Search

Background: The Step-Down Approach for Cow's Milk Allergy (SDACMA) trial evaluated the tolerability and the rate of immune tolerance acquisition in CMA children starting dietary treatment with amino acid-based formula (AAF) and then switching to EHCF containing the probiotic Lacticaseibacillus  rhamnosus GG (EHCF + LGG)., Methods: Randomized controlled trial involving IgE-mediated CMA children receiving AAF from at least 4 weeks. EHCF + LGG tolerance was evaluated by the results of double-blind placebo-controlled food challenge (DBPCFC). Subjects tolerating EHCF + LGG were randomly allocated to remain on AAF, or to switch to EHCF + LGG. Immune tolerance acquisition to cow's milk proteins was evaluated with DBPCFC after 12 months of treatment. Allergy screening tests and body growth were also monitored., Results: Sixty IgE-mediated CMA children were enrolled. The proportion of children treated with AAF who resulted tolerant to the first exposure of EHCF + LGG was 0.98 (exact 95% CI 0.91-0.99). The rate of the immune tolerance acquisition to cow milk proteins after 12 months treatment was higher in the EHCF + LGG (0.48, 95% exact CI 0.29-0.67, n/N = 14/29) than in the AAF group (0.03, 95% exact CI 0.001-0.17, n/N = 1/30). There was an absolute benefit increase (ABI) of tolerance rate equal to 0.45 (95% CI 0.23-0.63, Newcombe method 10) for EHCF + LGG versus AAF, corresponding to a NNT of 2 (2-4, Bender's method). A normal body growth pattern was observed in the two study groups., Conclusion: In IgE-mediated CMA children the step-down from AAF to EHCF + LGG is well tolerated and could facilitate the immune tolerance acquisition., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Milk oral immunotherapy (OIT) may increase the amount of milk protein that can be ingested without triggering an allergic reaction. It is important to understand why some patients benefit from the treatment while others do not., Objective: The aim was to define the differences in the milk allergen component-specific (casein, α-lactalbumin, ß-lactoglobulin) immunoglobulin (sIg [sIgE, sIgG4, and sIgA]) levels relative to the long-term outcomes of milk OIT., Methods: In this long-term, open-label follow-up study, 286 children started milk OIT between 2005 and 2015. Follow-up data were collected at two points: the post-buildup phase and long term (range 1-11 years, median 6 years). Comparisons of sIg levels were made among three outcome groups of self-reported long-term milk consumption (high-milk dose, low-milk dose, and avoidance)., Results: A total of 168 (59%) of the 286 patients on OIT participated. Most patients (57%) were in the high-dose group; here, 80% of these patients had a baseline casein sIgE value less than 28 kUA/L, they had the lowest casein sIgE levels at all time (p < .001), their casein sIgG4/IgE levels increased, and long-term casein sIgA was highest compared with the low-dose and avoidance groups (p = .02). Low-milk dose group had the highest casein sIgG4/IgE levels in long term (p = .002)., Conclusion: The baseline Ig profiles and responses to milk OIT differed depending on long-term milk consumption. Lower casein sIgE levels were associated with better outcome. Milk casein sIgA differed in the long term among high-milk consumers., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice sensitized with β-lactoglobulin (β-Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short-chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G-protein-coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor-β and IFN-γ (p < .05), but negatively with the serum concentrations of IL-17, IL-4, and IL-6 in the L. acidophilus-treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43., (© 2019 The Societies and John Wiley & Sons Australia, Ltd.)

Aim: This study evaluated whether 15 allergy, immunology or inflammatory markers predicted the long-term use of cows' milk or milk products seven years after the start of oral immunotherapy (OIT) for cows' milk allergy in children., Methods: The following laboratory parameters were measured before the OIT at Tampere University Hospital, Finland, and after the six-month escalation phase: serum total immunoglobulin (Ig) E, milk-specific IgG and IgG4, eosinophil cationic protein, eosinophil-derived neurotoxin, interleukins 4, 5, 6, 10 and 12p70 and serum adipokines adiponectin, adipsin, leptin and resistin. Follow-up data from a seven-year phone questionnaire in 2015 were available for 24 children: 14 successful and 10 unsuccessful milk users., Results: There were no significant differences in any of the 15 markers measured at the start of the study between the subjects who later formed the successful and unsuccessful groups. At the end of the six-month escalation phase of OIT, serum adipsin was higher in the group who were unsuccessful milk users at the seven-year follow-up study., Conclusion: None of the 15 allergy, immunology or inflammatory markers were useful in predicting the outcome of OIT. Preliminary evidence was found that high serum adipsin after the six-month escalation phase of OIT might predict unsuccessful outcome., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Oral immunotherapy (OIT) is a promising but still experimental method to treat children with cow's milk (CM) allergy (CMA). We evaluated changes in allergic, immunological and inflammatory parameters, which happened during the six-month OIT for CMA., Methods: We treated 28 school-aged children with CMA using OIT with a double-blind placebo-controlled design. After the controlled study finished, the placebo group was treated with the same but open-label OIT protocol. Sixteen immune variables were tested before and after the six-month OIT., Results: Before OIT, the median serum CM-specific immunoglobulin (Ig) E was 18.0kIU/L in the intervention group and 9.4kIU/L in the placebo group (p = 0.46). At six months, interleukin (IL)-6 and IL-10 were significantly higher in the intervention group. When the changes during the blinded and open OIT were analysed together for both groups, blood eosinophils and serum total IgE decreased and milk-specific IgG and IgG4, serum IL-4 and IL-6, and serum leptin and resistin increased significantly., Conclusion: Preliminary evidence was found that markers of allergy such as blood eosinophils and serum IgE decreased and milk-specific IgG and IgG4 increased during OIT. Adipokines, leptin and resistin, which functionally are cytokines linked to Th1-type response, increased during OIT., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Studies examining the long-term effect of oral immunotherapy in food-allergic patients are limited. We investigated cow's milk-allergic patients, >6 months after the completion of oral immunotherapy (n = 197). Questionnaires, skin prick tests, and basophil activation assays were performed. Of the 195 patients contacted, 180 (92.3%) were consuming milk protein regularly. Half experienced adverse reactions, mostly mild. Thirteen patients (6.7%) required injectable epinephrine. Higher reaction rate after immunotherapy was associated with more anaphylactic episodes before treatment and a lower starting dose (OR = 2.1, P = 0.035 and OR = 2.3, P = 0.035, respectively). Reaction rate in patients who were 6-15 months, 15-30 months, or >30 months post-treatment decreased from 0.28/month to 0.21/month to 0.15/month, respectively (P < 0.01). Milk-induced %CD63 and %CD203c expression was significantly lower in patients >24 months vs in patients <24 months post-treatment (P = 0.038 and P = 0.047, respectively). In conclusion, many patients experience mild adverse reactions after completing oral immunotherapy and some require injectable epinephrine. Progressive desensitization, both clinically and in basophil reactivity, occurs over time., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: This was a follow-up of 28 schoolchildren with cows' milk allergy (CMA) who attended a randomised double-blind placebo-controlled oral immunotherapy (OIT) study. In the original study, 26 (92.9%) completed the six-month escalation phase, and 25 (89.3%) used milk daily at 12 months and 24 (85.7%) at 36 months. This study evaluated the outcome seven years later, with special attention paid to milk consumption and symptoms., Methods: Outcome data were collected through a postal questionnaire completed three, four and five years after enrolment and by a phone questionnaire after seven years. We asked about the daily dose of milk products, any adverse reactions, any medication needed and possible discontinuation of daily milk consumption., Results: Data were available at the seven-year point for 24 children and 14 (58.3%) of these continued to use milk (≥200 mL) or milk products (protein ≥6400 mg) daily for seven years. However, three (21.4%) of these still reported symptoms associated with milk consumption. Of the 10 remaining children, two children used milk products daily but consumed less due to symptoms and eight (33.3%) had discontinued milk consumption., Conclusion: Oral immunotherapy was an effective and safe way of desensitising schoolchildren with persistent CMA., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Strict milk protein avoidance has been the standard therapy of cows' milk allergy (CMA) in children, but oral immunotherapy (OIT) seems to provide an alternative treatment. The aim of this study was to evaluate the impact of OIT on milk consumption during the first 2.5 years after a start of OIT., Methods: This open-label, noncontrolled, real-life OIT study was conducted in 74 children with CMA, who were aged 5-15. It included a 6-month induction phase and a 2-year maintenance phase. Data on the complete 2.5-year trial were available for 57 children., Results: Most of the children (82%) completed the 6-month induction phase and were able to consume at least 200 mL of milk or 6400 mg of milk protein a day. After the 2-year maintenance phase, half were consuming milk daily. Risk factors for OIT failure during the induction phase were asthma and high milk-specific immunoglobulin E, but a history of anaphylaxis before OIT was not. Allergies to eggs or wheat decreased the risk of immediate OIT failure., Conclusion: This study confirmed the efficacy of milk OIT in real life, including the whole spectrum of persistent CMA at school age, and revealed certain risk factors associated with OIT failure., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: A new treatment option for persistent cow's milk allergy (CMA) is oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG4 antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome., Methods: Seventy-six children (5-17 years) with challenge-verified CMA were subjected to a 6-month OIT protocol. The treatment aimed at reaching a maintenance dose of 200 ml CM (high dose = HD). Those who did not reach target were analysed as a low-dose (LD) group. Sera were characterized before and after OIT regarding serum levels of IgE and IgG4 to milk and five milk allergen components evaluated together with clinical CMA symptoms and outcome of OIT., Results: Fifty-five (72%) patients reached the maintenance dose (HD) during therapy. High specific IgE levels towards the milk allergens α-lactalbumin (P = 0.048), β-lactoglobulin (P = 0.006) and casein (P = 0.015) before OIT start were associated with lower maintenance dose reached. Patients who developed desensitization had a larger increase in IgG4 levels to α-lactalbumin (P = 0.034), β-lactoglobulin (P = 0.010), casein (P = 0.047) and lactoferrin (P = 0.030) during treatment than those who failed., Conclusions: Component-resolved diagnostics before OIT can help to identify children with lower probability of a successful OIT outcome, as high IgE levels to α-lactalbumin, β-lactoglobulin and casein are associated with lower maintenance dose reached. An increase in the IgG4 concentration to milk components during treatment indicated effective desensitization., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: Gastrointestinal symptoms, such as constipation, regurgitation and infant colic, occur in about half of infants. These symptoms are often functional, but they may also be caused by cow's milk protein allergy. We developed three algorithms for formula-fed infants, which are consensus rather than evidence-based due to the limited research available in the existing literature., Conclusion: We believe that these algorithms will help primary healthcare practitioners to recognise and manage these frequent gastrointestinal manifestations in infants., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aims:   To study the efficacy of oral immunotherapy (OIT) in schoolchildren with cow's milk (CM) allergy (CMA)., Methods:   Twenty-eight children aged 6-14 years with CMA documented by oral challenge were enrolled into a randomized, double-blind, placebo-controlled OIT study. In the active treatment, CM protein amount was increased during 23 weeks from 0.06 mg to a maximum of 6400 mg (200 mL of milk)., Results:   Twenty-four (86%) patients completed the protocol: 16/18 in active and 8/10 in placebo groups. All children in the active and 2/3 in the placebo group suffered from symptoms considered by the parents as induced by milk. The children were contacted by phone 12 months later, and 13 (81%) used daily CM or milk products corresponding 6400 mg of CM protein. After double-blind OIT, all 10 children in the placebo group completed successfully an open-label OIT by an identical protocol, and all used daily CM or milk products 6 months later. Three to 3.5 years later, one child more had discontinued daily milk use. Thus, the long-term success rate was 22/28 (79%)., Conclusions:   This placebo-controlled, double-blind study confirmed that OIT was effective in desensitizing schoolchildren with CMA. With occasional exceptions, the reached desensitization sustained for more than 3 years., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

Unlabelled: Cow's milk protein allergy (CMPA) may cause gastrointestinal motility disorders. Symptoms of both conditions overlap and diagnostic tests do not reliably differentiate between both. A decrease of symptoms with an extensive hydrolysate and relapse during challenge is not a proof of allergy, because hydrolysates enhance gastric emptying, a pathophysiologic mechanism of gastro-oesophageal reflux (GER). Thickened formula reduces regurgitation, and failure to do so suggests CMPA. A thickened extensive hydrolysate may induce more rapid improvement, but does not always differentiate between CMPA and GER. Different hypotheses are discussed: is the overlap between CMPA and functional disorders coincidence, or do both entities present with identical symptoms, or does the fact that symptoms are identical indicates that there is only one entity involved? Studies on the prevention of CMPA focused on 'at-risk families', and resulted in a decrease of CMPA and atopic dermatitis, but did not provide data on the incidence of GER., Conclusion:   As long as there are no objective diagnostic tools to separate GER from CMPA, the physician has two options: first treat the most likely diagnosis, and switch if after 2-4 weeks there is no improvement, or treat both conditions with one intervention, what will not result in a diagnosis., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

Background: Specific oral tolerance induction (SOTI) seems to be a promising treatment of food allergy. Specific oral tolerance induction and elimination diet were compared with respect to efficacy rate and patterns of clinical reaction., Methods: Children with challenge proven immunoglobulin E (IgE)-mediated cow's milk (CM) allergy or hen's egg (HE) allergy were randomly assigned to SOTI or elimination diet as a control group. Specific oral tolerance induction treatment was performed at home on a daily basis according to a study protocol with fresh CM or lyophilized HE protein. Re-evaluation of clinically relevant food allergy was performed by food challenge after a median of 21 months. Children in the SOTI group received a secondary elimination diet for 2 months prior to follow-up challenge to evaluate persistence of induced oral tolerance., Results: At follow-up challenge, nine of 25 children (36%) showed permanent tolerance in the SOTI group, three of 25 (12%) were tolerant with regular intake and four of 25 (16%) were partial responders. In the control group, seven of 20 children (35%) were tolerant. Allergen-specific immunoglobulin E decreased significantly both in children who developed natural tolerance during the elimination diet (P < 0.05) and in those with SOTI (P < 0.001)., Conclusions: Specific oral tolerance induction seems a valid treatment option for patients with persistent food allergy. Indications may be given if avoidance cannot be guaranteed or for those who are eager to eat the food in question. Advantages of SOTI are the increased threshold dose for allergic reactions and the substantially reduced risk of severe allergic reactions after inadvertent ingestion of the allergen. However, careful monitoring during SOTI is mandatory.

Background: Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms., Aim: To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg., Methods: In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests., Results: Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems., Conclusion: We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.

Objectives: To desensitize children with severe immunoglobulin (Ig)E-mediated cow's milk allergy in a period of 6 months by introducing increasing daily doses of cow's milk (CM) in order to enable the child to assume 200 ml of CM daily, or to induce tolerance of the highest possible CM dose., Study Design: Twenty-one children at least 6 years old with severe IgE-mediated CM allergy were admitted to the study. A convincing history of IgE-mediated CM allergy or a positive double-blind placebo-controlled food challenge with CM confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.06 mg of CM proteins., Results: Overall, 15 of 21 children (71.4%) achieved the daily intake of 200 ml during a 6-month period; three of 21 children (14.3%) tolerated 40-80 ml/day of undiluted CM; three of 21 children (14.3%) failed the desensitization because they presented allergic symptoms after ingesting minimal amounts of diluted CM., Conclusions: We successfully desensitized 15 of 21 children with severe IgE-mediated CM allergy in a period of 6 months. We stress the importance of the partial outcome in those three of 21 children who could not reach the maximum amount of 200 ml/day of whole CM, but were able to tolerate 40-80 ml/day of CM. In this way we dramatically reduced the risk of severe reactions after accidental or unnoticed introduction of low quantities of CM. We do not propose generalizing this method beyond trained staff.

We describe the case of a young man with IGE-mediated hypersensitivity to milk, casein, and lactoglobulin, who went into respiratory crisis every time he milked his sheep.