Within the GI tract, several distinct syndromes present themselves in relation to age and organ. Gastroesophageal reflux disease (GERD) is a disease that commonly occurs during the first year of life, and some forms of severe GERD have been shown to be associated with CMA. A double-blind placebo controlled food challenge (DBPCFC) study was performed in 45 children 3 years old and older with symptoms of GERD. Of these, 18 had severe GERD as indicated by endoscopic oesophagitis and/or reflux index (RI) >10% as measured by pH probe. Cow's milk hypersensitivity was demonstrated in 10 of 18 children reporting a significantly higher RI following 48 hours of pH monitoring compared with children without GERD or those with GERD only (P = 0.03; Figure 2) (11). RI is the percentage of time during a pH study that the patient's oesophagus is exposed to acid and the normal value for children older than 1 year is <6%. Subgroup classification demonstrated that in children with GERD and CMA:
* 4 of 10 had duodenal nodules, probably representing a nonspecific immune reaction.
Eosinophilic oesophagitis (EO) is a distinct entity that occurs mainly in children 5 to 15 years old, and appears to be related to food allergy and, to a lesser extent, aeroallergens, in the majority of cases (Figure 3) (12–14). Data from the United States indicate that there is an increasing prevalence of new cases of EO in children (13). Retrospective data from the US and Australia consistently demonstrate that the annual incidence is approximately 1/10,000 population (12,13,15). In adults and children, the symptoms of EO are dominated by the conventional symptoms of reflux but also include dysphagia, which is highly specific to EO (13). Significantly increased thickness of the oesophageal wall has also been demonstrated in patients with EO (16). Treatment includes allergen avoidance and, if ineffective, local steroid treatment (17).
Other syndromes include eosinophilic gastroenteritis and eosinophilic proctocolitis. Eosinophilic gastroenteritis is not clearly defined; it was previously classified into mucosal, mural, and serosal types. The latter is accompanied by protein loss. These forms of disease show a positive response to amino acid–based formula, however persistence of disease has been demonstrated 2.5 to 5.5 years after initiation (18). Eosinophilic proctocolitis is characterised by rectal bleeding (approximately 20% of cases caused by CMA) (19,20), diarrhoea, and colic and occurs in infants 0 to 24 months old. Eosinophilic proctocolitis can occur in infants who are exclusively breast-fed (19).
It is important to diagnose a food allergy given that only one third of patients who themselves or their parents believe that symptoms are caused by food allergy actually have that suspicion confirmed (3). Foods other than those suspected may be responsible for the symptoms. Adherence to a diet without proper guidance may have a negative effect on growth and development (16,21,22).
The diagnostic strategy in infants who are suspected of having food allergy should involve a 2- to 4-week elimination diet, followed by either an open challenge or a DBPCFC to confirm or exclude a food allergy. Based on previous experience (2), DBPCFC should be conducted in adults and in children 3 years old and older.
Differential diagnosis is important; infants can present with upper GI symptoms (eg, infection, colic, GERD, pyloric stenosis) or lower GI symptoms (eg, infection, constipation), which may or may not be related to food allergy. Children may present with infection, lactose intolerance, toddler's diarrhoea, constipation, malabsorption, and inflammatory bowel disease.
Treatment largely consists of a hypoallergenic diet and prevention, and in special cases antihistamines may be used. In patients with EO, local steroids have demonstrated efficacy in double-blind controlled challenges and leukotriene inhibitors have been shown to be effective in small uncontrolled studies. In infants with CMA, hydrolysed formula may be given, and in children a cow's milk–free diet should be initiated.
CMA is a common disease in early childhood, which is part of the “allergic march.” Recently recognised GI manifestations such as EO pose specific diagnostic challenges. It is important to diagnose CMA to avoid unnecessary elimination diets. The treatment of GI manifestations of CMA relies on avoidance of cow's milk protein and dietary measures depending on the age of the child. Supportive treatment may also be included (eg, local corticosteroids in EO). Appropriate formula substitutes such as those containing extensively hydrolysed protein or, if not tolerated, amino acid–based formulas, should be use to secure appropriate energy and micronutrient needs.
1. Bock SA. Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life. Pediatrics 1987; 79:683–688.
2. Høst A, Husby S, Osterballe O. A prospective study of cow's milk allergy in exclusively breast-fed infants. Incidence, pathogenetic role of early inadvertent exposure to cow's milk formula, and characterization of bovine milk protein in human milk. Acta Paediatr Scand 1988; 77:663–670.
3. Høst A, Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy 1990; 45:587–596.
4. Eggesbø M, Botten G, Halvorsen R, et al
. The prevalence of allergy to egg: a population-based study in young children. Allergy 2001; 56:403–411.
5. Hourihane JO, Roberst SA, Warner JO. Resolution of peanut allergy: case control study. BMJ 1998; 316:1271–1275.
6. Sicherer SH, Furlong TJ, Muñoz-Furlong A, et al
. A voluntary registry for peanut and tree nut allergy: characteristics of the first 5149 registrants. J Allergy Clin Immunol 2001; 108:128–132.
7. Lack G, Fox D, Northstone K, et al
. Factors associated with the development of peanut allergy in childhood. N Engl J Med 2003; 348:977–985.
8. Johansson SG, Hourihane JOB, Bousquet J, et al
. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001; 56:813–824.
9. Sampson HA. Update on food allergy. J Allergy Clin Immunol 2004; 113:805–819.
10. Sampson HA, Anderson JA. Summary and recommendations: classification of gastrointestinal manifestations due to immunologic reactions to foods in infants and young children. J Pediatr Gastroenterol Nutr 2000; 30(Suppl):S87–94.
11. Nielsen RG, Bindslev-Jensen C, Kruse-Andersen S, et al
. Severe gastroesophageal reflux disease and cow milk hypersensitivity in infants and children: disease association and evaluation of a new challenge. J Pediatr Gastroenterol Nutr 2004; 39:383–391.
12. Cherian S, Smith NM, Forbes DA. Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia. Arch Dis Child 2006; 91:1000–1004.
13. Liacouras CA, Spergel JM, Ruchelli E, et al
. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005; 3:1198–1206.
14. Blanchard C, Wang N, Rothenberg ME. Eosinophilic esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol 2006; 118:1054–1059.
15. Gill R, Durst P, Rewalt M, et al
. Eosinophilic esophagitis disease in children from West Virginia: a review of the last decade (1995–2004). Am J Gastroenterol 2007; 102:2281–2285.
16. Fox VL, Nurko S, Teitlebaum JE, et al
. High-resolution EUS in children with eosinophilic “allergic” esophagitis. Gastrointest Endosc 2003; 57:30–36.
17. Noel RJ, Putnam PE, Collins MH, et al
. Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol 2004; 2:568–575.
18. Chehade M, Magid MS, Mofidi S, et al
. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow-up. J Pediatr Gastroenterol Nutr 2006; 42:516–521.
19. Anveden-Hertzberg L, Finkel Y, Sandstedt B. Proctocolitis in exclusively breast-fed infants. Eur J Paediatr 1996; 155:464–467.
20. Arvola T, Ruuska T, Keränen J, et al
. Rectal bleeding in infancy: clinical, allergological, and microbiological examination. Pediatrics 2006; 117:e760–e768.
21. Yu JW, Pekeles G, Legault L, et al
. Milk allergy and vitamin D deficiency rickets: a common disorder associated with an uncommon disease. Ann Allergy Asthma Immunol 2006; 96:615–619.
22. Henriksen C, Eggesbø M, Halvorsen R, et al
. Nutrient intake among two-year-old children on cows' milk-restricted diets. Acta Paediatr 2000; 89:272–278.