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MikaelKuitunen

Cow's Milk Allergy

Essentials

  • Suspicion of cow's milk allergy is common. Verified milk allergy is much rarer.
  • Symptoms commonly seen in infants, such as redness of the skin, atopic dermatitis, crying tendency, restlessness, rumination and changes in the faecal consistency are common, benign and transient symptoms, and an underlying cow's milk allergy is often suspected.
  • The most common symptoms in cow's milk allergy are urticaria and vomiting.
  • Diagnosis is established by supervised elimination and challenge test.
  • Adequate nutrition and normal growth are secured during the elimination diet.
  • Achieved tolerance is demonstrated by rechallenge, and the elimination diet is then discontinued.

Epidemiology

  • About 2% of children less than 3 years of age show symptoms of allergy to cow's milk, usually appearing in infancy after starting to try formulas or other foods containing cow's milk protein.
  • Cow's milk allergy occurs in infants and small children, and may rarely appear during exclusive breast feeding.

Symptoms

  • Cow's milk allergy refers to an abnormal allergic inflammation precipitated by cow's milk proteins, with symptoms manifesting mainly in the skin (urticaria, exanthema) and in the gut (vomiting, diarrhoea).
  • Symptoms usually begin within days or a few weeks after the administration of a formula containing cow's milk was started.
  • Symptoms can be classified according to the time of appearance.
    1. Immediate symptoms that appear within minutes or, at the latest, within 1-2 hours after ingestion of cow's milk (urticaria, erythema of the skin, vomiting, more rarely respiratory or general symptoms and anaphylaxis), in which case it is an IgE-mediated allergic reaction.
    2. Symptoms appearing within hours or days after exposure: worsening atopic eczema (most often manifested as skin flare-ups or urticaria) and gastrointestinal symptoms (vomiting, diarrhoea). Excessive crying, colicky pains and restlessness have also been linked with milk allergy. Such symptoms are common in infants but are rarely caused by milk allergy. If the symptoms are intensive, the role of possible allergy should be investigated . In case of milk allergy, the symptoms are rapidly relieved during an elimination diet. The immunological mechanism is unclear, but usually it is a not IgE-mediated.
  • Lactose intolerance (hypolactasia) is not cow's milk allergy and it does not appear until the child has reached school age. Secondary lactose intolerance after severe virus-induced diarrhoea or in association with coeliac disease is possible.

Diagnosis

  • Diagnosis is based on elimination-challenge testing.
    1. Symptoms suggesting cow's milk allergy appear on a cow's milk protein-containing diet.
    2. Symptoms disappear or are clearly alleviated on (diagnostic) elimination of these products from the diet. This is not sufficient for diagnosis, as the symptoms recur only in some of the patients during later exposure.
    3. Any home reintroductions with positive results are confirmed by reappearance of similar symptoms on (diagnostic) clinical challenge that is performed under medical supervision (a symptom diary should be used for evaluating changes in symptoms).
  • Laboratory tests play a secondary role in the diagnostic work-up.
    • Specific IgE test or skin prick test for milk are sensitive but not specific enough.
    • Epicutaneous tests and anti-milk IgG or IgA antibody assays have no place in the diagnostics.

Clinical challenge (diagnostic and repeated)

  • Performed under the supervision of a physician on outpatient or inpatient basis. There must be readiness to treat anaphylaxis.
  • A symptom diary should be kept for a week before and a week after the challenge. See picture 1. Find out about locally available symptom diary forms.
  • The basic principle is to start with a small dose and gradually raise the dose to the amount consumed by a child of that age (unless symptoms occur).
  • Example:
    1. Place a small amount (e.g. ½-1 ml) of diluted milk in the mouth: observe possible reaction.
    2. After 30 minutes, if the child has no symptoms, give a small amount of milk, e.g. 2 ml, in the mouth. Observe for possible symptoms for 30 minutes.
    3. If the child remains symptomless, give increasing portions at 30 minute intervals (e.g. 10 ml-50ml-100ml).
    4. On appearance of unambiguous symptoms (write down), the challenge is immediately discontinued, and the diagnosis of cow's milk allergy can be established. When in doubt, consider readministration of the latest dose.
    5. If the child remains asymptomatic for 2 hours after the last dose, the challenge is continued at home (target 5 dl/24 hours) + a symptom diary.
    6. Arrange for a control by phone if challenge is continued at home. The diagnosis is confirmed by a physician.

Treatment , Prebiotics in Infants for Prevention of Allergic Disease and Food Hypersensitivity

  • The level of elimination should be individualized. A strict elimination diet is necessary if the symptoms are severe. If the symptoms are mild or only appear after ingestion of large portions, milk can be administered in amounts allowed by symptoms. This helps the child to get accustomed to the taste of milk and may quicken the development of tolerance.
  • If possible, a dietician should help in implementing the diet.
  • Give oral and written instructions.
  • Special formulas are necessary up to the age of 1.5-2 years, taking into account the variety of the child's diet and the growth development.
  • Special formulas: whey and casein hydrolysate, amino acid-based formulas (price rises in this order)
    • Use primarily a more degraded product (whey or casein hydrolysate).
    • Synthetic amino acid-based formulas may be used if the above-mentioned alternatives prove to be unsuitable in diagnostic challenge test. Studies show that less than 2% of infants allergic to cow's milk need an amino acid based formula.
    • Children over 2 years of age are given calcium supplementation (500 mg/day) if there is no sufficient calcium intake from other products. Sufficient intake of energy, proteins, vitamins and minerals should be ensured.
      • There are calcium-enriched drinks and other products based on soy, oat or rice on the market. These products can also be considered for children over 1 year of age if the diet otherwise is versatile and the child grows well. It should be noted that the nutritive content of these products does not correspond to that of cow's milk and that their calcium content should be checked.
  • Promising results have been obtained with probiotic bacteria in the treatment of food allergy, but the evidence is insufficient. Lactobacillus rhamnosus GG has been shown to accelerate the healing of eczema when given in short 4-week courses. The effects are strain-specific.

Follow-up

  • The diagnosis and initial treatment of cow's milk allergy take place in specialized care. Follow-up is carried out in primary care, except for children with severe symptoms who are followed up by a specialist.
  • Rechallenges are arranged at intervals of 6 months to 1 year up to the age of 4 years, then every 1 to 2 years. If the symptoms have been severe, the challenge is carried out under supervision. Otherwise, the trials are carried out at home, starting with small amounts.
  • Growth is monitored using a growth chart. Sufficient and well-balanced nutrition is secured.
  • Cow's milk elimination diet is not lifelong. Encouragement is required: otherwise the elimination diets are easily continued unnecessarily long which may make the eating habits of other family members complicated. The necessity of the elimination diet is regularly checked at visits to the child health clinic.

Prognosis

  • 60% of the children will recover by the age of 2 years and 75% by the age of 3 years.
  • IgE-mediated food allergy increases the risk of asthma and allergic rhinitis, especially if there is sensitization to inhalation allergens.
  • Strongly heated milk (> 180 °C for 30 minutes in the oven) may be suitable for some children with milk allergy and makes recovery quicker.

    References

    • Saarinen KM, Juntunen-Backman K, Järvenpää AL, Kuitunen P, Lope L, Renlund M, Siivola M, Savilahti E. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants. J Allergy Clin Immunol 1999 Aug;104(2 Pt 1):457-61. [PubMed]
    • Majamaa H, Isolauri E. Probiotics: a novel approach in the management of food allergy. J Allergy Clin Immunol 1997 Feb;99(2):179-85. [PubMed]
    • Viljanen M, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Kuitunen M. Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial. Allergy 2005 Apr;60(4):494-500. [PubMed]
    • Saarinen KM, Suomalainen H, Savilahti E. Diagnostic value of skin-prick and patch tests and serum eosinophil cationic protein and cow's milk-specific IgE in infants with cow's milk allergy. Clin Exp Allergy 2001;31(3):423-9. [PubMed]
    • Vandenplas Y, Dupont C, Eigenmann P et al. A workshop report on the development of the Cow's Milk-related Symptom Score awareness tool for young children. Acta Paediatr 2015;104(4):334-9. [PubMed]
    • Katz Y, Goldberg MR, Rajuan N et al. The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: a large-scale, prospective population-based study. J Allergy Clin Immunol 2011;127(3):647-53.e1-3. [PubMed]
    • Mennella JA, Griffin CE, Beauchamp GK. Flavor programming during infancy. Pediatrics 2004;113(4):840-5. [PubMed]
    • Nowak-Wegrzyn A, Bloom KA, Sicherer SH et al. Tolerance to extensively heated milk in children with cow's milk allergy. J Allergy Clin Immunol 2008;122(2):342-7, 347.e1-2. [PubMed]