Search was not restricted by publication type or language or study design. search on Medline via PubMed and Scopus was performed August 2017. Studies were included if they investigated possible sIgE and/or SPT cut-off ideals for cows milk allergy analysis in pediatric individuals. The quality of the studies was evaluated relating to QUADAS-2 criteria. Results The search produced 471 results on Scopus, and 2233 on PubMed. Thirty-one papers were included in the review and grouped relating to patients age, allergen type and cooking degree of the milk utilized for the oral food challenge. In children ?2?years, CMA analysis seems to be highly likely PKC 412 (Midostaurin) when sIgE to CM draw out are ?5 KUA/L or when SPT with commercial extract are above 6?mm or Prick by Prick (PbP) with new cows milk are above 8?mm. Any cut-offs are proposed for solitary cows milk proteins and for baked milk allergy in children more youthful than 2?years. In Children ?2?years of age it is hard to define practical cut-offs for allergy to fresh and baked cows milk. Cut-offs recognized are heterogeneous. Conclusions None of the cut-offs proposed in the literature can be used to definitely confirm cows milk allergy analysis, either to new pasteurized or to baked milk. However, in children ?2?years, cut-offs for specific IgE or SPT seem to be more homogeneous and may be proposed. strong class=”kwd-title” Keywords: Children, Cows milk allergy, Cut-offs, Predictive value, Skin prick test, -lactalbumin, -lactoglobulin, Casein, Positive predictive value, Specificity, Oral food challenge Background Cows milk (CM) is one of the first causes of food allergy in the 1st years of existence [1] and of food anaphylaxis in pediatric individuals [2]. Cows milk allergy (CMA) has a prevalence ranging between 1.8 and 7.5% in the first year of life [3]. CMA analysis is often based on a compatible clinical history and on the results of specific IgE (sIgE) and/or pores and skin prick checks (SPT). Specific IgEs and Col18a1 SPTs to CM draw out or to the solitary CM allergenic proteins display a good level of sensitivity but a low specificity. Consequently, sensitization does not PKC 412 (Midostaurin) correlate well with allergy [4]. If the analysis of CMA were only based on sIgE or SPT results, a group of sensitized but non-allergic subjects would uselessly undergo a CM-exclusion diet. Hence, Oral Food Challenge (OFC) is still considered as the platinum standard for CMA analysis, despite being expensive, time-consuming, and possibly causing allergic reactions which may actually result in anaphylaxis. It has been demonstrated that, the greater the food-sIgE levels and the SPTs wheal size, the higher the chances that patients react during an OFC [4]. This is the reason why some authors have investigated if it is possible to establish a cut-off for sIgEs and SPTs to CM or its proteins, that could forecast by itself whether a patient would react to an OFC. Several studies showed that cut-offs may vary with age [5], and earlier PKC 412 (Midostaurin) reviews proposed practical indications to diagnose of food allergy and suggest different diagnostic cut-offs for children, based on age [6C8]. However, cut-offs may vary also because of the cooking degree [9] or the type of allergen used to perform SPTs (commercial draw out vs. raw milk). Thus, in the present Systematic Review, we grouped studies relating to these three factors. The aim of this study was to compare, in children with suspected CMA, the levels of sIgEs and the wheal sizes of SPTs for CM or its three main allergenic molecules (-lactalbumin (LA), -lactoglobulin (LG), and casein) with the Research Standard (RS) test, OFC, in order to determine any validated cut-off value. We analyzed available data from a methodological perspective and tried to provide practical clinical indications for the analysis of CMA in children. At the best of our knowledge, such a classification has never been regarded as in previous studies [6C8]. Methods Inclusion and exclusion criteria for considering studies for this systematic review We included studies in which authors looked for any cut-off value for SPTs or sIgEs levels for the analysis of CMA in children. In most cases, analysis was based on the results of the OFC. Studies were also considered whenever a obvious relationship between CM exposure and allergic reaction was highlighted and sIgE or SPTs were carried.
