Cow's Milk Intolerance Research Articles

Comment on Soy Protein Intolerance

With great interest I read the report by Whitington and Gibson on soy protein intolerance (Pediatrics 59:730, May 1977). In the Archives of Diseases in Childhood of May 1975, the study group for gastrointestinal disorders at the Children's Hospital, University of Helsinki, Finland, presented 54 infants with the malabsorption syndrome with cow's milk intolerance.1 Thirty-five of these 54 infants received soy protein as a substitute for cow's milk. Four of these 35 infants had concomitant soy protein intolerance.

The Tonsillitis Habit

<i>The Tonsillitis Habit</i>by Osborn and Roydhouse is a small volume (100 pages) with an interesting title. The purpose of this book is to discuss the rationale and value of tonsillectomy and adenoidectomy. The book has several virtues and a number of debits. On the positive side there is an interesting discussion of the physiology and the pathology of "reversible forms" and "irreversible forms" of tonsillitis. The chapter by Holland on anesthesia for adenotonsillectomy presents a worthwhile review of the principles of anesthesia for tonsillectomy and stresses maintenance of the airway. The list of anesthestic agents may not suit every anesthesiologist, however. The chapters describing cow's-milk intolerance, modes of cross infection of infants, and peridontal disease are worth reading, since they are not stressed in most otolaryngology textbooks. On the debit side, however, is a real absence of significant correlation of the pathology of tonsil and adenoid disease to indications

Effect of Cow's Milk on the Gastrointestinal Tract: A Persistent Dilemma for the Pediatrician

The confusing area of cow's milk intolerance is explored in an attempt to define the various mechanisms whereby milk affects gastrointestinal function, resulting in clinical symptoms (diarrhea, vomiting, gastrointestinal bleeding, etc.). The adverse reaction of infants to cow's milk ingestion may relate to lactose intolerance (enzymatic), a direct toxic reaction to the mucosal surface resulting in epithelial damage, or it may be immunologically mediated. Factors such as increased intestinal permeability to milk proteins during the newborn period may also contribute to susceptibility of young infants to milk sensitivity. The relative roles of systemic (milk agglutinins) and local immunity (SIgA antibodies) in milk intolerance are discussed and differential immunologic responses (IgE versus IgA/IgM) considered in the pathogenesis. It was concluded that new techniques such as organ culture of intestinal biopsy specimens are needed to establish the diagnosis of hypersensitivity and to begin to provide ways of adequately treating the condition.

Occurrence of specific precipitins against bovine whey proteins in serum from children with gastrointestinal disorders.

Children with cow's milk intolerance, clinically non-confirmed cow's milk intolerance, coeliac disease, non-confirmed malabsorption, other gastrointestinal disorders and normal children were investigated for the presence of precipitins against 40 individual bovine whey proteins by means of the crossed immunoelectrophoresis with intermediate gel technique. In the various groups of children the amount and specificity of bovine whey precipitins were neither connected with the various gastrointestinal disorders nor with alternating diet and challenge with milk. Bovine whey-specific IgE could not be detected in any of the patients clinically suspected for cow's milk intolerance by cutaneous test, RAST or CRIE. The immunoglobulin level of the patients investigated did not differ significantly from the normal ranges. It is concluded that investigations of serum precipitins against bovine whey proteins do not give any significant information concerning cow's milk intolerance.

The intestinal microvillus. Ultrastructural variability in coeliac disease and cow's milk intolerance.

In 8 patients with coeliac disease, 2 patients with cow's milk intolerance and 10 patients with other gastrointestinal disturbances, intestinal biopsies were examined in order to compare the extent of alteration of surface vs. crypt microvilli (MV). In those diseases associated with the ingestion of a noxious agent, namely coeliac disease and cow's milk intolerance, a marked and abrupt difference between the severely damaged surface epithelium and its MV, and the preserved crypt epithelium was noted. The results of the examinations give reason to suppose that these morphological variations are caused by the higher gliadin or milk protein concentration over the avillous surface epithelium as opposed to the lower one in the elongated crypts.

Points from letters: Cow's milk intolerance

Points from letters: Cow's milk intolerance

Editorial: Cow's milk intolerance.

Editorial: Cow's milk intolerance.

INTESTINAL BIOPSY IN THE DIAGNOSIS OF COW'S MILK PROTEIN INTOLERANCE WITHOUT ACUTE SYMPTOMS

4 infants, suspected of cow's milk protein intolerance, were placed on an elimination diet and then challenged with cow's milk. None reacted clinically, yet in 2 of the 4 patients jejunal biopsy revealed clear histological, ultrastructural, and immunological changes. It is suggested that these changes are the objective criteria on which the diagnosis of cow's milk intolerance should be based, and that the clinical evidence derived from milk challenge after an elimination diet may be unreliable.

Malabsorption syndrome with cow's milk intolerance. Clinical findings and course in 54 cases.

Fifty-four infants with the malabsorption syndrome and cow's milk intolerence seen during 1962-1971 were investigated. All had diarrhoea and failed to thrive. Most had vomiting and about 20% had atopic eczema and recurrent respiratory infections. Laboratory investigations revealed malabsorption, raised serum IgA, and precipitins to cow's milk. Biopsies showed that the jejunal mucosa was damaged, and in about half the cases was flat. The patient did well on human milk but reacted clinically to cow's milk challenge, either in a few hours or gradually during 3-4 weeks. Some patients showed first a quick, but later a slow, reaction. Clinical symptoms of cow's milk intolerance disappeared at the age of about one year. At that time 81% had normal faecal fat, but only 29% had a normal proximal jejunal mucosa. Many of the patients developed intolerances to other food proteins, such as soya and wheat, if these were given during the sensitive period. Forty-two patients have been followed up for 2 years on a normal gluten-containing diet. Of these, 37 have a normal or nearly normal jejunal mucosa and 5 (12%) have subtotal villous atrophy indicative of coeliac disease. It is concluded that the malabsorption syndrome with cow's milk intolerance is a clear-cut clinical entity. However, the symptomatology, results of laboratory tests, and jejunal biopsy findings closely resemble those of other entities where damage to the intestinal mucosa causes a malabsorption snydrome. Follow-up studies showed that the disease is transient, but about 10% of the patients have coeliac disease, regarded in such cases as the primary disorder.

Response of the jejunal mucosa to cow's milk in the malabsorption syndrome with cow's milk intolerance. A light- and electron-microscopic study.

SUMMARYThree infants, in whom the malabsorption syndrome, small intestinal. mucosal damage and clinical cow's milk intolerance were found, were challenged with cow's milk after initial treatment with breast milk. The small intestinal mucosa was investigated with light and electron microscopy both before and after provocation.Clinically one patient reacted rapidly in a few hours and showed round cell infiltration in the surface epithelium and lamina propria 20 hours after a single challenge. Electron microscopy showed short microvilli, abnormal nuclei and thickened basement lamina in the surface epithelium. Two patients reacted slowly. One of them showed similar changes 4 days after commencement of the provocations, but the changes were much more evident 38 days later, when symptoms were also apparent. At this time large accumulations of lysosomes in the apical part of the surface epithelial cell and marked thickening of the basal lamina with accumulations of whirly collagen fibres were detected. The third patient reacted in a milder way, both clinically and morphologically. This study indicates that cow's milk, apparently through its protein fraction, may damage the surface epithelium of the small intestinal mucosa. These alterations during provocation periods resemble those found in coe‐liac disease during gluten provocation.

Immunochemical study of the malabsorption syndrome with cow's milk intolerance.

The effect of cow's milk provocation on the immunoglobulins in the intestinal mucosa, intestinal juice, stool extracts, as well as on the levels of antibodies to cow's milk and beta-1C/A in serum, was studied in 18 infants with the malabsorption syndrome. The infants improved on breast milk and were therefore suspected to be intolerant to cow's milk and challenged with it. At the time of clinical relapse a marked and uniform increase in the numbers of IgA- and IgM-containing cells, 2.4 times as many on the average as before challenge, was observed in the jejunal mucosa of eight reacting patients at nine provocations with cow's milk. There was no abnormality in the immunoglobulin-containing cells before challenge or in biopsy specimens taken shortly after the resumption of the elimination diet (breast milk). The clinical reaction was preceded by a pronounced rise in the IgA and IgM contents of stool extracts, and a rise in the titre of haemagglutinating antibodies and serum IgA, changes which subsided rapidly after withdrawal of cow's milk. There was no evidence that the reaction was IgE-mediated or complement-consuming. In some of the 10 patients who tolerated cow's milk challenge clinically there was an increase in both IgA- and IgM-containing cells suggestive of a local immunological reaction although no clinical intolerance was provoked and other immunological signs were weak or absent. In other non-reacting patients no immunological reaction was noted. Therefore it is evident that cow's milk is the agent responsible for the strong local intestinal reaction coinciding with the clinical symptoms.

RETICULIN ANTIBODY IN CHILDREN WITH MALABSORPTION

40 children with coeliac disease were retrospectively studied for reticulin antibody by indirect immunofluorescence. Prior to gluten withdrawal 27 (68%) had antibody in their sera. In some cases antibody titre fluctuated according to gluten withdrawal and provocation. In 20 cases of malabsorption syndrome with cow's milk intolerance, histologically and clinically indistinguishable from coeliac disease, reticulin antibody was not detected. When positive, the reticulin-antibody test should be of clinical value in differential diagnosis. 2 of the reticulin-antibody-positive cases of coeliac disease lacked IgA in their sera. The antibody was found in 4 out of 23 children lacking IgA but with normal jejunal structure.

Intestinal dipeptidases and disaccharidases in children with malabsorption.

SUMMARYIntestinal enzyme activities (dipeptidases and disaccharidases) and mucosal morphology were studied in two groups of paediatric patients: one coeliac group (n=13) and one “suspected cow's milk intolerance” group (n= 5). The patients were studied before and after dietary treatment. 49 children and adults with histologically normal intestinal mucosa served as a control group.Both groups of patients showed a marked secondary decrease in the dipeptidase and the disaccharidase activities. The decrease was more pronounced for the disaccharidase than for the dipeptidase activities, and was reversible on dietary treatment. Among the disaccharidases, the lactase and trehalase activities were most strongly depressed; in the coeliac group, the ala‐pro dipeptidase activity was more strongly affected than the other dipeptidases. However, as also the ala‐pro dipeptidase activity increased on dietary treatment, this does not provide any clue to the specificity of a hypothetical enzyme whose absence could be responsible for the disease.

Cow versus soy formulas. Comparative evaluation in normal infants.

SOY BEAN milk for infant feeding has the potential advantage of widespread availability and economy in areas where animal protein may be scarce and costly. Ernest Tso, noting the need for an alternative to cow's milk for artificial feeding of infants in China, reported in 1928 on a more or less successful attempt to feed an infant six weeks of age for eight months on soybean milk diet, 1 which he thought to be the first such report. This infant gained well, but developed rickets refractory to treatment with cod liver oil until cow's milk was substituted to provide adequate calcium intake. From that time to this the search has continued for improved soy formulas for those areas where cow's milk feeding is impractical, and for infants with cow's milk intolerance. Justly or unjustly, soy bean milks have been criticized for causing gastrointestinal upsets and for not being readily tolerated