Milk allergy is an adverse immune reaction to one or more of the protein constituents of cow's milk. Symptoms can be rapid or gradual in onset. The former may include anaphylaxis, a potentially life-threatening condition which requires treatment with epinephrine. The latter can take hours to days to appear. Presentations may include atopic dermatitis, inflammation of the esophagus, enteropathy involving the small intestine and proctocolitis involving the rectum and colon.
Management is by avoiding eating any food that contains dairy. Exposure to low levels of milk proteins is a health risk. In people with IgE-mediated food allergy the individual threshold dose capable of provoking an allergic reaction can vary widely, but is in a low milligram range. In the United States, 90% of allergic responses to foods are caused by eight foods: cow's milk, eggs, wheat, shellfish, peanuts, tree nuts, fish, and soy beans. Allergy to cow's milk is the most common. The United States, Japan, and the European Union it is a requirement to note on the label foods that intentionally contain dairy. This does not apply to the ingredients present unintentionally or potentially, as a consequence of cross-contact situations during manufacturing (residue or trace amount).
To prevent an allergy from developing, 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 an extensively hydrolyzed cow's milk formula is recommended. Soy infant formula can be considered, but about 10 to 15% of babies allergic to cow's milk will also react to soy. In the United States, milk allergy affects between 2% and 3% of babies and young children. The majority of people outgrow milk allergy. Predictors for adult-persistence are anaphylaxis, high milk-specific serum immunoglobulin E (IgE), robust response to the skin prick test and absence of tolerance to milk-containing baked foods. Oral immunotherapy is being researched, but as of 2014 it is of unclear benefit.
Video Milk allergy
Signs and symptoms
Food allergies can have rapid onset (from minutes up to 2 hours), delayed onset (up to 48 hours or even 1 week), or combinations of both, depending on the mechanisms involved. Immediate reactions are usually IgE-mediated, whereas delayed reactions may also involve non-IgE-mediated immune mechanisms. Symptoms may include: rash, hives, itching of mouth, lips, tongue, throat, eyes, skin, or other areas, swelling of 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 vary from incident to incident. Serious danger regarding allergies 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. Anaphylaxis occurs when IgE antibodies are involved, and areas of the body that are not in direct contact with the food become affected and show severe symptoms. Untreated, this can proceed to vasodilation, a low blood pressure situation called anaphylactic shock, and death (very rare).
For milk allergy, non-IgE-mediated responses are more common than IgE-mediated. The presence 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 cutaneous 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 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 which will resolve when the offending food is removed from the infant's diet. FPIES can be severe, characterized by persistent vomiting 1-4 hours after an allergen-containing food, to the point of lethargy. Watery and sometimes bloody diarrhea can develop 5-10 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 vice versa. International consensus guidelines have been established for the diagnosis and treatment of FPIES.
Maps Milk allergy
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 acute changes that occur shortly after eating, and may progress to anaphylaxis
- Non-IgE mediated - characterized by an immune response not involving immunoglobulin E; may occur hours to days after eating, complicating 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 the foods we eat. Why some proteins trigger allergic reactions while others do is not entirely clear, although in part thought to be due to resistance to digestion. Because of this, intact or largely intact proteins reach the small intestine, which has a large presence of white blood cells involved in immune reactions. 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, which can then either subside or progress into 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 called (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 system-wide (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 due to 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: ?s1-, ?s2-, ?-, and ?-casein from casein proteins and ?-lactalbumin and ?-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 milk or cheese. For milk allergy, non-IgE-mediated responses are more common than 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 flare up of atopic dermatitis and gastroinstestinal symptoms, including chronic diarrhea, blood in the stools, gastroesophageal reflux disease (GERD), constipation, chronic vomiting and colic.
Diagnosis
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 immunoglobulin E (IgE or sIgE). A negative IgE test does not rule out non-IgE mediated allergy, also described as cell-mediated allergy. Confirmation is by double-blind, placebo-controlled food challenges, conducted by an allergy specialist. SPT and sIgE have sensitivity around 88% but specificity of 68% and 48%, respectively, meaning these tests will probably detect a milk sensitivity but will also be positive for other allergens.
Attempts have been made to identify SPT and sIgE responses accurate enough to avoid the need for a confirming oral food challenge. A systematic review stated that for children younger than two years, cut-offs for specific IgE or SPT seem to be more homogeneous and may be proposed. For older children the tests were less consistent. It 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
Milk allergy can be confused with other disorders that present similar clinical features, such as lactose intolerance, infectious gastroenteritis, celiac disease, inflammatory bowel disease, eosinophilic gastroenteritis, and pancreatic insufficiency, among others.
Lactose intolerance
Milk allergy is distinct from lactose intolerance, which is a nonallergic food sensitivity, due to the lack of enzyme lactase in the small intestines to break lactose down into glucose and galactose. Lactose intolerance does not cause damage to the gastrointestinal tract. There are four types: primary, secondary, developmental, and congenital. Primary lactose intolerance is when the amount of lactase declines as people age. Secondary lactose intolerance is due to 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 made from birth.
Prevention
Two reviews on avoiding common allergy-inducing foods during pregnancy or lactation concluded that there is no strong evidence 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 the Cochrane review concluded that more research is needed.
Guidelines from various government and international organizations recommend that for the lowest allergy risk, infants be exclusively breastfed for 4-6 months. There does not appear to be any benefit to extending that period beyond six months. If a nursing mother decides to start feeding with an infant formula prior to four months the recommendation is to use a formula containing cow's milk proteins.
A different consideration occurs when there is a family history - parent or older siblings - of milk allergy. In this situation there are recommendations to avoid formula that contains intact cow's milk proteins. Options are substituting a product containing extensively hydrolyzed protein, or non-dairy protein, or free amino acids. The hydrolyzing process breaks intact proteins into fragments, in theory reducing allergenic potential. In 2006 the U.S. Food and Drug Administration (FDA) rejected a health claim proposed by Nestle that a formula based on partially hydrolyzed whey protein would reduce risk of developing allergy. Ten years later the FDA reconsidered and allowed a health claim, with the caveat that the claim include wording to the effect that the scientific evidence was weak at best. A meta-analysis published the same year disputed this, concluding that based on dozens of clinical trials there was no evidence to support a claim that a partially hydrolyzed formula could reduce the risk of eczema.
Once an infant has demonstrated milk allergy symptoms to a formula containing intact cow's milk proteins, a dairy-based hydrolyzed formula is not appropriate. Soy formula is a common substitution, but infants with milk allergy may have an allergic response to soy formula. Hydrolyzed rice formula is an option, as are the more expensive amino acid-based formulas.
Treatment
The need for a dairy-free diet should be reevaluated every six months by testing milk-containing products low on the "milk ladder", such as fully cooked, i.e., baked foods containing milk, in which the milk proteins have been denatured, and ending with fresh cheese and milk. Desensitization via oral immunotherapy holds some promise but is still being actively researched (see Research).
Treatment for accidental ingestion of milk products by allergic individuals varies depending on the sensitivity of the person. An antihistamine such as diphenhydramine (Benadryl) may be prescribed. Sometimes prednisone will be prescribed to prevent a possible late phase Type I hypersensitivity reaction. Severe allergic reactions (anaphalaxis) may require treatment with an epinephrine pen, i.e., an injection device designed to be used by a non-healthcare professional when emergency treatment is warranted. A second dose is needed in 16-35% of episodes.
Avoiding dairy
Most people find it necessary to strictly avoid any item containing dairy ingredients. Exposure to low levels of milk proteins is a health risk. In people with IgE-mediated food allergy a tiny amount of a few milligrams is able to promote allergic reactions. The individual threshold dose capable of provoking an allergic reaction can vary, and probably depend on the age group. About 1% of people allergic to milk reacts to few hundred micrograms of protein and 5% reacts to less than 30 milligrams. Infants could be at a higher risk of reactions caused by trace amounts than older children.
Beyond the obvious (anything with milk, cheese, cream, butter, or yogurt in the name), all food ingredient lists need to be examined. Many different ingredients contain milk proteins but often their names do not allow to know that they are derived from milk. Some examples are casein, caseinates (any form: calcium caseinate, sodium caseinate, etc.), curd, ghee, lactalbumin, lactoferrin, lactoglobulin, rennet, sour cream, and whey.
In general, milk from other species (goat, sheep...) should not be substituted for cow's milk, as milk proteins from other mammals are often cross-reactive. Nevertheless, some people with cow's milk allergy can tolerate goat's or sheep's milk, and vice versa. Milk from camels, pigs, reindeer, horses, and donkeys may also be tolerated in some cases.
Probiotic products have been tested, and some found to contain milk proteins which were not always indicated on the labels.
Cross-reactivity with soy
Infants - either still 100% breastfeeding or partially/entirely on infant formula - and also young children, are thought to be prone to a combined cow's milk and soy protein allergy referred to on various internet websites and blogs as milk soy protein intolerance (MSPI). Recommendations seen on these websites include that nursing mothers discontinue eating any foods that contain dairy or soy ingredients. There is at least one U.S. state government website that presents the same concept. However, a published scientific review stated that there was not yet sufficient evidence in the human trial literature to conclude that maternal dietary food avoidance during lactation would prevent or treat allergic symptoms in breastfed infants.
One review presented information on milk allergy, soy allergy and cross reactivity between the two in infants. Milk allergy was described as occurring in 2.2% to 2.8% of infants and declining with age. Soy allergy was described as occurring in zero to 0.7% of young children. According to several studies cited in the review, between 10% and 14% of infants and young children with confirmed cow's milk allergy were determined to be co-sensitized to soy and in some instances have a clinical reaction to soy. The research does not address whether the cause was two separate allergies or a cross-reaction due to a similarity in protein structure, as which occurs for cow's milk and goat's milk. For this reason, recommendations are that infants diagnosed as allergic to cow's milk infant formula be switched to an extensively hydrolyzed protein formula rather than a soy whole protein formula.
Regulation of labeling
In response to the risk that certain foods pose to those with food allergies, some countries have responded by instituting labeling laws that require food products to clearly inform consumers if their products contain major allergens or byproducts of major allergens. The U.S. Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA) requires companies to disclose on the label whether the product contains a major food allergen added intentionally: cow's milk, peanuts, eggs, shellfish, fish, tree nuts, soy and wheat. This list originated in 1999 from the World Health Organisation Codex Alimentarius Commission. FALCPA applies to foods regulated by the FDA, which does not include poultry, most meats, certain egg products, and most alcoholic beverages. The allergens have to clearly be called out in the ingredients list. Most companies selling food products in the United States additionally list ingredient allergens in a separate statement. To meet FALCPA labeling requirements, when an ingredient is derived from a major food allergen, its "food source name" must necessarily appear just once in the list of ingredients. For example, "casein (milk)". Dairy food listing is mandatory in the European Union and more than a dozen other countries.
The value of allergen labeling is controversial. Residues or trace amounts are not mandatory, that is to say, ingredients present unintentionally or potentially as a consequence of cross-contact or cross-contamination at any point along the food chain (during raw material handling, due to shared equipment or processing lines, during transport or storage, etc.). If allergen labeling is to be useful to consumers and healthcare professionals who advise and treat those consumers, ideally there should be agreement on which foods require labeling, threshold quantities below which labeling may be of no purpose, and validation of allergen detection methods to test and potentially recall foods that were deliberately or inadvertently contaminated.
Labeling regulations have been modified to provide for mandatory labeling of ingredients plus voluntary labeling, termed precautionary allergen labeling (PAL), also known as "may contain" statements, for possible, inadvertent, trace amount, cross-contamination during production. PAL labeling can be confusing to consumers, especially as there can be many variations on the wording of the warning. As of 2014 PAL is only regulated in Switzerland, Japan, Argentina, and South Africa. Argentina decided to prohibit precautionary allergen labeling since 2010, and instead puts the onus on the manufacturer to control the manufacturing process and label only those allergenic ingredients known to be in the products. South Africa does not permit the use of PAL, except when manufacturers demonstrate the potential presence of allergen due to cross-contamination through a documented risk assessment and despite adherence to Good Manufacturing Practice.
Lack of compliance with labeling regulations is also a problem. As an example, the U.S. Food and Drug Administration (FDA) documented failure to list milk as an ingredient in dark chocolate bars. The FDA tested 94 dark chocolate bars for the presence of milk. Only six listed milk as an ingredient, but of the remaining 88, the FDA found that 51 of them actually did contain milk proteins. Many of those did have PAL wording such as "may contain dairy." Others claimed to be "dairy free" or "vegan" but still tested positive for cow's milk proteins.
Prognosis
Milk allergy typically presents in the first year of life. The majority of children outgrow milk allergy by the age of ten years. One large clinical trial reported resolutions of 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. Children are better able to tolerate milk as an ingredient in baked goods relative to liquid milk. Resolution was more likely if baseline serum IgE was lower, or if IgE-mediated allergy was absent so that all that was present was cell-mediated, non-IgE allergy.
People with confirmed cow's milk allergy may also demonstrate an allergic response to beef, moreso to rare beef versus well-cooked beef. The offending protein appears to be bovine serum albumin. This is not the same beef allergy that is seen primarily in the southeastern United States, triggered by being bitten by a Lone Star tick.
Milk allergy has consequences. In a U.S. government diet and health surveys conducted in 2007-2010, 6,189 children ages 2-17 years were assessed. For those classified as cow's milk allergic at the time of the survey, mean weight, height and body-mass index were significantly lower than their non-allergic peers. This was not true for children with other food allergies. Diet assessment showed a significant 23% reduction of calcium intake and near-significant trends for lower vitamin D and total calorie intake.
Epidemiology
Incidence and prevalence are terms commonly used in describing disease epidemiology. Incidence is newly diagnosed cases, which can be expressed as new cases per year per million people. Prevalence is the number of cases alive, expressible as existing cases per million people during a period of time. Milk allergies are usually observed in infants and young children, and often disappear with age (see Prognosis), so prevalence of egg allergy may be expressed as a percentage of children under a set age. Milk allergy affects between 2% and 3% of infants in developed countries. This estimate is for antibody-based allergy; prevalence of allergy based on cellular immunity is unknown.
For all age groups, a review of fifty studies conducted in Europe estimated 6.0% for self-reported milk allergy and 0.6% for confirmed. National survey data in the United States collected 2005-2006 showed that from age six and older, the prevalence of serum IgE confirmed milk allergy was under 0.4%.
Society and culture
Whether food allergy prevalence is increasing or not, food allergy awareness has definitely increased, with impacts on the quality of life for children, their parents and their immediate caregivers. In the United States, the Food Allergen Labeling and Consumer Protection Act of 2004 causes people to be reminded of allergy problems every time they handle a food package, and restaurants have added allergen warnings to menus. The Culinary Institute of America, a premier school for chef training, has courses in allergen-free cooking and a separate teaching kitchen. School systems have protocols about what foods can be brought into the school. Despite all these precautions, people with serious allergies are aware that accidental exposure can easily occur at other peoples' houses, at school or in restaurants. Food fear has a significant impact on quality of life. Finally, for children with allergies, their quality of life is also affected by actions of their peers. There is an increased occurrence of bullying, which can include threats or acts of deliberately being touched with foods they need to avoid, also having their allergen-free food deliberately contaminated.
Research
Desensitization, which is a slow process of eating tiny amounts of the allergenic protein, until the body is able to tolerate more significant exposure, results in reduced symptoms or even remission of the allergy in some people and is being explored for milk allergy. This is called oral immunotherapy (OIT). Sublingual immunotherapy, in which the allergenic protein is held in the mouth, under the tongue, has been approved for grass and ragweed allergies, but not yet for foods. Oral desensitization for cow's milk allergy appears to be relatively safe and may be effective, however further studies are required to understand the overall immune response, and questions remain open about duration of the desensitization.
There is research - not specific to milk allergy - on probiotics, prebiotics and the combination of the two (synbiotics) as a means of treating or preventing infant and child allergies. From reviews, there appears to be a treatment benefit for eczema, but not asthma, wheezing or rhinoconjunctivitis. The evidence was not consistent. Several reviews concluded that the evidence cannot yet be recommended for clinical practice.
See also
- Food allergy (has images of hives, skin prick test and patch test)
- List of allergens (food and non-food)
References
External links
- Milk Allergy at Food Allergy Initiative
Source of article : Wikipedia
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