milk allergy milk allergy milk allergy is an adverse immune reaction to one or more proteins in cow's milk. symptoms may take hours to days to manifest, with symptoms including atopic dermatitis, inflammation of the esophagus, enteropathy involving the small intestine and proctocolitis involving the rectum and colon. however, rapid anaphylaxis is possible, a potentially life-threatening condition that requires treatment with epinephrine, among other measures. not to be confused with lactose intolerance; see section #differential diagnosis. milk allergya glass of cow's milkspecialtyemergency medicineallergy & immunologysymptomsitchiness, rash, swelling of lips, tongue or the whole face, eczema, wheezing and shortness of breath, nausea, vomiting, abdominal pain, diarrhea, anaphylaxiscausestype i hypersensitivityrisk factorschildhood in developed countries where cow's milk infant formula is introduced to supplement or after breast feeding endsdiagnostic methodmedical history and standard allergy testspreventionintroduction to allergenic foods during infancytreatmentepinephrineantihistamines (mild)prognosisapproximately 20% persist into adulthoodfrequency2–3% in infants, declining to 0.6% in adults in the united states, 90% of allergic responses to foods are caused by eight foods, and cow's milk is the most common. recognition that a small number of foods are responsible for the majority of food allergies has led to requirements to prominently list these common allergens, including dairy, on food labels. one function of the immune system is to defend against infections by recognizing foreign proteins, but it should not overreact to food proteins. heating milk proteins can cause them to become denatured, losing their three-dimensional configuration and allergenicity, so baked goods containing dairy products may be tolerated while fresh milk triggers an allergic reaction. the condition may be managed by avoiding consumption of any dairy products or foods that contain dairy ingredients. for people subject to rapid reactions (ige-mediated milk allergy), the dose capable of provoking an allergic response can be as low as a few milligrams, so such people must strictly avoid dairy. the declaration of the presence of trace amounts of milk or dairy in foods is not mandatory in any country, with the exception of brazil. milk allergy affects between 2% and 3% of babies and young children. to reduce risk, recommendations are that babies should be exclusively breastfed for at least four months, preferably six months, before introducing cow's milk. if there is a family history of dairy allergy, then soy infant formula can be considered, but about 10 to 15% of babies allergic to cow's milk will also react to soy. the majority of children outgrow milk allergy, but for about 0.4% the condition persists into adulthood. oral immunotherapy is being researched, but it is of unclear benefit. signs and symptoms rapid and delayed response food allergies can be classified as rapid-onset (with symptoms manifesting within minutes to an hour or two), delayed-onset (up to 48 hours) or combinations of both, depending on the mechanisms involved. the difference depends on the types of white blood cells involved. b cells, a subset of white blood cells, rapidly synthesize and secrete immunoglobulin e (ige), a class of antibody that binds to antigens, the foreign proteins. thus, immediate reactions are described as ige-mediated. the delayed reactions involve non-ige-mediated immune mechanisms initiated by b cells, t cells and other white blood cells. unlike with ige reactions, there are no specific biomarker molecules circulating in the blood, and confirmation of the allergy is achieved by removing the suspect food from the diet and determining if symptoms dissipate as a result. symptoms signs and symptoms of anaphylaxis ige-mediated symptoms include: rash, hives, itching of the mouth, lips, tongue, throat, eyes, skin, or other areas, swelling of the lips, tongue, eyelids, or the whole face, difficulty swallowing, runny or congested nose, hoarse voice, wheezing, shortness of breath, diarrhea, abdominal pain, lightheadedness, fainting, nausea and vomiting. symptoms of allergies vary from person to person and may also vary from incident to incident. serious allergic danger can begin when the respiratory tract or blood circulation is affected. the former can be indicated by wheezing, a blocked airway and cyanosis, the latter by weak pulse, pale skin and fainting. when these symptoms occur, the allergic reaction is called anaphylaxis, which occurs when ige antibodies are involved and areas of the body not in direct contact with food become affected and show severe symptoms. untreated, this can proceed to vasodilation, a low-blood-pressure situation called anaphylactic shock and very rarely, death. non-lge-mediated symptoms for milk allergy, non-ige-mediated responses are more common than are those that are ige-mediated. the presence of certain symptoms, such as angioedema or atopic eczema, is more likely related to ige-mediated allergies, whereas non-ige-mediated reactions manifest as gastrointestinal symptoms, without skin or respiratory symptoms. within non-ige cow's milk allergy, clinicians distinguish among food protein-induced enterocolitis syndrome (fpies), food protein-induced allergic proctocolitis (fpiap) and food protein-induced enteropathy (fpe). common trigger foods for all are cow's milk and soy foods (including soy infant formula). fpiap is considered to be at the milder end of the spectrum and is characterized by intermittent bloody stools. fpe is identified by chronic diarrhea that dissipates when the offending food is removed from the diet. fpies can be severe, characterized by persistent vomiting one to four hours after an allergen-containing food is ingested, to the point of lethargy. watery and sometimes bloody diarrhea can develop five to ten hours after the triggering meal, to the point of dehydration and low blood pressure. infants reacting to cow's milk may also react to soy formula, and those reacting to soy formula may react to cow's milk. international consensus guidelines have been established for the diagnosis and treatment of fpies. mechanisms conditions caused by food allergies are classified into three groups according to the mechanism of the allergic response: ige-mediated (classic) – the most common type, manifesting as acute changes that occur shortly after eating, and may progress to anaphylaxis non-ige mediated – characterized by an immune response not involving ige; may occur hours to days after eating, complicating the diagnosis ige- and non-ige-mediated – a hybrid of the above two types allergic reactions are hyperactive responses of the immune system to generally innocuous substances, such as proteins in food. some proteins trigger allergic reactions while others do not. one theory is that resistance to digestion occurs when largely intact proteins reach the small intestine and the white blood cells involved in immune reactions are activated. the heat of cooking structurally degrades protein molecules, potentially making them less allergenic. allergic responses can be divided into two phases: an acute response that occurs immediately after exposure to an allergen but may subside and a late-phase reaction prolonging the symptoms of a response and resulting in more tissue damage. in the early stages of acute allergic reaction, lymphocytes previously sensitized to a specific protein or protein fraction react by quickly producing a particular type of antibody known as secreted ige (sige), which circulates in the blood and binds to ige-specific receptors on the surface of other kinds of immune cells called mast cells and basophils. both of these are involved in the acute inflammatory response. activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes and prostaglandins) into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation and smooth-muscle contraction. this results in runny nose, itchiness, shortness of breath and potentially anaphylaxis. depending on the individual, the allergen and the mode of introduction, the symptoms can be systemwide (classical anaphylaxis) or localized to particular body systems; asthma is localized to the respiratory system, while eczema is localized to the skin. after the chemical mediators of the acute response subside, late-phase responses can often occur because of the migration of other white blood cells such as neutrophils, lymphocytes, eosinophils and macrophages to the initial reaction sites. this is usually seen 2–24 hours after the original reaction. cytokines from mast cells may also play a role in the persistence of long-term effects. late-phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils. six major allergenic proteins from cow's milk have been identified: αs1-, αs2-, β-, and κ-casein from casein proteins and α-lactalbumin and β-lactoglobulin from whey proteins. there is some cross-reactivity with soy protein, particularly in non-ige mediated allergy. heat can reduce allergenic potential, so dairy ingredients in baked goods may be less likely to trigger a reaction than would milk or cheese. for milk allergy, non-ige-mediated responses are more common than are ige-mediated. the former can manifest as atopic dermatitis and gastrointestinal symptoms, especially in infants and young children. some will display both, so that a child could react to an oral food challenge with respiratory symptoms and hives (skin rash), followed a day or two later with a flareup of atopic dermatitis and gastrointestinal symptoms, including chronic diarrhea, blood in the stools, gastroesophageal reflux disease (gerd), constipation, chronic vomiting and colic. diagnosis further information: food allergy skin prick testing for allergies. for a positive response, the skin will become red and raised. diagnosis of milk allergy is based on the person's history of allergic reactions, skin prick test (spt), patch test and measurement of milk protein specific serum ige. a negative ige test does not rule out non-ige-mediated allergy, also described as cell-mediated allergy. confirmation is achieved by performing double-blind, placebo-controlled food challenges conducted by an allergy specialist. spt and ige have a sensitivity of around 88% but specificity of 68% and 48% respectively, meaning that these tests will most likely detect a milk sensitivity but may also yield false positive results for other allergens. attempts have been made to identify spt and ige responses accurate enough to avoid the need for confirmation with an oral food challenge. a systematic review stated that in children younger than two years, cutoffs for specific ige or spt seem to be more homogeneous and may be proposed. for older children, the tests were less consistent. the review concluded: "none of the cut-offs proposed in the literature can be used to definitely confirm cow's milk allergy diagnosis, either to fresh pasteurized or to baked milk." differential diagnosis the symptoms of milk allergy can be confused with other disorders that present similar clinical features, such as lactose intolerance, infectious gastroenteritis, celiac disease, non-celiac gluten sensitivity, inflammatory bowel disease, eosinophilic gastroenteritis and pancreatic insufficiency, among others. lactose intolerance hydrolysis of the disaccharide lactose to glucose and galactose main article: lactose intolerance milk allergy is distinct from lactose intolerance, which is a nonallergic food sensitivity caused by the lack of the enzyme lactase in the small intestines to break lactose down into glucose and galactose. the unabsorbed lactose reaches the large intestine, where resident bacteria use it for fuel, releasing hydrogen, carbon dioxide and methane gases. these gases are the cause of abdominal pain and other symptoms. lactose intolerance does not cause damage to the gastrointestinal tract. there are four types: primary, secondary, developmental and congenital. primary lactose intolerance is caused by decreasing levels of lactase brought on by age. secondary lactose intolerance results from injury to the small intestine, such as from infection, celiac disease, inflammatory bowel disease or other diseases. developmental lactose intolerance may occur in premature babies and usually improves over a short period of time. congenital lactose intolerance is an extremely rare genetic disorder in which little or no lactase is produced from birth. prevention research regarding prevention seeks to determine the possibility of reducing the risk of developing an allergy before it manifests. reviews have concluded that no strong evidence exists to recommend changes to the diets of pregnant or nursing women as a means of preventing the development of food allergy in their infants. for mothers of infants considered at high risk of developing cow's milk allergy because of a family history, there is some evidence that the nursing mother avoiding allergens may reduce risk of the child developing eczema, but a cochrane review concluded that more research is needed. there is some evidence that formula supplement given within the first 24 hours of a babies life in hospital increases the incidence of cow's milk allergy for mothers who then go on to exclusively breast feed. guidelines from various government and international organizations recommend that for the lowest allergy risk, infants be exclusively breastfed for four to six months, but