Food allergies in pediatrics 
OBJECTIVE:  NUTRITION n°63 (Mai 2002) 
By Pr. Jean NAVARRO 
Hôpital Robert Debré, AP/HP, Paris, France 
 
In early childhood, food allergies mainly involve cow's milk proteins. 
In the majority of cases, an exclusion diet results in regression of symptoms, with allergies otherwise progressing towards recovery within 9 to 18 months. However, with age, other food allergies can occur, sometimes in combination, often dangerous and also requiring an allergenic protein-avoidance diet, which is not always easy to implement. 
 
Acute "allergic" reactions to animal proteins and in particular to cow's milk proteins are readily identifiable and have long been known. For a few dozen years, chronic and delayed onset manifestations have also been described, probably as a result of the increasing use of replacement foods, in particular infant formulas with newborns. 
 
ALLERGY TO COW'S MILK PROTEINS 
 
The incidence of allergy to cow's milk proteins is highly variable: from 0.3% in the general population up to 7.5% in children of atopic parents. 
The incidence of familial atopy ranges from 10 to 70 % according to the criteria chosen. Clinically, such familial atopy is manifested mainly by eczema, urticaria, asthma, seasonal spasmodic rhinorrhea and drug-related reactions, to a much greater extent than by digestive reactions. 
In a study mainly involving digestive forms, such reactions were observed in 95 % of cases during the first ten days of life. The occurrence of the first manifestations ranged from a few minutes or hours following administration of the very first bottle of milk, to a few months. Lastly, late-onset forms may occur even beyond 5 years of age. 
 
• Clinical manifestations 
 
IgE-mediated hyper-responsive acute forms, where symptoms are of immediate onset (0 to 1 hour after administration of cow's milk proteins) and intermediate forms (1 to 24 hours later) combine anaphylactic shock, fever, vomiting, profuse diarrhea, edema or skin rash. Delayed-type hypersensitivity forms (type IV T-lymphocyte mediated hypersensitivity) most commonly result, after several weeks or months, in a presentation of enteropathy due to sensitization to cow's milk proteins, with chronic diarrhea, a break in the weight curve and an intestinal malabsorption syndrome comparable to that of celiac disease. 
Indeed, the two types of manifestations, acute and chronic, may occur in succession in a given patient. 
Diarrhea is the most frequent gastro-intestinal symptom, observed in 50 to 90% of cases, and is the inaugural symptom in half of cases. It is highly variable, ranging from sudden explosive diarrhea with liquid or even bloody stools, possibly accompanied by painful whining and abdominal bloating up to cases with only copious, soft or pasty-like stools. Most commonly, chronic diarrhea occurs after an insidious and gradual onset. 
Vomiting, the second major GI symptom observed, frequently precedes diarrhea (in over 25% of cases). The correlation with ingestion of cow's milk is often easy to establish. 
Anorexia, a more inconstant symptom, is very rarely observed in isolation (<1%) 
Lastly, symptoms can sometimes be dominated by abdominal distention or paroxystic abdominal pain. 
Oro-pharyngeal manifestations are rare but very suggestive: i.e. perioral redness (and, curiously, peri-anal redness), oral pruritus and oral aphthae-like lesions that can be associated with mucosal fissures and sometimes angiotoxic edema. 
 
• Anatomic pathology data 
 
Villous intestinal atrophy tends to remain moderate in most chronic forms of enteropathy caused by sensitization to cow's milk proteins. Histological lesions may be limited to plasma cellular infiltration of the lamina propria (in particular IgE plasma cells). Frequently, lesions appear to be focalized. In more serious cases, total or subtotal villous atrophy can be as pronounced as in celiac disease but without hypertrophy of the crypts of Lieberkuhn. 
 
• Essential laboratory tests 
 
Hypereosinophilia is very inconstant. Thus, it is necessary to investigate the IgE response. A study of specific IgE using the RAST test method (...) in forms with both gastro-intestinal and systemic symptoms (eczema and asthma) proves to have approximately 70 % sensitivity, but a low positive predictive value. 
Prick-tests provide variable responses depending on allergens (60 % to 80 % positivity). The lymphoblast transformation test (LTT) is positive in 60 to 80 % of sub-acute gastro-intestinal forms. Gastrointestinal permeability tests are questioned. This increases the value of challenge testing. 
 
• Treatment : the exclusion diet 
 
In the majority of cases, the withdrawal of all cow's milk proteins, or more generally, of all food proteins known for being allergenic, results in regression of symptoms within a few days to two or three weeks. Indeed, desensitization methods are poorly or not suited to cow's milk protein allergy. However, cases of intolerance have been observed related to the ingestion of partial hydrolysates in cow's milk proteins. This illustrates that such formulas remain allergenic. Upward adjustment of the statural growth curve is delayed sometimes by several months. The repair of histological lesions is slower than clinical or biological recovery. 
 

 
 

 
 

 
 
OUTCOME OF FOOD ALLERGIES ACCORDING TO AGE 
 
Allergy to cow's milk proteins occurs mainly in infants. It disappears after the age of 2 years in the vast majority of pediatric patients. With age however, the range of sensitization to other proteins increases significantly. 
In a second phase the occurrence of allergies to other proteins (i.e., rice, soy, gluten, egg, shellfish, fish…) can be observed. The high allergenicity of soy proteins, in particular in subjects who are allergic to cow's milk proteins, justifies their avoidance in a disease situation. Recently, much emphasis has been placed on peanut allergies, which can take on an anaphylactic-like presentation, exposing the subject to life-threatening risks (peanut oil exists in excipients in some medications). 
Lastly, the percentage of non-gastrointestinal manifestations (i.e., eczema, urticaria, asthma) is high in populations with an atopic background (15 to 30% of cases according to series). 
 
Food allergies can also appear as an isolated finding, in children or teenagers without prior allergy to cow's milk proteins. Later on, allergies to celery, citrus fruit, strawberries, food colorings and preservatives are also observed. 
 

 
 
CONCLUSION 
 
Food allergies in pediatric practice are dominated in early childhood by allergies to cow's milk proteins. In the vast majority of cases, diagnosis is established by a constellation of evidence: allergic background, association in the field of atopy (eczema, asthma), relationship with ingestion of proteins, laboratory test evidence and possibly anatomical findings. 
Treatment is limited to total avoidance of such proteins. 
Generally, this reactivity is of a transient nature. With age, other food allergies, sometimes associated with each other, may occur, and in some cases prove to be dangerous (anaphylactic shock).

 
Pr. Jean NAVARRO 
Hôpital Robert Debré, AP/HP, Paris 
 

 
 
BIBLIOGRAPHY 
- Allergies alimentaires, J. Navarro, J. Schmitz in Gastroenterologie pédiatrique, 2eme édition - Médecine Sciences Flammarion, Paris 2000 : pp 255-272 
- ESPGAN Working group for the diagnostic criteria for food allergy : diagnostic criteria for food allergy with predominantly intestinal symptoms. J. Pediatr Gastroenterol. Nutr. 1992 ; 14 :108-112 
- Docena GH, Fernandez R., Chirdo FG., Fossati CA. Identification of casein as the major allergenic and antigenic protein of cow's milk. Allergy, 1996 ; 51 : 412-416 
- Hill DJ, Hosking CS, Cow milk allergy in infancy and early childhood. Clin. Exp. Allergy 1996 ; 26 : 243-246 
- Navarro J., Cezard JP, Intolerance to cow's milk proteins before the age of two diagnostic means incidence and evolution in milk tolerance and rejection. In J. Delmond, ed., Milk intolerance and rejection. Karger, Bassel, 1983 ; pp 133-137 
- Vandenplas Y., Hauser B., Van den Borre C. et al, Effect of whey hydrolysate prophylaxis of atopic disease. Ann. Allergy. 1992, 68 :419-424