In 2010, the diagnosis and treatment of IgE-mediated CMA were systematized in a GRADE guideline. After 6 years, the state of the knowledge in diagnosis and treatment of CMA has largely evolved. We summarize here the main advances, and exemplify indicating some specific points: studies aimed at better knowledge of the effects of breastfeeding and the production of new special formulae intended for the treatment of CMA. The literature (PubMed/MEDLINE) was searched using the following algorithms: (1) [milk allergy] AND diagnosis; (2) [milk allergy] AND [formul*] OR [breast*], setting the search engine [6-years] time and [human] limits. The authors drew on their collective clinical experience to restrict retrieved studies to those of relevance to a pediatric allergy practice. Several clinical studies did address the possibility to diagnose CMA using new tools in vitro and in vivo, or to diagnose it without any evaluation of sensitization. Some studies also addressed the clinical role of formulae based on milk hydrolysates, soy, or rice hydrolysates in the treatment of CMA. Many studies have elucidated the effects of selective nutrients in breastfed infants on their immunologic and neurologic characteristics. Evidence-based diagnostic criteria should be identified for non-IgE-mediated CMA. Debate is ongoing about the best substitute for infants with CMA. In particular, Hydrolyzed Rice Formulae have been widely assessed in the last six years. In the substitute choice, clinicians should be aware of recent studies that can modify the interpretation of the current recommendations. New systematic reviews and metanalyses are needed to confirm or modify the current DRACMA recommendations.

Background: Epicutaneous immunotherapy (EPIT) on intact skin with an epicutaneous delivery system has already been used in preclinical and clinical studies. In epicutaneous vaccination and immunotherapy, the stripping of skin before application of the allergen is suggested to facilitate the passage of allergen through immune cells.Objectives: The aim of this study was to compare the immunological response induced by EPIT performed on intact and stripped skin in a mouse model of peanut allergy.Methods: After oral sensitization with peanut and cholera toxin, BALB/c mice were epicutaneously treated using an epicutaneous delivery system (Viaskin® (DBV Technologies, Paris) applied either on intact skin or on stripped skin. Following EPIT, mice received an exclusive oral peanut regimen, aimed at triggering esophageal and jejunal lesions. We assessed eosinophil infiltration by histology, mRNA expression in the esophagus, antibody levels and peripheral T‐cell response.Results: EPIT on intact skin significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (2.7 ± 0.9, compared to Sham 19.9 ± 1.5, p < 0.01), mRNA expression of Th2 cytokines in tissue and intestinal villus sub‐atrophia (2.9 ± 0.2 vs Sham, 2.1 ± 0.2, p < 0.05). By contrast, EPIT on stripped skin reinforced Th2 systemic immunological response as well as eosinophil infiltration (26.8 ± 15.1), mRNA expression of Th2 cytokines and duodenal villus/crypt‐ratio (2.4 ± 0.3).Conclusions: Epicutaneous allergen‐specific immunotherapy needs the integrity of superficial layers of the stratum corneum to warranty safety of treatment and to induce a tolerogenic profile of the immune response.

Little is known about the effects of natural mineral water on constipation in adults. We assessed the effect of a magnesium sulfate-rich natural mineral water (Hépar; Nestlé Waters, Issy-les-Moulineaux, France) on gastrointestinal transit in constipated women. We performed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of Hépar in outpatients with functional constipation (based on the Rome III criteria). The study included 244 female patients, age 18 to 60 years, identified by 62 general practitioners throughout France. After a washout period, subjects drank 1.5 L natural low-mineral water daily (control, n = 77), 0.5 L Hépar and 1 L natural low-mineral water daily (Hépar 0.5 group, n = 85), or 1 L Hépar and 0.5 L natural low-mineral water daily (Hépar 1 group, n = 82) for 4 weeks. We collected information on the number and types of stools, abdominal pain, rescue medications, adverse events, and volume of water consumed. We observed no significant effect at week 1. At week 2, constipation was reduced in 21.1% of patients in the control group, in 30.9% in the Hépar 0.5 group (P = .099 vs controls), and in 37.5% in the Hépar 1 group (P = .013 vs controls). The Hépar 1 group also had a decreased number of hard or lumpy stools (Bristol scale, P = .030 vs baseline) and a substantial decrease in the use of rescue medication (P = .034 vs controls). Patient responses correlated with magnesium sulfate concentrations. Safety was very good; there were no serious adverse events among patients who drank Hépar. In a controlled trial, daily consumption of 1 L Hépar reduced constipation and hard or lumpy stools in a greater percentage of women with functional constipation than natural low-mineral water, as early as the second week of treatment.

Formulas adapted to infant feeding, although most of the time made from cow’s milk proteins, can be made from hydrolyzed rice protein but they must be classified as “formulas for specific medical needs”, according to European regulations. The nutritional quality of rice proteins is thus suitable to be used in infant formulas giving that it is supplemented by certain amino acids which can be lacking. Besides, hydrolysis is required to facilitate their water solubility and digestibility. Owing to a low allergenicity of rice and to the absence of the cross-allergy between milk proteins and rice proteins, these formulas are adapted to the diet of children with cow’s milk protein allergy (CMPA), which explains their growing use in some countries. However, CMPA, an expanding disorder, has consequences for growth, bone mineralization, and often has an association with allergy to other foods, including cow’s milk extensive hydrolysate, so that a surveillance of the adaption of hydrolyzed rice protein formulas (HRPF) to CMPA, the absence of unexpected side effects, and the appropriate response to its various health hazards seems mandatory. This paper analyses the health problem deriving from CMPA, the industrial development of hydrolyzed rice protein formulas, and the limited number of clinical studies, which confirms, at the moment, a good allergic tolerance and safety. The goal is to better advise heath care professionals on their use of HRPFs during CMPA.