Alpha Health Education

Allergy Center

Topics from the

Book of Allergy and Immunology

Immediate Hypersensitivity

Delayed Hypersensitivity

Hay Fever

Eczema

Hives

Asthma

Anaphylaxis

Food Allergy Center

Antihistamines

 Stephen  Gislason MD

The original concept of allergy included all immune-mediated disease and the term allergy was interchangeable with the term "hypersensitivity." An clinical immunology text will take the approach that allergy and autoimmune disease are the two major categories of hypersensitivity disease.

Allergy can be thought of as hypersensitivity disorders with external causes. Substances which trigger allergic responses are antigens, often proteins, that can be found in air, food and water. Airborne antigens such as plant pollens or house dust are well known.  Other airborne antigens and food antigens are less obvious. New and foreign substances introduced to the body such as drugs and herbs cause allergic reactions as the body identifies foreign antigens and then attempts to get rid of the alien.

Immediate and Delayed

The first distinction that recurs in the allergy literature is between immediate and delayed patterns of allergic reactivity which loosely correspond to IgE-mediated allergy and non-IgE mediated responses. Many authors refer to the original four categories of immune-mediated injury defined by Gell and Coombs. The concept of four mechanisms is just a starting point for understanding immune-mediated disease. These very complicated defense-injury sequences cause a variety of disease states.

The immediate or type 1 allergy pattern is easily recognized because it involves quick and dramatic symptoms. Hay fever is the most common type 1 allergy and can be diagnosed by allergy skin tests and by IgE antibody tests such as RAST or ELIZA. Delayed patterns of allergy are not so obvious and generally go unrecognized. Allergy skin tests do not show this problem.  Symptom onset is delayed many hours after exposure to the trigger. Allergic reactions to drugs such as penicillin and to foods is usually delayed hypersensitivity.

General Theory of Hypersensitivity Disease

Many of the major unsolved disease of our civilization are either degenerative and/or inflammatory and many are recognized to be immune-mediated or hypersensitivity diseases. The stakes are high both for individual patients and for the society as a whole. None of the hypersensitivity diseases have been solved, and most appear to rage on, afflicting increasing numbers of patients with chronic and disabling diseases.

Asthma, allergy, rheumatic diseases, autoimmune diseases, multiple sclerosis, type 1 diabetes, thyroiditis and psoriasis are examples of hypersensitivity diseases which involve humoral and cell-mediated immunity. The common specific problems that are obviously related to food allergy include asthma, rhinitis, otitis media, eczema (atopic dermatitis), hives (urticaria), anaphylaxis, angioedema, celiac disease, dermatitis herpetiformis, allergic gastroenteropathy, and allergic arthritis.

Many of the illnesses considered at this Web Site are expressions of hypersensitivity diseases in a continuum over time. Many patients will express a number of these hypersensitivity phenomena over a lifetime and demonstrate an underlying tendency to be hypersensitive. An important concern is the possibility that the chemical soup created by our civilization drives increasing numbers of individuals into hypersensitivity illness. The theory is that substances in the air, water and food supply can  drive immune networks into hypersensitive states and produce a variety of diseases.

A number of airborne chemicals, native food chemicals, food additives and contaminants are suspects in the generation of common and often non-specific forms of hypersensitivity. A group of patients present with shrinking tolerance to their environment and food supply. They report symptomatic responses to airborne chemicals and to  foods and many have limited their intake to a few foods, often with malnutrition as a consequence. The typical symptom complex involves gastrointestinal responses to foods followed by systemic responses - fatigue, myalgias, arthralgias, and cognitive dysfunction are the most common symptoms. Slow careful food re-introduction over several months may be tolerated and nutritional support is often required with nutrient supplements and an elemental nutrient formula. These common but ill-defined patterns of illness do not fit into the the standard definition of allergy and most of these patients report disappointing encounters with allergists who just do skin tests and then dismiss them when the tests are negative.

More on the General Theory

Name Confusion

There is confusion about the nature and mechanism of allergic reactions to foods. The confusion begins with the struggle over the meaning of the term "allergy", even among allergists and continues into the community where many improvised and nonsense tests and treatments for "food sensitivity" have become popular

The term "Food Intolerance" has been applied to metabolic derangements that occur when enzyme deficiencies such as lactase deficiency lead to intolerance of otherwise normal nutrients. Many physicians are more comfortable with the term "food intolerance" and are prepared to diagnose, for example, lactose intolerance when patients complain of gas, bloating and diarrhea. Other physicians prefer the term "food sensitivity" when a patient insists that eating certain foods bother them.

A common distinction in the allergy literature between food allergy and intolerance since 1984 has not helped to resolve the uncertainty about what mechanisms are operating in which patients. The growing tendency to limit the description "allergy" to those reactions that are IgE-mast cell mediated and to refer to symptom production otherwise as "food intolerance." The "intolerance" category includes the delayed patterns of food allergy. Bidndslev-Jensen C. et alsuggested that:

"No data demonstrate any major difference between food allergy and food intolerance concerning the type of symptoms elicited by food challenge... the time-course and dose relationship seem identical. The main difference between food allergy and food intolerance is the demonstration of the involvement of the immune system."

Strima and Bahna reported on conceptual differences on food allergy among US physicians.722 physicians from different specialties were polled. ENT physicians estimated the prevalence of food allergy at 21%; the mean estimate of prevalence was 12.9%. Symptom patterns were recognized in gastrointestinal tract , skin, CNS, respiratory tract and genitourinary tract. Proteins were identified as allergens by 68%, chemicals 22%, carbohydrates 7%, and fat 2%. The skin tests were not thought to be reliable and 49% of the food reactions were seen as delayed responses.

Clinical manifestations of food allergy can be separated into categories according to the patterns of illness and the time-course of symptom production. Only the immediate reactions appear to be IgE-mediated. Hill, for example, reported four clinical syndromes in children with milk allergy proven by cow's milk challenge in a hospital.

1. Anaphylactic - urticaria, angioedema, acute stridor, wheeze, syncope.
2. Episodic vomiting and/or diarrhea
3. Severe Colic
4. Chronic ill-health with multisystem disease, associated with failure to thrive and/or chronic diarrhea, and/or eczema, and/or bronchitic, wheezing symptoms.

These children also fell into three groups according to the nature and timing of symptoms following challenge with cow's milk.

Immediate onset - within one hour - generalized or perioral skin eruptions, vomiting, coughing, wheezing, stridor; high incidence of IgE antibodies to milk.

Intermediate- gastrointestinal symptoms developing within 24 hours - irritability, colic, vomiting, diarrhea. Low incidence of IgE antibodies. IgA deficiency was common.

Delayed - skin, respiratory, gastrointestinal tract and systemic symptoms - eg. diarrhea 24 hours after milk challenge in an infant presenting with failure to thrive, serum IgG anti-milk antibodies and elevated total IgM..

Immediate Reactions -Type 1 Hypersensitivity -

Patients who tend to have type 1 reactions are easily identified by their history; they tend to have hay fever, asthma, and eczema, as do family members. This triad of allergic manifestations has been called "atopy". An inherited tendency to make excessive amounts of IgE antibody is one characteristic of atopic individuals.    The type I food reactions tend to be immediate, dramatic and easily recognized by patients. Typical type 1 reaction patterns are anaphylaxis, acute abdominal pain, vomiting and diarrhea. Skin tests are useful in diagnosing inhalant allergies in atopic patients and will reveal some but not all food allergy. The skin test detects sub-dermal mast cells armed with antigen-specific IgE. Mast cell populations are heterogeneous. The reactivity of the skin mast cells correlates well with mast cells of the nose and less well or not at all with mast cells in other organs.

The desire for simple, definitive tests for food allergy is easy to understand, but difficult to fulfill. The idea of a simple office "test" for food allergy should seem unlikely if the complexity and variability of immune responses to food antigens is understood. The idea that standardized protein extracts of foods would be the most reliable and "scientific" tests for food allergy have been thwarted by observations that skin tests with fresh-extracts from food correlated better with symptoms on challenge testing. Food antigens can be complex, multiple, change and proliferate with cooking, digestion and food combinations. Patients who do not have a personal nor family history of atopy tend not to react to skin tests and generally the test is not useful with gastrointestinal disease and chronic illness caused by food.

American and Canadian allergists tend to focus on type 1 hypersensitivity mediated by IgE-armed basophils and mast cells. Some of these physicians view allergy practice as exclusively concerned with type I reactions and ignore or diminish any effort to describe, investigate and understand other forms of immune reactivity.

Thus two camps have arisen - the exclusively IgE group and the IgE plus other mechanisms group. Since the type 1 model is simpler, easier to study, and easier to deal with in practice, the exclusively IgE-group tends to dominate the allergy literature and this group tends to demand compliance with the IgE-model both in research and in clinical practice. The IgE model is simple and linear; the same responses are expected from a sensitized individual; skin tests, serum IgE measurement, and double-blind oral challenges are correlated

Even when applied to patients with clearly defined IgE-mediated allergy, the model is unrealistic since no human body is a linear machine. Single, discrete allergic responses do occur, but they are not the only reactions and are not fully characteristic of immune networks. Patients tend to have evolving and multiple reaction patterns over time, and show marked variability in their reactivity. Type 1 reactivity (manifesting as discrete "reactions") may be a marker for a more generalized hypersensitivity that will be expressed as chronic or, at least, chronically recurrent disease. The restrictive linear-model IgE definition of allergy has confused both patients and physicians who are not yet initiated into the esoteric issues of the trade.

Knowledge of the nature and mechanism of  allergic reactions to foods is limited. Uncertainty about mechanisms of food reactions continues into the community where many improvised and questionable tests and treatments for food allergy or "food sensitivity" have become popular. The relative neglect of food factors in medical practice creates interesting blind-spots in the handling of patients and the understanding of disease. A major shift of popular interest in food problems, however, has created a need for better informed physicians who are ready to grapple with the real-life issues of food, eating, and the multifaceted problem of adverse reactions to food. The subject of food allergy has never assumed the importance that it is due.

Many books in the popular literature talk about food allergy, sensitivity and intolerance. Many books and articles proclaim the benefits of diet revision and a ground-swell of interest and concern has engaged an ever-enlarging group of patients in the search for nutritional solutions to their health problems. A variety of practitioners have emerged with dubious schemes to  test for and treat "food sensitivity".  Some MD's, unfortunately, have retreated to the safe ground of ignorance & prejudice and believe that food allergy is something for quacks and charlatans and not real doctors.

Often, the patients who benefit from proper diet revision are distanced from a medical profession who is not interested or denies the problem of food allergy. Some of the issues that arise are semantic and political; some of the issues arise from vested interests attempting to control public opinion. Other issues involve the very complex biology of food-body interactions, which are not well understood. Yet other issues involve the changes in the food supply which have accelerated in the past few decades.

Mysterious Illnesses

When you do not know about food allergy mysterious diseases surround you. When you know about food allergy, a lot of common illness patterns begin to make sense. Linda Gamlin writing about food allergy in the New Scientist stated that: "Evidence is growing that many debilitating and chronic symptoms of ill health come from an intolerance for certain foods.

"The medical establishment finds many aspects of food intolerance difficult to swallow, but the main problem is the plethora of symptoms and the variations from one patient to another. Doctors working with food intolerance report more than 40 possible symptoms and conditions...the severity also varies. Some patients are said to have nothing more than the occasional migraine or bout of fatigue, while at the other end of the scale the sufferer is unable to work or lead any sort of normal life."