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.