Transcript 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
Major food allergens
Common food antigens
• Cow’s milk protein
– caseins, whey (beta-lactoglobulin, alphalactalbumin, bovine serum albumin, bovine
immunoglobulins).
• Soy protein
– 2S-globulin, soy tripsin inhibitor, soy
lectin
• Egg protein
– Ovalbumin
• Fish, shrimp, beef, pork
Common food antigens-2
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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 development
Epidemiology
• 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.
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
Food 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.
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 >1 food protein,
including 7 (50%) that reacted to >1 grain.
• Nine (64%) of all patients with solid
food–FPIES also had cow’s 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 product.
• 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 malabsorption.
• Anemia, edema, and hypoproteinemia occur
occasionally.
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 milkinduced 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 welldefined; it has been estimated that in 16%
to 42% of infants, GER is attributable to
CMA.
• Risk factors for milk’s being causal seem
to include esophagitis, malabsorption,
diarrhea, and atopic dermatitis.
Reflux and milk allergy
• Thus, for many infants with cow milkassociated 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 2003;111:1609 –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
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 melonswatermelon, etc.).
• They hypothesized that intolerance of
cow’s 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 cow’s 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 cow’s 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 cow’s milk had a
response.
• In all 44 children with a response, the response was
confirmed with a double-blind challenge with cow’s milk.
• Children with a response had a higher frequency of :
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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
cow’s-milk antigens
Other GI manifestations
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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 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.
• 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 acid–based 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.
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 acid–based 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.
Intolerance to protein hydrolysate infant
formulas: An underrecognized cause of
gastrointestinal symptoms in infants
• They concluded that not all infants
with apparent formula protein–
induced colitis respond to CHF
(J Pediatr 1997;131:741-4)
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
Early intervention to
prevent food allergy
Can we do it ???
• Aim: To assess the preventive effect of differently
hydrolyzed formulas compared with cow’s 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 factors.
• 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.
• 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 childhood
– 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 metaanalysis 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 2001;45:520-7
• 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, 0.591.19).
• 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 atopy.
• 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 2–5 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.
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
S
• Study design: Children <3.5 years
with documented IgE-associated
CMA (n = 93) were evaluated for soy
allergy by double-blind, placebocontrolled food challenge, open
challenge, or convincing previous
history of an anaphylactic reaction to
soy.
• 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.
• Study design: Infants (n = 170) with documented
cow’s 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.
• 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
non–IgE-associated cow’s 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 (<6 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 non–IgE-associated cow’s
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 cow’s 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 life.
– 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
SCORAD
CF
BBLGG
before therapy
after two months
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 2001;357:1076-9
• Purpose: To assess the effect on
prevention of atopic disease of
Lactobacillus GG given early in life.
• Design: Double-blind, randomized, placebocontrolled trial.
Probiotics in primary prevention of atopic disease: a
randomized placebo-controlled trial
Kalliomaki M et al. Lancet 2001;357:1076-9
• Patients: Mothers who had at least one firstdegree 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.
Probiotics in primary prevention of atopic disease: a
randomized placebo-controlled trial
Kalliomaki M et al. Lancet 2001;357:1076-9
• 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%].
‫אחז‬
‫תינוקות‬
atopic eczema
+
LGG
n=64
Plaebo
n=68
age= -1-24m
P< 0.008
Kalliomaki et al Lancet 2001
Probiotics in primary prevention of atopic disease: a
randomized placebo-controlled trial
Kalliomaki M et al. Lancet 2001;357:1076-9
• 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.
• 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
0·57, 95% CI 0·33–0·97).
• Five of 54 children in the placebo group
and ten of 53 in the lactobacillus group
had developed seasonal allergic rhinitis
(p=0·15)
• One in the placebo group and three in the
lactobacillus group had developed asthma
(p=0·30).
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 cow’s
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 heatinactivated 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 cow’s milk allergy.
Thank you
• Infants (n = 52) allergic to cow’s milk protein and
extensively hydrolyzed formulas received an
amino acid–based formula.
• The amino acid–based 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 cow’s milk protein earlier than children
with multiple food allergy. (J Pediatr
2002;141:271-3)