Antonio Carroccio, ,
, ,

Other Contributors:

February 06, 2009

Dear Sir, Some days ago we received a letter from colleagues in London asking us to comment on the article of Simeone and coll. reporting a lack of relationship between chronic constipation (CC) and cow’s milk allergy (CMA), recently published in ADC (1). Our English Colleagues referred that they had observed “dramatic cases” of chronic constipation unresponsive to laxative treatment which fully resolved on CM-free diet and as this is also our experience in many cases (2-5) they asked to “defend this truth”. However, we think that the study of Simeone and coll. is very different from our previous studies on CC and CMA. In their article (1) they investigated for an association between CC and atopic disease and to do this performed a series of IgE-mediated assays. It is, in part, not surprising that they did not find a more frequent association of atopy (positive assays and clinical history) in CC patients than in controls, as it is well known that the immunologic mechanisms of the majority of gastrointestinal manifestations of food allergy are not based on IgE- mediated mechanisms (6) and we ourselves have not found a higher frequency of positive IgE-based assays in patients with CC due to CMA. Thus, a lack of association between atopy or IgE-mediated assays and CC was to have been expected and does not mean that CC cannot be due to CMA. The only aspect of the Simeone study which could be compared with our and others’ previous studies (7-10), is that they placed eleven CC patients unresponsive to laxative treatment on CM-free diet. They found that none of these eleven patients improved on CM-free diet. On the basis of this very small patient sample they concluded that “the refractory constipation is not associated with CMA in the general paediatric population”. This could also be true in the general population, although we do have doubts about this, but more than eleven patients must be evaluated before a firm conclusion can be reached. What is certain is that in a tertiary gastroenterology clinic with experience in the food allergy-intolerance field – as ours is - the frequency of CC unresponsive to laxative treatments and due to food allergy is higher than one third of cases. Probably this high frequency is biased by the pre-selection of the patients referred to our clinic, but whatever the real frequency of the relationship between CC and food allergy may be, many prestigious research groups from England (7), the USA (10), Finland (11) and other centres world-wide (8,9) have reported results identical to ours and firmly confirmed that CC can be a manifestation of food allergy. Furthermore, the CC-CMA association has also been included in a review published in Gastroenterology (12). Finally, we recently suggested the possibility that the patients could be suffering from multiple food allergy and not simply from CM hypersensitivity. In fact, bowel movements normalised in some patients unresponsive to CM-free diet when they were placed on a more restricted oligoantigenic diet (5). Do paediatricians who first visit a child consider the hypothesis of CMA- related constipation? We believe they do, but this does not mean that a CM -free diet should be prescribed for every patient with CC. The first treatment approach must be a regular diet (water, fibre, etc) and laxatives. However, if the patient does not improve and especially when he/she has a previous history or a family history of CMA, the probability of a CMA diagnosis increases. In these cases a consultation with a specialist should be suggested and, after further evaluation, an elimination diet could be prescribed. We do not know how many paediatricians - or paediatric gastroenterologists - in the world use this approach, but we think there are too few. Despite the clear evidence, there are still many paediatricians who do not accept that CMA can be a cause of CC. The Naples Gastroenterology School is a medical teaching school which we have learned a great deal from and its members contribute to form opinions and guidelines in paediatric gastroenterology. Unfortunately, their experience with CC conflicts with the evidence in the literature about the relationship between CC and CMA and this certainly hinders the possibility of a correct treatment for patients with CC due to CMA. Our role can be to add further data to help better understand the problem and to offer further evidence of this relationship. Yours faithfully,

REFERENCES 1) Simeone D, Miele E, Boccia G, Marino A, Troncone R, Staiano A. Prevalence of atopy in children with chronic constipation. Arch Dis Child 2008;93;1044-1047 2) Iacono G, Carroccio A, Cavataio F, Montalto G, Cantarero MD, NotarbartoloA. Chronic constipation as a symptom of cow milk allergy. J Pediatr 1995; 126: 34–9. 3) Iacono G, Cavataio F, Montalto G, et al. Intolerance of cow’s milk and chronic constipation in children. N Engl J Med 1998; 338: 1100–4. 4) Carroccio A, Scalici C, Maresi M, et al. Chronic constipation and food intolerance: a model of proctitis causing constipation. Scand J Gastroenterol 2005; 40: 33–42 5) Iacono G, Bonventre S, Scalici C, et al. Food intolerance and chronic constipation: manometry and histology study. Eur J Gastroenterol Hepatol 2006; 18: 143–50. 6) Sampson H, Sicherer SH, Birnbaim AH. American Gastroenterological Association Medical Position Statement: guidelines for the evaluation of food allergies. Gastroenterology 2001; 120: 1023–5. 7) Shah N, Lindley K, Milla P. Cow’s milk and chronic constipation in children. N Engl J Med 1999; 340: 891–2. 8) Daher S, Sole` D, de Morais MB. Cow’s milk and chronic constipation in children. N Engl J Med 1999; 340: 891. 9) Daher S, Tahan S, Sole` D, et al. Cow’s milk protein intolerance and chronic constipation in children. Pediatr Allergy Immunol 2001; 12: 339–43. 10) Vanderhoof JA, Perry D, Hanner TL, Young RJ. Allergic constipation: association with infantile milk allergy. Clin Pediatr 2001; 40: 399–402 11) Turunen S, Karttunen TJ, Kokkonen J. Lymphoid nodular hyperplasia and cow’s milk hypersensitivity in children with chronic constipation. J Pediatr 2004; 145: 606–11. 12) Bischoff S, Crowe SE. Gastrointestinal food allergy: new insights into pathophysiology and clinical perspectives. Gastroenterology 2005; 128: 1089–113

Conflict of Interest

None declared