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Cow's Milk Allergy

Article  in  Sri Lanka Journal of Child Health · December 2015

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Cow’s milk allergy. Sri Lanka Journal of Child Health, 2015; 44(4): 220-225

Current practice

Cow’s milk allergy

Guwani Liyanage1

Sri Lanka Journal of Child Health, 2015; 44(4): 220-225

(Key words: Cow’s milk allergy)

Introduction CMA is classified based on the underlying immune

mechanism based on timing and organ system
Milk and milk based products are the mainstay of the involved4. IgE mediated reactions are more common
diet during infancy and early childhood. Cow’s milk and occur within minutes or mostly within one hour
allergy (CMA) presents in the first year of life, and in after ingestion of even a small amount of milk. These
general, prevalence is estimated to be 2-3%1,2. reactions can vary from minor skin rash to life
However, data on prevalence of cow’s milk allergy is threatening anaphylaxis4. Delayed reactions are non-
lacking in Sri Lanka. Adverse reactions to cow’s milk IgE mediated and generally onset is several hours to
could be immune or non-immune. CMA is defined as days following ingestion of a larger volume of
adverse reactions to one or more milk proteins milk3,4. Table I describes the diversity of
(casein or whey beta lactoglobulin) caused through presentations of CMA based on the immunological
immunological mechanisms that occur reproducibly reaction.
following intake of milk3. Lactose intolerance is a
non-immune adverse reaction that should be
distinguished from true allergy.

Table I: Manifestations of cow’s milk allergy based on immune mechanisms

Manifestation IgE mediated Mixed Non-IgE mediated
Systemic Anaphylaxis
Skin Urticaria Atopic dermatitis
Angio-oedema
Gastrointestinal Immediate GI symptoms Eosinophilic oesophagitis / Allergic proctocolitis
symptoms Gastroenteritis Food protein induced
enterocolitis syndrome
Respiratory Bronchospasm Heiner syndrome

Manifestations of IgE mediated immediate reactions contact of milk and symptoms are mild and are
confined to the area of contact6.
Skin symptoms: Acute urticaria and angioedema are
the most common manifestations3,4. Rash often Gastrointestinal symptoms: This includes vomiting,
occurs within several minutes after ingestion, diarrhoea, bloody stools, abdominal pain and reflux
accompanied by an itch. However, CMA is rarely a disease3,4.
cause of chronic urticaria5. Contact urticaria is also
an IgE mediated manifestation caused by direct Respiratory symptoms: Chronic respiratory
___________________________________________ symptoms such as asthma are uncommon in food
1
Senior Lecturer, Department of Paediatrics, Faculty allergy3,4. However, acute upper respiratory tract
of Medical Sciences, University of Sri symptoms (rhinitis, nasal congestion) and lower
Jayewardenepura respiratory tract symptoms (wheezing, cough and
Correspondence: [email protected] stridor) are not uncommon and some manifestations
The author declares that there are no conflicts of are potentially life threatening3,4. Airway compromise
interest. due to laryngeal oedema, broncospam and airway
Open Access Article published under the Creative collapse with mucus plugging is accountable for
hypoxia during an immediate reaction3,4.
Commons CC-BY-NC-ND Licence.

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Cow’s milk allergy. Sri Lanka Journal of Child Health, 2015; 44(4): 220-225

Cardiovascular symptoms: Hypotension and shock exclusively breast fed infant7. This is essentially a
are possible sequelae. However, they are rarely non-IgE mediated reaction and these infants
manifested in CMA3,4. generally outgrow this condition by the end of first
year7.
Manifestations of Non IgE mediated, predominantly
delayed onset reactions Manifestations of mixed IgE and non IgE mediated
reactions
Non IgE mediated reactions range from minor reflux
disease to life threatening gastrointestinal fluid loss in GI symptoms: Eosinophilic oesophagitis presents
food protein induced enterocolitis (FPIES)7. with abdominal pain, dysphagia, poor appetite, reflux
and failure to thrive11. Both IgE mediated and non-
Gastrointestinal (GI) symptoms: GI symptoms IgE mediated mechanisms are responsible for
predominate in non IgE mediated, delayed onset eosinophilic infiltration of gastrointestinal tract11.
reactions4. During infancy non specific symptoms
such as vomiting, possetting, irritability (infantile Skin symptoms: Cow's milk is responsible for
colic), failure to thrive, diarrhoea, constipation and exacerbations of eczema in some sensitized infants4.
blood in stools are evident4. Therefore, diagnosis However, 40% of infants with moderate to severe
relies on careful history and examination, pattern of eczema have food allergy12. Non eczematous
symptoms, failure to respond to standard (erythema, pruritus and urticaria) skin reactions in
management approaches and presence of other these children are immediate onset and IgE
evidence of allergy e.g. eczema. mediated4. Eczematous exacerbations are non-IgE
mediated occurring after hours or days13. It is
Gastro-oesophageal reflux is common in infants4. recommended that patients with eczema be treated
Non-allergic reflux is often effortless and pain free. with topical medications prior to considering a food
However, in the presence of gastro-oesophageal allergy, since the majority of cases do not seem to be
reflux due to milk allergy, these infants are irritable, caused by it.
have screaming episodes associated with back
arching and profuse vomiting4. They show little or no Natural history of CMA
response to anti-reflux medication4.
Most reactions are triggered by cow’s milk per se or
Occasionally constipation is the only symptom of cow’s milk based foods. However a small percentage
milk allergy4. History of milk allergy in the first year (0.4‐0.5%) is through breast milk from maternal milk
of life is associated with functional constipation in intake9. Symptoms usually develop within a week of
older children8. More often, it co-exists with other cow’s milk contact or could be delayed up to 36
allergies e.g. eczema, allergic rhinitis and weeks13. All are symptomatic before one year.
improvement is shown with elimination of cow’s Children with CMA should be monitored for
milk from the diet9. When compared to non allergic development of tolerance, since most will outgrow
infant with constipation these infants will have severe their allergy in childhood, 80% of them developing
distress and straining during defaecation and often tolerance by 5th birthday14. However, there is
passes softer stools. In these children it has been conflicting evidence and recent reports highlight that
shown that they have higher internal sphincter tone10. only 64% of children develop tolerance by 12 years
of age15. Resolution of symptoms in non-IgE-
Food protein induced enterocolitis (FPIES) is a life mediated allergy is faster than IgE-mediated
threatening condition with protracted vomiting, allergy14. Patients with high IgE content in the first 2
profuse watery diarrhoea which may be complicated years of life are more likely to have persistence of
by hypotension and acidosis within 1-3 hours of allergy to adulthood14. Other predictors of persistence
ingestion7. It is often misdiagnosed as sepsis and are presence of asthma or allergic rhinitis, immediate
these children will have high white cell counts. severe reactions at the onset and concomitant allergy
However, absence of fever and negative cultures are to other foods15.
clues to arrive at a diagnosis.
Diagnosis of CMA
Allergic proctocolitis is typically manifested with
frequent passage of stools with mucus mixed with Early and reliable diagnosis of CMA is important to
streaks of blood in an otherwise healthy infant7. avoid unnecessary dietary restrictions and to prevent
Symptoms subside with cessation of milk or milk life threatening events. Accuracy of diagnosis
products in the infant and maternal diet in an depends on a detailed history and proven underlying

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Cow’s milk allergy. Sri Lanka Journal of Child Health, 2015; 44(4): 220-225

immunological reaction. Oral food challenges and Mixed IgE and non IgE mediated reactions
elimination and reintroduction are useful when a In most instances it is difficult to diagnose food
doubt exists. In history taking, timing of onset of allergy as the history is frequently confusing owing
symptoms and cow’s milk ingestion, reproducibility to the severity of the eczema. A careful history and
and time when last symptoms occurred, should be elevated IgE levels (SPTs or sIgE assays) support the
recorded. Food diaries are useful for history taking. diagnosis. It is reported that 27.4% of children with
eczema have elevated cow’s milk specific IgE19.
IgE mediated CMA Diagnosis of eosinophilic oesophagitis is based on
Diagnosis of IgE mediated allergy is based on clinical presentation and biopsy after aggressive
clinical history, examination and the presence of therapy with anti reflux medications, and the
cow’s milk specific IgE antibodies (skin prick testing disappearance of eosinophils following an
or serum IgE)4. Skin prick testing (SPT) and serum appropriate elimination diet20. Owing to the mixed
IgE (sIgE) levels serve to detect the presence of reactions these children may have elevated IgE
tissue bound and circulating IgE antibodies, levels.
respectively. However, presence of IgE antibodies
denotes sensitization and cannot differentiate Diagnostic pitfalls
sensitization from clinical allergy4. In the presence
of a consistent history, reaction of larger than 3mm Heating, cooking and fermentation may influence the
above the negative control in SPT or sIgE ≥ amount milk allergen in the processed food item21.
0.35kU/L supports the diagnosis4. Higher wheal sizes Thus, tolerance to processed foods per se may not
and sIgE levels support greater likelihood of clinical exclude allergy to milk in the form of liquid, powder
allergy, although it does not correlate with severity of or ice cream. Further, baby jars, cereals and rusks
symptoms4. If the clinical diagnosis is doubtful, even contain small amount of milk in addition to other
higher SPT levels are considered irrelevant. Certain ingredients such as wheat and soy. Therefore, CMA
children would have higher sIgE levels without may be initially missed as a potential allergen or
clinical allergy. However, in younger children with misdiagnosed as wheat and soy allergy.
suggestive symptoms even lower SPT are predictive
of allergy than in older children16. Further, sIgE and MANAGEMENT
SPT are not helpful as screening tools since they have
a poor predictive value4. When diagnostic uncertainty Avoidance
(e.g. positive test and unconvincing history or history
is doubtful with negative IgE levels) exists, oral food The mainstay of therapy of cow’s milk allergy is
challenges are helpful in confirming CMA4 complete avoidance4. Elimination of milk from the
diet may lead to nutritional deficiencies, since milk is
Non- IgE mediated allergy an important source of calcium, fat and protein in
Cow’s milk specific IgE levels or SPT are not helpful early childhood. Milk may be found in candy,
if the symptoms do not suggest an IgE-mediated custard, puddings, hotdogs, sausages, margarine and
reaction, such as delayed gastrointestinal reactions salad dressing and more. Certain food establishments
and some cases of atopic dermatitis. Atopic patch keep shrimp in milk to avoid fishy odour. Due to
tests cannot be recommended for clinical diagnosis of shared utensils food can be contaminated with cow’s
non IgE mediated reactions since standardized milk. Certain bakery products are brushed with milk.
techniques and reagents are not established yet17. A Thus, it is a difficult to avoid cow’s milk since it is
careful and detailed history is valuable in making a found in a variety of food items. Ideally, authorities
diagnosis when symptoms are only gastrointestinal. should introduce legislation to list all the ingredients
Elimination and re-introduction is the gold standard of food items making it easier for the consumers to
diagnostic test. Re-appearance of symptoms with identify food items that they should avoid.
reintroduction supports the diagnosis18. In FPIES,
IgE-based allergy testing is commonly negative, and Many children with CMA may tolerate processed
a presumptive diagnosis is made based on a typical food items (baked or extensively heated) and oral
presentation, resolution of symptoms on elimination challenge test is useful in testing them for tolerability.
diets, and exclusion of other causes. Biopsy supports Although they can be allowed continue to consume
the diagnosis of proctocolitis and resolution of baked products, it is not known whether this will
symptoms with elimination. prevent, induce or delay the onset of tolerance to
cow’s milk. However, if they are reacting to
intermediate forms of milk (e.g. pudding, yogurt), it

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Cow’s milk allergy. Sri Lanka Journal of Child Health, 2015; 44(4): 220-225

is advisable that they should avoid all forms of milk Summary

including processed items.
CMA is manifested in a wide range clinical
Substitutes syndromes. Diagnosis of IgE mediated reactions is
based on a convincing clinical history and
If the infant is breast fed, mothers should be measurement of cow’s milk-specific IgE. Oral food
encouraged to continue breast feeding and milk challenge is useful for a definitive diagnosis in
substitutes are not necessary. However, since small doubtful cases. However, diagnostic tests for non-IgE
amount of cow’s milk protein beta lactoglobulin is mediated manifestations are lacking. Avoidance of
excreted in mother’s milk, if the infant is cow’s milk is the mainstay of therapy, although there
symptomatic while being breast fed, mother needs to is growing evidence for new modalities of treatment
avoid milk in her diet4. Soy infant formula is a valid such as oral and sublingual immunotherapy.
option if breast feeding is not possible for any reason.
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