The Update Classification of Allergy and Hypersensitivity Diseases
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:
a) Compatible clinical history; and
b) 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 (3).
A series of adverse reactions to foods do not involve an immune response and are not considered food allergies (4). These include metabolic disorders (for instance, lactose and alcohol intolerance), responses to pharmacologically active food components, as caffeine, theobromine in chocolate or tyramine 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 intolerances”, this term should not be used to define an allergic reaction (5). Host factors such as lactase deficiency, which are associated with lactose intolerance, or idiosyncratic responses may be responsible for other non-allergic reactions to foods.