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Cow's Milk Allergy

Cow's milk contains many proteins that are antigenic - they excite immune responses. Patients of all ages with gastrointestinal tract disease may have difficulty digesting these proteins and may absorb them as antigens. Milk problems may be attributed to lactose intolerance and the milk-sugar enzyme, lactase, may be prescribed. Milk allergy is a protein problem and is not improved by changing the milk sugar - often the diagnosis of "lactose intolerance" is incomplete or wrong and symptoms persist with only lactose exclusion.

Often, infant milk allergy is thought to be a specific and limited condition which children "outgrow." This idea can be misleading many children continue to have chronic symptoms from milk, although the original problem may disappear, the pattern of illness changes and confuses parents and physicians.

Some examples of milk allergy descriptions in the medical literature

Milk causes a rapid urticarial reaction on the skin of children with atopic dermatitis and milk allergy.

Salo OP; M?inen-Kiljunen S; Juntunen K. Acta Derm Venereol, 1986, 66:5, 438-42

Open skin challenge test with whole milk and its large and small molecular fractions was performed on intact skin of children with atopic dermatitis and suspicion of milk allergy. Of the 51 children challenged with milk 35 reacted within minutes with contact urticaria. The large molecular (m.w. greater than 10,000 d) fraction gave an urticarial reaction as often as whole milk, whereas the small molecular fraction gave only a few positive reactions. These were obviously caused by alpha-lactalbumin which was present only in small amounts in the small molecular fraction. These findings indicate that immediate contact allergy to relevant food allergens can be very common in children with atopic dermatitis and that the large molecular antigens readily penetrate children's skin.

Contact urticaria to cow milk.

Boso EB; Brestel EP Allergy, 1987 Feb, 42:2, 151-3

Abstract A patient with contact urticaria to cow milk is presented. Contact sensitivity was documented to whole cow milk, skim milk, commercial condensed milk, and milk heated to 80 degrees C for 30 min. Contact sensitivity was also documented to casein and lactalbumin. Unlike a previous report our patient's sensitivity to heated milk precluded its use in the diet. Thus, heating milk does not necessarily reduce allergenicity to its component proteins.

Cow's milk allergy, incidence and pathogenetic role of early exposure to cow's milk formula.

Author Stintzing G; Zetterstr? R Source Acta Paediatr Scand, 1979 May, 68:3, 383-7

Abstract A study was performed in infants under the age of 12 months born during 1974 and admitted to St. G?an's Children's Hospital with symptoms suggestive of cow's milk allergy (CMA). The aims of the study were to determine the role of early exposure to cow's milk formulas as a predisposing factor to CMA and to estimate the incidence of CMA in infancy. Twenty-five infants fulfilled the criteria for CMA. Available records were reviewed and a careful history was obtained from the mothers on two occasions. The patient group was compared with a control group. Sixteen of the 25 infants were exposed to cow's milk protein during their first week in the nursery for newborns, 6 were exposed before the end of the fourth week of life, and 3 infants were apparently not exposed. All infants were breast fed 3 to 26 weeks before re-exposure and occurrence of symptoms. Infants with CMA were given cow's milk formulas during their first 4 weeks of life significantly more often than infants in the control group (p less than 0.01).  The first 4 weeks after birth seem to be a particularly vulnerable period. Hence, in order to prevent CMA, infant formula should not be given--even occasionally--during this period.

Humoral immune response to cow's milk in children with cow's milk allergy.

Firer MA; Hoskings CS; Hill DJ  Int Arch Allergy Appl Immunol, 1987, 84:2, 173-7

Abstract In 47 infants and children aged 4-66 months with clinically proven cow's milk allergy and in a group of age-matched controls, serum IgG, IgA and IgM cow's milk-specific antibodies were determined with ELISA assays while IgE cow's milk-specific antibodies were measured with Pharmacia RAST. The patients were divided into three separate groups according to the time of clinical response to a standardized cow's milk challenge protocol. Immediate reactions (less than 45 min after challenge), which were mainly accompanied by urticarial skin eruptions, were associated with elevated IgE milk-specific antibody levels, indicating the involvement of an immediate hypersensitivity mechanism. Alternatively, intermediate reactions (1-20 h after challenge), which were mainly accompanied by vomiting and diarrhea, were not IgE-mediated. In the late reactions (greater than 20 h after challenge) both eczematous and gastrointestinal reactions were seen. Patients with eczematous eruptions also showed elevated IgE milk-specific antibody levels. IgG milk-specific antibody levels were similar in each of the patient groups but all groups were significantly lower than in the controls. Levels of IgA and IgM milk-specific antibodies were similar in patients and controls. The results indicate that different immunopathogenic mechanisms are operative in these subgroups of patients with cow's milk allergy.

Chronic constipation as a symptom of cow milk allergy.

 Iacono G; Carroccio A; Cavataio F; Montalto G; Cantarero MD; Notarbartolo A  J Pediatr, 126: 1, 1995 Jan, 34-9

Abstract  Twenty-seven consecutive infants (mean age, 20.6 months) with chronic "idiopathic" constipation were studied to investigate the possible relation between constipation and cow milk protein allergy (CMPA). The infants were initially observed on an unrestricted diet, and the number of stools per day was recorded. Subsequently the infants were put on a diet free of cow milk protein (CMP) for two periods of 1 month each, separated by two challenges with CMP. During the CMP-free diet, there was a resolution of symptoms in 21 patients; during the two consecutive challenges, constipation reappeared within 48 to 72 hours. In another six patients the CMP-free diet did not lead to improvement of constipation. Only four of the patients who improved on the CMP-free diet had concomitant symptoms of suspected CMPA, but a medical history of CMPA was found in 15 of the 21 patients cured and in only one of the six patients whose condition had not improved (p < 0.05); in addition, in 15 of the 21 cured patients, results of one or more laboratory tests (specific IgE, IgG, anti-beta-lactoglobulin, circulating eosinophils) were positive at the time of diagnosis, indicating hypersensitivity, compared with one of the six patients whose condition did not improve (p < 0.05). The endoscopic and histologic findings at the time of diagnosis showed proctitis with monocytic infiltration in two patients cured with the CMP-free diet; after 1 month on this diet, they were completely normal. We conclude that constipation in infants may have an allergic pathogenesis.

Food sensitive enteropathy: overview and update.

Walker-Smith J. SourceActa Paediatr Jpn, 36: 5, 1994 Oct, 545-9 Abstract There are two types of food sensitive enteropathy; permanent and temporary. Celiac disease belongs to the former, the temporary food sensitive enteropathies of early childhood to the latter. A food sensitive enteropathy is characterized by an abnormal small intestinal mucosa while having the offending food in the diet; the abnormality is reversed by an elimination diet, only to recur once more on challenge with the relevant food. These disorders are temporary and may follow gastroenteritis. Cow's milk sensitive enteropathy is the most frequent and best known example but soy protein, egg, fish, chicken meat, ground rice and probably gluten may also temporarily damage the small intestinal mucosa in infancy. Treatment is with an elimination diet and protein hydrolysates as a cow's milk substitute. The reason why these enteropathies are temporary has not yet been established.

Cow milk allergy within the spectrum of atopic disorders.

Hill DJ; Bannister DG; Hosking CS; Kemp AS Clin Exp Allergy, 24: 12, 1994 Dec, 1137-43

Abstract In order to examine the relationship between cow milk allergy (CMA) and atopic disorders in childhood, a consecutive group of 42 infants with IgE mediated CMA was followed for at least 2 years. The incidence of sensitization to common food and inhalant antigens and the development of eczema, asthma, and food allergies was examined for the cohort and compared between patients whose CMA remitted and those with persistent disease. In this cohort the prevalence of eczema was 57%, asthma 69%, egg allergy 67%, peanut allergy 55%, and 83% of infants demonstrated positive skin-prick tests to three or more allergens. At the end of the study CMA had remitted in 13 patients (median age 44 months) whereas in 29 patients it persisted (median age 44 months). Although there was no significant difference in the incidence of eczema or asthma during the study between these two patient groups, the incidence of allergy to egg and peanut butter was significantly greater for children with persistent CMA. Consistent with our hypothesis that children with persistent CMA have a more severe dysregulation of IgE synthesis than those whose disease remits, patients with persistent CMA had a significantly higher incidence of and level of skin sensitivity to inhalant and other dietary allergens. Sensitization to the inhalant allergens Dermatophagoides pteronyssinus, cat dander and rye grass was frequently seen in early infancy and increased during the study period. Thus, children with IgE mediated CMA frequently generate IgE responses to multiple dietary and inhalant allergens in infancy and early childhood and develop immediate hypersensitivity to other foods as well as clinical eczema, and asthma.

The regulation of intestinal hypersensitivity reactions to ovalbumin by omega-3 fatty acid enriched diet

Yamashiro Y; Ohtsuka Y; Yabuta K  Acta Paediatr Jpn, 36: 5, 1994 Oct, 550-6

Abstract In order to clarify the mechanisms of food-sensitive enteropathy, a food hypersensitive model was generated by feeding ovalbumin to female BALB/c mice after intraperitoneal injection of cyclophosphamide and morphological and immunological changes in the gut mucosa were investigated. Villus atrophy, crypt hyperplasia and increased numbers of intra-epithelial lymphocytes (IEL) were confirmed in this model, as seen in food-sensitive enteropathy in humans. Subpopulations of IEL and lamina propria lymphocytes were enumerated by immunohistochemical observation. CD8-positive cells were increased both in epithelium and lamina propria, whereas CD4-positive cells were decreased in lamina propria. We document here that orally administered food antigen actually induces food-sensitive enteropathy and mucosal damage is generated by lymphocytes that infiltrate the intestinal mucosa. We also investigated the effect of feeding an omega-3 fatty acid-enriched diet in this model and found that it was efficient in attenuating mucosal damage.

Milk proteins, cytokines and intestinal epithelial functions in children.

 Desjeux JF; Heyman M Acta Paediatr Jpn, 36: 5, 1994 Oct, 592-6

Abstract This paper discusses the relationship between food antigens, lymphocytes and the epithelial properties of the jejunum in children with cow's milk allergy. Experimental results indicate that increased protein permeability is not the primary cause of cow's milk allergy. Rather, results are interpreted as a secondary effect of an abnormal immunological response leading to mucosal inflammation and impairment of the endocytic process by the intestinal epithelial cells. Stimulation by cow's milk proteins caused the lymphocytes from infants with cow's milk allergy to release more tumor necrosis factor-alpha TNF alpha than those from control infants. After appropriate antigenic stimulation, the cytokines released by the activated lymphocytes from these infants perturbed epithelial function, in particular its barrier capacity. Tumor necrosis factor alpha, together with gamma interferon are involved in these adverse effects. It is thought that bovine beta-lactoglobulin present in the intestinal lumen may be responsible for the secretory diarrhea observed in children with cow's milk allergy, as a consequence of stimulation of electrogenic chloride secretion. In addition, luminal foreign protein may stimulate the submucosal cells. As a consequence, the submucosal release of mediators, including lymphokines, might alter the intestinal epithelial barrier. In conclusion, in physiological conditions, the subepithelial tissue that comprises the immune system and many other systemic systems receive information on the antigenic content within the intestinal lumen via the intestinal epithelium.

Hypersensitivity reaction in an infant fed hydrolyzed lactalbumin contained in a semielemental formula

 Heyman MB; Stoker TW; Rudolph CD; Frick OL   J Pediatr Gastroenterol Nutr, 10: 2, 1990 Feb, 253-6

Following introduction of milk protein formula feedings, a 6-month-old male developed profuse, watery diarrhea progressing to shock, requiring cardiopulmonary resuscitation. Reinstitution of enteral feedings with a formula containing hydrolyzed lactalbumin (Travasorb STD) resulted in recurrence of diarrhea with fever. Intestinal and rectal biopsies showed only nonspecific inflammatory changes. He was discharged on an elemental formula (Vivonex). Twenty-three months later, while admitted for evaluation of hypophosphatemic rickets, immunologic testing using the lymphocyte migration inhibition factor (LIF) test demonstrated positive reactions, especially to alpha-lactalbumin (56% inhibition) and whole cow's milk (22%, normal of less than 20% inhibition). Skin tests revealed sensitivity to cow's milk and eggs. Soy formula also produced diarrhea and bloody stools. Protein hydrolysate formulas, touted as hypoallergenic diets, are useful in infants with intolerance to milk protein. This is the first documented case of an immunological reaction to the hydrolyzed whey protein, lactalbumin. Although protein hydrolysate formulas are effective treatment in most infants with milk protein intolerance, allergic reactions are possible. Caution and close observation should be exercised in immunologically sensitized infants rechallenged with any formula.

Role of food allergy in serous otitis media

Nsouli TM; Nsouli SM; Linde RE; O'Mara F; Scanlon RT; Bellanti JA  Ann Allergy, 73: 3, 1994 Sep, 215-9

The relationship between IgE-mediated hypersensitivity and recurrent serous otitis media has not been completely established. OBJECTIVE. The purpose of the present study was to examine the prevalence of food allergy in patients with recurrent serous otitis media. METHODS. A total of 104 unselected patients (age range 1.5 to 9 years, mean 4.6 years) with recurrent serous otitis media were evaluated for food allergy by means of skin prick testing, specific IgE tests, and food challenge. Patients who were allergic to food(s) underwent an exclusion diet of the specific offending food(s) for a period of 16 weeks. A non-double blinded food challenge was performed with the suspected offending food(s). Their middle ear effusion was monitored and assessed by tympanometry (Welch Allyn Model 23600) during the pre-elimination, elimination and challenge diet phases. RESULTS. There was a significant statistical association, by chi-square analysis, between food allergy and recurrent serous otitis media in 81/104 patients (78%). The elimination diet led to a significant amelioration of serous otitis media in 70/81 (86%) patients as assessed by clinical evaluation and tympanometry. The challenge diet with the suspected offending food(s) provoked a recurrence of serous otitis media in 66/70 patients (94%). CONCLUSIONS. The possibility of food allergy should be considered in all pediatric patients with recurrent serous otitis media and a diligent search for the putative food allergen made for proper diagnostic and therapeutic intervention.

Milk formulae in the prevention of food allergy.

 Guesry PR; Secretin MC; Jost R; Pahud JJ; Monti JC  Nestle technical Assistance Company, Vevey, Switzerland. Allergy Proc, 12: 4, 1991 Jul-Aug, 221-6

Abstract Because food allergy is frequent and severe, all possible means should be used to try to prevent its manifestations or at least to delay them until the child is older and stronger and therefore better able to follow an exclusion diet. The capacity of breast-feeding for preventing food allergy has been challenged in the past, but a consensus seems to be emerging now that breast-feeding can indeed prevent food allergy if it is started at birth and is exclusive for at least 4, and preferably 6, months. In the most "at-risk" babies the breast-feeding mother should try to eliminate the most potent allergens (eggs, fish, soya, nuts, and cow's milk) from her diet. If a substitute or a complement to breast milk is necessary, neither goat's milk nor soy milk formula are adequate. Heat treatment alone will not be sufficient to make cow's milk hypoallergenic. Only a combination of protein hydrolysis and managed heat treatment can make cow's milk hypoallergenic and retain its nutritional value. This nutritional value should be assessed by animal studies and also by studying infant growth. The hypoallergenicity of a formula can be studied in vitro and with animal tests, but only clinical trials on human infants will prove its efficacy.

Anaphylactic sensitizing power of selected infant formulas.

 Piacentini GL; Benedetti M; Spezia E; Boner AL; Bellanti JA   Ann Allergy, 67: 4, 1991 Oct, 400-2

Abstract The purpose of the present study was to evaluate the anaphylactic sensitizing power of cow milk, soy milk, casein hydrolysate, and a new cow collagen soy protein hydrolysate (CCSPH) infant formula in a guinea pig model of anaphylactic sensitization. Various groups of animals were fed these formulas for 37 days following which they were challenged intravenously either with the sensitizing constituent or one of the infant formulations. The results of these studies indicate a high degree of sensitizing capability of cow milk formula (80% fatal and 20% nonfatal) with reactions in guinea pigs challenged with BLG and no reactions when challenged with casein hydrolysate. In animals sensitized to soy formula there were only nonfatal reactions in 30% when challenged with soy protein. Casein hydrolysate and CCSPH were shown to be nonsensitizing. The results of these studies support he use of derivative infant formulas for the prevention of cow's milk hypersensitivity in infants.

Cow's milk allergy in an adult patient.

Koers WJ; van der Elst AM; van Dijk AG; Berrens L Ann Allergy, 1986 Mar, 56:3, 267-9

Abstract A 22-year-old female patient is described who was repeatedly hospitalised on account of severe asthmatic attacks presumably due to the ingestion of cow's milk or milk-containing products. There were no signs of gastrointestinal disturbance, but some urticaria and angioedema occurred. Strongly positive RASTs were observed in the blood serum against the proteins in cow's milk, bovine serum, egg white, cod fish, and house dust. The symptoms were successfully controlled by rigorous dietary measures.

Basophil histamine release in children with adverse reactions to cow milk.

Prahl P; Krasilnikof F; Stahl Skov P; Norn S Paediatric Department, University Hospital, Gentofte, Denmark. Allergy, 1988 Aug, 43:6, 442-8

Abstract  Basophil histamine release was examined in 26 children suspected of having cow milk allergy (CMA). Following oral challenge with cow milk, the initial adverse reaction reappeared in 20 children, the majority developing urticaria. The urticaria patients showed a high degree of correlation between the results of histamine test, RAST and skin test. Children with gastrointestinal symptoms reacted to milk challenge, but only a few showed a positive histamine test, RAST and skin test. Among the patients with atopic dermatitis, the tests gave mostly negative results, which was in accordance with the lack of response to a milk challenge. The results obtained by removal from and fixation to the cell surface of IgE indicate an IgE-mediated reaction in CMA, which, in connection with the correlation between histamine test and RAST or skin test, suggests basophil histamine release as a suitable method for testing Type I allergy in children suspected of CMA.

Specificity of the human IgE response to the different purified caseins in allergy to cow's milk proteins.

Bernard H; Crinon C; Yvon M; Wal JM   Int Arch Allergy Immunol, 1998 Mar, 115:3, 235-44

Abstract  Cow's milk is one of the most frequent food allergens. Whole casein appears to be highly allergenic. It corresponds to an association of four different proteins, alpha(s1)-, alpha(s2)-, beta- and kappa-caseins in approximate proportions of 40, 10, 40, and 10%, respectively. METHODS: These different components were thus purified and used as immobilized antigens in an original enzyme immunoassay to measure specific serum IgE response in a population of 58 children (median age 11 months) allergic to cow's milk who were sensitive to whole casein. RESULTS: A great variability was observed in the affinity and specificity of specific IgE responses in milk-allergic patients' sera. 85% of the patients presented IgE against each of the four caseins. Statistically higher amounts of specific IgE were found to be directed against the most abundant fractions (alpha[s1]- and beta-casein). Co- and/or cross-sensitization to the different caseins were seen in most of the patients sensitive to whole casein. CONCLUSION: These results suggest that both distinct and common epitopes may occur on these different caseins. The major site of phosphorylation which is the most conserved domain in three caseins could be involved in the IgE response to casein and in immunocross-reactivity between these proteins.

 Milk hypersensitivity--key to poorly defined gastrointestinal symptoms in adults.

 Pelto L; Salminen S; Lilius EM; Nuutila J; Isolauri E  Allergy, 1998 Mar, 53:3, 307-10

Abstract Lactose intolerance is a common adverse reaction to milk in adults, while milk hypersensitivity is a disorder of infancy. We hypothesized that milk hypersensitivity may cause many unspecific gastrointestinal disorders in adults. Twenty adults were subjected to double-blind, placebo-controlled milk challenge. Phagocyte activity, and Fc gamma and complement receptor expression of phagocytes were assayed, and serum total IgE, milk-specific IgE, and serum reactivity to milk protein were determined. The challenge increased phagocyte activity and complement receptor expression of phagocytes in subjects designated milk-hypersensitive, who had gastrointestinal symptoms from milk ingestion but normal lactose tolerance. The increase was not detected in lactose-intolerant or control subjects. The milk-hypersensitive group was also distinguished from the lactose-intolerant group by enhanced serum reactivity to milk protein. Only two out of nine milk-hypersensitive subjects had detectable milk-specific serum IgE. It is concluded that milk hypersensitivity in adults, occurring as gastrointestinal reactions, may be more common than previously thought.

Humoral immune response to cow's milk in children with cow's milk allergy. Relationship to the time of clinical response to cow's milk challenge.

Firer MA; Hoskings CS; Hill DJ  Int Arch Allergy Appl Immunol, 1987, 84:2, 173-7

Abstract In 47 infants and children aged 4-66 months with clinically proven cow's milk allergy and in a group of age-matched controls, serum IgG, IgA and IgM cow's milk-specific antibodies were determined with ELISA assays while IgE cow's milk-specific antibodies were measured with Pharmacia RAST. The patients were divided into three separate groups according to the time of clinical response to a standardized cow's milk challenge protocol. Immediate reactions (less than 45 min after challenge), which were mainly accompanied by urticarial skin eruptions, were associated with elevated IgE milk-specific antibody levels, indicating the involvement of an immediate hypersensitivity mechanism. Alternatively, intermediate reactions (1-20 h after challenge), which were mainly accompanied by vomiting and diarrhea, were not IgE-mediated. In the late reactions (greater than 20 h after challenge) both eczematous and gastrointestinal reactions were seen. Patients with eczematous eruptions also showed elevated IgE milk-specific antibody levels. IgG milk-specific antibody levels were similar in each of the patient groups but all groups were significantly lower than in the controls. Levels of IgA and IgM milk-specific antibodies were similar in patients and controls. The results indicate that different immunopathogenic mechanisms are operative in these subgroups of patients with cow's milk allergy.


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