COW'S MILK PROTEIN INTOLERANCE
Dr. Sarath Gopalan *
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There are more than 30 different proteins in cow's milk and they are broadly categorized into two groups - the casein group and the whey group. When milk ferments, naturally or as a result of chemicals in the dairy industry, the milk changes into a solid component (curd) and a liquid component (whey). The solid portion contains proteins belonging to the casein group and the liquid component contains whey proteins.

Adverse reactions to cow's milk can be allergic (milk protein allergy) or intolerance (cow's milk protein intolerance). Different mechanisms cause different 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 cow's milk protein intolerance from the standpoint of mechanism of action is that allergy is always dependent on 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 protein allergy refers specifically to adverse reactions mediated by IgE antibodies to one or more protein fractions of milk belonging to casein or whey protein group. Casein proteins are heat-stable (cannot be broken down by boiling) and individuals allergic to casein proteins 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 viewpoint, the above distinction is not helpful as most IgE mediated reactions to cow's milk involve both casein and whey fractions which means that most individuals with cow's milk protein allergy cannot tolerate boiled cow's milk.

The age group most commonly affected is young children between 6 months and 1 year of age although both cows' milk protein allergy and intolerance can occur at any age. The information available from several studies throughout the world suggests that 1-7% of all children develop cow's milk protein allergy, 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:
  1. Type 1 - Skin reactions, which are observed within minutes after intake of very small volume of cow's milk (urticaria, eczema) with or without respiratory or gastrointestinal symptoms.
  2. Type 2 - Symptoms are vomiting and diarrhea and onset is usually several hours after intake of moderate volume of cow's milk,
  3. Type 3 - Symptoms consist predominantly of diarrhea, with or without respiratory or skin reactions and onset is delayed (usually several days) after ingestion of large volume of cow's milk.

All three types of clinical presentations may be encountered in both allergy and intolerance but Type 3 is most commonly observed in Cow's Milk Protein Intolerance (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 co-existing lactose intolerance. The diagnosis of CMPI is clinical 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 dietician.

Investigative methods, which help to substantiate the diagnosis of milk allergy such as the skin test and radioallergosorbent test (RAST) are not very useful in milk intolerance. An important finding on the duodenal mucosal (D2) biopsy in children with CMPI is that crypt hyperplasia is rarely encountered (unlike other malabsorptive GI disorders).

The management of children with CMPI consists of complete dietary avoidance of cow's milk till the child completes 2 years of age after which it can again be introduced cautiously. Cow's milk-free commercial preparations are available in India which contains soy milk (Nusobee, Prosoyal, Zerolac and Simyl MCT) and these are the mainstay of dietary intervention in these affected children. Unfortunately, approximately 15% of infants with allergy or intolerance to cow's milk are also intolerant to soy but currently there are no preparations available in India which are both cow's milk protein and soy-free.

When should an infant be suspected to be suffering from CMPI? Indications for referral to a Pediatric Gastroenterologist:
  1. History of exposure to milk other than human milk (even before 6 months), irrespective of age and infant subsequently developing diarrhea and failure to thrive.
  2. Exclusively breast-fed infant (till 6 months of age) who has developed persistent diarrhea after 6 months of age and subsequent failure to thrive.
  3. Investigative work-up not suggestive of infection, lactose intolerance not documented, infant currently consuming cow's milk and diarrhea not resolving.
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