Continuing Education Activity

Cow's milk allergy is an allergic reaction to the protein found in cow’s milk. Diagnosis can be difficult as it is primarily based on history and physical exam. This activity outlines the evaluation and management of cow's milk allergy and highlights the role of the interprofessional team in managing patients with this condition.

Objectives:

• Identify the pathophysiology of cow's milk allergy.
• Describe the typical history and physical findings in patients with a cow's milk allergy.
• Describe the treatment and management options available for cow's milk allergy.
• Summarize the importance of coordination among interprofessional teams to improve the care of children diagnosed with a cow's milk allergy.

Introduction

Cow's milk allergy is a common diagnosis in infants and children. It characteristically presents as an allergic reaction to the protein found in cow’s milk. Cow's milk allergy manifests as a variety of symptoms and signs which commonly develop in infants and can regress by the age of 6. It can be a source of parental and family stress due to a milk-free diet and can lead to a subsequent nutritional deficiency if not treated appropriately.

Etiology

Food allergies stem from the host's immune system. If an individual has an allergy to milk, the body’s immune system responds to a specific milk protein, triggers an immune response, and attempts to neutralize the triggering protein. The next time that the body comes into contact with the protein, the immune response recognizes the protein. It triggers the immune system to mount a response, including the release of histamine and other immune mediators. This release of chemicals causes the signs and symptoms of cow's milk allergy.

Epidemiology

It is difficult to determine the exact prevalence of cow's milk allergy due to a lack of a precise criterion for diagnosis. Often the term allergy is interchanged with intolerance or hypersensitivity. In the developed world, the prevalence appears to be 2 to 3% in infants.[1] There is no evidence that prevalence is increasing, and parents perceive cow's milk allergy more frequently than can be proven with an oral challenge.[2][3] By the age of 6, the prevalence has fallen to less than 1%.[4]

Pathophysiology

Cow's milk contains more than 20 protein fractions. The significant allergens belong to casein protein (alpha-s1-, alpha-s2-, beta-, and kappa-casein) and whey proteins (alpha-lactalbumin and beta-lactoglobulin).[5] Most individuals with cow's milk allergies have a sensitivity to both caseins and whey proteins.[6]  Immune-mediated adverse food reactions classify into two primary categories: IgE-mediated, non-IgE-mediated. A non-IgE mediated mechanism most frequently causes cow's milk allergy.[7]

History and Physical

Typically the presence of cow's milk allergy appears within the first few months of life and usually before six months. Symptoms can present a few days or weeks after the ingestion of cow’s milk protein. The symptoms can vary from diarrhea and emesis to life-threatening anaphylaxis. In cases that involve the GI tract, the child can become dehydrated and exhibit a failure to thrive.

Cow's milk allergy reactions classify into rapid onset; usually, IgE mediated, where symptoms occur within an hour after ingestion, and slow onset, non-IgE mediated, where symptoms take hours or days to present.[8][9]

Rapid onset symptoms can include:

• Urticaria/hives
• Wheezing
• Itching or a tingling feeling around the mouth or lips
• Angioedema: swelling of the lips, tongue, or throat
• Coughing or shortness of breath
• Vomiting
• Anaphylaxis

Slow onset symptoms can include:

• Diarrhea
• Hematochezia
• Abdominal cramps
• Colic

Anaphylaxis is a medical emergency requiring treatment with an epinephrine shot and evaluation in the emergency room. Signs and symptoms start soon after milk consumption and can include:

• Increased work of breathing
• Constriction of airways
• Swollen throat
• Facial flushing
• Itching

The clinician must recognize the difference between milk allergy and milk intolerance. The major difference is that intolerance does not involve the immune system. Common symptoms of milk intolerance include gas, bloating, or diarrhea after ingesting milk. The treatment of intolerances and allergies is different.[10]

Evaluation

There is no specific test to detect cow's milk allergy. The basis of diagnosis is primarily on the history of symptoms and physical exam. It is important to detail the timeline of symptoms and when they occur. Carrying out a diagnostic protocol in infants for suspected cow's milk allergy may help to rule in or out the disease.[11]

Primary tests, if used, include a skin prick test and serum-specific IgE. Both tests show high sensitivity but low specificity and can be positive in non-allergic subjects.[12]

Serum-specific IgE to cow’s milk allergy: This can aid in the diagnosis of IgE mediated cow's milk allergy and cut-off values are multifactorial and should be set by each allergist.[13]

Skin prick test: This is performable by an allergy specialist. 

Diet elimination: If suspected, an infant should receive a diet free of cow's milk protein for a month. If symptoms improve following elimination of the suspected food, then an oral food challenge is the gold standard test.[14] This challenge must be in a medical setting due to concern for systemic IgE mediated reaction. Patients should undergo reevaluation every 6 to 12 months to determine if they have developed a tolerance to cow's milk protein.[15]

Algorithm:

1: If there are signs of anaphylaxis or immediate reaction, then diet elimination is recommended, and testing for serum IgE should follow. If serum-specific IgE is positive, then the child is diagnosed with a cow's milk allergy. If IgE is negative and symptoms improve after diet elimination, an oral challenge should be next. If the symptoms reoccur, the diagnosis is confirmed. If the symptoms do not reoccur, then the diagnosis of cow's milk allergy is excluded.[9]

2: If the symptoms are not consistent with anaphylaxis or immediate reaction, then an elimination diet is recommended. If symptoms improve, then an oral challenge should be done, and if symptoms reoccur, the diagnosis is confirmed. If the symptoms do not reoccur, it excludes the diagnosis of cow's milk allergy.[16][9]

3: If symptoms do not improve after the elimination diet, this eliminates the diagnosis of cow's milk allergy, and further evaluation should be done to assess the patient.[9]

Treatment / Management

The definitive treatment for all food allergies is the strict elimination of the food from the diet. If a child starts on a milk-free diet, the doctor or dietitian can help plan nutritionally balanced meals. The parent or child may need to take supplements to replace calcium and nutrients found in milk, such as vitamin D and riboflavin.[15]

Breastfeeding: Rates of cow's milk allergy in breastfeeding infants is lower than formula-fed infants and have been reported to be about 0.5%.[17] Breastfeeding is recommended, particularly if the infant is at high risk of developing milk allergy. Cow's milk proteins passed through breastmilk to the child and may cause an allergic reaction. If the child has a cow's milk allergy, then the mother should eliminate all foods containing cow's milk protein, including cheese, yogurt, and butter from her diet.[9] 

Hypoallergenic formulas: These formulas are hydrolyzed via enzymes to break down the milk proteins. Depending on their processing level, products are classified as either partially or extensively hydrolyzed/elemental formulas. Recommendations are for extensively hydrolyzed formulas due to increased allergenicity and associated reactions in partially hydrolyzed formulas.[18]

Soy-based formulas: As many as 50% of children affected by cow's milk protein intolerance also develop soy protein intolerance if fed with soy-based formulas. Therefore, soy-based formulas are not generally a viable option for the treatment of cow's milk protein intolerance.[15][7]

Alternative milk: substitutes such as sheep’s and goat’s milk generally are not acceptable because of a high degree of cross-reactivity with cow's milk protein. However, research shows that there have been decreased incidents of cross-reactivity to camel’s milk.[19]

Acute treatment:

Despite the parent's best efforts, if a child accidentally consumes milk, medications such as antihistamines may reduce the mild allergic reaction.

If the parent or child has a serious allergic reaction, they may require an emergency epinephrine injection and a visit to the emergency room. If there is a risk of having a severe reaction, the parent or child may need to carry injectable epinephrine at all times. These individuals should have their doctor or pharmacist demonstrate how to use this device so that they are prepared for an emergency.[20][21]

Differential Diagnosis

Due to a wide variety of symptoms that can be caused by cow's milk allergy, the differential diagnosis can be extensive and include but not limited to: 

• Other food allergies
• Celiac disease
• Enteropathy
• GI infections
• Enterocolitis
• Inflammatory bowel disease
• Meckel diverticulum 
• Angioedema
• Lactose intolerance
• Idiopathic urticaria
• Anaphylaxis 

Prognosis

The prognosis for cow's milk protein allergy in infancy and young childhood is good. Approximately 50% of affected children develop tolerance by the age of 1 year, more than 75% by the age of 3 years, and over 90% are tolerant at 6 years of age.[4][22] 

Children who display an allergy to milk are more likely to develop other allergies to foods. Associated adverse reactions to different foods develop in up to 50% of children, and allergies against inhalants occur in 50% to 80% before puberty.[23]

Pearls and Other Issues

• Cow's milk allergy is a common diagnosis in infants and children.
• It is difficult to detect the exact prevalence of cow's milk allergy due to a lack of a precise criterion to diagnose.
• It can be classified into two major categories: IgE-mediated, non-IgE-mediated.
• Typically the presence of cow's milk allergy appears within the first few months of life and usually before six months.
• The clinician must recognize the difference between milk allergy and milk intolerance.
• The basis of diagnosis is primarily on the history of symptoms and physical exam.
• The definitive treatment for all food allergies is the strict elimination of the food from the diet.

Enhancing Healthcare Team Outcomes

The majority of children with cow's milk allergy are first seen by the primary caregivers including the pediatrician, family physician, and nurse practitioner. In most cases, avoidance of milk can solve the problem but since milk products are ubiquitous, the risk of an allergy cannot always be eliminated. Patients with continued allergies need to be referred to a specialist.

An allergist is best to diagnose a cow's milk allergy, but usually, the primary care provider will handle long-term care and monitoring. The patient and family should receive counseling and education on the medical condition and the importance of avoidance of foods containing cow’s milk protein. Parents need to be educated by the primary clinicians that cow's milk allergy can be a medical emergency, and if there is a history of rapid reaction or anaphylaxis, then epinephrine should be carried at all times.

Cow's milk allergy requires an interprofessional team approach, including physicians, specialists (most notably an allergist), specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. The family may be educated by the pediatric nurse, who provides updates to the rest of the team. Pharmacists may be involved in formula selection and assist in medication review. [Level 5]