Overview
Cow’s Milk Protein Allergy (CMPA) also known as Cow’s Milk Allergy (CMA) is one of the most common food allergies in infants and young children. Overall global prevalence probably ranges from 1 to 3%, though more recently the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) estimates a prevalence, based on a double blind placebo controlled food challenge (DBPCFC), to be < 1%.1 CMPA has been defined as, a reproducible adverse reaction to one or more milk proteins (usually caseins or whey beta-lactoglobulin) mediated through immunoglobulin (Ig) E and / or non-IgE mechanisms.2 CMPA occurs when the developing immune system responds negatively to the proteins found in milk or dairy products (e.g., milk, cheese, yogurt) from all ruminant animals (e.g., cow, sheep or goats), triggering an allergic reaction that causes a range of symptoms. IgE mediated CMPA can present as immediate reaction i.e. onset of symptoms within minutes (up to 2 hours) after ingesting the suspected food. Non IgE mediated CMPA tends to present as a delayed reaction, i.e. onset of symptoms within hours or days (possibly weeks) after ingesting the suspect food.
Symptoms
The non-specific signs and symptoms of CMPA, ranging from colic and reflux to constipation, sleeping problems, eczema, diarrhea and crying, make diagnosis a real challenge. Non-IgE–mediated CMPA in particular commonly includes different gastrointestinal manifestations, such as reflux and colic which overlap with many other infant conditions.1
The symptoms involve many different organ systems, predominantly the skin, the gastrointestinal and respiratory tracts. The involvement of two or more organ systems increases the likelihood of CMPA. 1,3
Diagnosis
The overall goal is to shorten the diagnosis process and reduce the patient burden. Three key steps were suggested by The European Academy of Allergy and Clinical Immunology (EAACI): 4,5
• Take an allergy-focused history
• Perform supportive IgE tests (when appropriate)
• Prepare the management plan
The IgE test results are interpreted along with the allergy-focused history. The diagnosis ideally should be confirmed through a diagnostic elimination diet followed by food reintroduction (food challenge). 1
The diagnostic elimination diet involves complete removal of cow’s milk protein (CMP) (or dairy) from the infant’s diet for 2-6 weeks. This includes eliminating CMP (dairy) from the mother’s diet, if they are breastfeeding or by the use of a hypoallergenic formula for the infant, with CMP (or dairy) free complementary feeding. If, after the elimination period, the symptoms do not improve, CMPA is highly unlikely. If symptoms do improve, an oral food challenge is usually performed. This is when CMP-based foods are re-introduced, in a controlled way, into the child’s diet to confirm the diagnosis of CMPA.
The Cow’s Milk related Symptom Score (CoMiSS TM ) is an awareness tool first developed by international experts in 2015. 6 It helps increase awareness of the most common symptoms seen in infants with CMPA supporting earlier diagnosis, and it may have a role in monitoring the response to a diagnostic elimination diet Vandenplas 2022. 6
Management of CMPA
Successfully managing cow’s milk protein allergy (CMPA) is always easier when it starts with an early, and accurate, diagnosis. Following the diagnosis, ongoing structured support is required for infants and young children with CMPA. In the first six months of an infant’s life, exclusive breastfeeding is recommended. In CMPA infants who are not exclusively breastfed (for whatever reason) then a hypoallergenic formula is necessary to ensure they receive all the nutrients required for growth and development. These formulas can be based on extensively hydrolyzed proteins such as whey or casein, or can be based on 100% free amino acids. Extensively hydrolyzed formulas (eHFs) with proven efficacy in children with CMPA are usually the first line choice for the majority of infants.1 When an eHF is ineffective at achieving symptom resolution (estimated to be <10%), or when the infant has had an anaphylactic reaction to cow’s milk/dairy, an amino acid-based formula (AAF) should be prescribed. 1
References
1. Vandenplas Y et al. An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386-413.
2. Hill DJ et al. The cow milk allergy complex: overlapping disease profiles in infancy. Eur J Clin Nutr. 1995 Sep;49 Suppl 1:S1-12.
3. Høst A et al. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy. 1990;45(8):587–96.
4. Skypala I.J et al. The development of a standardized diet history tool to support the diagnosis of food allergy. Clin Transl Allergy. 2015:5, 7.
5. Santos AF et al. EAACI guidelines on the diagnosis of IgE-mediated food allergy. Allergy. 2023 Dec;78(12):3057-3076.
6. Vandenplas Y et al. The Cow’s Milk Related Symptom Score: The 2022 Update. Nutrients 2022;14(13):2682.