Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy. Clinical course of cow's milk protein allergy/intolerance and atopic diseases in childhood. An extensively hydrolysed casein-based formula for infants with cows' milk protein allergy: tolerance/hypo-allergenicity and growth catch-up. Markers of gut mucosal inflammation and cow’s milk specific immunoglobulins in non-IgE cow’s milk allergy Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study. Evaluation of pancreatic function development after hydrolyzed protein-based and soy-based formulas in unweaned infants. Probiotics: a novel approach in the management of food allergy. The acquisition of tolerance toward cow's milk through probiotic supplementation: a randomized, controlled trial. Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow's milk allergy/intolerance and atopic dermatitis. Ass's milk in children with atopic dermatitis and cow's milk allergy: crossover comparison with goat's milk. Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy. Specific antibodies to cow’s milk proteins in infants: effect of early feeding and diagnosis of cow’s milk allergy The development and prediction of atopy in high-risk children: follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance. Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants. Probiotics Have a Different Immunomodulatory Potential in vitro versus ex vivo upon Oral Administration in Children with Food Allergy A randomized, single-blind and crossover study of an amino acid-based milk formula in treating young children with atopic dermatitis. Cow's Milk–Associated Gastrointestinal Symptoms Evaluated Using the Double-Blind, Placebo-Controlled Food Challenge Nutritional Value of a Rice-Hydrolysate Formula in Infants with Cows' Milk Protein Allergy: A Randomized Pilot Study Rectal Bleeding in Infancy: Clinical, Allergological, and Microbiological Examination Synbiotics in Children with Cow's Milk Allergy: A Randomized Controlled Trial A new protocol for specific oral tolerance induction in children with IgE-mediated cow's milk allergy. Combined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis. Oral desensitization in children with milk and egg allergies obtains recovery in a significant proportion of cases. A randomized study in 60 children with cow's milk allergy and 90 children with egg allergy.
Cow 's milk protein allergy ( CMPA ) is best treated by complete elimination of cow 's milk from the diet . For infants with CMPA who can not be breast-fed , formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow 's milk-based formulas . In this study , we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose ( eHF ) with those who were fed an amino acid formula ( AAF ) . This was a prospect i ve , multi-center , r and omized , reference-controlled study . Seventy-seven infants < 12 months old with suspected CMPA were enrolled . In 66 of these , CMPA was confirmed by oral challenge in a double-blind , placebo-controlled food challenge ( DBPCFC ) or by a medical history of severe allergic reaction to cow 's milk and a positive skin prick test . These infants were then tested for their reaction to eHF and AAF in a DBPCFC . All infants tolerated both formulas and were r and omized to receive either eHF ( n = 34 ) or AAF ( n = 32 ) for 180 days . Growth ( weight , length , and head circumference ) and tolerance [ skin , gastro-intestinal , and respiratory tract symptoms of allergy ] were evaluated after 30 , 60 , 90 , and 180 days . There were no significant differences between the two groups in any of the growth measurements . Length and head circumference were similar to Euro-growth st and ards , but weight was slightly lower . Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups . However , whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF , there was a slight decrease in those fed AAF . Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools . The new eHF is safe and well tolerated in infants diagnosed with CMPA A cohort of 1,749 newborns from the municipality of Odense , born during 1995 at the Odense University Hospital , were followed up prospect ively for the development of cow 's milk protein allergy/intolerance ( CMPA/I ) during the first year of life . Once a diagnosis of CMPA/I was confirmed , a milk-free diet was continued until a new milk challenge had shown development of tolerance . All infants with CMPA/I were rechallenged at 12 months of age and , in the event of continued clinical sensitivity to cow 's milk protein , controlled rechallenges were performed every 6 months up to 3 years of age ; and thereafter every 12 months until the age of 15 years . From the same birth cohort , 276 infants were r and omly selected at birth for prospect i ve non-interventional follow-up in order to investigate the natural course of sensitization and development of atopic disease during childhood . St and ardized question naires on atopic heredity , environmental factors and presence of atopic symptoms were answered at 0 , 6 , 12 and 18 months and at 5 , 10 and 15 years of age . Interviews on atopic history and environmental factors as well as physical examination were carried out at 18 months , 5 , 10 and 15 years of age . Skin prick test and specific sIgE ( Pharmacia CAP ) testing were performed at 18 months , 5 , 10 and 15 years of age against a panel of inhalant allergens ( birch , grass , mugwort , dog , cat , horse , Dermatophagoidespteronyssinus , Dermatophagoides farinae , alternaria and cladosporium herbarum ) . Furthermore , lung function measurements were performed in children when 10 and 15 years of age . Based on controlled milk elimination and challenge procedures , the diagnosis of CMPA/I was confirmed in 39 out of 117 infants , with symptoms suggestive of CMPA/I , thus result ing in a 1-year incidence of CMPA/I of 2.2 % . The overall prognosis of CMPA/I was good , with a total recovery of 56 % at 1 year , 77 % at 2 years , 87 % at 3 years , 92 % at 5 and 10 years and 97 % at 15 years of age . In children younger than 10 years of age , 41 % developed asthma and 31 % rhinoconjunctivitis . Children with non-IgE-mediated CMPI had a good prognosis , whereas children with IgE-mediated CMPA in early childhood had a significantly increased risk for persistent CMPA , development of other food allergies , asthma and rhinoconjunctivitis . During early infancy , recurrent wheezing was the most prevalent disease ( 20 % ) , followed by atopic dermatitis ( 14 % ) and food allergy ( 7 % ) at 18 months of age . Physician diagnosed asthma increased from 2 % at 1.5 years of age to 9 % at 10 years of age .  Rhinoconjunctivitis  increased from < 1 % at 1.5 years of age to 9 % at 10 years of age . Overall , the current prevalence of any atopic disease was 20 % at 1.5 years of age , declining to 14 % at 5 years of age and followed by an increase to 25 % at 10 years of age . Sensitization to inhalant and /or food allergens ( specific IgE of > or = class 2 ; CAP RAST ) showed a low rate of sensitization among asymptomatics ( 3 % , 10 % and 12 % ) compared with higher rates of sensitization of 8 % , 39 % and 30 % among symptomatic atopics at 1.5 , 5 and 10 years of age respectively . The highest rate of sensitization ( 53 % ) was found among children with current asthma at 10 years of age Children with cows ' milk protein allergy ( CMPA ) are at risk of insufficient length and weight gain , and the nutritional efficacy of hypo-allergenic formulas should be carefully assessed . In 2008 , a trial assessed the impact of probiotic supplementation of an extensively hydrolysed casein-based formula ( eHCF ) on acquisition of tolerance in 119 infants with CMPA . First analysis of the study results showed that the studied formula allowed improvement of food-related symptoms . The scoring of atopic dermatitis ( SCORAD ) index was assessed at r and omisation and after 6 months of feeding . A post hoc analysis was performed using WHO growth software 's nutritional survey module ( WHO Anthro version 3.2.2 ) . All infants who were fed the study formula tolerated it well . The SCORAD index significantly improved from r and omisation to 6 months of feeding with the study formula . Anthropometric data indicated a significant improvement in the weight-for-age , length-for-age and weight-for-length z scores , as well as in the restoration of normal BMI . The probiotic supplementation did not show any impact on these parameters . The present data showed that this eHCF was clinical ly tolerated and significantly improved the SCORAD index and growth indices Background Allergy to cow ’s milk protein ( CMP ) may cause gastrointestinal ( GI ) symptoms in the absence of CMP specific IgE. The immunological mechanisms involved in such disease are not fully understood . Therefore we examined markers of gut mucosal inflammation and the immunoglobulin profiles in children with Gl symptoms suspected of cow ’s milk protein allergy ( CMPA ) . Patients and methods We prospect ively recruited infants and young children ( n = 57 ; median age 8.7 months ) with gastrointestinal complaints suspected of CMPA . The diagnosis of CMPA was made using the double-blind , placebo-controlled food challenge . Serum and stool sample s were collected during CMP-free diet and after both placebo and active challenges . We analyzed the stool sample s for calprotectin , human β-defensin 2 and IgA. In serum , we analyzed the levels of β-lactoglobulin and α-casein specific IgA , and IgG antibodies ( total IgG and subclasses IgG1 and IgG4 ) . Control group included children with e.g. dermatological or pulmonary problems , consuming normal diets .  Results Fecal calprotectin levels were higher in the challenge positive group ( n = 18 ) than in the negative ( n = 37 ) , with respective geometric means 55 μg/g [ 95 % confidence interval 38–81 ] and 29 [ 24–36 ] μg/g ( p = 0.0039 ) , during cow ’s milk free diet . There were no significant inter-group differences in the fecal β-defensin and IgA levels . The CMP specific IgG and IgA were not elevated in patients with CMPA , but the levels of β-lactoglobulin-IgG4 ( p = 0.0118 ) and α-casein-IgG4 ( p = 0.0044 ) , and total α-casein-IgG ( p = 0.0054 ) and -IgA ( p = 0.0050 ) in all patient sample s ( regardless of CMPA diagnosis ) were significantly lower compared to the control group using dairy products . Conclusions Despite cow ’s milk elimination in children intolerant to cow ’s milk there might be ongoing low- grade inflammation in the gut mucosa . CMP specific IgG or IgA should not be used to diagnose non-IgE CMPA . The observed frequency of impaired CMP specific total IgA , IgG and IgG4 production in patients following cow ’s milk free diet warrants further studies In a prospect i ve study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk , a casein hydrolysate ( Nutramigen ) or a new ultrafiltrated whey hydrolysate ( Profylac ) on the development of cow milk protein allergy/intolerance ( CMPA/CMPI ) was assessed and compared . All the infants had biparental or severe single atopic predisposition , the latter combined with cord blood IgE > or = 0.5 kU/L. At birth all infants were r and omized to Nutramigen or Profylac , which was used when breastfeeding was insufficient or not possible during the first 6 months of life . During the same period this regimen was combined with avoidance of solid foods and cow milk protein . All mothers had unrestricted diets and were encouraged to do breastfeeding only . Moreover , avoidance of daily exposure to tobacco smoking , furred pets and dust-collecting material s in the bedroom was advised . The infants were followed prospect ively from birth to 18 months of age . All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI . A total of 154 ( 97 % ) were followed up and 141 followed the diet strictly . Eighty-eight ( 62 % ) of the infants were breastfed for at least 6 months , 20 ( 14 % ) were breastfed exclusively , 59 and 62 had varying amounts of Nutramigen or Profylac respectively . CMPA/CMPI was diagnosed in 1/20 , 1/59 and 3/62 in the breastfed , the Nutramigen and Profylac groups respectively , but 1 of the latter also had Nutramigen . None of the infants showed reactions against  Nutramigen or Profylac . In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk . ( ABSTRACT TRUNCATED AT 250 WORDS AIMS Different protein sources could determine differences in the maturation of the exocrine pancreas in humans during the first months after birth ; however , no studies have been carried out in man to evaluate the effect of a hydrolyzed protein diet on exopancreatic function . Our aim was therefore to determine the effect of two different milk formulas on pancreatic secretion in patients with cow 's milk protein allergy ( CMPA ) . METHODS We selected 12 infants ( median age , 3.0 months ) , fed for 6 weeks with a hydrolyzed casein-based formula , and 14 infants ( median age , 3.0 months ) who received a soy-protein based formula over the same period . As controls , two groups of age-matched infants with no gastrointestinal disease and receiving a free diet  were studied . In the patients with CMPA a secretin-cerulein test was performed at the commencement of the diet and after 6 weeks ; in the controls the same test was performed only once . Enzyme concentrations and outputs of trypsin , chymotrypsin , lipase , and phospholipase were assayed . RESULTS No significant difference was observed between the two groups of patients with CMPA for any of the enzymes studied , either at base line or after 6 weeks of diet . No difference was recorded between CMPA patients and age-matched controls on a free diet either . In both CMPA groups there was a significant increase over basal values in trypsin , chymotrypsin , and lipase concentrations after 6 weeks . Furthermore , there was a significant positive correlation between the age of the patients and enzyme concentrations . Mean daily weight gain was 27.4 + /- 3.9 g with hydrolyzed casein and 27.2 + /- 3.5 g in soyfed patients . CONCLUSIONS It is suggested that the diets with different protein content used in subjects with CMPA did not determine any difference in the stimulation of proteolytic and lipolytic pancreatic enzymes BACKGROUND The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier . We have previously shown that a human intestinal floral strain , Lactobacillus GG ( ATCC 53103 ) , promotes local antigen-specific immune responses ( particularly in the IgA class ) , prevents permeability defects , and confers controlled antigen absorption . OBJECTIVE The aim of this study was to evaluate the clinical and immunologic effects of cow 's milk elimination without ( n = 14 ) and with ( n = 13 ) the addition of Lactobacillus GG ( 5 x 10(8 ) colony-forming units/gm formula ) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow 's milk allergy . The second part of the study involved 10 breast-fed infants who had atopic eczema and cow 's milk allergy . In this group Lactobacillus GG was given to nursing mothers . METHODS The severity of atopic eczema was assessed by clinical scoring . The concentrations of fecal alpha 1- antitrypsin , tumor necrosis factor-alpha , and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention . RESULTS The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG . The concentration of alpha 1-antitrypsin decreased significantly in this group ( p = 0.03 ) but not in the group receiving the whey formula without Lactobacillus GG ( p = 0.68 ) . In parallel , the median ( lower quartile to upper quartile ) concentration of fecal tumor necrosis factor-alpha decreased significantly in this group , from 709 pg/gm ( 91 to 1131 pg/gm ) to 34 pg/gm ( 19 to 103 pg/gm ) ( p = 0.003 ) , but not in those receiving the extensively hydrolyzed whey formula only ( p = 0.38 ) . The concentration of fecal eosinophil cationic protein remained unaltered during therapy . CONCLUSION These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy , and by alleviating intestinal inflammation , may act as a useful tool in the treatment of food allergy BACKGROUND Cow 's milk allergy ( CMA ) is the most frequently diagnosed food allergy in infancy . In general , patients have a good prognosis because the majority acquire tolerance within the first years . Interventions have been proposed to accelerate tolerance and reduce morbidity . Probiotic supplementation could be effective through modulation of the immune system . OBJECTIVE We sought to determine whether supplementation with a combination of probiotics ( Lactobacillus casei CRL431 and Bifidobacterium lactis Bb-12 ) accelerates tolerance to cow 's milk ( CM ) in infants with CMA . METHODS We performed a double-blind , r and omized , placebo-controlled trial in 119 infants with CMA . Infants received CRL431 and Bb-12 supplemented to their st and ard treatment of extensively hydrolyzed formula for 12 months . Primary outcome was clinical tolerance to CM at 6 and 12 months of treatment . Furthermore , we analyzed T- and B-lymphocyte subsets ( CD3(+ ) , CD3(+)CD4(+ ) , CD3(+)CD8(+ ) , and CD20(+ ) ) in peripheral blood at r and omization and at 12 months with flow cytometry and examined the presence of viable probiotic strains in fecal sample s. RESULTS The cumulative percentage of tolerance to CM at 6 and 12 months was similar in both groups : 56 ( 77 % ) in the probiotics group versus 54 ( 81 % ) in the placebo group . Infants in the placebo group had higher percentages of CD3(+ ) and CD3(+)CD4(+ ) lymphocytes compared with those seen in probiotic-treated infants . Probiotic intake was confirmed because probiotics were isolated from feces more often in treated infants than in the placebo group . CONCLUSION Supplementation of CRL431 and Bb-12 to extensively hydrolyzed formula does not accelerate CM tolerance in infants with CMA Cow 's milk allergy/intolerance is treated by complete avoidance of cow 's milk proteins . Because cow 's milk is an important food for infants , its avoidance may lead to an increased risk of growth impairment . Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow 's milk formulate ( eHF ) in infants with cow 's milk allergy/intolerance , little is known about the effects of amino-acid-based formulae ( AA ) in such infants . We therefore performed a prospect i ve , controlled , multi-center trial to study the efficacy of AA in comparison with eHF , on the growth and clinical symptoms of 73 infants ( median age 5.7 months ) with cow 's milk allergy/intolerance and atopic dermatitis . Cow 's milk allergy/intolerance was proven in all infants by double-blind , placebo-controlled food-challenge . We observed a significant improvement in the SCORAD index in both groups , from a mean of 24.6 , at entry , to a mean of 10.7 ( p < 0.0001 ) after 6 months . In the AA group there was a significant increase in the length st and ard deviation score ( p < 0.04 ) , whilst there was no difference in the eHF group . The weight-for-length values were stable in both groups . The energy intake during the study was similar in both groups . Both an AA and eHF result ed in a significant clinical improvement in infants with an early onset of symptoms of cow 's milk allergy/intolerance . Feeding an AA result ed in improved growth compared with feeding eHF , despite similar dietary intakes , and may therefore be considered as a beneficial alternative in infants with severe cow 's milk allergy intolerance Cow milk allergy is a common disease of infancy , often associated with atopic dermatitis ( AD ) . Avoidance of cow milk ( CM ) implies the use of alternative dietary supports such as mammalian milks . In this study , we assessed the tolerability and clinical effect of ass 's milk ( AM ) , when compared with the largely used goat 's milk ( GM ) in a single-blind , controlled , r and omized crossover . Twenty-eight children with AD and ascertained allergy to CM were enrolled . The children were r and omized to AM or GM for 6 months , then switched to the other milk for further 3 months . The SCORAD index ( SI ) and a visual analog scale ( VAS ) were evaluated blindly . After termination of the study , food challenges with GM and AM were performed . An SDS-PAGE analysis of different milks was performed . Two children from the GM group dropped out after r and omization and 26 completed the study . Ass milk invariantly led to a significant improvement of SI and VAS of symptoms ( p < 0.03 vs. baseline and inter-group ) , whereas GM had no measurable clinical effect . At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM . Ass 's milk had a protein profile closer to human milk than GM . Ass milk is better tolerated and more effective than GM in reducing symptoms of AD . It may represent a better substitute of CM than the currently used GM OBJECTIVE To determine the antigenicity , nutritional adequacy , and growth-promoting efficacy of protein hydrolysate or amino acid-derived formulas in infants with cow milk allergy . STUDY DESIGN Several protein hydrolysate or amino acid-derived formulas were grade d for beta-lactoglobulin content and skin reactivity in 74 atopic children with cow milk allergy proved by a double-blind , placebo-controlled challenge . A r and omized , prospect i ve follow-up study of 9 months included 22 infants with a mean age of 6 months ( 95 % confidence interval , 4 to 7 ) , who were fed an extensively hydrolyzed whey formula ( group We ) , and 23 infants with a mean age of 17 ( 95 % confidence interval , 4 to 7 ) months , who were given an amino acid-derived formula ( group AA ) . RESULTS Both formulas were clinical ly and biochemically tolerated . The mean concentration of essential amino acids in plasma was lower in group We but higher in group AA compared with values for breast-fed control infants ( p = 0.001 ) . There was a different trend between the groups in weight ( p = 0.09 ) and length ( p = 0.006 ) . Growth was promoted in group AA during the follow-up ; it was constant during the first months , followed by a gradual decline in rate in group We . In both groups , atopic eczema improved significantly and progressively , and a downward trend was found in serum total and milk-specific IgE concentrations , proving the efficacy of both formulas . CONCLUSIONS Extensively hydrolyzed formulas are safe and effective for most infants ; an amino acid-derived formula may be preferable for infants with multiple food allergies , especially for the maintenance of normal growth Purpose To investigate whether specific IgA , IgG , IgG1 and IgG4 responses to cow ’s milk proteins differ between infants with cow ’s milk allergy and infants with cow ’s milk related symptoms ( control subjects ) , and whether early feeding affects these responses as well as specific IgE. Methods A cohort of 6,209 healthy , full-term infants in a double-blind r and omized trial received , as supplementary feeding at maternity hospitals ( mean duration 4 days ) , either cow ’s milk formula , extensively hydrolyzed whey formula or donor breast milk .  Infants who developed cow ’s milk associated symptoms ( n = 223 ) underwent an open oral cow ’s milk challenge ( mean age 7 months ) , which confirmed cow ’s milk allergy in 111 and was negative in 112 . We measured in sera cow ’s milk specific IgE levels with UniCAP ( Phadia , Uppsala , Sweden ) , and β-lactoglobulin and α-casein specific IgA , IgG1 , IgG4 and IgG levels with enzyme-linked immunosorbent assay . Results Infants with IgE-mediated cow ’s milk allergy had lower β-lactoglobulin and α-casein specific IgG1 , IgG4 and IgG levels ( p < 0.05 ) than infants with non-IgE-mediated cow ’s milk allergy or control subjects . Within the group of infants with cow ’s milk allergy , exposure to cow ’s milk during the first few days after birth led to higher β-lactoglobulin and α-casein specific IgG4 levels ( p < 0.005 ) compared to infants fed with either breast milk or extensively hydrolyzed formula . Conclusions Subdued IgG class responses to cow ’s milk proteins characterized IgE-mediated cow ’s milk allergy . In infants who developed cow ’s milk allergy early exposure to cow ’s milk result ed in a heightened specific IgG4 response BACKGROUND The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders . This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort , previously reported from birth to age 4 years . METHODS In this prospect i ve , r and omized , controlled study of food allergen avoidance in infancy , the prophylactic-treated group consisted of infants whose mothers avoided cow 's milk , egg , and peanut during the last trimester of pregnancy and lactation and who , themselves ,  avoided cow 's milk until age 1 year ( casein hydrolysate supplementation before age 1 ) , egg until age 2 years , and peanut and fish until age 3 years . The control group consisted of maternal/infant pairs who followed st and ard feeding practice s. RESULTS Despite a significant reduction in food allergy and milk sensitization before age 2 years , none of the following differed between the groups at age 7 years : food allergy , atopic dermatitis , allergic rhinitis , asthma , any atopic disease , lung function , food or aeroallergen sensitization , serum IgE level , or presence of nasal eosinophils or nasal basophilic cells .  Children with food allergy by 4 years evidence d higher 7-year ( current ) prevalences of allergic rhinitis and asthma ( p < 0.01 ) . Atopic diseases/parameters at age 7 years were shown , by multivariate analysis ( p < 0.05 ) , to be associated with several genetic and environmental risk factors ( male gender , maternal nonwhite ethnicity and asthma , and household smoking ) , as well as predictive atopic markers during infancy ( elevated serum IgE level ; egg , cow 's milk , and peanut sensitization ; and nasal eosinophils and nasal basophilic cells ) . CONCLUSIONS These findings help to : ( 1 ) eluci date the natural history of atopic disease in high-risk children ; ( 2 ) document the progression of allergy from atopic dermatitis , food allergy , and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy ; ( 3 ) identify allergy predictive markers ; and ( 4 ) exp and our appreciation of the interactions of genetic and environmental factors in the development of atopy Probiotic bacteria are proposed to alleviate intestinal inflammation in infants with atopic eczema/dermatitis syndrome ( AEDS ) and food allergy . In such infants we investigated effects of probiotic bacteria on faecal IgA , and on the intestinal inflammation markers tumour necrosis factor-alpha ( TNF-alpha ) , alpha1-antitrypsin ( AT ) , and eosinophil cationic protein ( ECP ) . A total of 230 infants with AEDS and suspected cow 's milk allergy ( CMA ) received in a r and omized double-blinded manner , concomitant with elimination diet , Lactobacillus GG ( LGG ) , a mixture of four probiotic strains ( MIX ) , or placebo for 4 wk . Four weeks after treatment , CMA was diagnosed with a double-blind placebo-controlled milk challenge . Faecal sample s of 102 infants , r and omly chosen for analysis , were collected before treatment , after 4-wk treatment , and on the first day of milk challenge . After treatment , IgA levels tended to be higher in probiotic groups than in the placebo group ( LGG vs. placebo , p=0.064 ; MIX vs. placebo , p=0.064 ) , and AT decreased in the LGG group , but not in other treatment groups . After challenge in IgE-associated CMA infants , faecal IgA was higher for LGG than for placebo ( p=0.014 ) , and TNF-alpha was lower for LGG than for placebo , but non-significantly ( p=0.111 ) . In conclusion , 4-wk treatment with LGG may alleviate intestinal inflammation in infants with AEDS and CMA Background : Previous studies suggest that administration of probiotics in vitro can stimulate regulatory and Th1 immune responses . We studied both the in vitro immunological effects of probiotics and the ex vivo immunological effects after oral administration of probiotics in children with food allergy , a Th2-mediated disease . Methods : Thirteen children were enrolled .  Probiotics ( n = 7 ) or placebo ( n = 6 ) were orally administered during 3 months . At baseline and after 1 and 3 months , peripheral blood mononuclear cells were stimulated with crude peanut extract , anti-CD3 , or anti-CD40 and IL-4 in the presence ( in vitro response ) or absence ( ex vivo response ) of probiotics . The proliferation and production of IFN-γ , IL-5 , IL-13 , IL-10 , TNF-α , IL-6 and IgE were analyzed . Sensitization to peanut , cow ’s milk and hen ’s egg was determined before and after treatment . Results : The in vitro addition of probiotics to peripheral blood mononuclear cell cultures result ed in enhanced proliferation and production of IFN-γ , IL-10 and TNF-α . After oral treatment , proliferation in the presence of probiotics increased , whereas in vitro IgE production decreased in the probiotics group compared to baseline . The ex vivo production of IL-10 , TNF-α and IL-6 tended to decrease . Th1 and Th2 cytokines were not altered . Sensitization remained unchanged . Conclusion : Probiotics enhanced the production of Th1 and regulatory cytokines in vitro . Oral administration of probiotics result ed in a slightly decreased ex vivo production of IL-10 , TNF-α and IL-6 . This indicates that probiotics have a different potential to modulate the immune response in vitro versus ex vivo Cow 's milk and soy protein allergies are commonly associated with atopic dermatitis ( AD ) in young children .  Amino acid (AA)-based elemental milk formula may improve AD control in these patients . This study investigates the efficacy of AA-based formula in treating young AD patients irrespective of their food allergy status . AD patients younger than 3 yr old were eligible . Sensitization to food allergens was ascertained by skin prick tests and allergen-specific immunoglobulin E ( IgE ) assay . Patients were then r and omly allocated to take either active treatment or pre-existing formulae ( placebo ) for 6 wk . They were allowed a 6-wk washout period before crossed over to the other intervention for another 6 wk . Fifteen AD patients , with median ( interquartile range , IQR ) age of 1.4 ( 0.6 - 2.6 ) yr , were recruited . Their median ( IQR ) SCORAD score was 23.9 ( 10.5 - 29.7 ) . Seven of them were sensitized to cow 's milk or soybean . Among 11 patients who completed the study , the median changes for all scores and urinary eosinophil protein X ( EPX ) concentration were not statistically significant . There was also no evidence of carry-over effects for SCORAD and its various components and global health score , except for urinary EPX concentration ( p = 0.05 ) . Our results do not support the use of AA-based elemental milk formula in treating young children with AD irrespective of their food allergy status Objective : The aim of this study was to evaluate the suspicion of cow's-milk allergy in infants with unspecific gastrointestinal ( GI ) symptoms using the double-blind , placebo-controlled food challenge . Methods : A prospect i ve cohort study , which recruited 57 consecutive children with gastrointestinally manifested symptoms suspected of cow's-milk allergy . All patients underwent a 5-day double-blind , placebo-controlled food challenge for cow 's milk . Results : The median age of the patients was 8.7 months . None had measurable cow's-milk – specific IgE. The food challenge was positive in 18 ( 32 % ) cases , with symptoms manifesting within 48 hours in 17 of 18 cases . The only symptom that correlated with the positive challenge was loose stools , reported as a presenting symptom in 78 % of challenge-positive and in 46 % of challenge-negative children ( P = 0.043 ) . During active challenge , the respective proportions were 82 % and 2 % ( P < 0.0001 ) . No serious adverse effects were manifested during the challenges . In the challenge-negative group , significant placebo reactions occurred in 18 ( 46 % ) patients . In the challenge-negative children , adult-type hypolactasia genotype CC frequency was higher ( 31 % , P = 0.033 ) than national prevalence of 18 % . Conclusions : In an infant with unspecific GI symptoms suspected of cow's-milk allergy , this diagnosis is seldom confirmed . Other reasons for the troublesome GI symptoms should also be identified This study was design ed to assess whether a rice-hydrolysate formula allows normal growth and adequate metabolic balance in infants with cows ' milk protein allergy . Infants ( seven females , nine males ; aged 6–14 months ) were r and omly assigned to receive a rice-hydrolysate formula ( n = 8) or a soy formula ( control group , n = 8) . St and ardized growth indices ( Z scores ) and biochemical parameters were evaluated during a 6-month treatment period . Infants in both groups showed normal growth patterns during the study , and no adverse reactions were seen . Mean plasma biochemical parameters were within the normal ranges , and did not differ between groups . In conclusion , rice-hydrolysate formula may be a nutritionally suitable alternative for infants with cows ' milk protein allergy . Larger studies , with satisfactory power , should be undertaken to confirm these findings OBJECTIVE . Rectal bleeding  is an alarming symptom and requires additional investigation . In infants it has been explained mainly by hypersensitivity . In addition to dietary antigens , intraluminal microbial agents challenge the immature gut mucosa . Although controlled in the mature gut , these antigens may induce inflammation in the developing gastrointestinal tract . The objectives of this study were to evaluate prospect ively the clinical course of rectal bleeding and evaluate the impact of cow 's milk allergy and aberrant gut microbiota on the condition . Because withdrawal of cow 's milk antigens from the infants ' diet is used as a first treatment without evidence of its efficacy , we also aim ed to asses the effect of a cow 's milk – elimination diet on the duration of rectal bleeding . METHODS .The study involved 40 consecutive infants ( mean age : 2.7 months ) with visible rectal bleeding during a 2-year period at the Tampere University Hospital Department of Pediatrics . Most of the infants ( 68 % ) were fully breastfed . At enrollment the infants were r and omly allocated to receive a cow 's milk – elimination diet ( n = 19 ) or continue their previous diet ( n = 21 ) for 1 month . Findings of colonoscopy , fecal bacterial culture , fluorescence in situ hybridization of selected gut genera , specific detection of fecal enteroviruses , rotaviruses , and adenoviruses , fecal electron microscopy for viruses , and mucosal electron microscopy for viruses were assessed . During each visit the severity of atopic eczema , if any , was assessed according to the SCORAD method . In evaluating the extent of sensitization , serum total immunoglobulin E ( IgE ) and specific IgE and skin-prick tests for cow 's milk , egg , and wheat were studied . Cow 's milk allergy was diagnosed by elimination and provocation testing . Five patients were hospitalized ; all others were treated on an outpatient basis . The follow-up visits were scheduled 1 month later and at the age of 1 year . Sixty-four healthy reference infants were selected as controls according to the following criteria : age and timing of fecal sampling being identical to within 1 month . RESULTS . Altogether , 32 ( 80 % ) infants manifested bloody stools during follow-up ( mean [ range ] : 2.1 [ 1–15 ] per day ) . The mean number of days with rectal bleeding on follow-up was 6 . Typically , bloody stools occurred irregularly , for which reason the mean time to the last occurrence of rectal bleeding was 24 ( range : 1–85 ) days from admission . Atopic eczema at presentation or during follow-up was diagnosed in 38 % of the infants . Increased specific IgE concentrations or a positive skin-prick test were uncommon . The growth of the infants was normal on admission and during follow-up . Colonoscopy revealed typically focal mucosal erythema and aphthous ulcerations . The mucosa appeared normal in less than half of the patients . No anorectal fissures or colonic polyps were found . Light microscopy revealed that the overall architecture of the mucosa was well maintained . Acute inflammation or postinflammatory state and focal infiltration of eosinophils in the lamina propria were the most common abnormalities . A cow 's milk – elimination diet did not affect the duration of rectal bleeding . Cow 's milk allergy was diagnosed in 7 ( 18 % ) patients .  Virus-particle aggregates were found in the microvillus layer of the colon epithelium in 8 cases . The surface epithelium of the virus-positive colon biopsy specimens regularly showed degenerative changes in the microvillus layer and epithelial cells . Electron microscopy study of the colon biopsies disclosed virus particles ( 30 nm in diameter ) on the surface of epithelial cells . Virus particles or RNA were present in feces in only a minority of the patients . All fecal cultures were negative for Salmonella , Shigella , and Yersinia . Campylobacter jejuni was found in the feces of 1 patient , and fecal cultures were positive for Clostridium difficile in 4 patients , Staphylococcus aureus in 8 patients , and yeast in 2 patients . Fluorescence in situ hybridization revealed that at the time of admission the total numbers of bacteria and the numbers of bifidobacteria and lactobacilli in feces were lower in the patients compared with controls . The fecal concentrations of microbes characterized in this study ( Bacteroides , bifidobacteria , Clostridium , lactobacilli , and enterococci ) did not differ significantly between the time of admission and the second visit in the patients or controls . At the age of 1 year , 7 patients still suffered from cow 's milk allergy , 5 of whom also suffered from multiple food allergies . Atopic eczema and histopathologically confirmed inflammation of the colonic mucosa at presentation were associated with persistence of cow 's milk allergy at the age of 1 year . No patients exhibited gastrointestinal complaints or visible blood in stools . CONCLUSIONS . Rectal bleeding  in infants is generally a benign and self-limiting disorder . Bloody stools occurred irregularly for only a few days during the following months . As in a previous report , most infants were exclusively breastfed . In the majority of the patients the cause of the condition remains unknown . An association with viruses can be seen in some patients . The microbes that commonly lead to bloody diarrhea in older children and adults , Salmonella , Shigella , and Yersinia , were absent in the present material . The low bifidobacterial numbers in fecal sample s may indicate a significant aberrance that may provide a target for probiotic intervention to normalize gut microbiota . The gut microbiota overall seemed stable , because the numbers of major groups of microbiota tested did not change significantly between the time of admission and after 1 month . Cow 's milk allergy among these patients is more uncommon than previously believed . Cow 's milk challenge is thus essential in infants who become symptom-free during a cow 's milk – free diet  to reduce the number of false-positive cow 's milk – allergy diagnoses Objective : Cow`s milk protein allergy usually occurs in infants within the first months of life . It can affect several organs , but gastrointestinal symptoms are the most clinical symptoms observed . The most effective treatment is restricting the cow ` s milk protein in mother and infant`s diet . Lactobacillus GG supplementation in infant could be effective through modulation of the immune system and the gut microflora . Methods : Thirty two breastfed infants with cow`s milk protein allergy were enrolled in a double-blinded r and omized controlled trial in which they received Synbiotic ( n=16 ) or placebo ( n=16 ) once a day for one month , simultaneously with cow`s milk protein restriction in mother and infant`s diet . Clinical gastrointestinal symptoms ( vomiting , colic , rectal bleeding and diarrhea ) , head circumference , body length and weight were recorded at the beginning , the end of the first and third month of study . Findings : Percentage of increment in head circumference and weight were statistically more in synbiotic group compared with placebo group at the end of the first and third month of study . There was no significant difference in resolution of clinical gastrointestinal symptoms ( vomiting , colic , rectal bleeding or diarrhea ) and percentage of increment in body length . Conclusion : Synbiotic supplementation in infants may improve increment of head circumference and weight gain , but has no effect on resolution of clinical symptoms IgE-mediated cow 's milk allergy ( CMA ) is a heavy burden for patients , particularly for children and their families . Allergen avoidance represents the only therapeutic option , but oral desensitization protocol s have been suggested . Because of the long duration and complexity of these protocol s we examined the feasibility of an oral tolerance induction protocol using a weekly up-dosing schedule . Children with IgE-mediated food allergy to milk , confirmed by a double-blind placebo-controlled food challenge , were recruited . Six of them were r and omized to double-blind desensitization with milk or soy formula as placebo .  Seven patients underwent the protocol in open fashion . The desensitization schedule started with one drop of whole CM diluted 1:25 every week . The dose was doubled weekly until the 18th week to achieve an intake of 200 mL in approximately 4 months . Of the 13 children enrolled , 10 children received CM and 3 control children received soy formula .  Full tolerance ( 200 mL of milk ) was achieved in 7 children ; in 2 children this therapeutic approach failed , because severe reactions occurred during the procedure . One patient achieved a partial tolerance ( 64 mL of milk ) . The three control children receiving placebo still showed a positive food challenge at the end of the study . A weekly up-dosing oral tolerance induction could be a viable alternative to traditional protocol s for children with IgE-mediated CMA 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 BACKGROUND Food allergy is treated by avoidance diets in order to prevent anaphylactic reactions and to cure chronic associated symptoms . However , the natural history is left unchanged . OBJECTIVE To search for a beneficial effect of an oral desensitization protocol to allergenic foods in IgE-dependent milk or egg allergies in children . METHODS 60 children with documented cow 's milk allergy ( 13 months-6.5 years ) , and 90 children with egg allergy ( 12 months-8 years ) , were consecutively included after 6 - 12 months of avoidance diet  , if a SBPCFC to 60 ml milk ( 60 ml ) or to 965 mg of raw egg white was negative . They were r and omized for uninterrupted avoidance or oral desensitization ( group A or OD ) . Six months later , a new SBPCFC was performed with , up to 200 ml of milk or 7 g of raw egg white . Prick tests and specific IgE levels were carried out simultaneously . RESULTS Data were obtained for 57 children with CMA ( 30 A and 27 OD ) , and 84 children with EA ( 35 A and 49 OD ) . The two groups ( AD or OD group ) were similar with regard to means of ages , the size of PT wheals and the level of IgEs at baseline . MILK ALLERGY : A SBPCFC to milk was positive in 11.1 % of those following OD vs. 40 % after A ( p < .025 ) . The size of PT decreased after OD and increased after A ( -3.4 mm vs. + 0.84 mm ; p < .002 ) . EGG ALLERGY : The SBPCFC to egg was positive in 30.6 % after OD vs. 48.6 % after A ( p < .1 ) . After 6 months , in the OD group , the mean size of the PT and the level of specific IgE were significantly reduced compared to the A group . In the A group , the threshold of reactivity was often lower , or more serious symptoms were observed . CONCLUSION Oral desensitization helps the egg and milk allergic children to overcome their allergies . Since the avoidance of these foods is likely to increase sensitization as well as to lower the threshold of reactivity , an active treatment is required . Further attempts to st and ardize the procedures of oral desensitization are expected
Conclusion : Limited low- quality evidence indicates that probiotic supplementation may be associated with earlier acquisition of tolerance to CMP in children with CMPA .
CMPA is associated with significant socioeconomic burden.• Elimination diet and extensively hydrolyzed formula is the mainstay of the management of CMPA.What is New:• This first systematic review of r and omized controlled trials shows that probiotics as an adjuvant can lead to earlier acquisition of tolerance to CMP  in children at 36 months of age .
However , the evidence is low quality and influenced by data from one large study .• Probiotic supplementation was not associated with earlier resolution of hematochezia
Cow ’s milk protein allergy ( CMPA ) is the commonest food allergy in infancy and is associated with significant health burden .
Given their immune modulatory properties , probiotics have been proposed as a strategy for management of CMPA .
We aim ed to systematic ally review efficacy and safety of probiotics in the management of CMPA .
Large well- design ed trials are essential to confirm these findings .What is Known:• Cow ’s milk protein allergy ( CMPA ) is one of the commonest food allergies in children .