Issue 128 imap

PAEDIATRIC

THE MAP MILK ALLERGY GUIDELINES: WHAT’S NEW? Carina Venter PhD, RD Assistant Professor University of Colorado Denver School of Medicine USA

Dr Trevor Brown MRCP (UK), FRCPCH Honorary Consultant in Paediatric Allergy, Children’s Allergy Service, Ulster Hospital, Northern Ireland Carina and Trevor are the joint first authors of the new updated version of the MAP guideline.

Carina is currently working in the Section of Allergy and Immunology at the Children's Hospital Colorado where she is conducting research and working with children and adults.

Trevor has acted as an advisor to the UK National Care Pathway for food allergy in children, the NICE food allergy guideline, NICE quality standard for food allergy and the NICE e-learning programme for food allergy.

In 2011, the UK Department of Health commissioned a National Institute for Health and Care Excellence (NICE) Guideline on Food Allergy with a very specific and targeted scope: the ‘Diagnosis and assessment of food allergy in children and young people in primary care and community settings’.1 They recommended that many presentations of food allergy should be managed in primary care UK, but no particular focus was placed on cows’ milk allergy (CMA).

CMA is the most common cause of food allergy in the early months of life and its diagnosis and management is complex.2 For example, the majority of infants in the UK and Europe present as suspected mild to moderate non-IgE-mediated CMA,3,4 which then requires challenges at home to confirm or exclude the diagnosis. Additionally, with regard to the initial elimination trial prior to the required challenge, there are added complexities; in the formula-fed infant, choosing the most appropriate formula and in the exclusively breastfed infant, advising and supporting a strict maternal elimination diet.5 Given these particular complexities in the initial assessment and diagnosis of CMA, and the then ongoing need to practically advise on the management of mild to moderate non-IgE-mediated CMA within UK primary care, a subgroup of the clinicians on the NICE Food Allergy guideline development group published the MAP (Milk Allergy in Primary Care) guidelines.

MAP particularly focused on the following questions:5 • How to distinguish between: i) IgE-mediated and non-IgEmediated presentations of CMA; ii) Severe and mild to moderate clinical expressions of CMA. • Which children should be considered for early specialist referral.

• How to provide guidance on formula choice in the initial diagnosis of CMA, based on the current international guidelines.

• How to provide guidance about confirming the diagnosis and then the ongoing management of mild to moderate non-IgE-mediated CMA in primary care.

To answer these questions, the MAP guideline authors developed a simple algorithm-based pathway covering the initial clinical presentations of CMA in infancy (both non-IgE and IgE), followed by the management in primary care of those children with confirmed mild to moderate nonIgE-mediated CMA. Since 2013, UK NICE followed up with two more publications: in 2015, a NICE Clinical Knowledge Summary (CKS) on the diagnosis and management in primary care of ‘Cows’ milk protein allergy in children’6 and in 2016, a NICE Quality Standard for food allergy.7 Since the publication of the MAP guideline in 2013, the British Society for Allergy and Clinical Immunology also published their specialist guidelines on cows’ milk allergy.8 The initial group of MAP guidelines authors therefore felt an update of the MAP guidelines was required to incorporate these.

Further, it became increasingly apparent that the MAP guideline was being used much more widely www.NHDmag.com October 2017 - Issue 128

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THIS IS HUGE After months of coping with the sleepless worry and heartbreaking cries of his cow’s milk allergy, suddenly, a little moment like this doesn’t seem so little after all.

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REFERENCES: 1. Sampson HA et al. J Pediatr 1991;118(4): 520-525. 2. Data on file. Abbott Laboratories Ltd., 2013 (Similac Alimentum case studies). 3. Borschel MW and Baggs GE. T O Nutr J 2015;9:1-4. 4. Koo WWK et al. J Am Coll Nutr 2006;25(2):117-122.

IMPORTANT NOTICE: Breastfeeding is best for babies, and is recommended for as long as possible during infancy.

Similac Alimentum is a Food for Special Medical Purposes and should be used under the supervision of a healthcare professional.

Date of preparation: July 2015 RXANI150143

than the UK, with almost 65,000 downloads worldwide from the Clinical and Translational Allergy website since 2013. To respond to this, the MAP authors decided to expand their guidelines development group to include authors from North America, South America, Africa, Asia and Australia.

This has led to iMAP - an ‘international’ interpretation of the MAP (Milk Allergy in Primary Care) guidelines.9 iMAP went through an extensive review process, taking almost two years to reach consensus on this very complex clinical presentation of CMA, mild to moderate non-IgE-mediated allergy.

We have summarised the changes we have made in the algorithms, formula choice and the milk ladder in Tables 1-5. The iMAP guidelines9 also now include a parent handout with information on non-IgE-mediated CMA. Some of the main changes that will particularly effect dietetic practice include: Symptoms of non-IgE-mediated CMA Although this will continue to be a topic of debate, the symptoms of ‘perianal redness’ and ‘respiratory symptoms’ have been removed.

Maternal diet when breastfeeding In the new iMAP guidelines, only the mother who is exclusively breastfeeding her child will be advised to remove all forms of cows’ milk from her diet, as opposed to any breastfeeding mother.

The authors realise that if a child only presents with symptoms upon introduction of formula or food, the amount of cows’ milk protein in breast milk is unlikely to trigger a reaction.

Formula choice The iMAP guidelines focus on the use of extensively hydrolysed formulas as they are most suited for this population group. The guidelines do not distinguish between whey and casein-based formulas.

The authors added in the option of using soy formula as that is often used as a first line treatment for non-IgE-mediated CMA outside of the UK. Reference to calcium and vitamin D supplements Actual doses for these recommended daily

supplements have been removed to allow for adhering to national guidance.

Elimination period The guidelines now recommend a four-week elimination period, with a minimum of two weeks.

Nomenclature change The guidelines now refer to home Reintroduction as opposed to home Challenge to confirm or exclude the diagnosis.

However, the biggest change in the iMAP guidelines relates to the Milk Ladder.

THE MILK LADDER

The revised Milk Ladder now has six steps opposed to 12 steps.

• The doses of milk protein have also been changed to allow reducing from 12 to six steps.

• Cultural foods, such as malted milk biscuit, digestive biscuits, shepherd’s pie, lasagna and Scotch pancakes, have been removed.

• Baked/heated cheese has been removed due to parent feedback highlighting ongoing confusion and frustration, e.g. allowing lasagna but not grilled cheese sandwiches.

• The recipes are now in units of grams, ounces and cups, to allow for international use.

• Sugar has been removed/reduced from the recipes to comply with WHO guidance.

• Commercial alternatives (malted milk biscuits, digestives) have been removed and the following statement was added: ‘Should you wish to consider locally available store-bought alternatives - seek the advice of your healthcare professional for availability’.

IN SUMMARY

The new iMAP guidelines have a range of authors with international expertise. An initial fact sheet for parents is provided. The latest cows’ milk allergy guidelines from the UK have been incorporated. Some slight changes have been made to symptoms relating to mild to moderate non-IgE-mediated cows’ milk allergy. www.NHDmag.com October 2017 - Issue 128

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Formula milk choice now focuses on extensively hydrolysed formulas and reference to soya milk is made for countries where this is used. Maternal cows’ milk avoidance is only recommended when exclusively breastfed and daily calcium and vitamin D supplements should be prescribed in doses according to national guidance.

The Milk Ladder covers six steps instead of 12 steps (see Table 4) and the recipes have been adapted to comply with WHO standards, parental needs for savoury options, international cooking/ baking practices and cultural food preferences.

Milk protein doses have been adapted to allow for six steps instead of 12 steps.

Table 1: MAP and iMAP guidelines - details MAP

iMAP

Year of publication

2013

2017

Title

MAP - Milk Allergy in Primary Care guideline

iMAP - an international interpretation of the MAP (Milk Allergy in Primary Care) guideline

Healthcare professional key target groups

Primary Care

Primary Care and ‘First Contact’ clinicians

Authorship

Five UK-based clinicians representing UK primary, secondary and tertiary level clinical allergy (no industry sponsorship)

Original five UK authors plus seven international tertiary care level paediatric allergy colleagues from USA, China, Australia, South Africa, and Brazil (no industry sponsorship)

Source material

UK NICE Food Allergy Guideline for children and young people in primary care and community settings CG 116 2011 World Allergy Organisation Guideline on cows’ milk allergy (DRACMA) 2010 USA NIAID Food Allergy Guideline 2010 USA AAP Guideline on Hypoallergenic Infant Formulas 2000 ESPGHAN Guidelines on the diagnosis and management of cows’ milk allergy 2012 Vandenplas et al ‘European’ Guideline on cows’ milk allergy 2007 Australian Consensus Statement on the diagnosis and management of cows’ milk allergy 2009

As per MAP Guideline development Constructive clinical feedback from widespread UK use of MAP Input from seven international co-authors UK NICE Clinical Knowledge Summary (CKS) on managing cows’ milk allergy in children under five years of age 2015 UK NICE Quality Standard for Food Allergy in Children for primary care healthcare professionals 2016 UK BSACI Specialist Guideline on cows’ milk allergy 2014

Centred on 2 Algorithms

1. ‘Presentation’ 2. ‘Management’

1. ‘Presentation’ 2. ‘Diagnosis and Management’

Table 2: Presentation Algorithm: symptoms MAP

iMAP

Initial advice

Initially advises on the need for an Allergy-focused Clinical History

Initially advises on the need for both an Allergy-focused Clinical History and Physical Examination

Mild to moderate non-IgE-mediated Symptom Box

‘One or more of these symptoms’

‘Usually several of these symptoms will be present’.‘Treatment resistance, e.g. to atopic dermatitis or reflux, increases likelihood of allergy’ Table continued overleaf www.NHDmag.com October 2017 - Issue 128

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PAEDIATRIC Table 2: Presentation Algorithm: symptoms - continued Mild to moderate non-IgE-mediated Symptom Box

Mild to moderate IgE-mediated Symptom Box

Gastrointestinal ‘Colic’ ‘Reflux’ – GORD Food refusal or aversion Loose or frequent stools Perianal redness Constipation Abdominal discomfort Blood and/or mucus in stools in an otherwise well infant

Gastrointestinal Irritability -‘Colic’ Vomiting - ‘Reflux’ - GORD Food refusal or aversion Diarrhoea-like stools loose and/or more frequent Constipation - especially soft stools with excessive straining Abdominal discomfort, painful flatus Blood and/or mucus in stools in an otherwise well infant (Perianal redness-removed)

Skin Pruritus, erythema Significant atopic eczema

Skin Pruritus (itching), Erythema (flushing) Non-specific rashes Moderate persistent atopic dermatitis

Respiratory ‘Catarrhal’ airway symptoms (usually in combination with one or more of the above symptoms)

Respiratory Symptoms-removed

‘One or more of these symptoms’ Skin Gastrointestinal Respiratory

‘One or more of these symptoms’ Skin - one or more usually present Gastrointestinal Respiratory

Table 3: Presentation Algorithm: initial dietary guidance and early referral to specialist care Initial dietary guidance

MAP

iMAP

‘Advise breastfeeding mother to exclude all cows’ milk containing foods from her own diet’, ‘and to take daily calcium (1000mg) and vitamin D (10mcg) supplements

‘Advise exclusively breastfeeding mother to exclude all cows’ milk containing foods from her own diet’ ‘and to take daily supplements of Calcium and Vitamin D according to local recommendations’

With suspected mild to moderate nonIgE-mediated CMA: ‘Can be managed in Primary Care See Management Algorithm’

With suspected mild to moderate NonIgE-mediated CMA: ‘Cows’ Milk Free Diet Extensively Hydrolysed Formula-eHF See Management Algorithm’

With suspected mild to moderate IgEmediated CMA: ‘Cows’ Milk Free Diet Extensively Hydrolysed Formula-eHF (Initial choice, but some infants may then need an Amino Acid Formula - AAF trial if not settling’

With suspected mild to moderate IgEmediated CMA: ‘Cows’ Milk Free Diet Initial 1st choice Extensively Hydrolysed Formula-eHF Soy may be used in some settings if not sensitised’ (There is little reference within the Algorithms on the role of amino acid-based hypoallergenic formulas as they are not initially indicated in children with suspected clinically mild to moderate cows’ milk allergy) Table continued opposite

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Cows' milk allergy is the most common cause of food allergy in the early months of life and its diagnosis and management is complex.

Table 3 continued Early referral to specialist care

When advised: ‘to a paediatrician with an interest in allergy’

When advised: ‘to local paediatric allergy service’ (emphasising need for multidisciplinary assessment and ongoing management)’

Table 4: Diagnosis and Management Algorithm: initial guidance to confirm the diagnosis of mild to moderate non-IgE-mediated CMA MAP

iMAP

‘Strict exclusion of cows’ milk containing foods from the maternal diet’

‘Strict exclusion of cow’s milk containing foods from the maternal diet’

‘Maternal supplements of calcium (1000mg) and vitamin D (10mcg) daily’

‘Maternal daily supplements of calcium and vitamin D according to local recommendations’ A maternal substitute milk should be advised’ ‘If atopic dermatitis or more severe gut symptoms, consider egg avoidance as well’

On confirmation of the diagnosis: ‘If top-up formula feeds needed use an AAF’

On confirmation of the diagnosis: ‘If top-up formula feeds should later be needed, eHF may well be tolerated. If not, replace with an AAF’

Formula feeding or ‘mixed feeding’ (breast and formula)

Mixed feeding - ‘Trial of a cows’ milk free Maternal Diet With eHF top-ups for infant if needed’

Mixed Feeding - ‘If symptoms only with introduction of top-up feeds, replace with eHF top-ups – mother can continue to consume cows’ milk containing foods in her diet’

All feeding categories

‘Agreed 2-4 week Elimination Diet’

‘An agreed Elimination Trial of up to 4 weeks - with a minimum of 2 weeks’

Re: Symptoms ‘Improvement’ - ‘No Improvement’

Re: Symptoms ‘Clear Improvement’ - ‘No Clear Improvement’

The diagnosis still needs to be confirmed by reintroduction of cows’ milk protein referred to as a ‘Home Challenge’

The diagnosis still needs to be confirmed by reintroduction of cows’ milk protein referred to as a ‘Home Reintroduction’

Involvement of dietetic support

When milk allergy is initially suspected:

When milk allergy is initially suspected:

Exclusively breastfeeding

‘Refer to dietitian’

‘Refer to dietitian’

Formula feeding or ‘mixed feeding’ (breast and formula)

‘Refer to dietitian’

Only: ‘If weaned - may need advice and support from dietitian’. Otherwise - on confirmation of CMA diagnosis following Home Reintroduction

Exclusively breastfeeding

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PAEDIATRIC Table 5: Diagnosis and Management Algorithm: on confirmation of diagnosis, later reintroduction at home using a Milk Ladder to test for acquired tolerance MAP

iMAP

iMAP Milk Ladder Indication for use

‘For children with mild to moderate non-IgE cows’ milk allergy under the supervision of a healthcare professional, ideally a dietitian’

‘To be used only for children with mild to moderate non-IgE cows’ milk allergy under the supervision of a healthcare professional’

Number of steps

12 Steps

6 Steps

The recipes

Those more culturally limited milk products, such as Scotch pancakes and shepherd’s pie, have been removed The necessary accompanying home recipes for the differing baked milk products have been more carefully researched with regard to exact amounts of cows’ milk protein - the timing and temperature of heating, the possible matrix effect of wheat and fat and also with regard to the effect of flour and other ingredients from UK, France, USA and Ireland The use of sugar in the recipes has been restricted in accordance with WHO guidance and plain/savoury options have been provided for those who choose not to use the sweeter recipes Allowance has been given where home baking may not be feasible: ‘Should you wish to consider locally available store-bought alternatives, seek the advice of your healthcare professional for availability’

References 1 Excellence NIfHaC: Diagnosis and assessment of food allergy in children and young people in primary care and community settings.

Walsh J, O'Flynn N (2011) 2 Fiocchi A, Brozek J, Schunemann H, Bahna SL, von Berg A, Beyer K, Bozzola M, Bradsher J, Compalati E, Ebisawa M et al. World Allergy Organisation (WAO). Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. Pediatr Allergy Immunol 2010, 21 Suppl 21:1-125 3 Venter C, Pereira B, Voigt K, Grundy J, Clayton CB, Higgins B, Arshad SH, Dean T: Prevalence and cumulative incidence of food hypersensitivity in the first 3 years of life. Allergy 2008, 63:354-359 4 Schoemaker AA, Sprikkelman AB, Grimshaw KE, Roberts G, Grabenhenrich L, Rosenfeld L, Siegert S, Dubakiene R, Rudzeviciene O, Reche M et al.: Incidence and natural history of challenge-proven cows' milk allergy in European children. EuroPrevall birth cohort.

Allergy 2015, 70:963-972 5 Venter C, Brown T, Shah N, Walsh J, Fox AT: Diagnosis and management of non-IgE-mediated cows' milk allergy in infancy - a UK primary care practical guide. Clin Transl Allergy 2013, 3:23 6 Excellence NIfHaC: Cows' milk protein allergy in children. NICE: Clinical Knowledge Summaries. Edited by; 2015 7 Excellence NIfHaC: NICE: Quality standard for food allergy NICE Quality Standard 118. Edited by; 2016 8 Luyt D, Ball H, Makwana N, Green MR, Bravin K, Nasser SM, Clark AT, Standards of Care Committee of the British Society for A, Clinical I: BSACI guideline for the diagnosis and management of cows' milk allergy. Clin Exp Allergy 2014, 44:642-672.

9 Venter C, Brown T, Meyer R, Walsh J, Shah N, Nowak-Wegrzyn A, Chen TX, Fleischer DM, Heine RG, Levin M, Vieira MC, Fox AT: Better recognition, diagnosis and management of non-IgE-mediated cows' milk allergy in infancy: iMAP - an international interpretation of the MAP (Milk Allergy in Primary Care) guideline. Clin Transl Allergy 2017, 7:26

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