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Food allergy in children the gastroenterologist perspective


Food allergy in children the gastroenterologist perspective Ron Shaoul MD Pediatric Gastroenterology Bnai Zion Medical Center Maccabi Health Services – PowerPoint PPT presentation

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Title: Food allergy in children the gastroenterologist perspective

Food allergy in children the gastroenterologist
  • Ron Shaoul MD
  • Pediatric Gastroenterology
  • Bnai Zion Medical Center
  • Maccabi Health Services

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Major food allergens
Common food antigens
  • Cows milk protein
  • caseins, whey (beta-lactoglobulin,
    alpha-lactalbumin, bovine serum albumin, bovine
  • Soy protein
  • 2S-globulin, soy tripsin inhibitor, soy lectin
  • Egg protein
  • Ovalbumin
  • Fish, shrimp, beef, pork

Common food antigens-2
  • Peanuts, nuts, beans.
  • Cocoa, chocolate.
  • Citrus fruits, apples, strawberries.
  • Wheat, cereals.
  • Spices, yeast.

Predisposing factors
  • Positive family hx of atopic disease.
  • GI mucosal barrier defect.
  • Early antigen exposure during postnatal gut

  • Occurs in 0.3 to 7.5 percent of otherwise normal
  • 82 percent of whom have symptoms within four
    months of birth and 89 percent by one year of

Gastrointestinal manifestations
  • Gastrointestinal food allergies are often the
    first form of allergy to affect infants and young
    children and typically present as irritability,
    vomiting or "spitting-up," diarrhea, and poor
    weight gain.
  • Cell-mediated hypersensitivities predominate,
    making standard allergy tests such as prick skin
    tests and RAST tests of little diagnostic value

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Food protein-induced enterocolitis syndrome
  • typically presents in the first several months of
    life with irritability, protracted vomiting, and
    diarrhea, not infrequently resulting in
  • Vomiting generally occurs 1-3 hr after feeding,
    and continued exposure may result in bloody
    diarrhea, anemia, abdominal distention, and
    failure to thrive.
  • Symptoms are most commonly provoked by cow's milk
    or soy protein-based formulas but occasionally
    result from food proteins passed in maternal
    breast milk.

Food protein-induced enterocolitis syndrome
  • A similar enterocolitis syndrome has been
    reported in older infants and children from egg,
    wheat, rice, oat, peanut, nuts, chicken, turkey,
    and fish sensitivity.
  • Hypotension occurs in about 15 of cases after
    allergen ingestion.

  • Fourteen infants with FPIES caused by grains
    (rice, oat, and barley), vegetables (sweet
    potato, squash, string beans, peas), or poultry
    (chicken and turkey) were identified.
  • Symptoms were typical of classical FPIES with
    delayed (median 2 hours) onset of vomiting,
    diarrhea, and lethargy/dehydration.
  • Eleven infants (78) reacted to gt1 food protein,
    including 7 (50) that reacted to gt1 grain.

  • Nine (64) of all patients with solid foodFPIES
    also had cows milk and/or soy-FPIES.
  • Initial presentation was severe in 79 of the
    patients, prompting sepsis evaluations (57) and
    hospitalization (64) for dehydration or shock.

  • We presented a series of four babies, previously
    suspected as having cow milk protein allergy that
    presented with severe life-threatening episodes,
    all related to unsupervised self-challenge with
    either a cow milk based formula or a dairy
  • Parental decisions, physician recommendations, or
    inadvertent ingestion resulted in these serious
    clinical presentations.

Food protein-induced enteropathy
  • Often presents in the first several months of
    life with diarrhea, not infrequently steatorrhea,
    and poor weight gain.
  • Symptoms include protracted diarrhea, vomiting in
    up to two thirds of cases, failure to thrive,
    abdominal distention, early satiety, and
  • Anemia, edema, and hypoproteinemia occur

Cow's milk sensitivity
  • is the most frequent cause of this syndrome in
    young infants, but it also has been associated
    with sensitivity to soy, egg, wheat, rice,
    chicken, and fish in older children.

Gastrointestinal anaphylaxis
  • generally presents as acute abdominal pain and
    vomiting that accompany other IgE-mediated
    allergic symptoms

Allergic eosinophilic gastroenteritis
  • occurs at any age and presents as symptoms
    similar to esophagitis as well as prominent
    weight loss or failure to thrive, which are the
    hallmarks of this disorder.
  • Up to 50 of patients are atopic, and
    food-induced IgE-mediated reactions have been
    implicated in a minority of patients.
  • Generalized edema secondary to hypoalbuminemia
    may occur in some infants with marked
    protein-losing enteropathy.

Allergic eosinophilic esophagitis
  • may present from infancy through adolescence.
  • In young children, it is primarily cell-mediated
    and presents as chronic gastroesophageal reflux
    (GER), intermittent emesis, food refusal,
    abdominal pain, dysphagia, irritability, sleep
    disturbance, and failure to respond to
    conventional reflux medications.
  • A study of children younger than 1 yr of age
    presenting with GER found that 40 had cow's
    milk-induced reflux.

Reflux and milk allergy
  • On the basis of studies using cow milk
    elimination and challenge, it is clear that a
    subset of infantile GER is attributable to cow
    milk allergy
  • The magnitude of the problem is not well-defined
    it has been estimated that in 16 to 42 of
    infants, GER is attributable to CMA.
  • Risk factors for milks being causal seem to
    include esophagitis, malabsorption, diarrhea, and
    atopic dermatitis.

Reflux and milk allergy
  • Thus, for many infants with cow milk-associated
    GER, the reflux is not an isolated symptom.
  • One group identified that in infants with
    CMA-induced GER, the pH probe shows a phasic
    pattern with a gradual and prolonged fall in pH
    after milk ingestion.
  • However, the phasic pattern has not been
    demonstrated by other investigators.
  • Taking the studies together, it is evident that
    CMA accounts for GER in some infants.

Sicherer SH Pediatrics 20031111609 1616
Oral allergy syndrome
  • Is an IgE-mediated hypersensitivity that occurs
    in many older children with birch pollen and
    ragweed-induced allergic rhinitis.
  • Symptoms are usually confined to the oropharynx
    and consist of the rapid onset of pruritus,
    tingling, and angioedema of the lips, tongue,
    palate, and throat, and occasionally a sensation
    of pruritus in the ears and/or tightness in the
  • Symptoms are generally short-lived and are due to
    local mast cell activation by fresh fruit and
    vegetable proteins that cross react with birch
    pollen (apple, carrot, potato, celery, hazel
    nuts, and kiwi) and ragweed pollen (banana and
    melons-watermelon, etc.).

  • They hypothesized that intolerance of cows milk
    can also cause severe perianal lesions with pain
    on defecation and consequent constipation in
    young children.

  • They performed a double-blind, crossover study
    comparing cows milk with soy milk in 65 children
    with chronic constipation.
  • All had previously been treated with laxatives
    without success 49 had anal fissures and
    perianal erythema or edema.
  • After 15 days of observation, the patients
    received cows milk or soy milk for 2 weeks.
    After a one-week washout period, the feedings
    were reversed.
  • A response was defined as eight or more bowel
    movements during a treatment period.

  • Forty-four of the 65 children (68 percent) had a
    response while receiving soy milk. Anal fissures
    and pain with defecation resolved.
  • None of the children who received cows milk had
    a response.
  • In all 44 children with a response, the response
    was confirmed with a double-blind challenge with
    cows milk.
  • Children with a response had a higher frequency
  • coexistent rhinitis, dermatitis, or bronchospasm
  • anal fissures and erythema or edema at base line
  • evidence of inflammation of the rectal mucosa on
  • signs of hypersensitivity, such as specific IgE
    antibodies to cows-milk antigens

Other GI manifestations ?
  • Recurrent oral aphtae
  • Bowel edema and obstruction
  • Occult GI bleeding
  • Infantile colic

Clinical applications
  • In infants with IgE-mediated CMA, most (86) will
    tolerate a soy formula, but the rate of tolerance
    is lower (50) for most of the cell-mediated
  • Infants with true CMA would be expected also to
    react to partially hydrolyzed formula,
    lactose-free cow milk-based formula, and most
    mammalian milks (eg, sheep, goat), so none of
    these is a good alternative.

  • In most cases (95), infants with CMA will
    tolerate extensively hydrolyzed cow milk formula,
    but for the few who continue to react (presumably
    as a result of residual allergens), an amino
    acid-based formula is required for therapy.

  • Any need for amino acid formula ?

Intolerance to protein hydrolysate infant
formulas An underrecognized cause of
gastrointestinal symptoms in infants
  • The purpose of this study was to determine the
    effectiveness of an amino acidbased infant
    formula in infants with continued symptoms
    suggestive of formula protein intolerance while
    they were receiving casein hydrolysate formula
  • Twenty-eight infants, 22 to 173 days of age, were
    enrolled each had received CHF for an average of
    40 days (10 to 173 days) and continued to have
    bloody stools, vomiting, diarrhea, irritability,
    or failure to gain weight, or a combination of
    these symptoms.

Intolerance to protein hydrolysate infant
formulas An underrecognized cause of
gastrointestinal symptoms in infants
  • Sigmoidoscopy with rectal biopsy was performed in
    all infants.
  • The infants then received an amino acidbased
    infant formula, Neocate, for 2 weeks.
  • After 2 weeks of treatment, 25 of the infants
    demonstrated resolution of their symptoms and
    underwent challenge with CHF.
  • Of the 25 who were challenged, eight tolerated
    the CHF and the remainder had recurrence of their
  • The histologic features in these infants varied
    from eosinophilic infiltration to normal.

Intolerance to protein hydrolysate infant
formulas An underrecognized cause of
gastrointestinal symptoms in infants
  • They concluded that not all infants with apparent
    formula proteininduced colitis respond to CHF
  • (J Pediatr 1997131741-4)

  • Natural history of food allergy

  • Most food allergy is acquired in the first 1 to 2
    years of life.
  • The prevalence of food allergy peaks at 6 to 8
    at 1 year of age and then falls progressively
    until late childhood, after which the prevalence
    remains stable at 1 to 2.
  • Most food allergy is indeed lost over time.

  • The process of outgrowing food allergies, varies
    a great deal for different foods and among
    individual patients.
  • It is also important to note that the process of
    outgrowing a food allergy may be helped by strict
    avoidance of the offending food, in that repeated
    exposures to even small quantities may delay the
    development of tolerance in some patients

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Early intervention to prevent food allergyCan we
do it ???
  • Aim To assess the preventive effect of
    differently hydrolyzed formulas compared with
    cows milk formula (CMF) in high-risk infants.
  • Methods 2252 infants with a hereditary risk for
    atopy were enrolled in the German Infant
    Nutritional Intervention Study and randomly
    assigned at birth to one of 4 blinded formulas
    CMF, partially hydrolyzed whey formula,
    extensively hydrolyzed whey formula, and
    extensively hydrolyzed casein formula (eHF-C).

  • The primary end point at 1 year of age was the
    presence of allergic manifestation, which was
    defined as atopic dermatitis (AD),
    gastrointestinal manifestation of food allergy,
    allergic urticaria, or a combination of these

  • Results The incidence of allergic manifestation
    was significantly reduced by using eHF-C compared
    with CMF (9 vs 16 adjusted OR, 0.51 95 CI,
  • The incidence of AD was significantly reduced by
    using eHF-C (OR, 0.42 95 CI, 0.22-0.79) and
    partially hydrolyzed whey formula (OR, 0.56 95
    CI, 0.32-0.99).
  • Family history of AD was a significant risk
    factor and modified the preventive effect of the

  • Conclusions Prevention of allergic diseases in
    the first year of life is feasible by means of
    dietary intervention but influenced by family
    history of AD.
  • The preventive effect of each hydrolyzed formula
    needs to be clinically evaluated.

  • Seven studies compared prolonged feeding of
    hydrolysed formula to cow's milk formula for
    allergy prevention.
  • Meta-analysis of 4 studies (386 infants) found a
    significant reduction in allergy incidence in
    infancy (RR 0.63)
  • One study reported a significant reduction in
    allergy incidence in childhood (RR 0.54).

  • Significant reductions were found in
  • asthma prevalence in childhood
  • eczema incidence in infancy and prevalence in
  • food allergy prevalence in childhood
  • CMA incidence in infancy.

  • Main results Five eligible studies were found,
    all enrolling infants at high risk of allergy on
    the basis of a family history of allergy in a
    first degree relative.
  • Conclusions Feeding with a soy formula should
    not be recommended for the prevention of allergy
    or food intolerance in infants at high risk of
    allergy or food intolerance.

  • Conclusions In breast-fed infants with atopy,
    gut barrier function is improved after cessation
    of breast-feeding and starting of hypoallergenic
    formula feeding.

  • Objective a systematic review with meta-analysis
    of prospective studies that evaluated the
    association between exclusive breast-feeding
    during the first 3 months after birth and atopic
  • Methods 18 prospective studies that met the
    predefined inclusion criteria.

J Am Acad Dermatol 200145520-7
  • Results The summary odds ratio (OR) for the
    protective effect of breast-feeding in the
    studies analyzed was 0.68 (95 confidence
    interval CI, 0.52-0.88).
  • This effect estimate was higher in the group of
    studies wherein children with a family history of
    atopy were investigated separately (OR 0.58
    CI, 0.41-0.92) than in those of combined
    populations (OR 0.84 CI, 0.59-1.19).

  • Conclusion Exclusive breast-feeding during the
    first 3 months of life is associated with lower
    incidence rates of atopic dermatitis during
    childhood in children with a family history of
  • This effect is lessened in the general population
    and negligible in children without first-order
    atopic relatives.

  • Results The summary odds ratio (OR) for the
    protective effect of breastfeeding was 0.70 (95
    CI 0.60 to 0.81).
  • The effect estimate was greater in studies of
    children with a family history of atopy (OR
    0.52) than in studies of a combined population
    (OR 0.73).
  • Conclusions Exclusive breast-feeding during the
    first months after birth is associated with lower
    asthma rates during childhood.

  • Aim to assess long-term outcome of asthma and
    atopy related to breastfeeding in a New Zealand
    birth cohort.
  • Methods the cohort consisted of 1037 of 1139
    children born in Dunedin, New Zealand.
  • Children were assessed every 25 years from ages
    9 to 26 years with respiratory questionnaires,
    pulmonary function, bronchial challenge, and
    allergy skin tests.
  • History of breastfeeding had been independently
    recorded in early childhood

  • Conclusions Prescription of an antigen avoidance
    diet to a high-risk woman during pregnancy is
    unlikely to reduce substantially her child's risk
    of atopic diseases, and such a diet may adversely
    affect maternal and/or fetal nutrition.
  • Prescription of an antigen avoidance diet to a
    high-risk woman during lactation may reduce her
    child's risk of developing atopic eczema, but
    better trials are needed.

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When to add solids ?
  • The relationship between early solid feeding
    practices and risks of recurrent or chronic
    eczema in childhood was examined in a birth
    cohort of New Zealand children studied to the age
    of 10.
  • By the age of 10 years, 7.5 of children had
    chronic or recurrent eczema.
  • There were clear and consistent associations
    between the diversity of the child's diet during
    the first 4 months and risks of eczema.
  • children exposed to four or more different types
    of solid food before 4 months had risks of
    recurrent or chronic eczema that were 2.9 times
    those of children who were not exposed to early
    solid feeding.

Fergusson DM et al Pediatrics. 1990
Age of Introduction of Complementary Foods
  • The optimal age of introduction of complementary
    foods remains controversial.
  • The appropriate time may represent a compromise
    between 2 competing health issues. On one hand,
    if complementary foods are introduced too late
    when breast milk alone no longer meets all the
    infant's energy and nutrient needs nutrient
    deficiencies and growth faltering may occur.
  • On the other hand, because these foods are often
    contaminated with microbial pathogens, premature
    introduction carries an unnecessary risk of
    transmission of infection.

WHO/UNICEF Review on Complementary
Feeding Pediatrics 2000
Age of Introduction of Complementary Foods
  • A sizeable number of observational studies and
    2 randomized trials have failed to identify any
    benefit of complementary foods for infant growth
    before 6 months of age, even in low birth weight
    term infants.
  • By contrast, several studies have documented a
    twofold or greater risk of enteric and other
    infections when these foods are provided before
    6 months.
  • Hence, the authors of the WHO/UNICEF report
    concluded that the optimal age of introduction of
    complementary foods is about 6 months.

Thank you
Soy story
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  • Study design Children lt3.5 years with documented
    IgE-associated CMA (n 93) were evaluated for
    soy allergy by double-blind, placebo-controlled
    food challenge, open challenge, or convincing
    previous history of an anaphylactic reaction to

  • Results Of this IgE-associated CMA cohort (ages
    3 to 41 months), 14 were determined to have soy
  • Conclusions Soy allergy occurs in only a small
    minority of young children with IgE-associated
  • As such, soy formula may provide a safe and
    growth-promoting alternative for the majority of
    children with IgE-associated CMA shown to be soy
    tolerant at the time of introduction of soy

  • Study design Infants (n 170) with documented
    cows milk allergy were randomly assigned to
    receive either a soy formula or an extensively
    hydrolyzed formula.
  • If it was suspected that the formula caused
    symptoms, a double-blind, placebo-controlled
    challenge (DBPCFC) with the formula was
  • The children were followed to the age of 2 years,
    and soy-specific IgE antibodies were measured at
    the time of diagnosis and at the ages of 1 and 2

  • Results An adverse reaction to the formula was
    confirmed by challenge in 8 patients (10)
    randomly assigned to soy formula and in 2
    patients (2.2) randomly assigned to extensively
    hydrolyzed formula.
  • Adverse reactions to soy were similar in
    IgE-associated and nonIgE-associated cows milk
    allergy (11 and 9, respectively).
  • IgE to soy was detected in only 2 infants with an
    adverse reaction to soy.
  • Adverse reactions to soy formula were more common
    in younger (lt6 months) than in older (6 to 12
    months) infants (5 of 20 vs 3 of 60,
    respectively, P .01).

  • Conclusions Soy formula was well tolerated by
    most infants with IgE associated and
    nonIgE-associated cows milk allergy.
  • Development of IgE-associated allergy to soy was
  • Soy formula can be recommended as a first-choice
    alternative for infants 6 months of age with
    cows milk allergy.

Probiotics for treatment
Atopic dermatitis
  • The Idea
  • In the hygiene hypothesis the progressive
    increase in frequency of atopic disease is
    attributed to reduced microbial exposure in early
  • Probiotics further degrade the food and antigens.
  • Regulation of the immune response and reduction
    of IgE secretion
  • Reduction of bowel permeability

Isolauri et al. Clin Exp Allergy 2000
Atopic dermatitis
  • Improvement is noted within 1 month of treatment
    and is further improved over the next 6 months

Probiotics in primary prevention of atopic
disease a randomized placebo-controlled trial
Kalliomaki M et al. Lancet
  • Purpose To assess the effect on prevention of
    atopic disease of Lactobacillus GG given early in
  • Design Double-blind, randomized,
    placebo-controlled trial.

Probiotics in primary prevention of atopic
disease a randomized placebo-controlled trial
Kalliomaki M et al. Lancet
  • Patients Mothers who had at least one
    first-degree relative (or partner) with atopic
    eczema, allergic rhinitis, or asthma, and their
  • Intervention Oral Lactobacillus GG was given for
    2 to 4 weeks prenatally to the mothers, and
    postnatally for 6 months to their infants.
  • Main outcome measures Chronic recurring atopic
    eczema evaluated at age 2 years.

Probiotics in primary prevention of atopic
disease a randomized placebo-controlled trial
Kalliomaki M et al. Lancet
  • Results Atopic eczema was diagnosed in 35
    children aged 2 years.
  • The frequency of atopic eczema in the probiotic
    group was half that of the placebo group 23
    vs. 46.

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Probiotics in primary prevention of atopic
disease a randomized placebo-controlled trial
Kalliomaki M et al. Lancet
  • Conclusions Lactobacillus GG was effective in
    the prevention of early atopic disease in
    children at high risk.
  • Thus, gut microflora may be a hitherto unexplored
    source of natural immunomodulators and probiotics
    for prevention of atopic disease.

  • To investigate whether the preventive effect of
    lactobacillus on atopic disease extends beyond
    infancy, they reexamined the cohort at the age of
    4 years.
  • Atopic eczema was diagnosed in 14 of the 53 (26)
    children on lactobacillus, compared with 25 of
    the 54 (46) on placebo (relative risk 057, 95
    CI 033097).

  • Five of 54 children in the placebo group and ten
    of 53 in the lactobacillus group had developed
    seasonal allergic rhinitis (p015)
  • One in the placebo group and three in the
    lactobacillus group had developed asthma

Not preventing all allergies
  • Objectives The aim of this study was to assess
    the efficacy of oral probiotic bacteria in the
    management of atopic disease and to observe their
    effects on the composition of the gut microbiota.
  • Methods The study population included 35 infants
    with atopic eczema and allergy to cows milk.
  • At a mean age of 5.5 months, they were assigned
    in a randomized double-blind manner to receive
    either extensively hydrolyzed whey formula
    (placebo group) or the same formula supplemented
    with viable (viable LGG group) or
    heat-inactivated Lactobacillus GG
    (heat-inactivated LGG group).

J Pediatr Gastroenterol Nutr, Vol. 36, No. 2,
February 2003
  • The changes in symptoms were assessed by the
    SCORAD method.
  • Results The treatment with heat-inactivated LGG
    was associated with adverse gastrointestinal
    symptoms and diarrhea.
  • Consequently, the recruitment of patients was
    stopped after the pilot phase.

  • Within the study population, atopic eczema and
    subjective symptoms were significantly alleviated
    in all the groups
  • The SCORAD scores decreased from 13 to 8 units in
    the placebo group, from 19 to 5 units in the
    viable LGG group, and from 15 to 7 units in the
    heat-inactivated LGG group.
  • The decrease in the SCORAD scores within the
    viable LGG group tended to be greater than within
    the placebo group.

  • Conclusions Supplementation of infant formulas
    with viable but not heat-inactivated LGG is a
    potential approach for the management of atopic
    eczema and cows milk allergy.

Thank you
  • Infants (n 52) allergic to cows milk protein
    and extensively hydrolyzed formulas received an
    amino acidbased formula.
  • The amino acidbased formula proved to be safe,
    with infants exhibiting an overall gain in length
    and weight.
  • Children with allergy restricted to extensively
    hydrolyzed formulas were diagnosed earlier and
    tolerated cows milk protein earlier than
    children with multiple food allergy. (J Pediatr

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