rhinoconjunctivitis and asthma at 10 years.</p

Percentage of children who had allergic rhinoconjunctivitis at 4.5 years among the groups with no airway symptoms, allergic rhinoconjunctivitis and asthma at 10 years.

<p>Percentage of children who had allergic rhinoconjunctivitis at 4.5 years among the groups with no airway symptoms, allergic rhinoconjunctivitis and asthma at 10 years.</p

Percentage of children who were diagnosed with asthma at 4.5 years in the groups with no airway symptoms, allergic rhinoconjunctivitis and asthma at 10 years.

<p>Percentage of children who were diagnosed with asthma at 4.5 years in the groups with no airway symptoms, allergic rhinoconjunctivitis and asthma at 10 years.</p

An overview of examinations and tests performed on the children with eczema on inclusion, at 4.5 years and at 10 years.

<p>An overview of examinations and tests performed on the children with eczema on inclusion, at 4.5 years and at 10 years.</p