Diagnosis and management of cow’s milk protein allergy

Rory Hafford reports on a recent meeting on the subject of paediatric nutrition — particularly the issue of cow’s milk protein allergy

What do you do when a distraught mother comes to you because her baby is inconsolable; crying excessively and nothing the parents do seems to give any respite? To make matters worse it appears to be the milk the baby is being fed that is causing the baby’s illness!
This is a problem facing more and more healthcare professionals, as the number of perceived or proven cases of CMPA (cow’s milk protein allergy) increases. With the chance to find out the answer from experts in the field, over 100 healthcare professionals filled a conference room in a south Dublin hotel recently.
Intolerance or allergy?
At the Mead Johnson sponsored event Prof Jonathan Hourihane, Paediatric Con-sultant, UCC, brought the scale of the CMPA problem into sharp relief. “Within Europe prevalence ranges between 2 and 7.5 per cent,” he said. “It’s so common; it’s hard to believe that it doesn’t receive more attention.” Both breast-fed and bottle-fed babies can develop CMPA; however, the prevalence in breast-fed babies is a fifth of the level of bottle-fed babies.
Worried parents often turn up at the surgery describing their baby as colicky and unsettled, wanting to know why their child keeps bringing up its feed. The trouble for those working with infants in a primary care setting is that they may not know about allergy in infants.
The greatest difficulty for practitioners is that there is no sign or symptom that is so characteristic of CMPA that it makes the diagnosis obvious. Allergic looking rashes can be caused by viral infection, for instance, so a carefully taken history is critical. The GP’s own potential uncertainty can make it doubly difficult to explain to parents.
It’s hardly surprising there’s a level of blurring. Prof Hourihane explained: “the same trigger food can give rise to different symptoms, resulting in an allergic reaction in one patient and signs of intolerance in another.” Prof Hourihane suggested that it was vital that those responsible for caring for children have a clear understanding of the difference between food allergy and food intolerance.
CMPA is a reaction to cow’s milk protein mediated by immunological mechanisms causing disturbance in one or several organ systems: the gut, skin or the respiratory system.
“Food allergies start in infancy. A food allergy is where the trigger food has been proven to elicit an abnormal immunological response,” said Prof Hourihane.
“The resulting allergy can be either IgE mediated or non-IgE mediated. IgE-associated food allergy is common. On the whole, a few foods cause most of the cases of anaphylaxis; however, it’s important to be aware that any food with a protein in it can cause anaphylaxis.”
Food intolerances, on the other hand, may be triggered by a number of other factors. This may explain why perceived food intolerances are 10 times more common than proven intolerances.
The exact nature of the intolerance can be difficult to determine: the reaction may be transient — it may be triggered today but not tomorrow. Add to this the ability of food intolerances to present in so many ways: pharmacologic reactions; idiosyncratic reactions; psychogenic reactions; toxic contaminants.
Then throw into the mix the added difficulty that food intolerances, unlike allergies, can build up over time. A child may be able to have Weetabix on a Monday, but not on a Monday, Tuesday and Wednesday. Intolerance to cow’s milk can occur for other reasons, such as a permanent or temporary reduction in lactase activity in the brush border of mucosal enterocytes. The resulting mal-absorption of the lactose in cows’ milk is intolerance, not an allergic reaction.
Key steps in diagnosis
Early and accurate diagnosis is the key. There are guidelines for the diagnosis of food allergy for specialists, yet there are no guidelines specifically to assist primary care physicians and general paediatricians.
In response to this, Dr Martin Brueton, Emeritus Consultant Paediatric Gastroenterologist, Chelsea and Westminster Hospital, London, and several international colleagues have amalgamated their combined knowledge from many years’ research and clinical work in this area. They have developed an algorithm to help those working in a primary care setting to identify infants under six months of age with CMPA. At this age CMPA is much more common than cow’s milk intolerance.
“I was really pushed into this area,” said Dr Brueton. There was earnestness about him as he remembered how his wife, a health visitor, had teased him for being a paediatrician who was not able to cure colicky babies.
“The average parent overestimates how much crying their baby does,” said Dr Brueton. A classic description of colic is where crying lasts for three or more hours per day, on more than three days a week for at least three weeks and resolving around three months.
He marvelled at how technological improvements, allowing for the production of smaller and smaller endoscopes, had enabled investigations in younger and younger patients.
“Most babies with CMPA develop symptoms within the first few months of life and most of them present with two or more symptoms. It is rare for symptoms to begin after 12 months,” said Dr Brueton.
Parents bring infants exhibiting myriad symptoms and combinations. For instance: 50-70 per cent of children presented with skin problems like eczema; 50-60 per cent of infants had gastrointestinal signs like vomiting; and a smaller number of infants, 20-30 per cent present with respiratory problems.
Key indicators
Severity of the symptoms is the first assessment to be made. The most frequent symptoms of suspected CMPA can affect various organ systems and can range from mild to moderate to severe. Infants with life threatening conditions, particularly respiratory symptoms or anaphylaxis, need to be referred immediately to the emergency department. Doctors should be vigilant for alarm symptoms, including: for those children in the mild-to-moderate category, their first port of call is the GP.
There are a number of clear pieces of information that will help with the diagnosis.
In addition to looking at the severity of colicky behaviour, a detailed family history should be taken. In some infants there may be a strong association between atopic dermatitis and CMPA, however many cases of atopic dermatitis are not related.
Age and severity are determining factors: the younger the infant and/or the more severe the atopic dermatitis, the stronger the association. The probability of this relation increases if there is a family history of atopy, i.e. one or other of the child’s parents previously suffered.
Preceding history of inter-current infections in the baby or the mother can also be a factor. “One question I always ask is, ‘Have there been any infections in the family or has the mother been on antibiotics?’” said Dr Brueton. “Exposure to infections in the first few months may cause predisposed babies to develop hypersensitivity.”
Treatment options
Knowledge about the considerable benefits of breast feeding is widespread; however, a small percentage of babies are affected by the cow’s milk protein present in the breast milk due to the mother’s diet.
In the first instance, some mothers are advised to avoid dairy products in their own diets. Eggs and peanuts are often eliminated at the same time. Egg proteins are the most common cause of allergy after CMPA in infants and young children.
Peanuts are not an essential part of the normal mixed diet and they are relatively easier to avoid than milk and eggs. If further measures are needed, care needs to be taken when eliminating foods from the mother’s diet; if too many proteins are removed, dieticians will need to be involved to maintain the mother’s health.
Severe forms of CMPA are very rare in exclusively breast-fed babies. The occasional cases that occur are usually severe atopic dermatitis with protein losses through the abraded skin and GI tract, with failure to thrive. In these cases, if CMP is the responsible allergen, the mother should continue to receive calcium supplements during the elimination diet. When the mother wants to wean her infant, the child should receive an extensively hydrolysed formula (eHF) with demonstrated efficacy.
Elimination diets should not go on longer than two to four weeks. If there is no improvement, further investigations should be done as there may be another cause for the failure to thrive that is unrelated to food proteins.
Infants not thriving due to vomiting or diarrhoea, with moderate to large amounts of blood in stools, and/or severe atopic dermatitis should be referred immediately to a specialist.
For cases where an infant does not present the above alarm symptoms, an eHF is the first choice. In more severe cases, where the child reacts to residual allergens in eHF, an amino acid formula (AAF) may be required. Some infants will accept AAF but refuse eHF since they vary in taste, both being slightly bitter . AAF is more expensive and should only be used if symptoms are severe or if the cost-benefit ratio favours the AAF over the eHF.
A mother whose breast-fed baby turns out to have a CMPA may feel guilty that she has ‘poisoned’ her child, because she didn’t breast-feed. Psychological support may be needed to help the mother emotionally should she need it. “There are some women for whom breast-feeding just is not an option. Other breast milk substitutes/infant formulae foods are not poison,” said Prof Hourihane, “but please avoid goat’s milk. Goat’s milk is not recommended in treatment or prophylaxis of food allergy for two reasons. Firstly, its proteins are very similar to those in cow’s milk, so there is a high chance (85 per cent) of cross-reactivity to goat’s milk in children with CMPA. Goat’s milk has caused anaphylaxis in CMPA children.
“Secondly, it is important to remember that goat’s milk is one food that contains very little folate or B12. If an infant or child is only given this type of milk, he/she can develop megaloblastic anaemia. Human milk contains sufficient folate to prevent an infant from developing folate deficiency.
Breast-feeding infants of vegan mothers are also at risk for developing megaloblastic anaemia because of low levels of vitamin B12 in the breast milk. Vitamin B12 is not found in plants and therefore strict vegetarians, who eat no dairy/ animal products are at risk for developing B12 deficiency.Parents should also be mindful of giving infants soy milk. Soya milk is not recommended for prophylaxis or treatment of CMPA under six months, when extensively hydrolysed formulae are recommended.
The meeting ended with an enthusiastic questions-and-answers session, which highlighted the fact that there is only one allergist in Ireland and there would appear to be a lot more work to do in this important area.