Lactose Intolerance versus Cow's Milk Allergy in Infants: A Clinical Dilemma

Abstract

Due to its very early introduction, cow's milk is one of the first foods that can cause adverse reactions in human beings. Lactose intolerance (LI) and cow's milk allergy (CMA) are the most common adverse reactions to cow's milk. While LI is due to insufficient small intestinal lactase activity and/or a large quantity of ingested lactose, CMA is an aberrant immune reaction to cow's milk proteins, particularly casein or β-lactoglobulin. However, the clinical manifestations of LI and CMA, particularly their gastrointestinal signs and symptoms, are very similar, which might lead to misdiagnosis or delayed diagnosis as well as nutritional risks due to inappropriate dietary interventions or unnecessary dietary restriction. Formula-fed infants with LI should be treated with formula with reduced or no lactose, while those with CMA should be treated with formula containing extensive hydrolyzed cow's milk protein or amino acids. This review is therefore written to assist clinicians to better understand the pathophysiologies of LI and CMA as well as to recognize the similarities and differences between clinical manifestations of LI and CMA.

Keywords: allergy; cow’s milk; lactase; lactose intolerance; protein.

Figure 1

Mechanism of lactose intolerance. Lactose intolerance (right) occurs due to insufficient small intestinal lactase activity and/or a large quantity of ingested lactose. Its clinical manifestations are due to the undigested lactose being fermented by intestinal microbes leading to the release of high amounts of gases and lactic acids as well as drawing water into the intestinal lumen, causing abdominal pain, flatulence and diarrhea or watery stools. In a sufficient amount of lactase (left), lactose will be hydrolyzed into glucose and galactose and absorbed in the intestinal mucosa.

Figure 2

The cascade of inflammation in cow’s milk allergy. Allergens’ exposure to inflammatory dendritic cells allow these cells to process and present allergen-derived peptides to naïve CD4⁺ T cells. In the presence of IL-4 (from an unknown source), naïve CD4⁺ T cells differentiate into proallergic T_H2 cells. Concurrently, it appears that there is an impairment of T_Reg cell frequency and/or activity, resulting in a lack of suppression of T_H2 cell activity. Subsequently, T_H2 cells will drive B cells, via cell contact as well as secreted IL-4 and IL-13, to undergo immunoglobulin class switch recombination, in which they eventually produce IgE. Along with antibody production, B cells also secrete significant amounts of κ and λ Ig-free light chains (Ig-fLCs). IgE and Ig-fLCs will then bind to mast cells and basophils, causing sensitization. Following subsequent exposure to allergens, cross-linking of surface-bound antibodies occurs, causing mast cells and basophils to degranulate and release their biologically active substances, including histamine, IL-4 and IL-5. Secreted IL-4 amplifies the differentiation between T_H2 and IgE-producing B cells, while secreted IL-5 by T_H2 cells causes accumulation and activation of eosinophils in the affected tissues. Similarly, histamine causes epithelial or endothelial cells to release eotaxin that attracts eosinophils into the tissues. Activated eosinophils release active substances, including major basic and eosinophilic cationic proteins that are toxic to the surrounding cells, contributing to further inflammation. This figure is reproduced with permission from reference [32].