The history of allergy makes interesting reading. In the 1870's,
grass pollens were identified as the trigger for seasonal hay
fever symptoms in the U.K., based on conjunctival provocation
using crude pollen extracts and the induction of a localized weal
and flare when used for skin testing. By 1916, skin testing had
become a widespread technique for confirming the presence of allergy,
although the mechanism remained obscure.
In 1919, Ramirez described a patient who developed
horse-allergic asthma for the first time after he had been transfused
using blood from a horse allergic donor. This suggested that "allergy"
could be transferred by a serum-derived factor. This hypothesis
was confirmed by Kustener (who was fish allergic) by injecting
his own serum into a colleague's skin, thereby passively transferring
sensitivity to fish with skin testing to his colleague.
It was only relatively recently (in 1967) that
Ishizaka defined Immunoglobulin E as this serum factor, named
for the "Erythema" induced by skin testing. It took
another 5 years before IgE receptors were identified on mast cells
and basophils, and to show that cross-linking of surface IgE would
lead to degranulation and mediator release.
IgE is produced by plasma cells, predominantly
in lymphoid tissue adjacent to the respiratory and gastrointestinal
tracts. Adult levels of IgE are reached by the age of 10 - 15
years, and are present in a non-linear distribution in the population.
Seasonal variation two to four fold of IgE occurs throughout the
year.
It is often erroneously assumed that an elevated
IgE makes an allergic explanation for obscure symptoms more likely,
and that a normal result virtually excludes the diagnosis. In
fact, increased IgE is observed in only 30% of patients with allergic
rhinitis, 60% of patients with asthma and in 80 - 90% of patients
with significant atopic eczema. An elevated IgE in conditions
such as urticaria, for example, usually means that the patient
has one of these conditions, rather than a food allergy as a cause
of their hives !
Conversely, IgE may also be increased in 10
- 20% of patients with non-allergic rhinitis or non-allergic asthma,
or in conditions like allergic bronchopulmonary aspergillosis,
some forms of immunodeficiency, neoplasia such as lymphoma, and
parasitic disease.
Total IgE therefore has a poor positive and
negative predictive value for the presence or absence of atopic
disease. Since total IgE is the sum of multiple individual allergen
specific IgE, it is much more productive to assess allergen-specific
IgE. This may be evaluated by skin prick testing, in which small
amounts of protein is introduced into the dermis by pricking the
skin through a drop of allergen extract. If the patient is allergic,
this allergen will cross-link mast cell bound IgE molecules, resulting
in histamine release and the development of a weal and flare after
a period of 15 - 30 minutes. This is why antihistamines (and other
medications like some antidepressants with similar activity) can
interfere with skin testing.
By contrast, RAST testing generally suffers
from problems of poorer sensitivity and specificity. It nonetheless
has a role to play when skin testing is not possible for technical
reasons (such as the presence of severe eczema or dermographism),
where there is concern at inducing severe reactions with testing
(rare), and in some children.
It should be remembered, however, that not
all patients with symptoms of asthma, respiratory disease or eczema
are atopic. Approximately 20% of patients seen with asthma, eczema
or symptoms suggestive of allergic rhinitis have no evidence of
atopic disease whatsoever. The implications are that allergen
avoidance measures and immunotherapy are not warranted.
