This article discusses practical issues in diagnosing cow's milk protein allergy and intolerance in children. It notes that these conditions are often difficult to distinguish based on clinical features alone. Cow's milk protein allergy is an immunoglobulin E-mediated reaction to proteins in cow's milk, while intolerance involves non-immunological mechanisms. The article provides guidance on differentiating the two and indicates when referral to a pediatric gastroenterologist is appropriate. It also reviews prevalence rates and common clinical presentations of cow's milk protein allergy and intolerance in infants and children.

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

2. Apollo Medicine 2011 December
Review 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.com
doi: 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

3. 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. VandenplasY, 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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