Clinical Manifestation of Cow’s Milk Protein Allergy as a Complex Disorders
Clinical Manifestation of cow’s milk protein allergy
Cow’s milk is a leading cause of food allergy especially in infants and children. Symptoms of cow’s milk allergy are non-specific; as a result, suspected cow’s milk allergy is far more common than proven allergy to cow’s milk. Cow’s milk allergy in infants is therefore most probably a fairly uncommon clinical picture; cow’s milk allergy is estimated to occur in less than one per cent of infants. The only valuable additional diagnostic tool is food challenge, preferably double blind.
A significant association between early neonatal exposure to cow’s milk formula feeding and subsequent development of CMPA/CMPI has been documented. The small amounts of ‘foreign’ protein in human milk may rather induce tolerance than allergic sensitization. The findings of specific IgE to individual cow’s milk proteins in cord blood of the majority of infants who later develop CMPA/CMPI suggests a prenatal sensitization may play a role in the pathogenesis of CMPA/CMPI. Perhaps a weak intrauterine education of low IgE-response may need to ‘boosted’ neonatally in order to cause clinical disease. The prognosis of CMPA/CMPI is good with a recovery of about 45-56% at one year, 60-77% at two years and 71-87% at three years. Associated adverse reactions to other foods, especially egg, soy, peanut and citrus develop in about 41-54%. Allergy to potential environmental inhalant allergens has been reported in up to 28% by three years and up to 80% before the age of puberty. Especially, infants with an early increased IgE response to cow’s milk protein have an increased risk of persisting CMPA, development of persistent adverse reactions to other foods and development of allergy against environmental inhalant allergens. Cow’s milk protein/intolerance (CMPA/CMPI), meaning reproducible adverse reactions to cow’s milk protein(s) may be due to the interaction between one or more milk proteins and one or more immune mechanisms, possible any of the four basic types of hypersensitivity reactions. Immunologically mediated reactions are defined as CMPA. Mostly, CMPA is caused by IgE-mediated (type I) reactions, but evidence for type III (immune complex) reactions and type IV (cell mediated reactions) have been demonstrated. Non immunologically reactions against cow’s milk protein(s) are defined as CMPI. However, it should be stressed that many studies on ‘cow’s milk allergy’ have not investigated the immunological basis of the clinical reactions. In most instances of cow’s milk protein hypersensitivity only diagnostic investigations such as skin prick test and RAST indicative of IgE-mediated reactions are performed. In fact, CMPA cannot be ruled out unless extensive diagnostic tests for type II-III-IV reactions have proved negative. Thus, the classification of adverse reactions to cow’s milk proteins depends on the extent and the quality of performed diagnostic tests for immune mediated reactions. At present, no single laboratory test is diagnostic of CMPA/CMPI, and differentiation between CMPA and CMPI cannot be based solely on clinical symptoms. Therefore the diagnosis has to be based on strict well-defined elimination and milk challenge procedure. Preferably, double-blind placebo-controlled challenges (DBPCFC) should be carried out in children older than 1-2 years of age. In infants open controlled challenges have been shown to be reliable when performed under professional observation in a hospital setting
Between 5% and 15% of infants show symptoms suggesting adverse reactions to cow’s milk protein (CMP),1 while estimates of the prevalence of cow’s milk protein allergy (CMPA) vary from 2% to 7.5%.2 Differences in diagnostic criteria and study design contribute to the wide range of prevalence estimates and underline the importance of an accurate diagnosis, which will reduce the number of infants on inappropriate elimination diets. CMPA is easily missed in primary care settings and needs to be considered as a cause of infant distress and diverse clinical symptoms. Accurate diagnosis and management will reassure parents. CMPA can develop in exclusively and partially breast-fed infants, and when CMP is introduced into the feeding regimen. Early diagnosis and adequate treatment decrease the risk of impaired growth
Cow’s milk protein (CMP) is usually one of the first complementary foods to be introduced into the infant’s diet and is commonly consumed throughout childhood as part of a balanced diet. CMP is capable of inducing a multitude of adverse reactions in children, which may involve organs like the skin, gastrointestinal (GI) tract or respiratory system. The diagnosis of CMP-induced adverse reactions requires an understanding of their classification and immunological basis as well as the strengths and limitations of diagnostic modalities. In addition to the well-recognised, immediate-onset IgE-mediated allergies, there is increasing evidence to support the role of CMP-induced allergy in a spectrum of delayed-onset disorders ranging from GI symptoms to chronic eczema. The mainstay of treatment is avoidance of CMP; this requires dietetic input to ensure that this does not lead to any nutritional compromise.
EVALUATION OF AN INFANT WITH SUSPECTED CMPA
A comprehensive history (including a family history of atopy) and careful physical examination form the foundation of both algorithms. The risk of atopy increases if a parent or sibling has atopic disease (20–40% and 25–35%, respectively), and is higher still if both parents are atopic (40–60%). In comparison to cow’s milk formula-fed infants, exclusive breast feeding during the first 4–6 months of life reduces the risk for CMPA and most severe allergic manifestations during early infancy. The distinction between breast-fed and formula-fed infants reflects the importance of ensuring an adequate duration of breast feeding. Management principles also differ. The management of breast-fed infants depends on reducing the maternal allergen load and strict avoidance of CMP in supplementary feeding. It is recommended that exclusive or partial breast feeding is continued, unless alarm symptoms require a different management.The earlier CMPA develops, the greater the risk of growth retardation
Clinical manifestations of CMA
|Gastrointestinal tract||Frequent regurgitation|
|Constipation (with/without perianal rash)|
|Blood in stool|
|Iron deficiency anaemia|
|Swelling of lips or eye lids (angio-oedema)|
|Urticaria unrelated to acute infections, drug intake or other causes|
|Respiratory tract||Runny nose (otitis media)20 21|
|(unrelated to infection)||Chronic cough|
|General||Persistent distress or colic (wailing/irritable for ⩾3 h per day) at least 3 days/week over a period of >3 weeks|
*Infants with CMPA in general show one or more of the listed symptoms.
Alarm symptoms and findings indicating severe CMPA as the possible cause
|Organ involvement||Symptoms and findings|
|Gastrointestinal tract||Failure to thrive due to chronic diarrhoea and/or refusal to feed and/or vomiting|
|Iron deficiency anaemia due to occult or macroscopic blood loss|
|Endoscopic/histologically confirmed enteropathy or severe colitis|
|Skin||Exudative or severe atopic dermatitis with hypoalbuminaemia or failure to thrive or iron deficiency anaemia|
|Respiratory tract||Acute laryngoedema or bronchial|
|(unrelated to infection)||obstruction with difficulty breathing|
Unusual clinical presentations of CMA
Unusual clinical presentations are as much a feature of CMA as one might expect from such a ubiquitous allergen source in food and the environment as milk
Unusual clinical manifestations and routes of exposure
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Links Article Cow’s Milk Allergy
- The Natural History of Cow’s Milk Allergy
- Clinical Manifestation of Cow’s Milk Protein Allergy as a Complex Disorders
- Update Management of cow’s milk protein allergy in infants
- Special Reference Cow Milk Allergy
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