Page 1267 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Immunotherapy of Allergic Disease

Anthony J. Frew

Specific-allergen immunotherapy (SIT), or allergen desensiti- that SIT for one allergy can alleviate symptoms caused by different
zation, is used to treat various forms of allergic disease that allergens. Before deciding to use SIT, it is, therefore, essential to
involve type I hypersensitivity. SIT involves the administration of assess the patient’s condition carefully, especially the role of
allergen extracts to modify or abolish symptoms associated with allergic triggers.
exposure to relevant allergens. SIT is used for three distinct types SIT was pioneered over 100 years ago and developed as an
of allergic condition: anaphylaxis, rhinoconjunctivitis, and asthma. empirical science of pollen vaccination, based on the mistaken
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In anaphylaxis, the patient is completely well between episodes; concept that hay fever was caused by infection. Early studies
exposure is infrequent and unexpected but provokes an immediate found that giving large doses of pollen would trigger allergic
and potentially catastrophic response. However, since exposure reactions, so regimes that start with extremely low doses and
only occurs occasionally, it can be difficult to know whether the build up to a maintenance dose that is given every few weeks
treatment has been effective until an accidental exposure event were developed. A great deal has been learned about the immu-
occurs. Allergic rhinoconjunctivitis is clearly driven by allergen nological events associated with clinically successful SIT, but
exposure, which is low level and may be either continuous or uncertainties remain about which of these events is truly
intermittent. Exposure and clinical relevance are most obvious important in delivering the clinical benefit. New and modified
for seasonal rhinitis (caused by pollens or molds), occupational forms of SIT have been developed to deliver these immunological
rhinitis, and for rhinitis caused by animal danders. Because there effects more efficiently, but none of these, as yet, has the efficacy
is no seasonal variation in perennial rhinitis, it is more difficult to of the standard approach.
be sure that allergen exposure drives symptoms—in some cases it Following initial reports from the United Kingdom, SIT was
clearly does, but in others there may be nonallergic or structural developed in the 1920s–30s in North America, where some
causes for the symptoms. The value of SIT for rhinoconjunctivitis differences in practice emerged compared with European practice.
is generally clearer when exposure is predictable, but assessing In particular, American allergists tend to treat patients for all
efficacy is complicated by year-to-year variations in pollen sensitivities identified on skin testing, using personalized mixtures
exposure because of weather patterns and individual activity. of extracts prepared from bulk vials, whereas in Europe, patients
The third indication for SIT is asthma, where the role of allergen are normally treated with single allergens, which are supplied
exposure is different from that in rhinoconjunctivitis. As discussed directly by the manufacturer. However, pollens from different
elsewhere, allergen sensitization is a risk factor for developing grasses or trees are often combined. Mixtures of allergens from
asthma in childhood, but it is less clear whether allergen exposure different sources (e.g., mites and pollens) are used in some parts
has a role in ongoing asthma. At the very least, the fact that of Europe as custom mixes from manufacturers. Different
allergen avoidance measures are not usually effective in asthma approaches are also taken for standardization of extracts. Allergen
begs the question whether modifying the response to allergen extracts used in Europe are standardized by their ability to elicit
will influence established disease. It is inherently more risky to a weal, whereas US standardization has been based on erythema
use SIT to treat patients with asthma compared with treating rather than weal.
those who do not have asthma, so the benefits and risks must Whichever form of extract is chosen, patients are started on
be weighed carefully when considering the use of SIT to treat a very low dose of allergen, and the dose is then increased, usually
patients with asthma. at weekly intervals, until reaching the maintenance dose, which
The general principles of managing any allergic condition is then given at 4- to 6-weekly intervals for 3–5 years. Alternative
are to make an accurate diagnosis, identify relevant trigger factors, induction protocols may involve several doses on each day
institute appropriate interventions to reduce the impact of those (semirush), or the whole series of incremental injections may
triggers, and control symptoms and disease progression. Allergen be given in a single day (rush). The main drawback to rush and
avoidance measures may help but are rarely sufficient to avoid semirush protocols is the frequency of adverse reactions, which
the need for other therapies. Drug treatments can be very effective, occur much more often than with conventional protocols.
but they only work as long as the drugs are taken. SIT is the However, full protection can be attained in a few days compared
only current therapy that modifies the immune response to with the 3 months required in the conventional regime. Normally,
allergens. It is specific in that treatment is targeted at those the doses are given by subcutaneous injection, but since 1990,
allergens recognized by the patient and physician as responsible there has been increasing interest in SIT administered by the
for symptoms. Although claims have been made for bystander sublingual route, which is more convenient for patients and has
benefits on unrelated allergens, there is little convincing evidence some advantages in terms of safety.

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