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Cow’s milk allergy Stefania Arasi, Arianna Cafarotti, and Alessandro Fiocchi
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REVIEWC URRENT
OPINION Cow’s milk allergy
Stefania Arasi, Arianna Cafarotti, and Alessandro Fiocchi
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Purpose of review
To highlight the most recent insights on cow’s milk allergy (CMA), its treatment, and management.
Recent findings
CMA is one of the most common food allergies among children. Burdened by the risk for fatal reaction,
CMA may imply also a severe impairment of health-related quality of life at individual and family level as
well as well as individual and societal costs. The updated Diagnosis and Rationale for Action against
Cow’s Milk Allergy series is going to provide a series of manuscripts that will offer a comprehensive state-
of-the-art specifically on CMA, including international evidence-based recommendations. The current results
from randomized clinical trials highlight that oral immunotherapy may be effective by itself in providing
desensitization. Preliminary data suggest that biologicals such as omalizumab may be able to increase the
threshold of reactivity to milk or several foods (if multiple food allergies) without requiring allergen
exposure. Breastfeeding is the first choice for infants with CMA. Extensively hydrolyzed formula and amino-
acid formula are valid alternatives and may be particularly helpful when eliminating multiple foods, with
severe complex gastrointestinal food allergies, eosinophilic esophagitis, severe eczema, or symptoms while
exclusively breastfeeding. Heed is needed to ensure the formula is nutritionally sufficient. Due to a high
degree of cross-reactivity with cow’s milk proteins and risk for allergic reactions, goats’ milk or other
mammals’ milk should not be used.
Summary
The adoption and implementation of evidence-based recommendations may guide a proper diagnostics
and management and awaited advances in knowledge will allow the development of a personalized
treatment tailored on the specific CMA patient’s profile.
Keywords
breastfeeding, children, milk allergy, omalizumab, oral immunotherapy
INTRODUCTION Non-IgE-CMA encompasses a wide range of dis-
Cow’s milk allergy (CMA) is probably the most orders affecting mainly the gastrointestinal tract
common food allergy (FA) in infancy and child- (food protein-induced enterocolitis syndrome
hood. It usually starts in the first few months of [FPIES], food protein-induced allergic proctocolitis
life, upon the introduction of milk-based formula, [FPIAP], food protein-induced enteropathy [FPE],
which notably precedes the recommended time- celiac disease, and CMA-induced iron deficiency
frame for protective early introduction of other anemia [5], the skin (contact dermatitis to foods
allergenic foods, and usually tends to resolve with and dermatitis herpetiformis), and more rarely the
age [1,2]. lungs (Heiner syndrome [6]). Mixed forms include
Based on the underlying immune mechanism, intrinsic atopic dermatitis [7], and eosinophilic gas-
in agreement with the definitions of FA issued by the trointestinal disorders (EGIDs) such as eosinophilic
European Academy of Allergy and Clinical Immu- esophagitis (EoE) [8]. Efforts are devoted at
nology and the American National Institute of
Allergy and Infectious Diseases, CMA is classified,
Translational Research in Pediatric Specialities Area, Division of Allergy,
into: immunoglobulin E (IgE) mediated (IgE-CMA),
Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
non-IgE mediated, and mixed [3] (Fig. 1).
Correspondence to Stefania Arasi, MD, PhD, Allergy Unit, Bambino
IgE-CMA is characterized by the involvement of Gesù Children’s Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome,
a hypersensitivity reaction (type I reaction of Gell Italy. Tel: +39 06 68593570; fax: +39 06 68592218;
and Coombs), and immediate onset clinical mani- e-mail: stefania.arasi@opbg.net
festations ranging from mild oral symptoms up to Curr Opin Allergy Clin Immunol 2022, 22:181–187
severe anaphylaxis [4]. DOI:10.1097/ACI.0000000000000823
1528-4050 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. www.co-allergy.com
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
, Food allergy
comprehensive state-of-the-art notably on CMA,
KEY POINTS including international evidence-based recommen-
CMA is one the most common food allergy, mainly in dations on diagnosis, on replacement therapy, and
European countries. The burden for the individual, the on cow’s milk oral immunotherapy (CM-OIT). This
family and the entire society may be impactful due to review aims to provide an overview on the recent
the impairment on health, quality of life, and costs. evidence on CMA, focusing on epidemiology, diag-
nostics, and treatment.
One of the main need is to provide a scientifically
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correct diagnosis, in order to prevent
CMA overdiagnosis.
COW’S MILK ALLERGY EPIDEMIOLOGY
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There is currently lack in knowledge to inform evidence- AND NATURAL HISTORY
based recommendations for a proper diagnosis of non-
Most studies have shown an increase in sensitization
IgE CMA.
to foods and reported FA at the turn of the 21st
‘Precision medicine’ algorithms are needed to provide century. Notwithstanding, it is still debated if an
patient-tailored and therapeutic approach based on a increase in prevalence is due to increased self-report,
proper risk stratification assessment. rather than a real change in sensitization, incidence,
A better knowledge is pivotal to guide a shared or persistence of FA and CMA. Furthermore, recent
decision-making and implement the adoption of proper data seems to show that the prevalence of FA and
therapeutic strategies. CMA seems to have plateaued in the last decades.
Two large German birth cohorts (recruiting new-
born born between 2015 and 2019), KUNO Kids
(n ¼ 1139) and U1m SPATZ Health (n ¼ 1006) studies
have shown results similar to the Euro Prevall cohort
international level in order to improve knowledge (recruitment in 2005) [9]. The point prevalence of
and properly support patients, health professionals, parent-reported FA symptoms at the ages of 1 and
and different stakeholders involved. In particular, 2 years was 13.2% (95% CI:11.2–15.2) and 13.9%
the updated Diagnosis and Rationale for Action (95% Cl:11.5–17.2); doctor’s diagnosed FA at 1 and
against Cow’s Milk Allergy (DRACMA) series is 2 years was 2.4% (95% CI:1.6–3.4) and 2.7% (95%
going to offer a series of manuscripts to provide a CI:1.2–4.3) in KUNO Kids and 2.3% (95% CI:1.3– 3.6)
FIGURE 1. Classification of cow’s milk allergies according to the immunological mechanism involved.
182 www.co-allergy.com Volume 22 Number 3 June 2022
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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