Discussion:
The most common allergens in milk protein involved in IgE mediated
reactions include the caseins (αs1-, αs2-, β- and κ-caseins) and the
whey proteins (α-lactalbumin and β-lactoglobulin), which constitutes
80% and 20% of reactions, respectively. Other minor allergens include
albumin, lactoferrin and immunoglobulins. The major allergens involved
in soy allergy are: β-conglycinin and glycinin, and they account for
about 30% and 40% of the total seed proteins, respectively[2]. The
German Multi-Centre Allergy Study revealed that IgE sensitization to soy
in infancy occur primarily via ingestion and is relatively
uncommon[9].
The best next step in the management of any IgE mediated allergy
including CMA is avoidance of the allergen causing the reaction[8].
However, children need special nutrient and caloric requirements to grow
and develop adequately. Elimination diets represent risks for
malnutrition and nutritional deficiencies in children which can result
in irreversible and profound effects in developing children [8].
The American Academy of Pediatrics (AAP) currently recommends
exclusive breastfeeding for about 6 months, with continuation
of breastfeeding for 1 year or longer as mutually desired by mother and
infant [10]. Despite all the recommendations and the outstanding
evidence of breastfeeding being the best source of nutrition for infants
and a protective factor for multiple conditions including atopic
disorders such as atopic dermatitis and recurrent early wheezing in
infancy[10], breastfeeding in the industrialized era sometimes seems
utopic. Several risk factors and barriers have been found to impact
negatively on breastfeeding, The Surgeon General’s Call to Action to
Support Breastfeeding, states that the most common barriers for
appropriate breast feeding are: lack of knowledge and social support,
poverty, barriers related to health services, embarrassment lactation
problems and employment [11]. In 2018, the Center for Disease
Control and prevention report on breastfeeding showed that 60.6 % of
mothers were breastfeeding by 6 months and only 34.1% at 12 months.
Exclusive breastfeeding was reported among only 25.5 % of mothers by 6
months. [12] In our case the mother’s decision to start formula
supplementation was driven by the need to start working, which is a
common reason in today’s society.
The AAP generally recommends cow’s milk formula supplementation when
breastfeeding is not possible and soy as an option in full term infants.
Some indications where a soy formula is preferred over a cow’s milk
formula includes galactosemia, hereditary lactase deficiency and
preference for a vegetarian diet. [13] The decision to trial soy for
our patient was based on a negative IgE immunocap and although most
evidence indicates that there is only a cross reactivity between 8-15%
between cow’s milk and soy protein, the risk for anaphylaxis or severe
allergic reactions is very low [14]. The European Society for
Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN )
indicates that soy could be used in IgE mediated reactions after 6
months of age[15]. Despite the low likelihood of IgE mediated
reactions our patient developed an immediate systemic reaction with a
soy formula challenge.
Extensively hydrolyze formulas (EHF) have been found to be a safe option
in cow’s milk allergy. The AAP recommends EHF in children in the setting
of cow’s milk allergy[13]. Although EHF has been deemed safe in
large studies, up to 2-18% of children will develop an allergic
reaction to EHF, still only a few cases of systemic IgE mediated
reactions have been reported. [16,17,18]. As per Chauveau, immediate
hypersensitivity to residual cow’s milk protein in eHF have been
nonexistent for the past 20 years. [16] Historically, it has been
known to exist and limited cases have been documented in the literature.
(Table 1)
After our patient developed a systemic reaction to an EHF, we decided to
try an AAF. This has been recommended by the DRACMA report (WAO),BSACI
and ESPHGAN guidelines as a possible first line formula in patients with
severe allergic reactions to milk or inability to tolerate
EHF[19,20,21]. A physician-supervised challenge to EHF has also been
recommended as an alternative to AA formula in the setting of a severe
allergic reaction to milk [18].To date, there are no current
guidelines in the U.S. that address the use of AA based formulas, and
the cost and palatability of these formulas are still factors to
consider in our patients[18]. Our patient tolerated an AA formula
without further reactions and was discharged home with an Epi Pen, with
recommendations to continue breast milk and to use AA formula for
supplementation.
Our patient’s mother limited ingestion of milk products due to a history
of lactose intolerance. She was encouraged to limit milk product
ingestion due to a risk of a possible severe reaction during
breastfeeding.[15] Contrary to what was previously known, evidence
is showing that the early introduction of highly allergenic foods such
as peanuts (LEAP study) allows tolerance and decrease the risk of
allergic reaction in infants[22]. It is interesting to note, that
since our patient’s mother had avoided all milk products during her
pregnancy it is reasonable to theorize that our patient never developed
tolerance to milk products due to lack of exposure. However, this will
need to be further evaluated in future studies. Some studies have
already found that regular exposure of CM starting in the
1st month of life might prevent IgE mediated CMA but
larger prospective studies are also needed to yield larger scale
recommendations[23].
Breastfeeding is still the best source of nutrition for the infant and
continued efforts are needed to ensure and support this practice. In
patients with CMA, consensus guidelines for needs to be reached for an
adequate management of this common problem in infants. Soy milk in
children with CMA even in the setting of IgE mediated reactions, needs
to be used with caution due to cross reactivity concerns. Furthermore,
extensively hydrolyzed formulas are not devoid of adverse reactions and
special attention should be undertaken for children with systemic
allergic reactions to cow’s milk. Thus, the use of an AAF should be the
first choice to be considered in this high-risk population when breast
milk is not available. We conclude that extensively hydrolyzed and
soymilk formulas should be used with caution in children with systemic
reactions. In this subset of patients with a history of a severe IgE
mediated reaction to cow’s milk an AAF should be considered the first
choice when breastmilk is not available.