Cow’s milk protein allergy and intolerance-practical issues in diagnosis

Apollo Medicine 2011 DecemberReview Article

Volume 8, Number 4; pp. 305–306

© 2011, Indraprastha Medical Corporation Ltd

Cow’s milk protein allergy and intolerance—practical issues in diagnosis

Sarath Gopalan**Senior Consultant, Paediatric Gastroenterologist, Indraprastha Apollo Hospitals, Sarita Vihar, Executive Director, Center for Research on Nutrition Support Systems, New Delhi, India.

ABSTRACT

The main objective of this very brief review article is to draw the attention of the practicing paediatrician to key issues from a practical standpoint in the diagnosis of both cow’s milk protein allergy and intolerance and, even more impor-tantly, clinical features that help to distinguish between these two entities. It also educates the reader regarding a growing realization based on scientific evidence from the developing world that these are entities which need to be recognized even in this part of the world. This article provides useful practical tips to the practicing paediatrician regarding the specific indications and timing of referral to a paediatric gastroenterologist for the management of individuals with cow’s milk protein allergy or intolerance. The article does not discuss the management of cow’s milk protein allergy and intolerance.

Keywords: Allergy, cow’s milk protein, immunological, intolerance

Correspondence: Dr. Sarath Gopalan, E-mail: crnssindia@gmail.comdoi: 10.1016/S0976-0016(11)60013-6

Adverse reactions to cow’s milk can be allergic (milk pro-tein allergy) or intolerance (cow’s milk protein intolerance [CMPI]). The underlying mechanisms causing varied clini-cal presentations of adverse reactions and the resulting symptoms may be very different from or even confusingly similar to each other. The major differentiating feature between cow’s milk protein allergy and intolerance from the standpoint of mechanism of action is that allergy is always dependent on the production of immunoglobulin E (IgE) antibodies to milk protein and is IgE (reaginic) mediated. The mechanism underlying milk protein intolerance is less clearly understood but is not IgE-mediated. Cow’s milk pro-tein intolerance is largely mediated by mechanisms that are nonimmunological but a small proportion of CMPI is IgA mediated. Cow’s milk protein allergy refers specifically to the adverse reactions mediated by IgE antibodies to one or more protein fractions of milk belonging to casein or whey protein group. Casein is heat-stable (cannot be broken down by boiling) and the individuals allergic to casein will be unable to tolerate even boiled cow’s milk. On the contrary, whey proteins are heat-labile (broken down by boiling). However, from a practical standpoint, the above distinction is not helpful as most IgE-mediated reactions to cow’s milk

involve both casein and whey protein fractions, which mean that most individuals with cow’s milk protein allergy cannot tolerate boiled cow’s milk.

Most individuals with cow’s milk protein allergy and/or CMPI present clinically for the first time between the ages of 6 and 12 months—a period during which the infant is introduced to milk of animal origin and complementary foods other than breast milk. The information available from sev-eral studies throughout the world suggests that 1.8–7.5% of all children develop cow’s milk protein allergy1; however, the exact prevalence has not been determined till date.

There are three patterns of clinical presentation of cow’s milk protein allergy, which have been recognized as follows:• Type 1: Skin reactions, which are observed within min-

utes after the intake of very small volume of cow’s milk (urticaria, eczema) with or without respiratory or gastro-intestinal symptoms.

• Type 2: Symptoms are vomiting and diarrhea, and the onset is usually several hours after the intake of moderate volume of cow’s milk.

• Type 3: Symptoms consist predominantly of diarrhea with or without respiratory or skin reactions and the onset

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306 Apollo Medicine 2011 December; Vol. 8, No. 4 Gopalan

© 2011, Indraprastha Medical Corporation Ltd

is delayed (usually several days) after ingestion of large volume of cow’s milk.

All three types of clinical presentations may be encoun-tered in both allergy and intolerance but Type 3 is most commonly observed in CMPI. Infants and young children with allergy may also present with recurrent and chronic otitis media. Iron-deficiency anemia observed in some of these children may be explained by occult blood loss in stools. Almost 60% of clinical presentations in the young child reacting to cow’s milk constitute the delayed onset (intolerant) variety (Type 3) and unlikely to give a positive blood or skin test. Some children with CMPI may have coexisting lactose intolerance. The diagnosis of CMPI is clinical2 and is confirmed by the Elimination Challenge Test (relief of symptoms on omitting cow’s milk from diet and recurrence of some symptoms on re-introduction of cow’s milk 6 weeks later). This should be supervised by the treating doctor and dietitian.

Investigative tools have limited utility in confirming a diagnosis of cow’s milk protein allergy or intolerance and the diagnosis of these conditions is purely clinical. Recently, however, a rectal mucosal biopsy demonstrating > 6 eosi-nophils per high power field has been shown to be an important supportive (but not confirmatory) finding by some investigators.3

The indications for referral to a paediatric gastroenter-ologist are as follows:• History of exposure to milk other than human milk (even

before 6 months), irrespective of age and infant subse-quently developing diarrhea and failure to thrive.

• Exclusively breast-fed infant (till 6 months of age) who has developed persistent diarrhea after 6 months of age and subsequent failure to thrive.

• Investigative work-up not suggestive of infection, lactose intolerance not documented, infant currently consuming cow’s milk and diarrhea not resolving.

REFERENCES

1. Host A. Cow’s milk protein allergy and intolerance in infancy. Some clinical, epidemiological and immunological aspects. Pediatr Allergy Immunol 1994;5:1–36.

2. Vandenplas Y, Brueton M, Dupont C, et al. Guidelines for the diagnosis and management of cow’s milk protein allergy in infants. Arch Dis Child 2007;92:902–8.

3. Poddar U, Yachha SK, Krishnani N, Srivastava A. Cow’s milk protein allergy: an entity for recognition in developing coun-tries. J Gastroenterol Hepatol 2010;25:178–82.

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