Go To an Explanation of Prick Skin Test
Atopy is a form of immune response occuring in about 20 - 30% of the population and involving a different control mechanism than the classical immune response. The latter governs the immune response to foreign material such as viruses and bacteria. Atopy is defined as an inherited immune response in which excess IgE antibody is made to common substances such as foods, mites, dander pollens etc.[1] If both parents are allergic, there is a 50 - 70% likelihood that the child will be allergic[2][3][4]. If one parent is atopic then there is a 30 - 50% likelihood and even with neither parent allergic[5], there is still around 20% possiblity of atopy. The atopic immune response is associated with allergic diseases such as asthma, rhinitis, eczema and food allergy. These allergic diseases are diseases resulting from inflammation in certain target organs and the atopic immune response is a mechanism for creating inflammation usually involving a particular cell, the eosinophil.
It has been known for a long time that certain substances termed allergens, when pricked or injected into the skin of "sensitized" individuals would lead to an "immediate" reaction in the skin site resulting in a wheal (swelling) and flare (redness). This was demonstrated in 1921 by Prausnitz and Kustner who showed that intracutaneous injection of fish extract into a sensitive individual gave a wheal-flare reaction and this reaction could be transferred to "non-sensitized" individuals with serum from the sensitized subject. If the serum was injected into the skin of a non-sensitized individual and then a period of time allowed to pass after which the allergen was injected into the skin, an immediate reaction would occur specific for the allergen recognized by the sensitized serum donor. This ability of the appropriate serum to transfer an immediate reaction was termed "reaginic activity". In 1967, the Ishizakas showed that reaginic activity in serum was carried by an new class of immunoglobulins termed IgE.[6] In the past we thought the allergic response was governed by IgE antibodies that sit on the surface of cells such as mast cells and basophils. When these antibodies are cross-linked by binding allergen, a process is initiated by which these cells release soluble mediators, including histamine, tryptase, leukotrienes, and prostaglandins[7]. These mediators then result in effects such as dilatation of blood vessels, leaking of fluid from the vessels, constriction of smooth muscle and these cascading effects lead to an "immediate" allergic response. This immediate allergic response occurs within 15 - 20 minutes after the combination of allergen and antibody and is over in 1 - 2 hours. Since the immediate allergic reaction to allergen can create bronchospasm, it was thought to be the model for asthma and the other allergic diseases. While this model fits the clinical picture of anaphylaxis to a food allergen such as peanut, it did not fit the clinical picture of asthma which is a chronic indolent disease as opposed to sudden episodes of bronchospasm. There was a sea-change in our understanding of allergy when Dr. Jerry Dolovich of McMaster University in Canada described the late-phase reaction in the early 70s [8].
Dr. Dolovich performed a series of simple but elegant experiments in which he observed that the early wheal and flare reaction of a skin test which arose in 15 to 20 minutes and then subsided over the next 30 minutes to 1 hour (the immediate reaction) could be followed by a slower "late phase reaction" beginning at 2 hours as an ill-defined swelling of the skin around the site of the immediate reaction. The late phase reaction peaked at about 6 hours and biopsy of the involved skin showed edema with a sparse infiltrate of cells including eosinophils.
Numerous investigators confirmed Dr. Dolovich's observation[9],[10],[11],[12], and the description of the late-phase reaction led to an expansion of our thinking about the effects of allergen immune responses to include cellular inflammation, usually involving eosinophils. For example, Dr. Fred Hargreave, who with Dr. Jerry Dolovich had been investigating late asthmatic responses to allergen, [13] postulated that that response was a cell-mediated event.[14] These observations paved the way for a new understanding of the allergic immune response which now included a cellular inflammatiory component. That model has proven to be much more appropriate for the understanding of allergic diseases such as asthma.
Immunoglobulins of all classes are produced by B lymphocytes under the regulation of T lymphocytes specifically T-helper cells. In 1987, Dr. Tim Mosmann and colleagues studying clones of mouse T cells described a subset of T cells, termed Th2, that were associated with a pattern of cytokines that differed from another group of T cell clones termed Th1[15].Th2 cells produce interleukin-4 which plays a significant role in the production of IgE antibodies but also interleukin-5 which has a major effect on eosinophils. Eosinophils are the effector cells that are thought to be responsible for a significant portion of the cellular inflammatory events in allergic immune responses and are therefore thought to be responsible for the cellular pathology of allergic diseases such as rhinitis, asthma and eczema. It has now been shown that there are many cytokines or interleukins involved in the allergic immune response, some of which have a pro-inflammatoty effect and some an anti-inflammatory effect.
The papers cited are just a few in a voluminous literature that has begun to explain the nature of allergic disease. It is expected that as we come to understand the pathophysiogy of these diseases, better methods of treatment will follow.
If a child becomes allergic in the first two years of life, they generally react to food proteins such as milk, egg or peanut. Later, at around 3 years of age, the allergic response moves away from foods to aeroallergen sensitivity often animal danders. This observation was first made by the Swedish investigator, Dr. Tony Foucard[16] and confirmed by others including ourselves.[17],[18].
Foucard used the in vitro RAST test to quantitate the serum concentration of IgE antibodies to different antigens. By following the clinical course of the children, the investigators demonstrated that severe eczema was associated with food allergy but the eczema improved in the majority of children and many of them developed asthma and allergic rhinitis.[19]
The early and late phase response in allergy provides a basis for understanding the role of atopy in allergic diseases. Allergic rhinitis can be associated with immediate sneezing and itching and rhinorrhea which can be blocked successfully with an antihistamine. These acute symptoms can be accounted for by the immediate IgE-mediated allergic response. However the acute symptoms gradually give way to nasal obstruction due to swelling of the nasal mucosa. The swelling is associated with edema and cellular infiltrate into the mucos (lining) of the nose. The late phase and eosinophlic inflammation response explains these symptoms which do not respond well to antihistamine but can be treated with topical nasal steroid sprays. Similarly, each of the allergic diseases can be explained by the two phases of the atopic immune response with diseases such as anaphylaxis dependent to a greater degree on the immediate response i.e. release of mast cell mediators and diseases such as asthma and atopic dermatitis, more dependent on the late phase and cellullar portion of the allergic immune response.