Immunotherapy Safety for the Primary Care ... - U.S. Coast Guard

J ALLERGY CLIN IMMUNOL
VOLUME 120, NUMBER 3
Cox et al S33
maintenance concentrate for the build-up phase or if the
patient cannot tolerate the maintenance concentrate.
The maintenance dose (or effective therapeutic dose)is
the dose that provides therapeutic efficacy without significant
adverse local or systemic reactions. The effective
therapeutic dose may not be the initially calculated projected
effective dose.
The maintenance goal (or projected effective dose) is
the allergen dose projected to provide therapeutic efficacy.
The maintenance goal is based on published studies, but a
projected effective dose has not been established for allergens.
Not all patients will tolerate the projected effective
dose, and some patients experience therapeutic efficacy
at lower doses.
The maintenance phase begins when the effective therapeutic
dose is reached. Once the maintenance dose is
reached, the intervals between the allergy injections are
increased. The dose generally is the same with each injection,
although modifications can be made based on several
variables (ie, new vials or a persistent large local reaction
causing discomfort). The intervals between maintenance
immunotherapy injections generally ranges from 4 to 8
weeks for venom and every 2 to 4 weeks for inhalant allergens
but can be advanced as tolerated if clinical efficacy is
maintained.
A major allergen is an antigen that binds to the IgE sera
from 50% or more of a clinically allergic group of patients.
Such allergens are defined either by means of immunoblotting
or crossed allergoimmunoelectrophoresis.
For a definition of projected effective dose, see maintenance
goal.
Rush immunotherapy is an accelerated immunotherapy
build-up schedule that entails administering incremental
doses of allergen at intervals varying between 15 and 60
minutes over 1 to 3 days until the target therapeutic dose
is achieved. Rush immunotherapy schedules for inhalant
allergens can be associated with a greater risk of systemic
reactions, particularly in high-risk patients (eg, those with
markedly positive prick/puncture test responses), and
premedication with antihistamines and corticosteroids
appears to reduce the risk associated with rush immunotherapy.
However, rush protocols for administration of
Hymenoptera VIT have not been associated with a similar
high incidence of systemic reactions.
Off the board into one syringe is a phrase that describes a
method of allergen immunotherapy preparation and administration
that involves specifically mixing the patient’s
allergenimmunotherapy injectionina single syringe,which
is not recommended. This syringe might be inserted into
more than one allergen extract vial, and this poses a risk of
cross-contamination of the allergen extracts and might dull
the needle with repeated penetration of the rubber stopper.
Shared specific patient vials is a method of allergen immunotherapy
preparation and administration in which the
allergy immunotherapy extract is withdrawn from a shared
vial (eg, mixed vespids or dust mite mix). This is sometimes
referred to as off the board, but it is distinct from
the method of off the board into one syringe in that the
syringe enters only one allergen extract vial.
INTRODUCTION
Immunity has been defined as protection against certain
diseases. The initial immunotherapeutic interventions,
which included the use of preventive vaccines and xenogenic
antisera by Jenner, Pasteur, Koch, and von
Behring, were effective for disease prevention. These
initial efforts in immune modulation served as a model for
later developments in the field of allergen immunotherapy.
From its humble empiric emergence in 1900, when
ragweed injections were proposed as therapy for autumnal
hay fever, allergen immunotherapy has progressed in both
theory and practice from the passive immunologic approach
to the active immunologic procedures pioneered
by Noon 19 and Freeman. 20,21 Advances in allergen immunotherapy
have depended on the improved understanding
of IgE-mediated immunologic mechanisms, the characterization
of specific antigens and allergens, and the standardization
of allergen extracts. Proof of the efficacy of
allergen immunotherapy has accumulated rapidly during
the past 10 years. Numerous well-designed controlled
studies have demonstrated that allergen immunotherapy
is efficacious in the treatment of allergic rhinitis, allergic
asthma, and stinging insect hypersensitivity. Some studies
have suggested that allergen immunotherapy might prevent
the development of asthma in individuals with allergic
rhinitis. 6-9
Effective subcutaneous allergen immunotherapy appears
to correlate with administration of an optimal
maintenance dose in the range of 5 to 20 mg of major
allergen for inhalant allergens, 22-26 and it should be differentiated
from unproved methods, such as neutralizationprovocation
therapy and low-dose subcutaneous regimens
based on the Rinkel technique, which have been found
to ineffective in a double-blind placebo-controlled
study. 27,28
SUMMARY STATEMENTS
Mechanisms of immunotherapy
Summary Statement 1: Immunologic changes during
immunotherapy are complex. D
Summary Statement 2: Successful immunotherapy is
associated with a change toward a T H 1 CD4 1 cytokine
profile. A
Summary Statement 3: Allergen immunotherapy is also
associated with immunologic tolerance, defined as a
relative decrease in allergen-specific responsiveness and
by the generation of CD4 1 CD25 1 regulatory T lymphocytes.
A
Summary Statement 4: Efficacy from immunotherapy
is not dependent on reduction in specific IgE levels. A
Summary Statement 5: Increases in allergen-specific
IgG antibody titers are not predictive of the duration and
degree of efficacy of immunotherapy. However, alterations
in the allergen-specific IgG specificity with immunotherapy
might play a role in determining clinical
efficacy. A