High incidence and remission of reported food hypersensitivity in Swedish children followed from 8 to 12 years of age – a population based cohort study

Background: Few population-based cohort studies have examined reported food hypersensitivity longitudinally. We investigated prevalence, incidence and remission of perceived food hypersensitivity among schoolchildren from 8 to 12 years of age, and risk factors associated with incidence and remission. Methods: A population-based cohort including all 7–8 year-old children in three Swedish towns was recruited in 2006. A total of 2,585 (96% of invited) children participated in a parental questionnaire. The children in two of the towns, n = 1,700 (90% of invited) also participated in skin-prick-testing with airborne allergens. The cohort was followed using the same methods at 11–12 years of age. At study follow up, specific IgE to foods was analyzed in a randomized subset of children (n = 652). Results: The prevalence of perceived food hypersensitivity increased from 21% at 8 years to 26% at 12 years of age. During this four-year-period, the cumulative incidence of food hypersensitivity was high (15%), as was remission (33%). This pattern was particularly evident for hypersensitivity to cow´s milk, while the incidence of hypersensitivity to other foods was lower. Female sex, allergic heredity, current rhinitis and allergic sensitization were associated with the incidence of food hypersensitivity and allergic sensitization was negatively associated with remission. Risk-factor-patterns for both incidence and remission were different for hypersensitivity to milk compared with hypersensitivity to other foods. Generally, the agreement between reported food hypersensitivity and IgE-sensitization to the implicated food was poor. Conclusions: In this longitudinal, population-based cohort-study perceived food hypersensitivity was common among children between ages 8 and 12, often transient and not well correlated with food-specific IgE. While these findings suggest an overestimated prevalence of food hypersensitivity, the public-health-significance remains high as they reflect the perceived reality to which the children adapt their life and food intakes

Food hypersensitivity among schoolchildren : prevalence, Health Related Quality of Life and experiences of double-blind placebo-controlled food challenges

Background: The prevalence of reported food hypersensitivity among children has increased in Western countries. However, the prevalence varies largely due to differences in methods used in different studies. Double-blind placebo-controlled food challenge (DBPCFC) is the most reliable method to verify or exclude food hypersensitivity. The use of double-blind food challenges is increasing in clinical praxis, but since the method is time- and resource consuming it is rarely used in population-based cohort studies. There is a lack of knowledge on how adolescents and mothers experience participation in double-blind placebocontrolled food challenges and to what extent the food is reintroduced after a negative challenge. While several studies have described the impact of IgEmediated food allergy on Health-Related Quality of Life (HRQL), few studies have described HRQL among children with other food hypersensitivity phenotypes. Aim: The aim of this thesis was to estimate the prevalence of reported food hypersensitivity, associated risk factors, and symptom expressions among schoolchildren. We also examined HRQL among children with total elimination of cow's milk, hen’s egg, fish or wheat due to food hypersensitivity as a group compared with children with unrestricted diet, and after we categorised the children with eliminated foods into different phenotypes of FHS. Finally, adolescents' and mothers' experience of DBPCFC was examined as well if the food had been reintroduced. Methods: Three studies were based on the Obstructive Lung Disease in Northern Sweden (OLIN) paediatric cohort II. The cohort was recruited in 2006 when all children in first and second grade (7-8 years) in three municipalities in Norrbotten were invited to a parental questionnaire study and 2,585 (96% of invited) participated. The questionnaire included questions about food hypersensitivity, asthma, rhinitis, eczema and possible risk factors. The children in two municipalities were also invited to skin prick testing with 10 airborne allergens, and 1,700 (90%) participated. Paper I is based on this initial survey of the cohort. Four years later, at age 11-12 years, the cohort was followed up using the same methods and with the same high participation rate. At the follow-up, 125 children (5% of the cohort) reported total elimination of cow's milk, hen's egg, fish or wheat due to food hypersensitivity. These children were invited to a clinical examination and to complete a generic (KIDSCREEN-52) and a diseasespecific HRQL questionnaire (FAQLQ-TF) (n=75). Based on the clinical examination the children were categorised into different phenotypes of food hypersensitivity: current food allergy, outgrown food allergy and lactose intolerance. In addition, a random sample of children with unrestricted diet from the same cohort, answered the generic questionnaire (n=209). Paper II is based on this HRQL study. Children categorised as having current food allergy were invited to a further evaluation including DBPCFC. Eighteen months after the challenges, these children were interviewed about their experiences during and after the challenge (n=17). Paper III is based on these interviews. Paper IV was based on interviews with mothers to children referred to a paediatric allergy specialist for evaluation of food allergy using DBPCFC (n=8). In the two interview studies results were analysed using qualitative content analysis. Results: At age 7-8 years, the prevalence of reported food hypersensitivity was 21%. Food hypersensitivity to milk, egg, fish, wheat or soy was reported by 10.9% and hypersensitivity to fruits or nuts by 14.6%. The most common essential food to trigger symptoms was milk, reported by 9%. The most frequently reported food induced symptoms, were oral symptoms mainly caused by fruits, followed by gastrointestinal symptoms mainly caused by milk. The risk factor pattern was different for food hypersensitivity to milk compared to hypersensitivity to other foods. No significant difference in distribution in generic or disease-specific HRQL was found among children with reported total elimination of milk, egg, fish and/or wheat due to FHS compared to children with unrestricted diet. However, a trend indicated that the disease-specific HRQL was most impaired among children with current food allergy compared to children with outgrown food allergy and lactose intolerance. The proportion of poor HRQL defined as ≥75 percentile was significantly higher among children with current food allergy than the other phenotypes. A DBPCFC was an opportunity for the adolescents and the mothers to overcome the fear of reactions to food that had been eliminated for a long time. After the challenge, when the food was partially or fully reintroduced, socializing became easier and both adolescents and mothers experienced more freedom regarding food intake. A negative challenge was not consistently associated with reintroduction of the food. Reasons for reintroduction failure were fear of allergic reactions, that the adolescent did not like the taste of the food, or that living with an elimination diet was considered as normal. Conclusion In this population-based study, one in five of children at age 7-8 years reported food hypersensitivity to any food. The generic HRQL was similar among children with and without food hypersensitivity. However, poor disease-specific HRQL was more common among children with current food allergy compared to children with other FHS phenotypes. If the tested food was reintroduced after a DBPCFC, both adolescents and mothers described a changed life with less fear, and that life had become easier regarding meal preparations and social events. As reintroduction failure was present despite a negative food challenge, follow-ups and evaluations of food reintroduction should be performed independent of the outcome of a food challenge.Bakgrund: Andelen barn med rapporterad födoämnesöverkänslighet har ökat. Prevalensen varierar mycket beroende på var studien genomförts och vilka metoder som använts. Dubbel-blinda placebo-kontrollerade födoämnesprovokationer (DBPCFC) är den mest tillförlitliga metoden för att utesluta eller verifiera födoämnesöverkänslighet. I klinisk praxis används DBPCFC alltmer, men eftersom metoden är resurskrävande används den sällan i populationsbaserade studier. Det saknas kunskap om mödrars och tonåringars egna upplevelser av att delta i DBPCFC och i vilken utsträckning livsmedlet återintroduceras efter en negativ provokation. Studier har beskrivit IgE-medierad födoämnesallergi och dess påverkan på hälsorelaterad livskvalitet men det saknas studier om livskvalitet bland barn med andra fenotyper av födoämnesöverkänslighet. Syfte: Syfte med avhandlingen var att undersöka rapporterad förekomst av födoämnesöverkänslighet, riskfaktorer och symtomyttringar bland skolbarn. Vi har även studerat hälsorelaterad livskvalitet bland barn som helt eliminerat baslivsmedel, som hel grupp jämfört med barn utan eliminerad föda, samt efter att barnen kategoriserats i olika fenotyper av födoämnesöverkänslighet. Ett ytterligare syfte var att beskriva ungdomars och mödrars upplevelser, konsekvenser av DBPCFC samt i vilken omfattning livsmedlet återintroducerades. Metod: Tre studier baseras på en barnkohort som rekryterades 2006 inom OLIN studierna (Obstruktiv Lungsjukdom i Norrbotten). Kohorten innefattade alla barn i årskurs 1 och 2 (7-8 år) i Luleå, Kiruna och Piteå där 2585 (96 % av de inbjudna) deltog i en föräldrabesvarad enkät. Enkäten innehöll frågor om födoämnesöverkänslighet, astma, rinit, eksem och möjliga riskfaktorer. Barn från Kiruna och Luleå inbjöds även till pricktest med 10 luftburna allergen och 1700 (90 %) deltog. Artikel I baseras på denna initiala enkätstudie. Fyra år senare följdes kohorten upp med samma metoder och höga deltagande. Totalt 125 barn (5 % av kohorten) uppgav total elimination av mjölk, ägg, fisk och/eller vete på grund av födoämnesöverkänslighet. Dessa barn inbjöds till en klinisk undersökning och 94 barn deltog. Sjuttiofem (80 %) av dessa barn besvarade hälsorelaterade livskvalitetsfrågor innefattande det generiska mätinstrumentet KIDSCREEN-52 samt det sjukdomsspecifika frågeformuläret FAQLQ-TF. Frågeformuläret KIDSCREEN-52 skickades även till ett slumpurval av barn utan eliminationskost från samma kohort, och 209 barn (65 %) deltog. Artikel II baseras på denna hälsorelaterade livskvalitetsstudie. Baserat på den kliniska undersökningen kategoriserades barnen med eliminerad kost i olika fenotyper av födoämnesöverkänslighet: pågående födoämnesallergi, utläkt födoämnesallergi och laktosintolerans. De barn som bedömdes ha pågående födoämnesallergi inbjöds till DBPCFC. Arton månader efter provokationen intervjuades deltagarna om sina upplevelser av provokationen och i vilken omfattning livsmedlet återintroducerades. Artikel III baseras på dessa intervjuer. Den fjärde studien baseras på intervjuer av mödrar vars barn remitterats till en pediatrisk barnallergolog för utredning av misstänkt födoämnesallergi med DBPCFC. Intervjuerna har analyserats med kvalitativ innehållsanalys. Resultat: Vid 7-8 år var prevalensen av rapporterad födoämnesöverkänslighet 21 %. Överkänslighet mot basföda (mjölk, ägg, fisk, vete eller soja) rapporterades av 10.9% och 14.6% uppgav att de reagerade på frukt eller nötter. Klåda i munnen var det vanligaste rapporterade födoämnesutlösta symtomet som huvudsakligen orsakades av frukt. Det näst vanligaste symtomet var mag- och tarmbesvär, huvudsakligen orsakat av mjölk. Riskfaktormönstret för födoämnesöverkänslighet mot mjölk skiljde sig från överkänslighet mot andra födoämnen. Vi fann ingen statistiskt signifikant skillnad i generisk eller sjukdomsspecifik hälsorelaterad livskvalitet mellan barn som helt eliminerat mjölk, ägg, fisk eller vete på grund av födoämnesöverkänslighet jämfört med barn utan eliminerad kost. En trend indikerade att barn med pågående födoämnesallergi hade sämre sjukdomsspecifik hälsorelaterad livskvalitet jämfört med barn med utläkt födoämnesallergi eller laktosintolerans. Dålig livskvalitet, definierat som den ≥75e percentilen i det sjukdomsspecifika frågeformuläret, var vanligast hos barn med pågående födoämnesallergi. Deltagande i DBPCFC var en möjlighet för tonåringar och mödrar att övervinna rädslan för födoämnesorsakade symtom. I de fall då det testade livsmedlet helt eller delvis återintroducerades efter provokationen, upplevde både tonåringarna och mödrarna att det sociala umgänget blev lättare och att de inte längre behövde ha samma kontroll över födoämnesintaget. Ett negativt provokationsutfall resulterade inte alltid i att det testade livsmedlet återintroducerades i kosten. Orsaker till att inte återintroducera födoämnet var rädsla för allergiska reaktioner, att livsmedlet inte smakade gott och att det upplevdes som normalt att leva ett liv utan det eliminerade livsmedlet. Slutsats: Vart femte barn rapporterade någon form av födoämnesöverkänslighet i denna populationsbaserade studie. Det var ingen signifikant skillnad i generisk livskvalitet mellan barn med och utan födoämnesöverkänslighet men barn med pågående födoämnesallergi tenderade att ha sämre sjukdomsspecifik livskvalitet jämfört med barn med utläkt födoämnesallergi och laktosintolerans. De deltagare som återintroducerade det testade livsmedlet efter provokationstestet upplevde att livet var mindre begränsat jämfört med innan provokationen. Alla återintroducerade inte det testade livsmedlet trots en negativ provokation, vilket styrker vikten av uppföljning och utvärdering av födoämnesprovokationer

Food protein-induced enterocolitis syndrome among children in northern Sweden—A retrospective review from 2004–2018

Aim: To describe clinical presentation and development of tolerance among children with Food protein-induced enterocolitis syndrome (FPIES) in a population in northern Sweden. Methods: A retrospective review of medical records of children presenting with FPIES symptoms from 1 January 2004, to 31 May 2018. Results: Sixty children (65% boys) with FPIES were included. The estimated incidence gradually increased to 0.45% in 2016–2017. The most common food triggers were cow's milk (40%), fish (37%) and oat (23%). Symptoms presented in 31 (60%) children before 6 months and in 57 (95%) before 1 year of age. The median age for FPIES diagnosis was 7 (range 3–134) months and for fish FPIES 13 (range 7–134) months. By 3 years of age, 67% of children with FPIES to milk and oat but none of the children with fish FPIES had developed tolerance. Allergic conditions like eczema and asthma were reported in 52% of the children. Conclusion: The cumulative FPIES incidence was 0.45% in 2016–2017. Most children presented with symptoms before 1 year of age, but the diagnosis was often delayed, especially for FPIES to fish. Tolerance development occurred at an earlier age when FPIES was triggered by milk and oat compared to fish

Diagnostic intervention improved health-related quality of life among teenagers with food allergy.

ObjectivesThe aim was to examine if a diagnostic intervention set up to assess current food allergy to cow's milk, hen's egg, fish, or wheat among teenagers had an impact on generic and disease specific health-related quality of life (HRQL). The study compared HRQL scoring before and two years after the intervention, and in relation to age matched controls without reported food allergy.MethodsThe study was performed within the Obstructive Lung Disease in Northern Sweden (OLIN) studies where a cohort study on asthma and allergic diseases among 8-year-old schoolchildren was initiated in 2006. At age 12 years, the 125/2612 (5%) children who reported allergy to cow's milk, hen's egg, fish, or wheat were invited to a diagnostic intervention including clinical examination, blood tests and evaluation by a pediatric allergist. Of 94 participants, 79 completed generic and disease specific HRQL questionnaires. Additionally, a random sample of 200 (62% of invited) children without food allergy from the OLIN cohort answered the generic HRQL questionnaire. The respondents of the HRQL questionnaires were re-examined two years later and 57 teenagers with and 154 without reported allergy participated.ResultsThere were no significant differences in generic HRQL scores between teenagers with and without reported food allergy at study entry, or after the intervention. Among those with reported food allergy, we found a significant improvement in disease specific HRQL after the intervention (mean values: 3.41 vs 2.80, pConclusionThe diagnostic intervention showed a long-term improvement of disease specific HRQL but not generic HRQL

Median scores in KIDSCREEN-52 domains among children with and without food allergy (FA), respectively, before intervention.

Median scores in KIDSCREEN-52 domains among children with and without food allergy (FA), respectively, before intervention.</p

Median scores in KIDSCREEN-52 domains among children with and without food allergy (FA), respectively, after intervention.

Median scores in KIDSCREEN-52 domains among children with and without food allergy (FA), respectively, after intervention.</p

S2 File -

ObjectivesThe aim was to examine if a diagnostic intervention set up to assess current food allergy to cow’s milk, hen’s egg, fish, or wheat among teenagers had an impact on generic and disease specific health-related quality of life (HRQL). The study compared HRQL scoring before and two years after the intervention, and in relation to age matched controls without reported food allergy.MethodsThe study was performed within the Obstructive Lung Disease in Northern Sweden (OLIN) studies where a cohort study on asthma and allergic diseases among 8-year-old schoolchildren was initiated in 2006. At age 12 years, the 125/2612 (5%) children who reported allergy to cow’s milk, hen’s egg, fish, or wheat were invited to a diagnostic intervention including clinical examination, blood tests and evaluation by a pediatric allergist. Of 94 participants, 79 completed generic and disease specific HRQL questionnaires. Additionally, a random sample of 200 (62% of invited) children without food allergy from the OLIN cohort answered the generic HRQL questionnaire. The respondents of the HRQL questionnaires were re-examined two years later and 57 teenagers with and 154 without reported allergy participated.ResultsThere were no significant differences in generic HRQL scores between teenagers with and without reported food allergy at study entry, or after the intervention. Among those with reported food allergy, we found a significant improvement in disease specific HRQL after the intervention (mean values: 3.41 vs 2.80, pConclusionThe diagnostic intervention showed a long-term improvement of disease specific HRQL but not generic HRQL.</div

Scores in KIDSCREEN-52 domains before intervention among girls and boys, with and without food allergy, respectively.

Scores in KIDSCREEN-52 domains before intervention among girls and boys, with and without food allergy, respectively.</p

S1 File -

ObjectivesThe aim was to examine if a diagnostic intervention set up to assess current food allergy to cow’s milk, hen’s egg, fish, or wheat among teenagers had an impact on generic and disease specific health-related quality of life (HRQL). The study compared HRQL scoring before and two years after the intervention, and in relation to age matched controls without reported food allergy.MethodsThe study was performed within the Obstructive Lung Disease in Northern Sweden (OLIN) studies where a cohort study on asthma and allergic diseases among 8-year-old schoolchildren was initiated in 2006. At age 12 years, the 125/2612 (5%) children who reported allergy to cow’s milk, hen’s egg, fish, or wheat were invited to a diagnostic intervention including clinical examination, blood tests and evaluation by a pediatric allergist. Of 94 participants, 79 completed generic and disease specific HRQL questionnaires. Additionally, a random sample of 200 (62% of invited) children without food allergy from the OLIN cohort answered the generic HRQL questionnaire. The respondents of the HRQL questionnaires were re-examined two years later and 57 teenagers with and 154 without reported allergy participated.ResultsThere were no significant differences in generic HRQL scores between teenagers with and without reported food allergy at study entry, or after the intervention. Among those with reported food allergy, we found a significant improvement in disease specific HRQL after the intervention (mean values: 3.41 vs 2.80, pConclusionThe diagnostic intervention showed a long-term improvement of disease specific HRQL but not generic HRQL.</div

Mean scores in FAQLQ-TF domains before and after intervention.

Mean scores in FAQLQ-TF domains before and after intervention.</p