Specific IgE and skin prick tests to diagnose allergy to fresh and baked cow’s milk according to age: a systematic review

BACKGROUND: The diagnosis of IgE-mediated cow’s milk allergy is often based on anamnesis, and on specific IgE (sIgE) levels and/or Skin Prick Tests (SPT), which have both a good sensitivity but a low specificity, often causing positive results in non-allergic subjects. Thus, oral food challenge is still the gold standard test for diagnosis, though being expensive, time-consuming and possibly at risk for severe allergic reactions. AIM: The aim of the present study was to perform a systematic review of the studies that have so far analyzed the positive predictive values for sIgE and SPT in the diagnosis of allergy to fresh and baked cow’s milk according to age, and to identify possible cut-offs that may be useful in clinical practice. METHODS: A comprehensive search on Medline via PubMed and Scopus was performed August 2017. Studies were included if they investigated possible sIgE and/or SPT cut-off values for cow’s milk allergy diagnosis in pediatric patients. The quality of the studies was evaluated according 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 according to patients’ age, allergen type and cooking degree of the milk used for the oral food challenge. In children < 2 years, CMA diagnosis seems to be highly likely when sIgE to CM extract are ≥ 5 KU(A)/L or when SPT with commercial extract are above 6 mm or Prick by Prick (PbP) with fresh cow’s milk are above 8 mm. Any cut-offs are proposed for single cow’s milk proteins and for baked milk allergy in children younger than 2 years. In Children ≥ 2 years of age it is hard to define practical cut-offs for allergy to fresh and baked cow’s milk. Cut-offs identified are heterogeneous. CONCLUSIONS: None of the cut-offs proposed in the literature can be used to definitely confirm cow’s milk allergy diagnosis, either to fresh 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.