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Better recognition, diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy

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Presentation and recognition of cow’s milk allergy

  • An allergy-focused clinical history forms the ‘cornerstone of diagnosis’ in suspected food allergy in children and young people
  • Symptoms of the infant at first presentation are a key feature in the diagnostic process. Possible symptoms can be variable and overlap with common infant health issues such as irritability (colic), gastro-oesophageal reflux and atopic dermatitis that may not necessarily be cow’s milk allergy (CMA)-related (see iMAP guideline—presentation of suspected cow’s milk allergy in the first year of a child’s life algorithm
  • As part of the allergy-focused healthcare consultation, it is important to carry out a physical examination, particularly looking for signs indicating any allergy-related comorbidities such as atopic dermatitis and, in addition, performing weight, length and head circumference measurements

Taking an allergy-focused clinical history—ask about:

  • A family history of atopic disease (atopic dermatitis, asthma, allergic rhinitis or food allergy) in parents or siblings. A reported history along with symptoms of suspected cow’s milk allergy makes the diagnosis more likely; this applies to both IgE-mediated and non-IgE-mediated
  • Sources of cow’s milk protein and how much is being or was ingested:
    • exclusive breast feeding—when cow’s milk protein from maternal diet comes through in the breast milk (low risk of clinical allergy)
    • mixed feeding—when cow’s milk protein is given to the breast feeding infant e.g. top-up formulas, on weaning with solids
    • formula feeding infant—the commonest presentation, particularly in countries where there is poor adherence with the WHO guidance of exclusive breast feeding for 6 months
  • Presenting symptoms, to include:
    • if more than one symptom, the sequence of clinical presentation of each one
    • age of first onset
    • timing of onset following ingestion (atopic dermatitis—such ‘timing’ can be very variable)
      • IgE-mediated—usually within minutes, but can be up to 2 hours
      • non-IgE-mediated—usually after ≥2 hours or even days
    • duration, severity, and frequency
    • reproducibility on repeated exposure
    • amount and form of milk protein that may be causing symptoms
  • Details of any:
    • concern with feeding difficulties and/or poor growth
    • changes in diet and any apparent response to such changes 
    • other previous management, including medication, for the presenting symptoms and any apparent response to this

iMAP guideline—presentation of suspected cow’s milk allergy in the first year of a child’s life

iMAP guideline presentation of suspected cow’s milk allergy in the first year of a child’s life

iMAP guideline—diagnosis and management of mild to moderate non-IgE cow’s milk allergy (CMA) (no initial IgE skin prick tests or serum-specific IgE assays necessary)

iMAP guideline diagnosis and management of mild to moderate non IgE cow’s milk allergy (cma) (no initial ig e skin prick tests or serum specific ig e assays necessary)

Diagnosis of suspected non-IgE-mediated CMA in primary care

  • If the clinical history suggests non-IgE-mediated CMA and the child ‘has not had a severe delayed reaction’, it is recommended to offer a trial elimination of the suspected allergen and subsequent reintroduction (see iMAP guideline—diagnosis and management of mild to moderate non-IgE cow’s milk allergy (CMA) (no initial IgE skin prick tests or serum-specific IgE assays necessary) algorithm)
  • Extensively hydrolysed formulas (eHFs) continue to be recommended as the initial prescribed formulas for most infants presenting with suspected mild-to-moderate CMA
  • In some countries, an amino acid-based formula (AAF) is used as the initial diagnostic trial formula for CMA. Such practice is based on local services, reimbursements of formulas and not due to clinical evidence-based indications for AAF
  • When an exclusively breastfed infant reacts to the amount of milk protein passed on from maternal consumption during breast feeding, it is recommended to avoid cow’s milk from the maternal diet as the first priority. Then if a supplemental formula should be needed, an eHF may well be tolerated, if not, replace with an AAF
  • The reintroduction step, following clear improvement of symptoms (but not necessarily a complete resolution of symptoms) during the elimination trial, is of ultimate importance to confirm the diagnosis

Management of confirmed mild-to-moderate non-IgE-mediated CMA in primary care (see management algorithm)

  • Management will include continuation of treatment with a suitable alternative formula or, if indicated, maternal allergen avoidance. Most importantly, milk free weaning advice should be provided by the dietitian not only to ensure that cow’s milk is avoided in the infant’s complementary diet, but also to address growth, nutritional and feeding problems in the short and long term
  • The on-going management then includes a second planned reintroduction of milk protein when the time comes to test for acquired tolerance. The iMAP management algorithm guides on the timing of this as well. It is usually carried out in the form of a graduated ‘milk ladder’. Ideally at this stage a dietitian will be taking the lead

Referral

  • Any specialist allergy service for children should be led by a paediatrician or other appropriately trained physician, supported by a multidisciplinary team made up of specialist dietitians, nurses and ideally a clinical psychologist all with the necessary expertise in childhood food allergy. Due to the multisystem involvement of CMA, other medical specialities may also need to be readily accessible, including gastroenterology and dermatology 

Suspected severe non-IgE-mediated CMA

  • In the uncommon situation of the infant presenting with more severe symptoms leading to a suspected severe expression of non-IgE-mediated CMA, the appropriate change in the infant’s diet will need to be made, early onward referral to a specialist allergy service is required

Suspected IgE-mediated CMA

  • Early onward referral to a specialist allergy service is likely to be necessary. The iMAP presentation algorithm also guides on this and on the initial necessary change to either the maternal diet or infant formula. It may also be helpful to direct parents to national patient support websites

Home Reintroduction versus Challenge

  • The iMAP early Home Reintroduction to confirm diagnosis and then the iMAP home milk ladder to test for later acquired tolerance should only be used in children with mild-to-moderate non-IgE-mediated CMA and not in other presentations such as IgE-mediated CMA or severe non-IgE-mediated CMA
  • For most of these infants presenting with either suspected severe non-IgE-mediated or IgE-mediated CMA, the severity of the symptoms and/or their significant improvement on commencing the elimination diet will be enough to confirm the diagnosis. However, should they still need an early food Challenge to confirm or exclude the diagnosis that will need to be done within an appropriate facility under the active supervision of appropriately trained staff

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full guideline available from…
ctajournal.biomedcentral.com/articles/10.1186/s13601-017-0162-y

Venter C, Brown T, Meyer R et al.Clinical and Translational Allergy 2017, 7: 26. August 2017.

First included: February 2014, updated September 2017. 

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Read the Guidelines in Practice article Milk allergy: MAP publishes international update for more information on implementing the iMAP group guidance on Better recognition, diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy