Allergies are one of the most common chronic diseases. An allergy occurs when the body’s immune system sees a substance as harmful and overreacts to it. The substances that cause allergic reactions are allergens. When someone has allergies, their immune system makes an antibody called immunoglobulin E (IgE). Allergies occur when the body treats a harmless substance as a threat and the immune system produces an unnecessary response to it. In biomedical terms, it is an inappropriate immune response to a particular protein, often involving immunoglobulin E antibodies (IgE).
IgE-mediated allergic reactions are the most common and well understood, and cause conditions such as asthma, hay fever, allergic dermatitis and many food allergies. Non-IgE allergies, involving other antibodies, are rarer and more complex. The first step of developing an IgE allergy is sensitization: the immune system mistakenly produces IgE antibodies when it detects the presence of a certain protein.
These antibodies bind to the surface of white blood cells called mast cells, leaving them ‘sensitized’ to the substance. The next time the person comes across this allergen, mast cells with these specific antibodies attached release inflammatory substances, such as histamines and propagandist, which act on the surrounding tissues. Symptoms can be mild and localized to life threatening and affecting the entire body. Cross-reactive allergies occur when a person is sensitive to one allergen, but another substance has proteins on its surface that are similar enough to trigger the same allergic response.
- Allergies are reactions caused by the immune system as it responds to environmental substances that are usually harmless to most people. They may occur in response to a range of different material (called allergens), such as food, pollen, dust mites, animals, insect stings, or medicines. The ‘hygiene hypothesis’ has been around since the late 1980s, and suggests that exposure to bacteria and other substances reduce a child’s risk of developing allergies. It is thought that as our living conditions have improved, this exposure has been reduced, and this could in some way be influencing how our immune systems behave.
- In a similar vein, the ‘old friends mechanism’ suggests that exposure to bacteria helps form a healthy micro bio me (gut flora), which in turn helps us to develop a well-functioning immune system.
- It is generally accepted that food allergy affects approximately 2.5% of the general population, but the spread of prevalence data is wide, ranging from 1% to 10%. .Fish allergy prevalence ranges from 0% to 7% and the prevalence of shellfish allergy from 0% to 10.3%, depending on the method used for diagnosis.
- Researchers estimate that32 million Americans have food allergies, including 6 million children under age 18. That’s one in 13 children, or roughly two in every classroom.
The classification of allergic and hypersensitivity diseases was established by the European Academy of Allergy and Clinical Immunology (EAACI) and the World Allergy Organization (WAO) in 2004 (1). The definitions and concepts of allergic and hypersensitivity conditions beyond the allergy community have often created misunderstanding (2). For an optimal clarification:
- the term “atopy” is used when individuals have an IgE sensitization as documented by IgE antibodies in serum or by a positive skin prick test;
- “hypersensitivity” is defined as “conditions clinically resembling allergy that cause objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects”, and
- “Allergy” is defined “a hypersensitivity reaction initiated by proven or strongly suspected immunologic mechanisms”.
Based on these definitions, a correct diagnosis of allergic disease must adhere to the following conditions:
- Compatible clinical history
- Positivity to in vivo and/or in vitro tests to prove underlying mechanism and etiology.
The tests alone cannot be used because many people are sensitized (positive results to in vivo and/or in vitro tests), but not allergic (no reactions).
Specifically for ‘food allergy’, this term is used when a causal relationship (ideally, with a specific immunological mechanism) has been defined.
There are three broad groups of immune reactions: IgE-mediated, non-IgE-mediated and mixed. The IgE-mediated reactions are usually divided into immediate-onset reactions (arising up to 2 hours from the food ingestion) and immediate plus late-phase (in which the immediate onset symptoms are followed by prolonged or ongoing symptoms). Non-IgE-mediated reactions, which are poorly defined both clinically and scientifically, are believed to be generally T-cell-mediated.
They are typically delayed in onset, and occur 4 to 28 hours after ingestion of the offending food(s). Mixed IgE and non-IgE mediated reaction are conditions associated with food allergy involving both IgE- and non-IgE-mediated mechanisms A series of adverse reactions to foods do not involve an immune response and are not considered food allergies. These include metabolic disorders (for instance, lactose and alcohol intolerance), responses to pharmacologically active food components, as caffeine, the bromine in chocolate or thiamine in fermented cheeses, or toxic reactions.
Toxic reactions to food can occur in any patient, if a sufficient amount of the food is ingested; they are due to toxins in the food, e.g., to histamine in scombroid fish or bacterial toxins in food. While sometimes these, and other presumed food allergic reactions, are defined “food intolerance”, this term should not be used to define an allergic reaction. Host factors such as lactate deficiency, which are associated with lactose intolerance, or idiosyncratic responses may be responsible for other non-allergic reactions to foods
Mechanisms of Food Allergy
Typical food allergies are IgE-mediated, but several reactions involve different immunologic mechanisms. These food allergies are defined as non–IgE-mediated or mixed IgE- and non–IgE-mediated. The symptoms of IgE-mediated, non-IgE–mediated, and mixed IgE- and non–IgE-mediated food allergy are presented in IgE-mediated symptoms develop within minutes to 1-2 hours of ingesting the food, non–IgE-mediated and mixed IgE- and non–IgE-mediated food allergies present with their symptoms several hours after the ingestion of the food.
All these manifestations derive from a failure to develop or a breakdown of food tolerance, resulting in excessive production of food-specific IgE antibodies or in altered cellular events, leading to allergic reactions. Environmental influences and genetic factors of the host underlie the immune pathogenesis of food allergy and its manifestations. Some clinical studies have revised our understanding of the cause of food allergy. For example, functional genetic variants in the IL-12 receptor b1, Toll-like receptor 9, and thymic stromal lymphopoietin genes and even IL-4 gene polymorphism have been associated with an increased risk of food sensitization.
In the future, the elucidation of the gene-environment interactions will be crucial for understanding the food allergy pathogenesis. Micro biome, i.e., -omic, studies are an emerging field of interest to define allergy pathogenesis and, in a not too distant future; the micro biome could offer novel therapeutic possibilities.
Food allergy is described as an increasing disease over time. It is generally accepted that food allergy affects approximately 2.5% of the general population, but the spread of prevalence data is wide, ranging from 1% to 10%. Accurate determination of the prevalence is still one of the major problems with food allergy, considering that many factors influence the reported prevalence of food allergy.
The varied factors include differing criteria for making food allergy diagnosis, study methodologies, geographic variation, ages, and dietary exposures to name a few. In European birth cohorts, the incidence ranges from 2.18% (United Kingdom) to 0.07% (Greece) The most common foods, eaten separately or included as an ingredient, even in trace amounts (hidden food), that elicit hypersensitivity reactions are milk, egg, wheat, fish, and nuts.
Despite the fact that up to 2.5% of newborn during the first years of life are diagnosed as allergic to cow’s milk, recent European prevalence data fix the prevalence of cow’s milk allergy (CMA) to 0.7%
Within the Euro Prevall birth cohort, the mean adjusted incidence of hen’s egg allergy was 1.23% (10), while the Australian Health nuts study reports a prevalence of 9%
The prevalence of peanut allergy among children in the United Kingdom, North America, and Australia has been reported doubled in 10 years and is approximately 1.8%, 1.4%, and 3.0% respectively.
Fish allergy prevalence ranges from 0% to 7% and the prevalence of shellfish allergy from 0% to 10.3%, depending on the method used for diagnosis. The only study using food challenges report a prevalence of fish allergy of 0% – 0.3% and a prevalence of shellfish allergy ranging between 0% and 0.9%. Fish allergy seems more frequent in Asia than in Western countries Epidemiological studies reveal that among food-allergic infants, approximately 80% will reach tolerance by the fifth birthday, but 35% of them may eventually develop hypersensitivity to other foods.
Those with the highest IgE levels, with the most serious clinical manifestations (anaphylaxis and asthma), and with the wider co-sensitizations are less likely to overgrowth their food allergy. The natural history of food allergy also depends on the specific food sensitization, with children allergic to milk and egg displaying a better prognosis than those allergic to peanuts, tree nuts and fish
- v Cross-Reactivity and Food Allergens: Component Resolved Diagnosis (CRD) elucidated the link between a severe allergy to pollen and the increase of oral allergy syndrome (OAS), exercise induced asthma and anaphylaxis when eating certain foods. Such reactions are due to cross-reactive allergens as pathogenesis related (PR), profilins, or lipid transfer proteins (LTP). These proteins are ubiquitous in pollens, plants, fruits and food. Individuals sensitive to house dust mites have been reported with oral allergy syndrome following ingestion of shellfish Children with CMA may react to beef in up to 20% of cases, to goat’s milk in 98%, and to donkey milk in 20% of cases
IgE-Mediated Food-Related Disorders
Skin Manifestations: Acute urticarial and angioedema are the most frequent manifestation of food allergy. The onset of symptoms may be rapid, within minutes, following the ingestion of the offending food. Foods most often implicated include milk, fish, vegetables and fruits. In atopic dermatitis, also a frequent symptom of food allergy, immediate reactions can be followed by late cutaneous reactions.
Gastrointestinal Tract: Symptoms caused by immediate sensitivity in the gastrointestinal tract typically develop within minutes to 2 hours of ingesting the offending food. Symptoms can include lip, tongue and palatal pruritus and swelling, laryngeal edema, nausea, abdominal cramping, vomiting and diarrhea. Severe reactions can result in most or all symptoms associated with anaphylaxis.
Oral allergy syndrome (OAS), a form of contact urticarial confined to the lips and oropharynx, most commonly occurs in pollen-allergic patients. Symptoms include or pharyngeal itching, with or without facial angioedema, and/or tingling of the lips, tongue, palate and throat.
Respiratory Reactions: Allergic rhino conjunctivitis and asthma can occur following food challenge testing, but respiratory symptoms from food allergy in the absence of skin or gastrointestinal manifestations are rare. When respiratory symptoms occur following food challenge, both early- and late-phase IgE-mediated mechanisms are probably involved.
Systemic reaction: Anaphylaxis is an explosive systemic reaction. About 50% of anaphylaxis reactions are due to food allergy. It occurs within few minutes to hours after food ingestion Ninety per cent of patients experience skin (urticarial, angioedema) plus respiratory symptoms such as asthma, rhinitis or conjunctivitis; in 30% of the cases, they also develop gastrointestinal symptoms or hypotension, and shock and cardiac arrhythmias may occur. All of this is caused by the massive release of mediators from mast cells and basophile.
A form of anaphylaxis associated to food is the exercise-induced food-dependent anaphylaxis, occurring, generally, 2-4 hours after ingestion of a food to which the individual is allergic. Food or exercise alone will not cause this reaction. Risk factors for food-induced anaphylaxis include asthma and previous allergic reactions to the causative food.