Cow’s Milk Allergy diagnosis and management

• CMA is an immune mediated reaction to the proteins within cow's milk and affects 2-3% of infants¹. It can often get confused with lactose intolerance, which does not involve the immune system but instead is the inability to digest the sugar in cow’s milk (lactose).
• Most cases of CMA present in the first year of life, with the majority of children outgrowing by the age of 5 years¹.
• Non-IgE mediated CMA can be complex to diagnose as many symptoms can overlap with common symptoms that present in early life (e.g reflux and colic), compared to IgE mediated symptoms that are easier to identify²

Symptoms can affect the skin, gastrointestinal tract and respiratory system.

Data from the UK shows3 :

• It takes an average of 3.6 months from initial GP visit to formal diagnosis

Delayed diagnosis prolongs the distress for infants and their parents and has the potential to impact on an infant’s growth and development. Furthermore, it imposes substantial financial burden to the NHS, with one study highlighting a mean 18.2 clinician visits, costing the NHS an estimated £25.6 million during the first 12 months after initial presentation³ .

Prompt and accurate diagnosis is paramount for the management of CMA. It is also fundamental with the removal of cow's milk that the nutritional requirements of the infant/child are met via breastmilk, specialist formulas and dietary modification which is why a referral to a specialist dietitian is recommended. 

NICE have produced a guideline (CG 116)4 to aid in the diagnosis and assessment of food allergy in children and young adults. Within NICE there is also a clinical knowledge summary (CKS) for the management of CMA5.  This also includes useful case studies.

The core principles of the NICE food allergy guidance include:

1. To recognise the broad range of possible presenting symptoms
2. Take an allergy focused clinical history
3. Decide whether the clinical history suggests IgE or non-IgE mediated mechanism
4. Test accordingly to mechanism (IgE mediated allergy)
5. Provide information and support
6. Refer as appropriate 

NICE states to consider food allergy in a child or young person who:

• has one or more signs and symptoms of possible food allergy (pay particular attention to persistent symptoms that involve different organ systems) or
• has had treatment for atopic eczema, gastro-oesophageal reflux disease or chronic gastrointestinal symptoms (including chronic constipation) but their symptoms have not responded adequately.

An allergy focused history is the cornerstone to diagnosis and should be conducted by a healthcare professional (HCP) with the appropriate competencies. Do not offer allergy tests without first taking an allergy-focused clinical history, tailored to the presenting symptoms and age of the child or young person using the questions below.

The clinical history should include:

• any personal history of atopic disease (asthma, eczema or allergic rhinitis)
• any individual and family history of atopic disease (asthma, eczema or allergic rhinitis) or food allergy in parents or siblings
• details of any foods that are avoided and why
• an assessment of presenting symptoms and other symptoms that may be associated with food allergy, including:

- age at first onset

- speed of onset

- duration, severity and frequency

• setting of reaction (for example, at school or home)
• reproducibility of symptoms on repeated exposure
• what food and how much exposure to it caused a reaction
• cultural and religious factors that affect the child's diet
• who has raised the concern and suspects the food allergy
• what the suspected allergen is
• the child's feeding history, including age of weaning and whether they were breastfed or formula-fed (if the child is currently being breastfed, consider the mother's diet)
• details of previous treatment, including medication, for the presenting symptoms, and the response to this
• any response to the elimination and reintroduction of foods

Based on the clinical history, physically examine the child or young person, paying particular attention to:

- growth and physical signs of malnutrition

- signs indicating allergy-related comorbidities (atopic eczema, asthma and allergic rhinitis)

There are many other tools to support HCPs to take an accurate allergy focused history which can be found here:

• IMAP²
• EAACI⁶
• RCPCH⁷
• EATERS⁸

CMA can be classified according to whether the allergic reaction is an IgE mediated allergy (rapid onset) within 2 hours of ingestion or a non-IgE mediated allergy (delayed onset) between 2-72 hours after ingestion. Below are recommendations from the NICE guideline which outline the tests that should be used to confirm diagnosis.

There are two tests used to aid in the diagnosis of IgE mediated food allergy. These include skin prick test and/or specific IgE blood testing and should only be conducted after a thorough allergy focused history has been taken.

The choice of test is based on:

• the clinical history and
• the suitability, safety for, and acceptability to the child or young person (or their parent or carer) and
• the available competencies of the healthcare professional

Tests should only be undertaken by healthcare professionals with the appropriate competencies to select, perform and interpret results in the context of information provided in the allergy focused history.  

Only undertake skin prick tests where there are facilities to deal with an anaphylactic reaction. Do not use atopy patch testing or oral food challenges to diagnose IgE-mediated allergy in primary care or community settings.

In non-IgE mediated allergy, if CMA is suspected an elimination diet between 2 to 6 weeks is recommended. Unlike IgE mediated allergy, there is no validated test other than an exclusion with a reintroduction challenge.

Alternative diagnostic tools are not recommended. Do not use the following alternative diagnostic tests in the diagnosis of food allergy:

• vega test
• applied kinesiology
• hair analysis
• serum-specific IgG testing

These tests are not evidence based and may cause unnecessary restriction which could lead to nutritional deficiencies, malnutrition and reduced quality of life. 

CMA is managed by excluding cow's milk protein from the diet; either a maternal exclusion is required or a prescribed hypoallergenic formula. NICE recommends that the advice of a dietitian with appropriate competencies should be sought to assist with nutritional adequacies, timings of elimination and reintroduction, and follow-up.

HCP’s should actively support continuation of breastfeeding with CMA. If an infant is being breast fed, the mother needs to follow an exclusion diet with the support of the dietitian to ensure that the maternal diet is adequate.

It is recommended to have a calcium and vitamin D supplement. For breastfeeding mums, calcium requirements almost double to 1250mg a day. For vitamin D, a supplement containing 10ug a day is recommended as well as a vitamin D drops for baby (8.5-10ug a day). 

Combination of formula-fed infants will need to be provided with a replacement hypoallergenic formula, either an extensively hydrolysed (EHF) or amino acid formula (AAF). An extensively hydrolysed formula is the first line formula in mild – moderate non-IgE mediated CMA. There are specific times where the use of an amino acid formula is indicated such as faltering growth, anaphylaxis, severe gastrointestinal allergies and infants reacting to an extensively hydrolysed formula⁹. 

As well as providing information to support breast or formula feeding, HCPs must also consider socioeconomic, cultural and religious issues and offer information on:

• what foods and drinks to avoid
• how to interpret food labels
• alternative sources of nutrition to ensure adequate nutritional intake
• the duration, safety and limitations of an elimination diet
• oral food challenge or reintroduction procedures, if appropriate, and their safety and limitations

There are many patient organisations that provide further information and support to patients including Allergy UK and Anaphylaxis UK. Specific factsheets on the management of CMA can also be found in the IMAP guideline too².

Consider referral when the child or young person has:

• faltering growth in combination with one or more of the gastrointestinal symptoms described in signs and symptoms of possible food allergy
• not responded to a single-allergen elimination diet
• had one or more acute systemic reactions
• had one or more severe delayed reactions
• confirmed IgE mediated food allergy and concurrent asthma
• significant atopic eczema where multiple or cross-reactive food allergies are suspected by the parent or carer

There is:

• persisting parental suspicion of food allergy (especially in children or young people with difficult or perplexing symptoms) despite a lack of supporting history
• strong clinical suspicion of IgE mediated food allergy but allergy test results are negative
• clinical suspicion of multiple food allergies