Cow’s Milk Protein Allergy Treatment

Negative Challenge: No Cmpa

Children who do not develop symptoms on the cow’s milk formula during challenge and up to 1week after followup can resume their normal diet, although they should be monitored. Clinicians should advise parents to be attentive for delayed reactions, which may evolve over several days following the challenge.2

What Tests Will Be Done To Diagnose A Milk Allergy

An allergist may use different allergy tests to help diagnose a milk allergy based on your symptoms. These tests may include:

Blood test

During a blood test, your allergist will use a thin needle to withdraw a small amount of blood from a vein in your arm. The blood sample goes to a laboratory. The lab adds milk proteins to your blood sample and measures the levels of IgE antibodies in it.

It may take a week or longer to get the results from a blood test.

Skin prick test

This test exposes your body to small amounts of milk proteins.

Your allergist will first clean a test area of your skin with iodine or alcohol. The test area is usually on your forearm or upper back.

Your allergist will use a thin needle to prick your skin with a small amount of liquid containing milk proteins. The lancet wont go deep into your skin. Youll only feel a tiny pinch, and you wont bleed.

Some allergists may use a different method for skin testing. They place a droplet of liquid milk proteins on your skin. They then use a lancet to scratch your skin lightly. The droplets will enter your skin through the scratch. Youll only feel slight discomfort, and you wont bleed.

After skin testing, youll wait 15 minutes. The allergist will then measure any discolored spots on your skin from the milk test or the controls with a ruler.

A skin prick test takes less than an hour.

Graded oral challenge

A graded oral challenge may take up to four hours.

A Child Fed With Cow’s Milk Formula With Severe Symptoms

Figure 3

Algorithm for children < 1 year fed with cow’s milk formula and severe symptoms. In child less than1 year of age, infant formula is not compulsory.

Immediate severe symptoms are considered laryngeal edema, acute asthma with severe respiratory difficulty, anaphylaxis. The following are delayed onset severe symptoms: chronic diarrhoea or chronic vomiting with poor growth, intestinal bleeding with iron deficiency anaemia, protein losing enteropathy with hypoalbuminemia, eosinophilic gastroenteropathy confirmed by biopsy .

If any of these immediate symptoms are observed as a consequence of suspected CMPA, infants should follow a cow’s milk free diet. As substitutes, SF or eHF or AAF can be used. eHF and SF should be started under medical supervision because of possible clinical reactions. If an AAF is adopted, it may be administered for 2 weeks and then the infant may be switched to SF or eHF.

In children with late severe gastrointestinal symptoms with poor growth, anaemia or hypoalbuminemia or eosinophilic oesophagogastroenteropathy, it is recommended to start an elimination diet with AAF and then switched with eHF. The effect of the diet should check out within 10 days for enterocolitis syndrome, 1-3 weeks for enteropathy and 6 weeks for eosinophilic oesophagogastroenteropathy.

Children with any severe symptoms should be referred to a specialized centre.

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Cows Milk Protein Allergy In Children: Identification And Treatment

How pharmacists and pharmacy professionals can diagnose this complex problem and advise parents and carers on options for management.

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Allergy is an adverse overreaction by the immune system to a harmless substance. A food allergy occurs when specific components of a food are recognised by allergen-specific antibodies or cells, eliciting specific immunological reactions that result in characteristic symptoms. Food allergy is an important public health problem that affects both adults and children.

Cows milk protein allergy is the abnormal response to proteins found in cows milk or products containing milk proteins. The reported prevalence of CMPA varies owing to possible misinterpretations of presumed reactions to milk and diagnostic criteria, and is often overestimated. A pan-European study using the gold standard food challenge test for diagnosis confirmed CMPA in around 1% of children aged up to two years.

This article provides an overview of how pharmacists, pharmacy teams and other healthcare professionals can help to identify a child with possible CMPA, ensuring a timely diagnosis and initiation of the most appropriate management plan. Further information can be found in the Milk Allergy in Primary Care guideline.

Tolerance Induction And Immunotherapy

Sublingual desensitisation is a technique used in the realm of respiratory allergies and can be adapted to be used in the assessment of food allergies. A study of this type, on patients with persistent CMPA, was carried out using half-skimmed milk placed under the tongue every day for 2 min before breakfast, at an initial dose of 0·1 ml, increased by 0·1 ml every 15 d, and reaching a dose of 1 ml. The OFC showed an increase in the milk dose inducing a reaction after 6 months, and the diet could be normalised in 50 % of patients. This technique appears to reduce the risk of accidental allergic reactions to small amounts of milk or even to cure some children it is simple to perform and without serious adverse effects, but its benefit must be confirmed in randomised studies to determine the amount of milk to use and the time required to optimise the results.

It is also possible to envisage the use of a patch as a desensitisation technique, and an initial study has analysed its safety, tolerance and potential benefits.

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What Causes Cows Milk Allergy

Cows milk allergy occurs because the immune system of those affected fights the cows milk protein. However, the defense system does not recognize it as harmless. In all, there are over 20 different proteins in cows milk, and each has the potential to cause an allergy. Most patients are allergic to caseins and the whey proteins -lactoglobin and -lactalbumin.

Sheeps and goats milk also has the potential to cause an allergy because the milk proteins are similar. In rare cases, breast milk can also cause allergic symptoms. In this case it is due to the milk proteins that the mother has ingested and which are excreted in breast milk.

The two types of allergy are based on the way the immune system deals with the proteins. In the immediate type, the immune system forms specific antibodies against cows milk protein, the so-called IgE. They network with each other through the cows milk proteins and thus trigger the allergic reaction.

In delayed-type allergies, the cells of the immune system play a major role. This activates special cells, the so-called T-cells, which have previously been sensitized to cows milk proteins. The T cells then attract more inflammatory cells, which amplify the allergic reaction.

The majority of patients suffer from immediate-type allergy with symptoms within minutes to hours of ingesting cows milk. Some show both immediate and delayed symptoms.

The Role Of In Vitro And In Vivo Testing For Cmpa

None of the available diagnostic tests prove or disprove that the child suffers from CMPA.8 Because of these limitations, allergen elimination diets and challenge procedures remain the gold standard for the diagnosis of mildtomoderate CMPA in formulafed infants. Clinicians can consider performing SPT or determining specific IgE against whole milk or single individual CMPs. SPTs with fresh cow’s milk resulted in larger wheal diameters than with commercial extracts, although the difference was not significant.33 Conversely, wheal diameters were significantly larger with fresh foods for the other food allergens.33 The overall concordance between a positive prick test and positive challenge was 58.8% with commercial extracts and 91.7% with fresh foods.33 These results indicate that fresh foods may be more effective for detecting sensitivity to food allergens. Fresh foods should be used for primary testing for egg, peanut and cow’s milk sensitivity.33

Patch testing in the investigation of CMPA is still a subject of ongoing research and can aid the diagnosis of nonIgEassociated reactions. Patch tests may contribute to the diagnosis of food allergy, even when SPT and RAST were negative.34 However, the patch test method needs to be standardised.

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Symptoms Of Cows’ Milk Allergy

Cows’ milk allergy can cause a wide range of symptoms, including:

• skin reactions such as an itchy rash or swelling of the lips, face and around the eyes
• digestive problems such as stomach ache, vomiting, colic, diarrhoea or constipation
• hay fever-like symptoms such as a runny or blocked nose
• eczema that does not improve with treatment

Occasionally CMA can cause severe allergic symptoms that come on suddenly, such as swelling in the mouth or throat, wheezing, cough, shortness of breath, and difficult, noisy breathing.

A severe allergic reaction is a medical emergency. Call 999 for an ambulance immediately if you think your child has anaphylaxis .

About Cow’s Milk Allergy

An allergy to cows milk and related dairy products affects one in 50 in babies and is different to lactose intolerance. Very few adults are allergic to cows milk. People who are allergic to cows milk can also be allergic to milk from other animals such as goats, sheep and buffalo.Symptoms of milk allergy vary and range from mild reactions to a severe allergic reaction . Some people experience symptoms immediately, but in others, the symptoms can take time to develop.If you think you, or someone in your care, have a cows milk allergy, visit your doctor for a diagnosis. To manage a cows milk allergy, all food containing milk must be avoided .

Exclusion and reintroduction of cow’s milk and other dairy foods should only be undertaken with advice from a medical specialist , particularly in cases of anaphylaxis. If long-term exclusion is required, an alternative source of calcium and protein is needed, to ensure adequate nutrition and growth.

Do not change your childs diet without consulting a doctor or your child could suffer from nutritional deficiencies.Food allergies can be life threatening. If you, or someone in your care, have a severe allergic reaction , call triple zero for an ambulance. Do not stand or walk. Administer adrenaline via injector , if available.

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Dietary Management Of Cows’ Milk Protein Allergy

A Child Fed With Cow’s Milk Formula With Mild

Figure 2

In infants with immediate symptoms or late symptoms , constipation) a CMPA can be suspected . Other causes are to be considered for patients unresponsive to treatment. Infant colic is not unanimously considered as a consequence of CMPA. The paediatrician has to consider the opportunity of a cow’s milk free diet in the most troublesome cases . Mild immediate reactions may be of difficult interpretation because they can be the result of causes different from CMPA. However, if these symptoms are strongly related to cow’s milk ingestion, we recommend to eliminate cow’s milk and follow the algorithm for severe reactions .

Regarding delayed onset gastrointestinal symptoms, other pathologies should be excluded before investigating allergic sensitization.

In mild atopic dermatitis, investigations for CMPA are not necessary in the absence of a clear relation between cow’s milk intake and onset of symptoms.

When a CMPA is suspected, infants should go on a 2-4 week diet without cow’s milk protein. Four weeks should be considered for chronic gastrointestinal symptoms. Infants should be fed with eHF or SF in children aged more than 6 months and without gastrointestinal symptoms.

When there is strong suspicion of IgE-mediated reactions, in infants who do not respond to a diet with eHF or SF an attempt may be made with a 14-days diet with AAF.

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Cow’s Milk Protein Allergy: When Should We Doubt

A positive atopic familiar history is common in children with suspected CMPA . The diagnosis of CMPA is based on a detailed history of symptoms , skin prick test and serum specific IgE to cow’s milk protein, elimination diet and oral food challenge. Clinical manifestations due to CMPA can be divided into IgE-mediated immediate clinical reactions and non IgE-mediated delayed reactions , most affecting the skin and the gastrointestinal system. However, immediate and delayed reactions can be associated in atopic eczema and in eosinophilic oesophageal gastroenteritis .

Figure 1

The negative predictive value of skin prick test/specific IgE for immediate reaction is excellent , however a small number of these patients can have clinical reaction. Therefore, despite negative IgE tests if there is a strong suspicion of CMPA, an oral food challenge is necessary to confirm the absence of clinical allergy. On the other hand, about 60% of children with positive IgE tests have CMPA . Prick by prick test with cow’s milk substitutes may be considered.

Oral food challenge, open or blind, remains the ‘gold standard” to definitely ascertain children with food allergy when the diagnosis is unclear . OFC should be performed under medical supervision in a setting with emergency facilities, especially in case of positive skin prick test or serum specific IgE to cow’s milk and in infants at risk of an immediate reaction.

Cows’ Milk Protein Hydrolysates

eHF comply with the European regulations for biological standards and animal testing. Unfortunately, very few clinical studies have confirmed their efficacy in the treatment of CMPA.

eHF available in many European countries are all lactose-free, and the protein portion consists of either cows’ milk casein hydrolysates , with the same hydrolysed protein, Allernova® and Nutriben CMPA® ), or cows’ milk whey protein hydrolysates , Alfaré® and Althéra®, Nutrilon Pepti®).

Table 1 Extensively hydrolysed formulae and amino acid -based formulae available in Europe for children with cows’ milk protein allergy*

* Based on products also available in France only infant formula when applicable.

Hydrosylate identical to that of Althéra®.

The MW of peptides and residual allergenicity of the cows’ milk hydrolysates are shown in Table 2, where the lowest residual allergenicity is observed with Nutramigen®, which is lower than that of Alfaré®, Peptijunior® and Nutrilon Pepti®, respectively. Recent modifications of the hydrolysate used in Alfaré led to a reduction of its MW profile, similar to that of the newly launched Althéra® , characterised by a median peptide size of 362 Da, with 99·7 % of peptides < 2400 Da.

Table 2 Residual molecular weights of peptides and residual allergenicity of cows’ milk hydrolysates

CMPA, cows’ milk protein allergy IgE-m, IgE-mediated P, prospective R, randomised DB, double blind multi-A, multi-allergic O, open B, blind CO, cross-over.

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Diagnostic Workup In Symptomatic Infants With No Alarm Symptoms

In a case of suspected mildtomoderate CMPA, CMP elimination should start with a therapeutic formula for CMPA. The guidelines define a therapeutic formula as one that is tolerated by at least 90% of CMPA infants.31 These criteria are met by some eHFs based on whey, casein or another protein source, and by amino acidbased formulae . Preferentially, all supplementary food should be stopped during the diagnostic elimination diet. If this is not possible in infants beyond 6months, only a few supplementary foods should be allowed with dietary counselling. Nevertheless, the diet should not contain CMP or hen’s eggs, soy protein or peanut. Referral to a paediatric specialist and dietary counselling may be needed for patients who do not improve. In such cases, further elimination of other allergenic proteins such as fish and wheat may be appropriate. In most cases, the therapeutic elimination diet should be given for at least 2weeks, although this may need to be increased to up to 4weeks in gastrointestinal manifestations and atopic dermatitis before deciding that the intervention has failed.

Dietary Restrictions For Cows Milk Allergy Should Be Supervised

Exclusion and reintroduction of cow’s milk and other dairy foods should only be undertaken with advice from a medical specialist , particularly in cases of anaphylaxis. If long-term exclusion is required, an alternative source of calcium and protein is needed, to ensure adequate nutrition and growth.

Excluding foods from the diet during breastfeeding is rarely required, and if recommended, the maternal nutritional intake should be supervised, assessed and reviewed by a dietitian. Assessment and review by a dietitian is also recommended for babies and children who need to exclude cows milk and other dairy foods.

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Cows Milk Allergy: Immediate

Patients with the immediate type of cows milk allergy complain of symptoms just one to two hours after consuming cows milk. Above all, they show:

• Rash in the form of hives , redness with itching or sudden swelling
• Gastrointestinal complaints such as abdominal pain , nausea, vomiting, diarrhea
• Respiratory impairments such as allergic rhinitis , coughing , breathing difficulties, in rare cases life-threatening anaphylactic shock with shortness of breath and circulatory failure occurs