*2.3. FA Diagnosis*

The diagnosis of FA was based on history, physical examination, COMISS evaluation, specific IgE in the blood, elimination and oral provocation tests.

COMISS (Cow's milk-related symptoms score) was assessed based on the standard questionnaire [37]. Scores ≥ 12 were regarded as indicating a high probability of FA. Other factors taken into consideration were: (i) in breastfed children: remission on elimination diet and relapse on reintroduction of milk, according to EAACI [38]; in children fed with milk formula: remission on elimination diet and positive outcome of open oral food provocation test according to ESPGHAN and EAACI [19,39], (ii) typical symptoms related to cow's milk protein intake (frequent regurgitation or vomiting; extended periods of diarrhea with negative microbiological tests; blood in stools; chronic poor weight gain on milk inclusion; iron deficiency anemia due to cryptic or macroscopic blood loss with stools and not due to infection or insufficient iron intake); eosinophilic enteropathy confirmed with endoscopy; running nose, wheezing and chronic coughing unrelated to infection; atopic eczema (moderate or severe, defined as persistent or frequently recurring eczema with typical morphology and distribution, requiring frequent need for prescription topical corticosteroids, calcineurin inhibitors, despite appropriate use of emollients.); urticarial (i.e., unrelated to infections, drug intake and other causes) swelling of skin or hives; recurrent itchy or flushed skin; anaphylaxis [19].
