Correspondence
Cow's Milk and Chronic Constipation in Children
N Engl J Med 1999; 340:891-892March 18, 1999
- Article
To the Editor:
Iacono et al. (Oct. 15 issue)1 report that in young children, chronic constipation can be a manifestation of intolerance of cow's milk. They suggested the link between constipation and hypersensitivity to cow's milk on the basis of positive assays for milk-specific IgE antibody and positive skin-prick tests. The criteria for positivity that they used do not, however, correspond to those that are generally recognized. The results of the Phadebas radioallergosorbent test kit for the measurement of milk-specific IgE antibody were considered positive when there was a score of more than 1. According to the manufacturer and previous studies,2 such results may be false positives and may only reflect nonspecific background activity, especially in children with atopy and elevated total IgE antibody levels. Similarly, the results of the skin-prick tests may have been overinterpreted, since the criterion for positivity was a wheal whose diameter was more than one fourth the diameter of the wheal induced by histamine. The criteria for positivity used by most authors are those of Bock and coworkers: a wheal whose diameter is at least 3 mm greater than that of the control.3
The results of allergy testing in the patients studied by Iacono et al. should be reinterpreted according to these criteria. The accepted standard for the diagnosis of an allergy to cow's milk is the double-blind, placebo-controlled food challenge. As recognized by Iacono et al., it was difficult to maintain blinding, and the validity of the challenge test is questionable. Until the immune-system mechanisms have been clearly established in children who have chronic constipation and a response to the elimination of milk from their diet, hypersensitivity to cow's milk should not be identified as a cause of chronic constipation. Diets that do not include milk may be detrimental in children4 and should be recommended only after a rigorous diagnostic evaluation.
4 ReferencesPhilippe A. Eigenmann, M.D.
Samuel A. Zamora, M.D.
Dominique C. Belli, M.D.
University Hospital of Geneva, 1211 Geneva 14, Switzerland1
Iacono G ,Cavataio F ,Montalto G , et al. Intolerance of cow's milk and chronic constipation in children. N Engl J Med 1998;339:1100-1104
Full Text | Web of Science | Medline2
Sampson HA ,Albergo R . Comparison of results of skin tests, RAST, and double-blind, placebo-controlled food challenges in children with atopic dermatitis. J Allergy Clin Immunol 1984;74:26-33
CrossRef | Web of Science | Medline3
Bock SA ,Buckley J ,Holst A ,May CD . Proper use of skin tests with food extracts in diagnosis of hypersensitivity to food in children. Clin Allergy 1977;7:375-383
CrossRef | Medline4
Isolauri E ,Sutas Y ,Salo MK ,Isosomppi R ,Kaila M . Elimination diet in cow's milk allergy: risk for impaired growth in young children. J Pediatr 1998;132:1004-1009
CrossRef | Web of Science | Medline
To the Editor:
Iacono et al. suggest that intolerance of or an allergy to cow's-milk protein is a cause of chronic constipation in children. We studied 25 children ranging in age from 3 months to 11 years who had chronic constipation. The diagnosis of constipation was made on the basis of a history of reduced frequency of stools, pain during the passage of hard stools, and soiling. All the children followed a diet free of cow's milk for four weeks and were evaluated clinically and with use of the following laboratory tests: measurement of total serum IgE; whole-milk–specific, lactalbumin-specific, casein-specific, and β-lactalbumin–specific IgE antibody assays (radioallergosorbent tests); and skin tests with whole cow's milk, lactalbumin, casein, and β-lactalbumin. In 7 of the 25 children (28 percent), the constipation disappeared while they were following a diet free of cow's-milk protein and reappeared within 48 to 72 hours after challenge with cow's milk. One child (age, 3 months) did not undergo the challenge; however, biopsy of the colon revealed allergic colitis with eosinophilic infiltration. Five of the seven children had high serum levels of total IgE, and two had positive skin tests and detectable levels of specific IgE antibody.
Our results are in agreement with those of Iacono et al.1,2 and provide confirmatory data, as called for by Loening-Baucke in her editorial.3 The lower incidence of intolerance of cow's milk in the children with chronic constipation whom we assessed might be related to the fact that we included children up to 11 years of age.
3 ReferencesSilvia Daher, M.D.
Dirceu Solé, M.D.
Mauro Batista de Morais, M.D.
Federal University of São Paulo, CEP 04025-002 São Paulo, SP, Brazil1
Iacono G ,Carroccio A ,Cavataio F ,Montalto G ,Cantarero MD ,Notarbartolo A . Chronic constipation as a symptom of cow milk allergy. J Pediatr 1995;126:34-39
CrossRef | Web of Science | Medline2
Iacono G ,Cavataio F ,Montalto G , et al. Intolerance of cow's milk and chronic constipation in children. N Engl J Med 1998;339:1100-1104
Full Text | Web of Science | Medline3
Loening-Baucke V . Constipation in children. N Engl J Med 1998;339:1155-1156
Full Text | Web of Science | Medline
To the Editor:
Iacono et al. provide evidence that in a selected population of children, dietary protein intolerance may be associated with constipation. We prospectively studied, in a tertiary referral hospital, 20 consecutive children (11 boys and 9 girls; median age, 3.1 years; age range, 0.5 to 6.7) who were referred because of intractable constipation for which no physical cause could be found and for which conventional treatment with adequate doses of laxatives had been unsuccessful. Fourteen of the children had a personal history of atopy, and 12 had a family history of atopy. Eight had a parent with a clear history of dietary protein intolerance. In 11 of the 14 children with atopy, constipation improved after a six-week diet that was free of cow's milk. In two of the other three children with atopy, the constipation subsequently improved after the removal of wheat from their diets.
We studied the role of motility in the 14 children with atopy by means of intestinal transit studies (with the use of radiopaque pellets)1 before dietary manipulation. In 8 of the 14, the results indicated that the delay in fecal passage was a consequence of retention of stool in the rectum and not of a generalized motility disorder. In four of these eight children, the study was repeated after the dietary exclusion, and all four had normal intestinal transit. Among six children who underwent rectal mucosal biopsy, all six had infiltration of the lamina propria with eosinophils and one had eosinophilic cryptitis.
Three of the 14 children with atopy underwent anorectal manometry before dietary manipulation. All three had evidence of high external-anal-sphincter tone, with normal rectoanal inhibitory reflexes at normal or minimally elevated rectal-distention volumes.2
We conclude that refractory constipation in children with atopy is commonly associated with mucosal eosinophilia and increased mouth-to-anus transit times in association with rectoanal retention of stool and that dietary manipulation should be an integral part of the treatment protocol for such children.
2 ReferencesNeil Shah, M.R.C.P.
Keith Lindley, Ph.D., M.R.C.P.
Peter Milla, F.R.C.P.
Great Ormond Street Hospital, London WC1N 3JH, United Kingdom1
Champion MC, Orr WC. Evolving concepts in gastrointestinal motility. Oxford, England: Blackwell Science, 1996:104-6.
2
Corazziari E ,Cucchiara S ,Staiano A , et al. Gastrointestinal transit time, frequency of defecation, and anorectal manometry in healthy and constipated children. J Pediatr 1985;106:379-382
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Eigenmann and colleagues suggest that we overestimated the number of positive results for the milk-specific IgE antibody assay and skin-prick tests. For both these tests, however, we selected cutoff values derived from those in age-matched subjects without atopic diseases who were examined in our laboratory. We evaluate several hundred patients with suspected atopy each year; thus, the cutoff values for immunologic tests were derived from a very large group. The criteria that we used have been validated in our previous studies.1,2 Food intolerance cannot be diagnosed on the basis of an immunologic test; therefore, the results of radioallergosorbent tests and skin tests can only be considered indicative of the probability that children with constipation will have a response to an elimination diet.
With regard to the double-blind, placebo-controlled challenge with cow's milk, as we stated in our article, we cannot rule out the possibility that psychological factors may have influenced the results, since the tastes of the formulas that we used were different. However, the very fact that a high percentage of children with constipation had a response to a diet free of cow's milk after previous treatments — often over a period of months or years — were unsuccessful is evidence of the strong link between constipation and intolerance of cow's milk.
Both Daher et al. and Shah et al. report interesting findings that confirm our results. Daher et al. found a 28 percent frequency of constipation related to cow's milk in an unselected series of children, whereas Shah et al. report a higher frequency in children with atopy. Thus, the selection criteria used for patients are decisive in the ability to predict the success of the elimination diet. Daher et al. also confirm our observation that a diet free of cow's milk can be effective in children without IgE-mediated immunologic mechanisms. Shah et al. provide further data on intestinal motility, which confirm our hypothesis that children with intolerance of cow's milk and constipation retain stool in the rectum because of pain on defecation.
2 ReferencesAntonio Carroccio, M.D.
University of Palermo, 90127 Palermo, ItalyFrancesca Cavataio, M.D.
Giuseppe Iacono, M.D.
Di Cristina Hospital, 90134 Palermo, Italy1
Iacono G ,Carroccio A ,Cavataio F ,Montalto G ,Cantarero MD ,Notarbartolo A . Chronic constipation as a symptom of cow milk allergy. J Pediatr 1995;126:34-39
CrossRef | Web of Science | Medline2
Iacono G ,Carroccio A ,Cavataio F , et al. Gastroesophageal reflux and cow's milk allergy in infants: a prospective study. J Allergy Clin Immunol 1996;97:822-827
CrossRef | Web of Science | Medline
- Citing Articles (19)
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Yee Ian Yik, Timothy M. Cain, Coral F. Tudball, David J. Cook, Bridget R. Southwell, John M. Hutson. (2011) Nuclear transit studies of patients with intractable chronic constipation reveal a subgroup with rapid proximal colonic transit. Journal of Pediatric Surgery 46:7, 1406-1411
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Vera Loening-Baucke. 2011. Constipation and Fecal Incontinence. , 127-135.
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Inaki Irastorza, Berta Ibañez, Lissette Delgado-Sanzonetti, Natalia Maruri, Juan Carlos Vitoria. (2010) Cowʼs-Milk–free Diet as a Therapeutic Option in Childhood Chronic Constipation. Journal of Pediatric Gastroenterology and Nutrition 51:2, 171-176
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Osvaldo Borrelli, Giovanni Barbara, Giovanni Di Nardo, Cesare Cremon, Sandra Lucarelli, Tullio Frediani, Massimiliano Paganelli, Roberto De Giorgio, Vincenzo Stanghellini, Salvatore Cucchiara. (2009) Neuroimmune Interaction and Anorectal Motility in Children With Food Allergy-Related Chronic Constipation. The American Journal of Gastroenterology 104:2, 454-463
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May Loo. 2009. Constipation. , 269-280.
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Ralf G. Heine. (2008) Allergic gastrointestinal motility disorders in infancy and early childhood. Pediatric Allergy and Immunology 19:5, 383-391
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Elesa CROWLEY, Lauren WILLIAMS, Tim ROBERTS, Peter JONES, Richard DUNSTAN. (2008) Evidence for a role of cow's milk consumption in chronic functional constipation in children: Systematic review of the literature from 1980 to 2006. Nutrition & Dietetics 65:1, 29-35
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Peter J. Milla. (2007) Fisiopatología del estreñimiento. Annales Nestlé (Ed. española) 65:2, 55-61
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A. CARROCCIO, G. IACONO. (2006) Review article: chronic constipation and food hypersensitivity ? an intriguing relationship. Alimentary Pharmacology and Therapeutics 24:9, 1295-1304
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Ralf G Heine. (2006) Gastroesophageal reflux disease, colic and constipation in infants with food allergy. Current Opinion in Allergy and Clinical Immunology 6:3, 220-225
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A. C. Hauer. (2006) Kuhmilchallergie. Monatsschrift Kinderheilkunde 154:5, 406-416
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Mich??le Scaillon, Samy Cadranel. (2006) Food allergy and constipation in childhood: how functional is it?. European Journal of Gastroenterology & Hepatology 18:2, 125-128
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Giuseppe Iacono, Sebastiano Bonventre, Calogero Scalici, Emiliano Maresi, Lidia Di Prima, Maurizio Soresi, Giuseppe Di Ges??, Davide Noto, Antonio Carroccio. (2006) Food intolerance and chronic constipation: manometry and histology study. European Journal of Gastroenterology & Hepatology 18:2, 143-150
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Jonathan R. Sutcliffe, Sebastian K. King, Bridget R. Southwell, John M Hutson. (2004) Paediatric constipation for adult surgeons − article 1: targeting the cause. ANZ Journal of Surgery 74:9, 777-780
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Ralf G. Heine, Said Elsayed, Clifford S. Hosking, David J. Hill. (2002) Cow??s milk allergy in infancy. Current Opinion in Allergy and Clinical Immunology 2:3, 217-225
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Vera Loening-Baucke. (2002) Encoprésie. Acta Endoscopica 32:3, 329-342
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Silvia Daher, Soraia Tahan, Dirceu Sole, Charles K. Naspitz, Francy Reis Da Silva Patricio, Ulysses Fagundes Neto, Mauro Batista De Morais. (2001) Cow's milk protein intolerance and chronic constipation in children. Pediatric Allergy and Immunology 12:6, 339-342
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Alan M. Lake. (2001) Dietary protein enterocolitis. Current Allergy and Asthma Reports 1:1, 76-79
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Samuel Nurko. (2000) Advances in the management of pediatric constipation. Current Gastroenterology Reports 2:3, 234-240
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