Cow's Milk Challenge Research Articles

Whey and casein specific IgE and the cow's milk challenge test for atopic children.

We studied 30 atopic children who suspected of milk allergy by past history (age ranging from 1 yr 4 mo to 9 yr 6 mo, mean age: 5.03 yr.) diagnosed as having asthma, atopic dermatitis and/or allergic rhinitis. These 30 atopic children had been screened from the patients at our outpatient clinic by the Pharmacia CAP system RAST FEIA. All of them showed the presence of at least Class II (greater than 0.7 ku/l) IgE specific to proteins in cow's milk. Further analysis found IgE specific to alpha-lactoalbumin (alpha-LA) elevated in 1 patient (3.3%), 1 patient (3.3%) to beta-lactoglobulin (beta-LG), 4 patients (13.3%) to alpha-LA and beta-LG, 5 patients (16.7%) to casein, 8 patients (26.7%) to casein and alpha-LA, 11 patients (36.7%) to casein, alpha-LA and beta-LG. After 3 weeks' cow-milk-free diet, the patient's milk challenge test was performed at our outpatient clinic. According to the test result, none of these 30 atopic children showed clinical evidence of significant allergic reaction to cow's milk in the skin, the gastrointestinal tract or the respiratory tract either within two hours after the challenge test or within 3 days after they went home. We therefore conclude that: (1) No single major allergen is apparent in cow's milk: casein, alpha-LA and beta-LG all show a high proportion of positive reaction. (2) Many atopic children fully tolerate cow's milk, although they have high titer of IgE antibodies specific to cow's milk. The RAST test is only the first step to screen patients with suspected IgE-mediated allergies. To make sure, any positive reaction must be confirmed by the "golden standard" for diagnosis, i.e., the double-blind placebo-controlled food challenge.

Differences in skin‐prick and patch‐test reactivity are related to the heterogeneity of atopic eczema in infants

Current data indicate an obvious relation between food allergy and atopic eczema in infants. However, diagnostic methods for food allergy need to be supplemented. The objective was to study the relevance of food patch testing in the detection of food allergy in correlation with oral food challenge and skin prick tests in atopic infants. Infants with atopic eczema (n = 113) aged 2-24 months were studied. Each patient was subjected to double-blind, placebo-controlled, or open cow's milk challenge, and skin prick and patch tests. Polysensitization, as judged from skin test results, was common in patients with atopic eczema (79/113). Cow's milk challenge was positive in 54/113 infants; reactions were immediate in 36/54 and delayed in 18/54. Immediate-type reactions were associated with skin prick test positivity and delayed reactions with patch test positivity. Altogether 26% of the cow's milk-allergic infants were detected by patch testing only. Patch testing improved the accuracy of skin testing in the diagnosis of food allergy in infants with atopic eczema, but it needs to be standardized. Polysensitization appears to be more common than generally believed among infants with atopic eczema.

TUMOR NECROSIS FACTOR ALPHA, FAECAL MARKER OF FOOD ALLERGY IN CHILDREN WITH INTESTINAL SYMPTOMS

The aim of the study is the search for faecal markers of cow's milk allergy (CMA), as non-invasive means of diagnosis.and follow-up. It has been demonstrated by Heyman and al (Gastroenterology 1994; 106: 1514-1523) that in CMA, the production of tumor necrosis factor alpha (TNFα), cytotoxic on enterocytes, is stimulated in peripheral blood mononuclear cells by the presence of cow's milk protein (CMP). The cationic eosinophil protein (ECP) is released during IgE mediated reactions, which increase its blood level. We measured the concentration of these two cytokines in the stools of children with CMA manifested by intestinal symptoms. Fourteen patients, aged 4-60 months (mean 17±15) and on cow's milk elimination diet, were included. Stool samples were collected and immediately frozen, one before a cow's milk challenge and another one after the challenge, either simultaneously to the occurrence of symptoms or 15 days after the challenge in the absence of reaction. Control subjects were 10 children aged 9-36 months (mean 20±8) with no bowel disorder or familial history of atopic disease. Cytokines measurements were performed on defrost samples, after extraction with PBS/PMSF 0,01 M buffer, ultracentrifugation and collection of the supernatant, using ELISA (Medgenix) for TNFα and CAP-System (Pharmacia) for ECP. Results were expressed per mg of N2 in stool, in order to avoid bias from stool hydration. During cow's milk challenge, 6 patients had a clinical reaction (group Patient I) and 8 patients had no reaction, being considered as having recovered (group Patient II). The concentration of faecal TNFα before challenge was comparable in groups Patient I and Control, 7±7.9 vs 4.2±1.9 pg/mg N2, p=0.27. It increased significantly after challenge in group Patient I, 17.2±13.9 vs 7±7.9 pg/mg N2, p=0.01, and the level after challenge was significantly higher than in the Control group, p=0.007. Faecal TNFα concentration was not altered after challenge in group Patient II, 3.4±2.9 vs 3.3±3.2 pg/mg N2, p=0.98. Faecal ECP concentration did not exhibit any variation. In conclusion, the increase of faecal TNFα after challenge is consistent with the involvement of this cytokine in the immune reaction in CMA with intestinal symptoms, in contrast with ECP. The measurement of faecal TNFα may constitute a non-invasive method of diagnosis and follow-up of CMA.

EARLY FEEDING OF COW'S MILK FORMULA - A RISK FOR COW'S MILK ALLERGY

Feeding of cow's milk formula during neonatal life, particularly in delivery hospitals, has been incriminated as a major factor in the development of cow's milk allergy (CMA), the proof being, however, defective and coincidental. We examined prospectively, in a double-blind fashion, the effects of different feeding regimens given in delivery wards on the development of CMA in a large unselected group of newborn infants. Altogether 6211 healthy, term infants of mothers, who volunteered to the study within 12 hours from the delivery, in three delivery hospitals entered the study. In addition to breastfeeding, 5236 (84%) infants were given supplemental milk at hospital. Three different supplementary feeds were used. They were coded and changed every month; different delivery hospital used different supplements each months. The three study supplements were: pasteurized, pooled, human milk (HM), adapted, liquid cow's milk formula (AF; Tutteli, Valio, Finland) or whey hydrolysate formula (HF; Pepti-Junior, Nutricia Fennica, The Netherlands). Exact time and dose of every feed of the infants in the study was recorded in the delivery ward. The control group consisted of exclusively breast-fed infants. The mothers recorded the feeding regimen of the infants daily during the first 8 weeks. Family history of atopy was recorded during the stay at the hospital. If the child presented with symptoms suggestive to CMA, a milk challenge test was performed after 2-4-week elimination period in the hospital in a carefully scrutinized way during one day, the challenge continued at home, all infants were seen five days after the beginning of the challenge test. Out of 248 cow's milk challenges performed, 118 (48%), were positive, giving an incidence of 1.9% of CMA in the whole study group. In the feeding groups the results were: Table The group on AF had higher incidence of CMA than those in the other three groups (p=0.02). The difference was significant also between AF group and combined HF and HM groups; 2.6% vs 1.6% (p=0.02). Infants with CMA were equally often breast-fed exclusively for the first eight weeks in the three study groups (42% in AF, 42% in HF and 48% in HM groups). In the control group the percentage was significantly larger (94%). The incidence of allergy in family members of infants in different groups was similar. The study proves that adapted cow's milk formula given to a newborn infant during the first few days increases the risk for CMA. Hydrolysed whey formula and pasteurized human milk were as safe as exclusive breast-feeding during the first days of life. On the other hand. the exclusive breast-feeding during the first eight weeks did not protect from the CMA.

Oral cow milk challenge abolishes antigen-specific interferon-gamma production in the peripheral blood of children with atopic dermatitis and cow milk allergy

Oral cow milk challenge abolishes antigen-specific interferon-gamma production in the peripheral blood of children with atopic dermatitis and cow milk allergy

Oral cow milk challenge abolishes antigen‐specific interferon‐γ production in the peripheral blood of children with atopic dermatitis and cow milk allergy

A major feature of atopic dermatitis (AD) is the propensity to generate IgE to environmental antigens. Despite extensive information on IgE dysregulation in AD, the nature of immune responses to ingested allergens is poorly characterized. To determine the clinical and immunological responses to food in AD patients. To characterize the type and timing of clinical reactions to oral cow milk, 83 AD patients aged 2 to 60 months were subjected to double-blind placebo-controlled food challenge (DBPCFC). IFN-gamma and IL-4 production by their peripheral blood mononuclear cells (PBMC) was determined before and after DBPCFC. Of 50 patients positive to DBPCFC. 46% manifested exanthematous-type immediate-onset reactions and 54% eczematous-type late-onset reactions. In either group, the production of IL-4 and IFN-gamma by Concanavalin A-stimulated PBMC was comparable before and after DBPCFC. For immediate-reacting patients, the median IFN-gamma production by milk-stimulated PBMC was 11.5 (4.2-17.2) pg/ml as against 2.3 (0.2-5.7) pg/ml by unstimulated PBMC, P = 0.0008 before DBPCFC, and 4.6 (2.8-10.3) pg/ml. vs 4.2 (1.7-9.0) pg/mL, p = 0.40, correspondingly after DBPCFC. Before DBPCFC, immediate-reacting but not late-reacting patients were found to be capable of allergen-specific IFN-gamma production in vitro, indicating the heterogeneity in AD patients. After DBPCFC, the IFN-gamma generation abolished, indicating the effect of oral allergen exposure on IFN-gamma producing responses of AD patients.

Combined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis

BACKGROUND: Early recognition of dietary allergies in infants with atopic dermatitis is essential for avoidance of unnecessary elimination diets, amelioration of the skin disease, and secondary prevention of the development of multiple food allergies. Simple and accurate methods of identifying provocative foods are urgently needed. METHODS: The usefulness of skin prick and patch tests as indicators of cow milk allergy was evaluated in 183 patients ranging in age from 2 to 36 months with double-blind, placebo-controlled ( n = 118) or open ( n = 65) cow milk challenges. RESULTS: The oral cow milk challenges were interpreted as positive in 54% of both challenge types. Positive challenge rapidly elicited pruritus, urticaria, and/or exanthema in 49% of cases and delayed-onset eczematous lesions in 51%. The skin prick and patch tests gave markedly discrepant results; prick tests were positive in 67% of the cases with acute-onset reactions to milk challenge, whereas patch tests tended to be negative. Patch tests were positive in 89% of those with delayed-onset reactions, although prick tests were frequently negative. CONCLUSIONS: The observations indicate that IgE and T cell-mediated responses to cow milk can be distinguished in atopic dermatitis. Parallel skin testing with combined prick and patch tests can significantly enhance the accuracy in diagnosis of specific dietary allergies in patients with atopic dermatitis. (J A LLERGY C LIN I MMUNOL 1996;97:9-15.)

Increased intestinal sugar permeability after challenge in children with cow's milk allergy or intolerance.

The diagnosis of cow's milk allergy or intolerance (CMAI) is based on clinical improvement on exclusion diet and relapse after challenge with milk. The aim of this work was to investigate the value of the cellobiose/mannitol (C/M) sugar permeability test, performed before and after cow's milk challenge, as a tool for the diagnosis of CMAI. Thirty-two patients underwent milk challenge at a median age of 13 months (range 3-84 months). A dual sugar (C/M) permeability test with an iso-osmolar solution was performed before and 24 h after challenge. Of the 10 patients who developed symptoms after challenge, nine showed increased postchallenge C/M ratio, whereas such an increase was observed in only one of the 22 nonrelapsed subjects. The postchallenge C/M ratio increase in relapsed subjects is to be attributed to both higher cellobiose and lower mannitol urinary excretion. These results suggest the use of the sugar permeability test, in addition to clinical observation, as an aid in the evaluation of provocation tests in infants with suspected CMAI.

Evidence for eosinophil activation in cow's milk allergy

To assist in identifying pathogenetic mechanisms in different clinical manifestations of cow's milk allergy (CMA), the involvement of eosinophil cells in immunoinflammatory reactions was evaluated. The study population comprised 28 patients, aged from 5.8 to 43.0 months, who had challenge-proven CMA, manifested either cutaneously (n = 17) or gastrointestinally (n = 11). A clinical cow's milk challenge was performed in hospital after a 4 week cow's milk elimination period. Eosinophil activation in vivo was studied by measuring the serum level of eosinophil cationic protein (ECP) before the oral cow's milk challenge, mean (SD) 27 (12) hours after commencing the challenge and one week later. These results were compared to those of 80 non-allergic age-matched controls. During the challenge, the level of ECP increased from 6.2 (4.5, 8.0) micrograms/L to 20.0 (9.5, 30, 4) micrograms/L in CMA patients with skin manifestations but not in those with gastrointestinal symptoms. The increase was shown to be transient. We conclude that eosinophil degranulation is an important immunologic mechanism leading to allergic inflammation in cutaneously manifested CMA.

New concepts of allergy to cow's milk.

CMA is a diagnostic and therapeutic problem in the field of pediatrics. The response to oral cow's milk challenge was evaluated in patients with suspective CMA. To investigate immune mechanisms in different subtypes of CMA, suppressor activity, in vitro IFN-gamma and IL-4 generation, eosinophil activation and humoral immune response were measured. Also, changes in the function of the immune system were evaluated when patients had clinically recovered from CMA. The results of different measurements were correlated with the patients' clinical response to cow's milk challenge. The prechallenge suppressor activity was found to be low in patients with challenge-proven CMA when compared with those clinically negative to oral cow's milk challenge but had normalized after a 4-18 month milk-elimination period in patients who had recovered from CMA. IFN-gamma generation was low in patients with active CMA but had clearly enhanced in patients recovering from CMA. The serum concentration of ECP increased significantly during oral cow's milk challenge in patients with cutaneously manifested CMA. Measured by the ELISPOT method, the patients with active CMA mounted a high, non-antigen-specific immune response but were unable to direct the antigen-specific response, especially in the IgA class. After a follow-up of a mean 13.5 months on cow's milk elimination diet, the immune response to cow's milk antigens had developed in patients who had recovered from CMA. The development in the capacity to mount an adequate immune response to specific protein antigens, especially in the IgA class, can be interpreted as deriving from the development in T-lymphocyte regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats

Background: Lactobacilli constitute a major part of the microflora throughout the gastrointestinal tract. This study aimed to investigate the effect of lactobacilli on the gut mucosal barrier. Methods: Rat pups were divided into three experimental feeding groups at the age of 14 days. In addition to normal maternal milk, group “milk” received a daily gavage of cow milk, group “milk-GG” received Lactobacillus casei strain GG with cow milk, and controls were gavaged with the same volume of water. At 21 days, the absorption of horseradish peroxidase across patch-free jejunal segments and segments containing Peyer's patches was studied in Ussing chambers. Results: The mean absorption of intact horseradish peroxidase expressed in ng· h−1·cm−2, was significantly different in the study groups in both patch-free segments (controls, 9 [95% confidence interval, 7–12]; milk, 72 [60–87]; and milk-GG, 15 [4–52]) and in segments containing Peyer's patches (controls, 3 [1–17]; milk, 80 [43–151]; and milk-GG, 15 [4–56]). There was a significant increase in the frequency of cells secreting antibodies to β-lactoglobulin (enzyme-linked immunospot assay) in the milk-GG group. Conclusions: Prolonged cow milk challenge in suckling rats increases gut permeability to intact proteins, whereas Lactobacillus GG counteracts this permeability disorder. The results suggest a link between the intensity of the antigenspecific immune response and stabilization of the mucosal barrier.

Effect of disodiumcromoglycate on intestinal permeability changes and clinical response during cow's milk challenge

Oral disodiumcromoglycate (DSCG) has been used for many years in the prevention of food allergic reactions. The reported effectiveness varies widely and little is known about the mode of action. The aim of this study was to evaluate the effect of DSCG pretreatment (2 x 100 mg) on intestinal permeability (IP), as measured with a sugar absorption test (SAT), in relation to the clinical response during food challenge in 30 children suspected of cow's milk allergy. In the SAT the urinary Lactulose/Mannitol (L/M) ratio was measured after oral administration of these compounds. DSCG pretreatment did not alter the number of clinically positive challenges. Children with clinically positive challenges showed a significant increase in the L/M ratio with placebo pretreatment as compared to children with clinically negative challenges (p = 0.0008). This difference was reduced to nonsignificant levels after DSCG pretreatment (p = 0.07). We conclude that DSCG in this dosage probably reduces the local intestinal response but does not prevent the extraintestinal reactions.

The role of cow's milk protein intolerance in steroid-resistant nephrotic syndrome.

The role of cow's milk protein intolerance in steroid-resistant nephrotic syndrome was evaluated in 17 children. Cow's milk was excluded from the diet for at least 14 days without changing previously ineffective prednisone dosage. Six patients with minimal change or mesangial proliferation went into remission 3 to 8 days after elimination of cow's milk. After a period of 2-3 weeks of remission, cow's milk challenge was positive in three patients. After one year on a cow's milk-free diet, two of six patients became milk tolerant and are in remission of NS, one of six became steroid-dependent, two of six are still unable to tolerate cow's milk and are in remission on a cow's milk-free diet and one of six children was lost from observation. The role of cellular mechanisms in steroid-resistant nephrotic syndrome is suggested.

Cow's milk provocation induces an immune response to unrelated dietary antigens.

The activation of immune mechanisms was evaluated by the solid phase enzyme linked immunoassay of immunoglobulin and specific antibody secreting cells in 27 patients (aged from nine to 69 months), subjected to a diagnostic cow's milk challenge or a rechallenge. A significant rise in the total number of immunoglobulin secreting cells was associated with clinically positive (n = 17), but not a negative (n = 10) cow's milk challenge in all immunoglobulin isotypes. The number of specific antibody secreting cells against beta lactoglobulin, mean (95% confidence interval), increased from 4.8 (1.4, 15.8) to 16.9 (5.5, 52.7) specific antibody secreting cells/10(6) cells, p = 0.02, and against casein from 2.2 (0.8, 6.1) to 7.5 (2.5, 22.5) specific antibody secreting cells/10(6) cells, p = 0.01, in patients positive to challenge in the IgM class only, indicating defective immune elimination of milk antigens. In addition to the specific immune response to cow's milk antigens, an increase in IgM specific antibody secreting cells against an unrelated dietary antigen, gliadin, from 8.2 (2.1, 31.1) to 31.0 (14.2, 67.6) specific antibody secreting cells/10(6) cells, p = 0.01, was observed. These results indicate that cow's milk challenge, in patients who have cow's milk allergy, induces a strong non-antigen specific immune response that includes a response against unrelated antigens concomitantly present in the intestinal lumen. Activation of such immune mechanisms may hence reflect increased antigenic load caused by the immune mediated lesion in the gut mucosa.

The status of lactose absorption in Hong Kong Chinese children.

Lactose malabsorption was investigated in 169 Chinese children aged between two and 16 years using the breath hydrogen test. The challenge was either lactose solution (1 g/kg) or cow's milk (10 ml/kg). Overall, 68% of the children showed a significant increase in breath hydrogen following the lactose challenge while only 17% showed an increase after the cow's milk challenge and 13% after both challenges. The number of malabsorbers increased significantly (p less than 0.001) with age and no associated gastrointestinal symptoms or signs were found in any of the children following the challenges, suggesting a gradual and partial loss of intestinal lactase activity. We conclude that the prevalence of lactose malabsorption in Hong Kong children is very high using the standard lactose tolerance test but when a more realistic amount of lactose and a natural medium such as a glass of milk is used as the challenge, the number of malabsorbers becomes small and clinically insignificant.

Low Colostral IgA Associated with Cow's Milk Allergy

During a nutritional study of 198 infants, seven became allergic to cow's milk. The seven infants showed acute cutaneous manifestations during cow's milk challenge tests in hospital and six had increased levels of IgE cow's milk-specific antibodies. Neither in the development of the levels of immunoglobulins G, A and M, nor in that of the cow's milk-specific antibodies of these isotypes did these seven patients differ from the remaining infants. Beta-lactoglobulin content and levels of cow's milk-, and beta-lactoglobulin-specific antibodies and of immunoglobulins A, G and M were measured in samples of colostrum and milk from the mothers of the seven infants with cow's milk allergy and from a comparison group (non-atopic mothers of non-atopic infants). The milk of the mothers whose infants became allergic to cow's milk contained less IgA through the lactation: 95% confidence intervals of the groups did not overlap. The difference was most marked in the colostrum. All other measurements were similar in the two groups. This suggests that an infant is more likely to develop cow's milk allergy if the mother's colostrum had a low total IgA content.

Gastrointestinal permeability in children with cow's milk allergy: effect of milk challenge and sodium cromoglycate as assessed with polyethyleneglycols (PEG 400 and PEG 1000).

Sixteen children with immediate-type cow's milk allergy were challenged with increasing amounts of cow's milk. Gastrointestinal permeability was investigated before and after challenge by the 6-hr urinary recovery of a mixture of different-sized polyethyleneglycols (PEG 400 and PEG 1000). The results were related to clinical symptoms in the individual patients. The majority of the children displayed changed permeability characteristics after the challenge, both with respect to the maximum uptake of a small test molecule (usually 370 dalton PEG) and/or a large molecule (1074 dalton PEG), and to size-dependent exclusion of probe molecules. When corrected for the dose of milk taken, the children showing the most severe immediate-type symptoms also displayed the greatest alteration of permeability. Treatment with sodium cromoglycate (SCG) before the challenge diminished the effect on the uptake of probe molecules, usually decreased the severity of elicited symptoms, allowing about a ten-fold increase in the milk dose. Cow's milk challenge in healthy children caused only minor permeability changes, whereas challenge in the sensitized subjects significantly changed (increased or decreased) the recovery of a large test molecule. The difference between healthy and allergic subjects was most obvious when correcting for dose of milk ingested. We conclude that oral challenge with cow's milk in allergic subjects affects the mucosal barrier, and peroral treatment with SCG moderates immediate hypersensitivity reactions with respect to both tolerated antigen dose and intestinal permeability properties.

COW'S MILK SPECIFIC ANTIBODIES, SERUM IMMUNOGLOBULINS COMPLEMENT FRACTIONS, LYMPHOCYTE SUBSETS AND STIMULATION OF LYMPHOCYTES IN COW'S MILK ALLERGY

A cow's milk (CM) challenge test was done to 34 children aged from 3 to 51 months suspected to have CM allergy. Nineteen of them had clinical relapse during the CM challenge: 16 (84 %} showed cutaneous, 4 (21 %} gastrointestinal and 6 {32 %) respiratory manifestations. Fourteen showed immediate reaction within an hour of ingestion or skin contact with CM, in five the reaction took place later. Before and during the challenge test we measured serum levels of immnunoglobulins G, A, M and E, complement fractions 3 and 4, of class specific cow's milk antibodies, numbers of lymphocyte subsets and the stimulation of lymphocytes in whole blood by photohemaagglutinin, concanavalin A and betalactoglobulin. Of the 19 patients with positive CM challenge, 11 (61 %) showed increased levels of CM specific IgE antibodies, and of the remaining 8, betalactoglobulin stimulation was positive in 5, in half the helper/suppressor ratio increased during the challenge and 3 had decreased serum level of C3. None of the laboratory methods used could alone discriminate between children who reacted to CM in challenge and who did not. The combination of increased level of CM specific IgE with decreased serum IgG and C3 gave the sensitivity of 83 % and specificity of 55 % to predict clinical reaction.

Cowʼs Milk Protein-Sensitive Enteropathy

Summary: Intestinal biopsy is an essential procedure in the diagnosis of cow's milk protein-sensitive enteropathy. The number and timing of biopsies, however, is still controversial. Twenty-two infants who were clinically suspected of having cow's milk protein intolerance were put on a milk-free diet, during which they all improved. In the first 14 infants (Group I), milk withdrawal lasted 6-8 weeks; in the following 8 infants (Group II), milk withdrawal lasted 3.5-4 months. At the end of the withdrawal period, each patient was submitted to an oral lactose tolerance test and then to a first jejunal biopsy, followed by a cow's milk challenge, and a second biopsy (1-2 days later). None of the infants showed evidence of lactose intolerance, but they all reacted adversely to milk reintroduction. In Group I, the distribution of mucosae from grade 0 (normal) to III was almost the same before and after challenge (p > 0.5); this is considered to be due to the severe mucosal damage still present in prechallenge biopsies. In Group II, however, a significant difference was found in the distribution of mucosae before and after challenge (p < 0.05), and a deterioration could be observed in each case after challenge. Intraepithelial lymphocyte counts and mitotic index determinations before and after milk reintroduction were of no diagnostic value in either group. It is suggested that the diagnosis of cow's milk protein-sensitive enteropathy may rely on two biopsies, the first after a period of 3.5-4 months on milk-free diet and the second following milk challenge.

Cowʼs Milk Protein-Sensitive Enteropathy

Intestinal biopsy is an essential procedure in the diagnosis of cow's milk protein-sensitive enteropathy. The number and timing of biopsies, however, is still controversial. Twenty-two infants who were clinically suspected of having cow's milk protein intolerance were put on a milk-free diet, during which they all improved. In the first 14 infants (Group I), milk withdrawal lasted 6-8 weeks; in the following 8 infants (Group II), milk withdrawal lasted 3.5-4 months. At the end of the withdrawal period, each patient was submitted to an oral lactose tolerance test and then to a first jejunal biopsy, followed by a cow's milk challenge, and a second biopsy (1-2 days later). None of the infants showed evidence of lactose intolerance, but they all reacted adversely to milk reintroduction. In Group I, the distribution of mucosae from grade 0 (normal) to III was almost the same before and after challenge (p greater than 0.5); this is considered to be due to the severe mucosal damage still present in prechallenge biopsies. In Group II, however, a significant difference was found in the distribution of mucosae before and after challenge (p less than 0.05), and a deterioration could be observed in each case after challenge. Intraepithelial lymphocyte counts and mitotic index determinations before and after milk reintroduction were of no diagnostic value in either group. It is suggested that the diagnosis of cow's milk protein-sensitive enteropathy may rely on two biopsies, the first after a period of 3.5-4 months on milk-free diet and the second following milk challenge.