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Milk allergy: Management

Milk allergy: Management
Literature review current through: Jan 2024.
This topic last updated: Apr 29, 2022.

INTRODUCTION — The management of cow's milk allergy (CMA) does not differ from that of other food allergies [1-3]. It requires instructions on avoidance and education about treatment of reactions in the event of accidental exposure. It also includes monitoring for the resolution of the allergy. (See "Management of food allergy: Avoidance" and "Anaphylaxis: Emergency treatment" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

This topic reviews various aspects of the management of CMA, including instructions about avoidance of cow's milk (CM) protein, replacement of CM with alternative protein and calcium sources, education in the proper management of accidental exposures, and monitoring for resolution of the allergy. The epidemiology, pathogenesis, clinical features, and diagnosis of CMA are discussed separately. (See "Milk allergy: Clinical features and diagnosis".)

The management of food allergy in the specific settings of schools and camps is discussed in detail separately. (See "Food allergy in schools and camps" and "Food allergy in college and university students: Overview and management".)

General discussions of food allergy are presented separately in appropriate topic reviews.

AVOIDANCE — The most straightforward approach in managing any food allergy is complete avoidance of the culprit food. Eliminating CM from the diet can be difficult and can pose nutritional as well as quality-of-life concerns since CM is a ubiquitous food in many cultures and diets and is an important source of fat and protein in early childhood [4]. CM is or may be an ingredient in baked goods, cereals, chocolate, candy, custard, pudding, sherbet, luncheon meats, hot dogs, sausages, margarine, salad dressing, breaded foods, casseroles, soups, and potato, pasta, and vegetable dishes (Food Allergy Research and Education [FARE]). It may also be found in some milk, cream, and butter substitutes, even those labeled "nondairy." Accidental exposures are common. In one prospective series of 500 infants aged 3 to 15 months with suspected or confirmed hen's egg (HE) and/or CMA, 72 percent had an allergic reaction, most commonly to CM, HE, or peanut, during a three-year period, with an annualized reaction rate of 0.81 per year [5]. Eighty-seven percent of these reactions were due to accidental exposures. (See "Management of food allergy: Avoidance" and "Management of food allergy: Nutritional issues" and "Food allergy: Impact on health-related quality of life" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Role of avoidance'.)

Counseling about avoidance should include discussions about the following issues:

Cross-contact and hidden ingredients – Patients must be counseled about accidental exposure to food allergens via cross-contact (ie, inadvertent exposure to the allergenic food by contamination of "safe" foods with small amounts of the culprit food). This can happen anywhere food is served, including at restaurants using knives and counters contaminated with a CM product and on shared grills. In addition, breads and pastries may be brushed with CM.

Food labels – Patients must read all food labels (FARE). Legislation has been enacted in the United States and many other countries mandating that ingredient labels on food packages plainly identify the presence of CM protein when it is an intended ingredient. (See "Management of food allergy: Avoidance", section on 'Food labeling'.)

Advisory labeling – Some products in the United States and other countries have advisory labeling, such as "may contain milk." This type of labeling is not regulated. The risk of allergic reactions to these products is not known, and the frequency and amount of CM contamination in these products are variable but have been noted to be high or common in some cases, particularly for dark-chocolate products [6]. (See "Management of food allergy: Avoidance", section on 'Advisory labeling'.)

Cross-reactivity – Most patients with CMA do not tolerate milk from sheep and goats, and they are unlikely to tolerate milk from deer, ibex, and buffalo as well. However, some patients with CMA may tolerate milk from other mammals, such as camels, pigs, reindeer, horses, and donkeys. Most patients with immunoglobulin E (IgE)-mediated CMA tolerate soy and cooked beef. (See "Management of food allergy: Nutritional issues", section on 'Children >1 year old' and "Food allergens: Clinical aspects of cross-reactivity", section on 'Cow's milk'.)

Dairy substitutes – CM is an essential fat and protein source, especially for infants and toddlers. Thus, counseling should include a discussion about milk/dairy alternatives and substitutes (table 1 and table 2 and table 3 and table 4). Commercial products marketed as "nondairy" or as milk/dairy substitutes or alternatives may have CM ingredients. Alternative milk beverages are discussed in detail separately. (See "Management of food allergy: Nutritional issues", section on 'Cow's milk allergy' and "Food allergens: Clinical aspects of cross-reactivity", section on 'Cow's milk'.)

Unexpected and nonfood sources – Medications, various health foods, cosmetics, and craft items may have ingredients derived from CM. Labeling of nonfood items is not strictly regulated in the United States and most other countries. (See "Management of food allergy: Avoidance", section on 'Food allergens in nonfood items'.)

The following scenarios illustrate some of the issues involved and our approach to avoidance. Individual clinicians may decide to adopt different strategies depending upon their level of expertise and the resources available (eg, ability to perform oral food challenges [OFCs]). Our approach to reintroducing various forms of CM are discussed below. (See 'Monitoring for resolution and reintroduction' below.)

If a patient with an allergy to CM in any or all forms or of any severity wishes to avoid all CM, we do not discourage this approach.

We allow persons with IgE-mediated allergy to continue to eat CM in more processed forms than what triggered their reaction(s) if they have eaten CM in these forms regularly and in the recent past (similar to passing an OFC). In most cases, this involves patients who reacted to straight CM or lightly processed forms of CM (eg, ice cream, cheese) but have a history of tolerating extensively heated CM (eg, CM in baked goods). We generally suggest that these patients avoid more intermediate forms of cooked or processed CM, such as pudding, yogurt, casseroles, and milk chocolate, unless they have shown tolerance of such products at home or have passed an OFC to an intermediate form of CM such as cheese pizza. However, if the patient wishes to avoid all CM-containing foods, we do not discourage this approach. In many cases, the history of past tolerance is unclear. In these patients, a medically supervised OFC is required to confirm if extensively heated CM (eg, CM in baked goods like a muffin) or heated cheese (eg, pizza) is tolerated before instructing the patient that the food can be incorporated into the diet at home because of the risk of reactions including anaphylaxis. In contrast to IgE-mediated CMA, we generally recommend that patients with mixed or non-IgE-mediated CMA, such as eosinophilic esophagitis (EoE), avoid CM protein in all forms during the diagnostic phase. Challenge to baked CM is an option in patients with EoE after symptoms and histology have improved. (See 'Extensively heated (baked) cow's milk' below and 'Our approach' below and "Oral food challenges for diagnosis and management of food allergies" and "Dietary management of eosinophilic esophagitis".)

One caveat to this approach that should be discussed with patients is that it is possible that a patient may have a reaction due to ingestion of a larger amount of CM or a more lightly cooked or processed form of CM than usual (eg, normally tolerates CM in pancakes but has a reaction when blueberries are used in the pancakes and the batter does not cook completely around the blueberries).

We advise patients who have reacted to extensively heated CM to avoid all forms of CM.

MANAGEMENT OF REACTIONS

Acute IgE-mediated reactions — Patients with IgE-mediated CMA are at risk for severe reactions (table 5 and table 6), and the severity of symptoms can vary from reaction to reaction [7-11]. Thus, we prescribe epinephrine autoinjectors for all patients with a history of anaphylactic reactions to CM and typically do so for patients with milder IgE-mediated reactions to CM as well. In addition, the patient should have a written anaphylaxis emergency action plan (Anaphylaxis Emergency Action Plan - English) (Anaphylaxis Emergency Action Plan - Spanish). These measures are discussed in detail separately. (See "Anaphylaxis: Emergency treatment" and "Prescribing epinephrine for anaphylaxis self-treatment".)

As in other forms of food allergy, the severity of symptoms in a given person with CMA may vary considerably between reactions [12], and the severity of an initial reaction does not predict the patient's subsequent risk [13-16]. As examples:

Four of eight cases of fatal food-induced anaphylaxis reported over a 10-year period in the United Kingdom were caused by CM [9], and 4 of 31 cases reported over a five-year period in the United States were due to CM [12].

In a small study investigating whether children with CMA of varying severity could tolerate extensively heated forms of CM, 35 percent of children who reacted to extensively heated CM required treatment with epinephrine [10].

In another series of children who underwent oral food challenges (OFCs) for evaluation of food allergy and failed challenges to CM, 37 percent had moderate reactions, and 27 percent had severe reactions on challenge [11].

Children whose only apparent clinical manifestation of food allergy is atopic dermatitis are at risk of an acute systemic reaction upon reintroduction of that food after an elimination diet [13-16].

Delayed gastrointestinal reactions — Guidelines on management of non-IgE-mediated CMA for primary care and "first contact" clinicians were published in 2017 [17]. The management of children with non-IgE-mediated CMA, including food protein-induced enterocolitis syndrome and patients with eosinophilic esophagitis (EoE), is presented in the specific topic reviews. (See "Food protein-induced allergic proctocolitis of infancy" and "Food protein-induced enterocolitis syndrome (FPIES)" and "Treatment of eosinophilic esophagitis (EoE)" and "Dietary management of eosinophilic esophagitis".)

MONITORING FOR RESOLUTION AND REINTRODUCTION — Children with CMA should be monitored for resolution of the allergy since most will outgrow the allergy in childhood. Monitoring for resolution includes assessing history of any accidental exposures and reactions, serial testing for sensitization (in vitro and/or skin prick testing [SPT]), and oral food challenges (OFCs). The general steps taken to determine if an allergy has resolved are covered in detail separately. The approach for CMA is outlined here. (See "Milk allergy: Clinical features and diagnosis", section on 'Natural history' and "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Overview of resolution' and "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Natural history of specific allergies'.)

Factors that improve the odds of passing a CM challenge include:

Lower CM-specific IgE levels [18]

Downward trends over time in CM-specific IgE or SPT reaction

Absence of an interval history of symptoms triggered by accidental exposure

Fewer failed OFCs, longer interval since last failed challenge, and failure at a higher dose

Extensively heated (baked) cow's milk — Approximately 70 percent of children with CMA can tolerate extensively heated or baked forms of CM [10,19]. However, the only available diagnostic test to determine which persons can tolerate extensively heated CM (unless it is currently in their diet) is an OFC. In persons with CMA without recent tolerance of baked CM, medically supervised OFC rather than home introduction is recommended to determine whether they can safely include extensively heated CM in their diet because of the risk of reactions and the predictive limitations of in vitro and SPT. The absolute level of CM-specific IgE and the size of the skin test reaction both correlate with likelihood of clinical reactivity to extensively heated forms of CM [20,21]. However, there is substantial overlap between levels among those who react and those who do not, and test results may vary depending upon the population studied. Thus, there are no absolute cutoffs that preclude challenge to baked CM. Casein-specific IgE may aid in risk assessment as low levels are associated with high chance of tolerance of CM protein baked into goods [22,23].

Data suggest that tolerance to extensively heated CM is a good prognostic factor for the development of tolerance to less heated forms of CM, such as pizza cheese or CM heated in rice pudding. In addition, including extensively heated CM in the diet may accelerate the development of tolerance, eventually even to unheated forms of CM [24-26], although randomized trials are lacking [27], and reactions appear to be common [24]. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Role of baked milk in resolution of CMA' and "Oral food challenges for diagnosis and management of food allergies" and "Component testing for animal-derived food allergies", section on 'Cow's milk'.)

In a 2008 study of 100 children with CMA, 66 percent tolerated baked CM with CM-specific IgE of <20 kU/L, and 90 percent tolerated it with a level <5 kU/L [10]. In that same study, 85 percent with a skin test wheal <10 mm and 100 percent with a skin test wheal <5 mm tolerated baked CM. In a retrospective series of 206 patients who were challenged to baked CM between 2009 and 2014, the 48 percent who passed the challenge had a median CM IgE of 4.8 kU/L (interquartile range [IQR] 2.5-10.2) compared with 23 kU/L (IQR 5.4-26.0) for those who failed [24].

While the majority of children with CM and hen's egg (HE) allergies tolerate baked forms of these foods, one study of 174 OFCs to baked HE, baked CM, cooked HE, CM, peanut, or tree nuts in 158 children found that those who react during OFCs to baked CM or HE were more likely to develop symptoms ≥60 minutes after stopping the OFC but were less likely to have mucocutaneous reactions compared with patients challenged to other foods [28]. In addition, hypoxemia and hypotension were only observed in baked-HE and baked-CM challenges. Extending the dosing interval, adding more dosing steps, early treatment of subjective symptoms, and/or prolonging the observation time may be warranted in patients who are at higher risk for reacting to baked-CM OFC (eg, higher IgE levels, recent reactions, history of more severe reactions or anaphylaxis). (See "Egg allergy: Management", section on 'Extensively heated (baked) HE'.)

In the 2008 series, 99 (48 percent) patients who passed the challenge were instructed to continue baked CM in their diet [24]. Of the 107 patients who failed the challenge, all but 19 who had reacted to a small dose of baked CM or had a more severe reaction were advised to include some amount of baked CM in their diet. A majority of patients in the group that passed the challenge were able to advance ingestion, with 54 percent tolerating unheated CM (resolution of CMA) and an additional 22 percent making lesser advancements. However, a number of patients who passed the challenge were not successful in introducing baked CM into the diet, with 19 percent continuing complete avoidance of CM at the end of the follow-up period. Among those who failed the challenge but were instructed to introduce some baked CM, 26 patients (30 percent) had resolution of their CMA, and an additional 33 percent were able to consume some baked CM, less cooked CM, or baked cheese in their diet, although strict avoidance was continued in 38 percent. Continued avoidance was more common among those who required treatment during the challenge. CMA resolved in two patients (10 percent) instructed to continue avoidance of baked CM after a failed initial challenge. Successful introduction of baked CM was associated with younger age, lower specific IgE level, and passing the initial challenge. Reactions with home dosing were common, including to previously tolerated forms and amounts, and 14 percent were severe. Six patients developed eosinophilic esophagitis (EoE) with baked CM introduction.

Our approach — For patients with lower CM-specific IgE levels (≤2 kU/L) and/or smaller SPT reactions (less than or equal to the histamine control) on follow-up testing, especially if the clinical history is reassuring, we typically challenge initially to straight CM rather than extensively heated (baked) CM. The chance of success with these challenges is approximately 50 percent (based upon CM-IgE levels) [29]. Patients who fail the direct CM challenge are eligible for a baked CM challenge.

There is greater variability in the approach to baked CM introduction. Some allergy specialists offer challenges to baked CM every two years in most patients, regardless of history and test results, given the significant implications for quality of life that passing a baked CM challenge brings and the poor discriminatory ability of available testing. However, the odds of passing are low when skin tests are large (>14 mm) or IgE levels high (>35 kU/L) [10]. In addition, caution is needed because severe reactions can occur from this type of OFC. Others use various test cutoffs, for example, CM-IgE ≤20 kU/L, casein-IgE <5, or CM-SPT ≤12 mm, to help determine when to offer a baked CM challenge. Clinical history and trends and discrepancies (eg, large SPT but low CM-IgE) in measures of sensitization can also help inform the likelihood of passing the challenge and may influence the decision to offer a challenge. Some patients (or their parents/caregivers) may prefer to continue avoidance of all CM until it is felt that they are ready for a straight CM challenge. (See 'Avoidance' above and 'Extensively heated (baked) cow's milk' above.)

The approach to the patient after a baked CM challenge is highly individualized. For patients who fail the challenge with just a mild reaction after ingesting a large dose, one option is to have them include a smaller amount of baked CM in their diet and slowly increase the amount over time. For patients who tolerate this approach and for those who passed the baked CM challenge, some allergy specialists allow many of their patients to gradually advance their diet at home, from baked CM, to less heated CM (eg, cheese on pizza), to uncooked forms of CM [24]. Others prefer to have most of their patients continue ingestion of just baked CM and return to clinic for a straight CM challenge prior to full introduction of CM into the diet, offering advancement at home in selected, reliable caregivers, taking into consideration CM-IgE levels, history of past reactions, and presence or absence of asthma. An additional option is performing a challenge to an intermediate form of CM, such as a cheese pizza, prior to the straight CM challenge.

MANAGEMENT OF YOUNGER SIBLINGS — Parents/caregivers often inquire about what measures to take to prevent CMA (eg, maternal avoidance during pregnancy and lactation) and when to introduce CM and CM-containing products in a younger sibling of a child with CMA. In these cases, avoidance of CM is not recommended for nursing mothers or the infant, and CM proteins can be included in the infant diet without any specific delay. Delayed introduction of CM-containing products beyond six months of age is not recommended, unless the infant is showing signs of allergic disease (straight CM is delayed until one year of age for nutritional reasons). These issues are discussed in greater detail separately. (See "Pathogenesis of food allergy", section on 'Genetics' and "Introducing formula to infants at risk for allergic disease", section on 'Formula selection for the high-risk infant' and "The impact of breastfeeding on the development of allergic disease" and "Primary prevention of allergic disease: Maternal diet in pregnancy and lactation" and "Introducing highly allergenic foods to infants and children", section on 'Introduction in higher-risk populations'.)

FUTURE TREATMENTS — There are no treatments that can cure or provide long-term remission from food allergy. However, several treatment strategies are under investigation. These approaches are either allergen specific or aimed at modulating the overall allergic response. (See "Experimental therapies for food allergy: Immunotherapy and nonspecific therapies" and "Oral immunotherapy for food allergy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Food allergy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)" and "Patient education: Food allergen avoidance (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Overview – Management of cow's milk allergy (CMA) includes instructions about avoidance of cow's milk (CM) protein (Food Allergy Research and Education [FARE]), replacement of CM with alternative protein and calcium sources (table 2 and table 1), education in the proper management of accidental exposures (Anaphylaxis Emergency Action Plan - English) (Anaphylaxis Emergency Action Plan - Spanish), and monitoring for resolution of the allergy. (See 'Introduction' above.)

Avoidance and substitutes – The most straightforward approach in managing any food allergy is complete avoidance of the culprit food. Eliminating CM from the diet can be difficult and can pose nutritional as well as quality-of-life concerns since CM is a ubiquitous food in many cultures and diets and is an important source of fat and protein in early childhood. Counseling should include a discussion about CM alternatives and substitutes (table 1 and table 2 and table 3 and table 4). Most patients with CMA do not tolerate milk from sheep, goats, deer, ibex, and buffalo. However, some patients may tolerate milk from other mammals, such as camels, pigs, reindeer, horses, and donkeys. In addition, evaluation of the allergy followed by an oral food challenge (OFC) to extensively heated CM is an option since a majority of those with CMA will tolerate CM in extensively heated (baked) products, such as a muffin. (See 'Avoidance' above and "Management of food allergy: Nutritional issues" and 'Extensively heated (baked) cow's milk' above.)

Autoinjectable epinephrine – Patients with immunoglobulin E (IgE) mediated CMA are at risk for severe reactions, and the severity of symptoms can vary from reaction to reaction. Thus, we prescribe epinephrine autoinjectors for all patients with a history of anaphylactic reactions to CM and typically do so for patients with milder IgE-mediated reactions to CM as well. (See 'Acute IgE-mediated reactions' above.)

Monitoring for allergy resolution – Children with CMA should be monitored for resolution of the allergy since most will outgrow the allergy in childhood. Monitoring for resolution includes assessing history of any accidental exposures and reactions, serial testing for sensitization (in vitro and/or skin prick testing [SPT]), and OFCs. (See 'Monitoring for resolution and reintroduction' above.)

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References

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