Title: Food allergy in children the gastroenterologist perspective
1Food allergy in children the gastroenterologist
perspective
- Ron Shaoul MD
- Pediatric Gastroenterology
- Bnai Zion Medical Center
- Maccabi Health Services
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3Major food allergens
4Common food antigens
- Cows milk protein
- caseins, whey (beta-lactoglobulin,
alpha-lactalbumin, bovine serum albumin, bovine
immunoglobulins). - Soy protein
- 2S-globulin, soy tripsin inhibitor, soy lectin
- Egg protein
- Ovalbumin
- Fish, shrimp, beef, pork
5Common food antigens-2
- Peanuts, nuts, beans.
- Cocoa, chocolate.
- Citrus fruits, apples, strawberries.
- Wheat, cereals.
- Spices, yeast.
6Predisposing factors
- Positive family hx of atopic disease.
- GI mucosal barrier defect.
- Early antigen exposure during postnatal gut
development
7Epidemiology
- Occurs in 0.3 to 7.5 percent of otherwise normal
infants - 82 percent of whom have symptoms within four
months of birth and 89 percent by one year of
age.
8Gastrointestinal 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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11Food protein-induced enterocolitis syndrome
FPIES))
- typically presents in the first several months of
life with irritability, protracted vomiting, and
diarrhea, not infrequently resulting in
dehydration. - 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.
12Food 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.
13- 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.
14- 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.
15- 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
product. - Parental decisions, physician recommendations, or
inadvertent ingestion resulted in these serious
clinical presentations.
16Food 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
malabsorption. - Anemia, edema, and hypoproteinemia occur
occasionally.
17Cow'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.
18Gastrointestinal anaphylaxis
- generally presents as acute abdominal pain and
vomiting that accompany other IgE-mediated
allergic symptoms
19Allergic 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.
20Allergic 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.
21Reflux 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.
22Reflux 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
23Oral 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
throat. - 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.).
24- They hypothesized that intolerance of cows milk
can also cause severe perianal lesions with pain
on defecation and consequent constipation in
young children.
25- 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.
26- 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
of - coexistent rhinitis, dermatitis, or bronchospasm
- anal fissures and erythema or edema at base line
- evidence of inflammation of the rectal mucosa on
biopsy - signs of hypersensitivity, such as specific IgE
antibodies to cows-milk antigens
27Other GI manifestations ?
- Recurrent oral aphtae
- Bowel edema and obstruction
- Occult GI bleeding
- Infantile colic
28Clinical applications
29- 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
disorders. - 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.
30- 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.
31- Any need for amino acid formula ?
32Intolerance 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
(CHF). - 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.
33Intolerance 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
symptoms. - The histologic features in these infants varied
from eosinophilic infiltration to normal.
34Intolerance 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)
35- Natural history of food allergy
36- 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.
37- 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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41Early intervention to prevent food allergyCan we
do it ???
42- 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).
43- 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
factors.
44- 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,
0.28-0.92), - 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
hydrolysates.
45- 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.
46- 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).
47- Significant reductions were found in
- asthma prevalence in childhood
- eczema incidence in infancy and prevalence in
childhood - food allergy prevalence in childhood
- CMA incidence in infancy.
48- 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.
49- Conclusions In breast-fed infants with atopy,
gut barrier function is improved after cessation
of breast-feeding and starting of hypoallergenic
formula feeding.
50- 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
dermatitis. - Methods 18 prospective studies that met the
predefined inclusion criteria.
J Am Acad Dermatol 200145520-7
51- 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).
52- 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
atopy. - This effect is lessened in the general population
and negligible in children without first-order
atopic relatives.
53- 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.
54- 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
55- 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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58When 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
59Age 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
60Age 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.
61Thank you
62Soy story
S
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64- 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
soy.
65- Results Of this IgE-associated CMA cohort (ages
3 to 41 months), 14 were determined to have soy
allergy, - Conclusions Soy allergy occurs in only a small
minority of young children with IgE-associated
CMA. - 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
formula.
66- 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
performed. - 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
years.
67- 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).
68- 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
rare. - Soy formula can be recommended as a first-choice
alternative for infants 6 months of age with
cows milk allergy.
69Probiotics for treatment
70Atopic dermatitis
- The Idea
- In the hygiene hypothesis the progressive
increase in frequency of atopic disease is
attributed to reduced microbial exposure in early
life. - Probiotics further degrade the food and antigens.
- Regulation of the immune response and reduction
of IgE secretion - Reduction of bowel permeability
71Isolauri et al. Clin Exp Allergy 2000
SCORAD
72Atopic dermatitis
- Improvement is noted within 1 month of treatment
and is further improved over the next 6 months
73Probiotics in primary prevention of atopic
disease a randomized placebo-controlled trial
Kalliomaki M et al. Lancet
20013571076-9
- Purpose To assess the effect on prevention of
atopic disease of Lactobacillus GG given early in
life. - Design Double-blind, randomized,
placebo-controlled trial.
74Probiotics in primary prevention of atopic
disease a randomized placebo-controlled trial
Kalliomaki M et al. Lancet
20013571076-9
- Patients Mothers who had at least one
first-degree relative (or partner) with atopic
eczema, allergic rhinitis, or asthma, and their
infants. - 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.
75Probiotics in primary prevention of atopic
disease a randomized placebo-controlled trial
Kalliomaki M et al. Lancet
20013571076-9
- 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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77Probiotics in primary prevention of atopic
disease a randomized placebo-controlled trial
Kalliomaki M et al. Lancet
20013571076-9
- 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.
78- 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).
79- 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
(p030).
80Not preventing all allergies
81- 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
82- 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.
83- 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.
84- 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.
85Thank you
86- 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
2002141271-3)
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